Mijiao formula regulates NAT10-mediated Runx2 mRNA ac4C modification to promote bone marrow mesenchymal stem cell osteogenic differentiation and improve osteoporosis in ovariectomized rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The Mijiao (MJ) formula, a traditional herbal remedy, incorporates antlers as its primary constituent. It can effectively treat osteoporosis (OP), anti-aging, enhance immune activity, and change depression-like behavior. In this study, we investigated that MJ formula is a comprehensive treatment strategy, and may provide a potential approach for the clinical treatment of postmenopausal osteoporosis. AIM OF THE STUDY: The purpose of this study was to determine whether MJ formula promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and improved osteoporosis in ovariectomized rats by regulating the NAT10-mediated Runx2 mRNA ac4C modification. MATERIALS AND METHODS: Female Sprague-Dawley (SD) rats were used to investigate the potential therapeutic effect of MJ formula on OP by creating an ovariectomized (OVX) rat model. The expression of osteogenic differentiation related proteins in BMSCs was detected in vivo, indicating their role in promoting bone formation. In addition, the potential mechanism of its bone protective effect was explored via in vitro experiments. RESULTS: Our study showed that MJ formula significantly mitigated bone mass loss in the OVX rat model, highlighting its potential as an OP therapeutic agent. We found that the possible mechanism of action was the ability of this formulation to stabilize Runx2 mRNA through NAT10-mediated ac4C acetylation, which promoted osteogenic differentiation of BMSCs and contributed to the enhancement of bone formation. CONCLUSIONS: MJ formula can treat estrogen deficiency OP by stabilizing Runx2 mRNA, promoting osteogenic differentiation and protecting bone mass. Conceivably, MJ formulation could be a safe and promising strategy for the treatment of osteoporosis.

Specific molecular weight of Lycium barbarum polysaccharide for robust breast cancer regression by repolarizing tumor-associated macrophages.

The pro-tumorigenic M2-type tumor-associated macrophages (TAMs) in the immunosuppressive tumor microenvironment (TME) promote the progression, angiogenesis, and metastasis of breast cancer. The repolarization of TAMs from an M2-type toward an M1-type holds great potential for the inhibition of breast cancer. Here, we report that Lycium barbarum polysaccharides (LBPs) can significantly reconstruct the TME by modulating the function of TAMs. Specifically, we separated four distinct molecular weight segments of LBPs and compared their repolarization effects on TAMs in TME. The results showed that LBP segments within 50-100 kDa molecular weight range exhibited the prime effect on the macrophage repolarization, augmented phagocytosis effect of the repolarized macrophages on breast cancer cells, and regression of breast tumor in a tumor-bearing mouse model. In addition, RNA-sequencing confirms that this segment of LBP displays an enhanced anti-breast cancer effect through innate immune responses. This study highlights the therapeutic potential of LBP segments within the 50-100 kDa molecular weight range for macrophage repolarization, paving ways to offer new strategies for the treatment of breast cancer.

Improvement of 2D cine image quality using 3D priors and cycle generative adversarial network for low field MRI-guided radiation therapy.

BACKGROUND: Cine magnetic resonance (MR) images have been used for real-time MR guided radiation therapy (MRgRT). However, the onboard MR systems with low-field strength face the problem of limited image quality. PURPOSE: To improve the quality of cine MR images in MRgRT using prior image information provided by the patient planning and positioning MR images. METHODS: This study employed MR images from 18 pancreatic cancer patients who received MR-guided stereotactic body radiation therapy. Planning 3D MR images were acquired during the patient simulation, and positioning 3D MR images and 2D sagittal cine MR images were acquired before and during the beam delivery, respectively. A deep learning-based framework consisting of two cycle generative adversarial networks (CycleGAN), Denoising CycleGAN and Enhancement CycleGAN, was developed to establish the mapping between the 3D and 2D MR images. The Denoising CycleGAN was trained to first denoise the cine images using the time domain cine image series, and the Enhancement CycleGAN was trained to enhance the spatial resolution and contrast by taking advantage of the prior image information from the planning and positioning images. The denoising performance was assessed by signal-to-noise ratio (SNR), structural similarity index measure, peak SNR, blind/reference-less image spatial quality evaluator (BRISQUE), natural image quality evaluator, and perception-based image quality evaluator scores. The quality enhancement performance was assessed by the BRISQUE and physician visual scores. In addition, the target contouring was evaluated on the original and processed images. RESULTS: Significant differences were found for all evaluation metrics after Denoising CycleGAN processing. The BRISQUE and visual scores were also significantly improved after sequential Denoising and Enhancement CycleGAN processing. In target contouring evaluation, Dice similarity coefficient, centroid distance, Hausdorff distance, and average surface distance values were significantly improved on the enhanced images. The whole processing time was within 20 ms for a typical input image size of 512 × 512. CONCLUSION: Taking advantage of the prior high-quality positioning and planning MR images, the deep learning-based framework enhanced the cine MR image quality significantly, leading to improved accuracy in automatic target contouring. With the merits of both high computational efficiency and considerable image quality enhancement, the proposed method may hold important clinical implication for real-time MRgRT.

Modulation of smoker brain activity and functional connectivity by tDCS: A go/no-go task-state fMRI study.

Background: Transcranial direct current stimulation (tDCS) applied to particular brain areas may reduce a smoker's smoking cravings. Most studies on tDCS mechanisms are performed on brains in the resting state. Therefore, brain activity changes induced by tDCS during tasks need to be further studied. Methods: Forty-six male smokers were randomised to receive anodal tDCS of the left/right dorsolateral prefrontal cortex (DLPFC) or sham tDCS. A go/no-go task was performed before and after stimulation, respectively. Brain activity and functional connectivity (FC) changes during the task state before and after tDCS were used for comparison. Results: This study revealed that the anodal stimulation over one DLPFC area caused decreased activity in the ipsilateral precuneus during the go task state. Right DLPFC stimulation increased the FC between the bilateral DLPFCs and the right anterior cingulate cortex (ACC), which is closely associated with cognition and inhibition of executive functions. Additionally, the study showed variations in brain activity depending on whether the anode was positioned over the right or left DLPFC (R-DLPFC or L-DLPFC). Conclusion: During the go task, tDCS might exert a suppressive effect on some brain areas, such as the precuneus. Stimulation on the R-DLPFC might strengthen the FC between the right ACC and the bilateral DLPFCs, which could enhance the ability of behavioural decision-making and inhibition to solve conflicts effectively. Stimulating the L-DLPFC alone could increase the FC of bilateral DLPFCs with some brain regions associated with response inhibition.

Structural characteristics and structure-activity relationship of four polysaccharides from Lycii fructus.

At present, the structure-activity relationship of polysaccharides is a common and important focus in the fields of glycobiology and carbohydrate chemistry. To better understand the effect of specific polysaccharide structures on bioactive orientation, four homogeneous polysaccharides from Lycii fructus, one neutral along with three acidic polysaccharides, were purified, structurally characterized and comparatively evaluated on the antioxidative and anti-aging activities. The GC-MS-based monosaccharide composition analysis and methylation results showed that the LFPs had similar glycosyl types but varied proportions. Nuclear magnetic resonance (NMR) spectroscopy showed that LFPs consisted of arabinogalactan, rhamnogalacturonan and homogalacturonan structural domains. The results of the structure-activity relationship indicated that the antioxidative activity was positively correlated with the galacturonic acid (GalA) content, while the neutral multi-branched chains might be responsible for the anti-aging activity. This study is the first time to compare the principal structures and multiple biological activities of LFPs, which provided a reference for the industrial development and deep excavation of the health value of LFPs.

[Structure-activity relationship of Lycium barbarum polysaccharides].

As a traditional Chinese herb and functional food, the fruits of Lycium barbarum has been widely used for thousands of years in China. L. barbarum polysaccharides(LBPs) are predominant active components, which have immunomodulatory, antioxidant, hypoglycemic, neuroprotective, anti-tumor, and prebiotic activities. The molecular weight, monosaccharide composition, glycosidic bond, branching degree, protein content, chemical modification, and spatial structure of LBPs are closely related to their biological activity. Based on the previous studies of this research team, this paper systematically combed and integrated the research progress of structure, function, and structure-activity relationship of LBPs. At the same time, some problems restricting the clarification of the structure-activity relationship of LBPs were considered and prospected, hoping to provide references for the high value utilization of LBPs and in-depth exploration of their health value.

Identification of chromosome region and candidate genes for canary-yellow flesh (Cyf) locus in watermelon (Citrullus lanatus).

Genetic control of fruit flesh color in watermelon is complex, and significant knowledge gaps still exist. In the present study, we investigated the genetic basis of canary-yellow flesh color in watermelon inbred line PI 635597 using a segregating population derived from a cross between PI 635597 and another inbred line, Cream of Saskatchewan (pale yellow flesh color). We showed that a single dominant gene controls the canary-yellow flesh color for the Cyf (canary-yellow flesh) trait. Bulk segregant analysis (BSA) and fine genetic mapping narrowed down the Cyf locus to a 79.62-kb region on chromosome 6, which harbors 10 predicted genes. Sequence variation analysis in the promoter and coding regions and gene expression analysis in both parental lines and selected watermelon accessions with diverse fruit flesh colors support Cla97C06G122050 (unknown protein) and Cla97C06G122120 (pentatricopeptide repeat) as predicted candidate genes for the Cyf locus. Marker-assisted selection and sequence alignment showed that the Cyf locus could differentiate canary-yellow flesh and pale-yellow flesh. Our results indicate that the Cyf locus might be responsible for canary-yellow flesh color and carotenoid accumulation levels.

Enhanced CT-based texture analysis and radiomics score for differentiation of pleomorphic adenoma, basal cell adenoma, and Warthin tumor of the parotid gland.

OBJECTIVE: To evaluate the diagnostic performance of computed tomography (CT) radiomics analysis for differentiating pleomorphic adenoma (PA), Warthin tumor (WT), and basal cell adenoma (BCA). METHODS: A total of 189 patients with PA (n = 112), WT (n = 53) and BCA (n = 24) were divided into a training set (n = 133) and a test set (n = 56). The radiomics features were extracted from plain CT and contrast-enhanced CT images. After dimensionality reduction, plain CT, multiphase-enhanced CT, integrated radiomics signature models and radiomics score (Rad-score) were established and calculated. The receiver operating characteristic (ROC) curve analysis was taken for the assessment of the model performance, and then comparison was conducted among these models. Decision curve analysis (DCA) was adopted to assess the clinical benefits of the models. Diagnostic performances including sensitivity, specificity, and accuracy of the radiologists were evaluated. RESULTS: Seven, nine, fourteen, and fourteen optimal features were used to constructed plain scan, arterial phase, venous phase, and integrated radiomics signature models, respectively. ROC analysis showed these four models were able to differentiate PA from BCA and WT, with the area under the ROC curve (AUC) values of 0.79, 0.90, 0.87, and 0.94 in the training set, and 0.79, 0.89, 0.86, and 0.94 in the test set, respectively. The integrated model had better diagnostic performance than single-phase radiomics model, but it had similar diagnostic performance to that of the radiomics model based on the arterial phase (p > 0.05). The sensitivity, specificity, and accuracy in the diagnosis of PA were 0.86, 0.46, and 0.70 for the non-subspecialized radiologist and 0.88, 0.77, and 0.84 for the subspecialized radiologist, respectively. Six venous phase parameters were finally selected in differentiating WT from BCA. The predictive effect of the model was favorable, with AUC value of 0.95, sensitivity of 0.96, specificity of 0.83, and accuracy of 0.92. The sensitivity, specificity, and accuracy in the diagnosis between WT and BCA were 0.26, 0.87, and 0.45 for the non-subspecialized radiologist and 0.85, 0.58, and 0.77 for the subspecialized radiologist, respectively. CONCLUSION: The CT-based radiomics analysis showed favorable predictive performance for differentiating PA, WT, and BCA, thus may be helpful in the clinical decision-making.

Chinese Medicine, Succinum, Ameliorates Cognitive Impairment of Carotid Artery Ligation Rats and Inhibits Apoptosis of HT22 Hippocampal Cells via Regulation of the GSK3ß/ß-Catenin Pathway.

Succinum is an organic mineral formed from the resin of ancient coniferous and leguminous plants, which is applied for tranquilizing mood, promoting blood circulation, and removing blood stasis in Chinese medicine. For quite a long time, the modern research of succinum mainly focuses on the study of physical and chemical properties and authenticity identification while few reports on its medicinal mechanism. In current study, we evaluated different solvent extracts of succinum on carotid artery ligation rats mimicking vascular dementia. It was found that ethyl acetate extracts of succinum significantly improved the learning and memory abilities of model rats and inhibited neuronal apoptosis in the hippocampus. On a mice hippocampal neuronal cell line (HT22), ethyl acetate extracts of succinum also exerted better action trend in inhibiting cell apoptosis induced by oxygen glucose deprivation (OGD). By using XAV-939 on both in vivo and in vitro studies, it was found that ethyl acetate extracts of succinum might exert these functions by regulating the GSK3ß/ß-catenin pathway. These studies revealed the neuronal function of succinum, which explained the traditional effects of succinum and provided more modern scientific basis for its clinical application.

Smoking related attention alteration in chronic obstructive pulmonary disease-smoking comorbidity.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a respiratory disease that causes a wide range of cognitive impairments. Although COPD-Smoking comorbidity is common, the relationship between smoking and cognitive function in COPD-Smoking comorbidity remains unclear. This study aimed to investigate the effect of smoking on cognitive function like attention in COPD-Smoking patients. METHODS: In this study, we used the Montreal Cognitive Assessment (MoCA) scale and resting-state functional magnetic resonance imaging (fMRI) to explore the effect of smoking on attention in patients with COPD. RESULTS: Behavioral analysis revealed that among patients with COPD the smokers had a shorter course of COPD and showed a worse attention performance than the non-smokers. Resting-state fMRI analysis revealed that among patients with COPD smokers showed lower regional homogeneity (ReHo) value of the fusiform gyrus than non-smokers. Importantly, the ReHo of the fusiform gyrus is positively associated with attention and mediates the effect of smoking on attention in COPD. CONCLUSIONS: In summary, our study provides behavioral and neurobiological evidence supporting the positive effect of smoking on attention in COPD. This may be helpful for understanding and treating COPD and even other diseases comorbid with smoking.

Label-free coronavirus disease 2019 lesion segmentation based on synthetic healthy lung image subtraction.

PURPOSE: Coronavirus disease 2019 (COVID-19) has become a global pandemic and is still posing a severe health risk to the public. Accurate and efficient segmentation of pneumonia lesions in computed tomography (CT) scans is vital for treatment decision-making. We proposed a novel unsupervised approach using a cycle consistent generative adversarial network (cycle-GAN) which automates and accelerates the process of lesion delineation. METHOD: The workflow includes lung volume segmentation, healthy lung image synthesis, infected and healthy image subtraction, and binary lesion mask generation. The lung volume was first delineated using a pre-trained U-net and worked as the input for the following network. A cycle-GAN was trained to generate synthetic healthy lung CT images from infected lung images. After that, the pneumonia lesions were extracted by subtracting the synthetic healthy lung CT images from the infected lung CT images. A median filter and k-means clustering were then applied to contour the lesions. The auto segmentation approach was validated on three different datasets. RESULTS: The average Dice coefficient reached 0.666 ± 0.178 on the three datasets. Especially, the dice reached 0.748 ± 0.121 and 0.730 ± 0.095, respectively, on two public datasets Coronacases and Radiopedia. Meanwhile, the average precision and sensitivity for lesion segmentation on the three datasets were 0.679 ± 0.244 and 0.756 ± 0.162. The performance is comparable to existing supervised segmentation networks and outperforms unsupervised ones. CONCLUSION: The proposed label-free segmentation method achieved high accuracy and efficiency in automatic COVID-19 lesion delineation. The segmentation result can serve as a baseline for further manual modification and a quality assurance tool for lesion diagnosis. Furthermore, due to its unsupervised nature, the result is not influenced by physicians' experience which otherwise is crucial for supervised methods.

Structural elucidation of a novel arabinogalactan LFP-80-W1 from Lycii fructus with potential immunostimulatory activity.

Polysaccharides are the most important effective components of Lycii fructus, which has a variety of biological activities and broad application prospects in the fields of medicine and food. In this study, we reported a novel arabinogalactan LFP-80-W1 with potential immunostimulatory activity. LFP-80-W1 was a continuous symmetrical single-peak with an average molecular weight of 4.58 × 104 Da and was mainly composed of arabinose and galactose. Oligosaccharide sequencing analyses and NMR data showed that the LFP-80-W1 domain consists of a repeated 1,6-linked ß-Galp main chain with branches arabinoglycan and arabinogalactan at position C-3. Importantly, we found that LFP-80-W1 could activate the MAPK pathway and promote the release of NO, IL-6, and TNF-α cytokines in vitro. Therefore, our findings suggest that the homogeneous arabinogalactan from Lycii fructus, can be used as a natural immunomodulator.

Chinese Medicine Formula Kai-Xin-San Ameliorates Neuronal Inflammation of CUMS-Induced Depression-like Mice and Reduces the Expressions of Inflammatory Factors via Inhibiting TLR4/IKK/NF-κB Pathways on BV2 Cells.

Kai-Xin-San (KXS) is a traditional Chinese medicinal formula composed of Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma, and Poria for relieving major depressive disorder and Alzheimer's disease in traditional Chinese medicine (TCM) clinics. Previous studies on the antidepressant mechanism of KXS mainly focused on neurotransmitter and neurotrophic factor regulation, but few reports exist on neuronal inflammation regulation. In the current study, we found that KXS exerted antidepressant effects in chronic unpredictable mild stress-induced depression-like mice according to the results of behavioral tests. Meanwhile, KXS also inhibited the activation of microglia and significantly reduced the expression of pro-inflammatory cytokines such as IL-1ß, IL-2, and TNF-α in the hippocampus of mice. In mice BV2 microglia cell lines, KXS extract reduced the expression of inflammatory factors in BV2 cells induced by lipopolysaccharide via inhibiting TLR4/IKK/NF-κB pathways, which was also validated by the treatment of signaling pathway inhibitors such as TAK-242 and JSH-23. T0hese data implied that the regulation of pro-inflammatory cytokines in microglia might account for the antidepressant effect of KXS, thereby providing more scientific information for the development of KXS as an alternative therapy for major depressive disorder.

Dendrobium officinale flos increases neurotrophic factor expression in the hippocampus of chronic unpredictable mild stress-exposed mice and in astrocyte primary culture and potentiates NGF-induced neuronal differentiation in PC12 cells.

Dendrobium officinale flos (DOF) is the flower of Dendrobium officinale Kimura et Migo, which is usually regarded as a by-product of Dendrobii Offcinalis Caulis. Based on its use as an alternative medicine, we evaluated the antidepressant-like effect of DOF extracts on chronic, unpredictable, mild stress-induced, depression-like behaviour in mice and tested the effects of DOF on the regulation of neurotrophic factors in mouse astrocyte primary cultures and PC12 cell lines. Oral treatment with DOF ethanol extract (DOF-E) could alleviate depression-like behaviours in stress-exposed mice, as evidenced by increased sucrose consumption and decreased immobile time in a forced swim test. In the hippocampus, DOF extracts increased the expression of NGF and BDNF, both at the transcriptional and protein levels. In astrocytes, DOF-E increased the expression of NGF and BDNF via a cAMP-dependent mechanism and regulated plasminogen and matrix metallopeptidase 9 (MMP-9), which are related to the metabolic regulation of neurotrophic factors. In PC12 cells, DOF-E induced the expression of neurofilaments and potentiated the induction of neurite outgrowth upon treatment with a low dose of NGF. Based on these findings, DOF might be used as a supplement for antidepressant therapy in patients with depression.

Elaphuri Davidiani Cornu Improves Depressive-Like Behavior in Mice and Increases Neurotrophic Factor Expression in Mouse Primary Astrocytes via cAMP and ERK-Dependent Pathways.

Elaphuri Davidiani Cornu (EDC) is the natural shedding horn of Elaphurus davidiauus Millne-Edwards that was used by people in ancient China for maintaining physical and mental health. We evaluated the antidepressant effect of EDC using depression-like animal models and explored possible mechanisms in mouse primary astrocyte cultures. We found that aqueous extracts of EDC significantly improved depression-like behavior in a mouse model of depression. The extracts enhanced expression of nerve growth factor and brain-derived neurotrophic factor neurotrophic factors in mouse prefrontal cortex and hippocampus tissues. In the mouse primary astrocyte cultures, the EDC aqueous extracts significantly increased the neurotrophic factor expression both at the transcriptional and protein levels. EDC extracts might exhibit these functions by regulating matrix metalloprotein-9 of the nerve growth factor and brain-derived neurotrophic factor metabolic pathways and might enhance expression of neurotrophic factors via the cAMP- and ERK-dependent pathways. We confirmed this possibility by showing the effects of related inhibitors, providing scientific evidence that supports the utility of EDC in the development of drugs to treat major depressive disorders.

Chinese medicine formula Kai-Xin-San ameliorates depression-like behaviours in chronic unpredictable mild stressed mice by regulating gut microbiota-inflammation-stress system.

ETHNOPHARMACOLOGICAL RELEVANCE: Kai-Xin-San (KXS) has been prescribed by TCM doctors for treating psychiatric diseases with the core symptoms of anhedonia, amnesia, and dizziness. According to the symptoms of patients, KXS series formulae are created by varying the compatible ratio of herbs. Today, these formulae are still used in the clinic to treat major depressive disorders. AIM OF THE STUDY: We hoped to evaluate the antidepressant-like effect of Kai-Xin-San via regulation of the gut-brain axis. MATERIALS AND METHODS: Standardized extracts of three representative compatible ratios of KXS had been prepared, and quality control of the extracts was performed by HPLC-MS/MS. Chronic unpredictable mild stress (CUMS)-induced depression-like mice were used as the depression animal model. After KXS treatment, the antidepressant-like effects of KXS were assessed by behavioural tests. The gut microbiota compositions in the faeces were determined by 16S rRNA sequencing technology. The levels of LPS, pro-inflammatory cytokines and HPA-axis-related hormones were measured by ELISA kits, and the expression of barrier proteins in the small intestines and prefrontal cortex were determined by Western blot analysis. Furthermore, antibiotics were used to determine the correlation between KXS exerting an antidepressant-like effect and regulating the gut-brain axis. RESULTS: KXS alleviated depression-like behaviours in CUMS-exposed mice. Furthermore, these parameters were also found to be changed after KXS treatment. Alteration of the gut microbiota composition were found in the small intestines. A decrease in the LPS and the pro-inflammatory cytokines were found in both the small intestine and brain. An increase in the tight junction proteins was found in the gut epithelium barrier and the blood-brain barrier. A decrease in the stress-related hormones was found in the central nervous system. Furthermore, antibiotic treatment attenuated the antidepressant-like effect of KXS in CUMS-exposed mice. CONCLUSIONS: KXS exerted an antidepressant-like effect regulating the gut-brain axis, which included gut micro-environment modification, suppression of neuronal inflammation in the brain and inhibition of HPA axis activation in CUMS-induced depression-like mice.

Jia-Wei-Kai-Xin-San, an Herbal Medicine Formula, Ameliorates Cognitive Deficits via Modulating Metabolism of Beta Amyloid Protein and Neurotrophic Factors in Hippocampus of Aß1-42 Induced Cognitive Deficit Mice.

Jia-Wei-Kai-Xin-San (JWKXS) is a Chinese medicine formula applied for treating morbid forgetfulness in ancient China. Today, this formula is frequently applied for Alzheimer's disease and vascular dementia (VD) in clinic. Here, we developed it as granules and aimed to evaluate its anti-AD effect on ß amyloid protein 1-42 (Aß1-42) induced cognitive deficit mice and reveal the possible molecular mechanisms. Firstly, daily intra-gastric administration of chemically standardized of JWKXS granules for 7 days significantly ameliorated the cognitive deficit symptoms and inhibited cell apoptosis in hippocampus on Aß1-42 injection mice. JWKXS granules significantly decreased Aß level, increased superoxide dismutase activity and decreased malondialdehyde level in hippocampus of model mice. It also restored acetylcholine amounts, inhibited acetylcholinesterase activities and increased choline acetyltransferase activities. In addition, JWKXS granules enabled the transformation of precursors of NGF and BDNF into mature forms. Furthermore, JWKXS granules could regulate gene expressions related to Aß production, transportation, degradation and neurotrophic factor transformation, which led to down-regulation of Aß and up-regulation of NGF and BDNF. These findings suggested that JWKXS granules ameliorated cognitive deficit via decreasing Aß levels, protecting neuron from oxidation damages and nourishing neuron, which could serve as alternative medicine for patients suffering from AD.

Active components, derived from Kai-xin-san, a herbal formula, increase the expressions of neurotrophic factor NGF and BDNF on mouse astrocyte primary cultures via cAMP-dependent signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Kai-Xin-San (KXS), an ancient formula composed of Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma and Poria, was frequently applied for Alzheimer's disease and major depression disorders for thousands of years. However, its active components and molecular mechanism have not clearly been investigated. AIM OF THE STUDY: We aimed to reveal the active components of KXS on regulating neurotrophic factor NGF and BDNF expressions and its mechanisms on mouse astrocyte primary cultures. MATERIALS AND METHODS: Extracts of KXS had been prepared by water reflux and chemical standardization was carried out by HPLC-MS/MS. Various ethanol elution components were prepared by eluting ethanol on macro pore resin column and compound identification was carried out by high-resolution mass spectrometry. KXS extract, elution components and identified chemicals were applied on mouse astrocytes and expressions of NGF and BDNF and related metabolic enzymes were analyzed by qPCR and western blotting analysis. RESULTS: One compatible ratio of KXS named D-652 exerted the best effect on stimulation of NGF and BDNF expressions on mouse astrocytes. 70% ethanol elution fraction of D-652 exerted the highest increase tendency on expressions of NGF and BDNF by activating cAMP-dependent signaling pathway as well as stimulating enzymes accounting for neurotrophic factor synthesis. Combined with compound identification by high-resolution mass spectrometry, ginsenoside Rg1 and Rb1 might be the active compounds of this fraction on increasing NGF and BDNF expressions. CONCLUSIONS: The active compounds of KXS on increasing NGF and BDNF expressions might be the ginsenosides via activating cAMP-dependent signaling pathway as well as stimulating enzymes accounting for neurotrophic factor synthesis, which partly reveal the target of this formulae supported the clinically usage of this decoction.

Is the excessive use of microblogs an Internet addiction? Developing a scale for assessing the excessive use of microblogs in Chinese college students.

More and more college students are using microblogs, with some excessive users demonstrating addiction-like symptoms. However, there is currently no published scale available for use in assessing excessive use of these microblogs, a significant impediment to advancing this area of research. We collected data from 3,047 college students in China and developed a Microblog Excessive Use Scale (MEUS) for Chinese college students, comparing it with criteria used for assessing Internet addiction. Our diagnostic scale featured three factors, two of which--"withdrawal and health problem" and "time management and performance"--are already included in Internet addiction assessment scales. The third factor, "social comfort," does not appear in Internet addiction assessment scales. Our study found that females have significantly higher MEUS scores than males, and that total MEUS scores positively correlated with scores from "self-disclosure" and "real social interaction" scales. These findings differ from results obtained in previous investigations into Internet addiction. Our results indicate that some characteristics of the excessive use of microblogs are different to those of Internet addiction, suggesting that microblog overuse may not correspond exactly to the state of Internet addiction.