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.

[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.

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.

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.

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.