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1.
J Ethnopharmacol ; 332: 118339, 2024 May 20.
Article En | MEDLINE | ID: mdl-38777083

ETHNOPHARMACOLOGICAL RELEVANCE: Tao Hong Si Wu Decoction (THSWD), a traditional Chinese herbal medicine, is widely utilized in clinical settings, either alone or in combination with other medications, for the treatment of breast cancer. AIM OF THE STUDY: The specific targeting molecule(s) of THSWD and its associated molecular mechanisms remain unclear. This research aims to elucidate the underlying molecular mechanisms of THSWD in the treatment of breast cancer. MATERIALS AND METHODS: The pharmacological properties of THSWD were investigated in breast cancer cells and tumor tissues using a range of methods including Acridine Orange/Ethidium Bromide (AO/EB) staining, Transwell assay, flow cytometry, immunofluorescence assay, and breast cancer mice models. RESULTS: Our findings demonstrate that THSWD induces necrosis and/or apoptosis in breast cancer cells, while significantly inhibiting cell migration. Target proteins of THSWD in anticancer activity include EGFR, RAS, and others. THSWD treatment for breast cancer is associated with the EGFR/ERK1/2 signaling pathway. CONCLUSION: Our findings offer initial insights into the primary mechanism of action of THSWD in breast cancer treatment, indicating its potential as a complementary therapy deserving further investigation.

2.
Nat Commun ; 15(1): 3902, 2024 May 09.
Article En | MEDLINE | ID: mdl-38724527

Radiation-induced in situ tumor vaccination alone is very weak and insufficient to elicit robust antitumor immune responses. In this work, we address this issue by developing chiral vidarabine monophosphate-gadolinium nanowires (aAGd-NWs) through coordination-driven self-assembly. We elucidate the mechanism of aAGd-NW assembly and characterize their distinct features, which include a negative surface charge, ultrafine topography, and right-handed chirality. Additionally, aAGd-NWs not only enhance X-ray deposition but also inhibit DNA repair, thereby enhancing radiation-induced in situ vaccination. Consequently, the in situ vaccination induced by aAGd-NWs sensitizes radiation enhances CD8+ T-cell-dependent antitumor immunity and synergistically potentiates the efficacy immune checkpoint blockade therapies against both primary and metastatic tumors. The well-established aAGd-NWs exhibit exceptional therapeutic capacity and biocompatibility, offering a promising avenue for the development of radioimmunotherapy approaches.


Nanowires , Polymers , Nanowires/chemistry , Animals , Mice , Polymers/chemistry , Cell Line, Tumor , Gadolinium/chemistry , Gadolinium/pharmacology , Mice, Inbred C57BL , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/drug effects , Cancer Vaccines/immunology , Female , Humans , Vaccination/methods , Neoplasms/immunology
3.
Clin Transl Radiat Oncol ; 47: 100787, 2024 Jul.
Article En | MEDLINE | ID: mdl-38770061

Background: We aimed to assess the value of stereotactic body radiotherapy (SBRT) delivered under the situation of controlled or progressed disease during ICI therapy in advanced or recurrent NSCLC. Methods: We retrospectively collected patients with advanced or recurrent NSCLC who received SBRT concurrently with ICI in our institution between January 2017 and December 2021. Patients were divided into two groups, including those for whom SBRT was delivered initially or to the residual tumors during the first- or later-line ICI treatment (Group 1), and those for whom SBRT was given to the progressed tumors irrespective of first- or later-line ICI treatment (Group 2). Results: A total of 144 patients were included. With median follow-up duration of 25.6 (range: 3.6 to 56.2) months, median progression-free survival (PFS) was 13.7 (95 % CI: 10.4 to 17.1) months and median overall survival (OS) was 52.8 [95 % CI: 30.6 to not available (NA)] months. In Group 1 (n = 78), median PFS was 17.9 (95 % CI: 14.5 to 29.8) months while median OS was not reached and 5-year OS rate was 61.2 %. In Group 2 (n = 66), median PFS was 8.0 (95 % CI: 6.0 to 13.1) months and median OS was 30.6 (95 % CI: 21.5 to NA) months. Conclusions: SBRT combined with ICI demonstrated favorable survival for advanced or recurrent NSCLC, delivered in a controlled-disease situation as well as to progressed diseases with salvage-intent. Future prospective studies are warranted to investigate the optimal SBRT dose regimen and appropriate combination strategy to synergize ICI.

4.
Life Sci ; 346: 122648, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38631668

AIMS: Acute lung injury (ALI) is a life-threatening lung disease characterized by inflammatory cell infiltration and lung epithelial injury. Icariside II (ICS II), one of the main active ingredients of Herba Epimedii, exhibits anti-inflammatory and immunomodulatory effects. However, the effect and mechanism of ICS II in ALI remain unclear. The purpose of the current study was to investigate the pharmacological effect and underlying mechanism of ICS II in ALI. MAIN METHODS: Models of neutrophil-like cells, human peripheral blood neutrophils, and lipopolysaccharide (LPS)-induced ALI mouse model were utilized. RT-qPCR and Western blotting determined the gene and protein expression levels. Protein distribution and quantification were analyzed by immunofluorescence. KEY FINDINGS: ICS II significantly reduced lung histopathological damage, edema, and inflammatory cell infiltration, and it reduced pro-inflammatory cytokines in ALI. There is an excessive activation of neutrophils leading to a significant production of NETs in ALI mice, a process mitigated by the administration of ICS II. In vivo and in vitro studies found that ICS II could decrease NET formation by targeting neutrophil C-X-C chemokine receptor type 4 (CXCR4). Further data showed that ICS II reduces the overproduction of dsDNA, a NETs-related component, thereby suppressing cGAS/STING/NF-κB signalling pathway activation and inflammatory mediators release in lung epithelial cells. SIGNIFICANCE: This study suggested that ICS II may alleviate LPS-induced ALI by modulating the inflammatory response, indicating its potential as a therapeutic agent for ALI treatment.


Acute Lung Injury , Extracellular Traps , Flavonoids , Lipopolysaccharides , Mice, Inbred C57BL , Neutrophils , Acute Lung Injury/drug therapy , Acute Lung Injury/chemically induced , Acute Lung Injury/pathology , Acute Lung Injury/metabolism , Acute Lung Injury/immunology , Animals , Mice , Extracellular Traps/drug effects , Extracellular Traps/metabolism , Humans , Neutrophils/drug effects , Neutrophils/metabolism , Neutrophils/immunology , Flavonoids/pharmacology , Male , Lung/pathology , Lung/drug effects , Lung/metabolism , Inflammation/drug therapy , Inflammation/metabolism , Inflammation/pathology , Anti-Inflammatory Agents/pharmacology
5.
Front Plant Sci ; 15: 1364284, 2024.
Article En | MEDLINE | ID: mdl-38444535

Heterosis is widely used in crop production, but phenotypic dominance and its underlying causes in soybeans, a significant grain and oil crop, remain a crucial yet unexplored issue. Here, the phenotypes and transcriptome profiles of three inbred lines and their resulting F1 seedlings were analyzed. The results suggest that F1 seedlings with superior heterosis in leaf size and biomass exhibited a more extensive recompilation in their transcriptional network and activated a greater number of genes compared to the parental lines. Furthermore, the transcriptional reprogramming observed in the four hybrid combinations was primarily non-additive, with dominant effects being more prevalent. Enrichment analysis of sets of differentially expressed genes, coupled with a weighted gene co-expression network analysis, has shown that the emergence of heterosis in seedlings can be attributed to genes related to circadian rhythms, photosynthesis, and starch synthesis. In addition, we combined DNA methylation data from previous immature seeds and observed similar recompilation patterns between DNA methylation and gene expression. We also found significant correlations between methylation levels of gene region and gene expression levels, as well as the discovery of 12 hub genes that shared or conflicted with their remodeling patterns. This suggests that DNA methylation in contemporary hybrid seeds have an impact on both the F1 seedling phenotype and gene expression to some extent. In conclusion, our study provides valuable insights into the molecular mechanisms of heterosis in soybean seedlings and its practical implications for selecting superior soybean varieties.

6.
Int J Mol Sci ; 25(5)2024 Feb 23.
Article En | MEDLINE | ID: mdl-38473826

Zearalenone (ZEA) is a common non-steroidal estrogenic mycotoxin found in a range of animal feeds and poses a serious threat to the reproductive health of farm animals and humans. However, the mechanism underlying ZEA-induced reproductive toxicity in sheep remains unknown. Granulosa cells are crucial for egg maturation and the fertility of female sheep. In this study, we aimed to examine the impact of different ZEA concentrations on sheep follicular granulosa cells and to elucidate the potential molecular mechanism underlying ZEA-induced toxicity using transcriptome sequencing and molecular biological approaches. Treating primary sheep follicular granulosa cells with different concentrations of ZEA promoted the overproduction of reactive oxygen species (ROS), increased lipid peroxidation products, led to cellular oxidative stress, decreased antioxidant enzyme activities, and induced cell apoptosis. Using transcriptome approaches, 1395 differentially expressed genes were obtained from sheep follicular granulosa cells cultured in vitro after ZEA treatment. Among them, heme oxygenase-1 (HMOX1) was involved in 11 biological processes. The protein interaction network indicated interactions between HMOX1 and oxidative and apoptotic proteins. In addition, N-acetylcysteine pretreatment effectively reduced the ZEA-induced increase in the expression of HMOX1 and Caspase3 by eliminating ROS. Hence, we suggest that HMOX1 is a key differential gene involved in the regulation of ZEA-induced oxidative stress and apoptosis in follicular granulosa cells. These findings provide novel insights into the prevention and control of mycotoxins in livestock.


Mycotoxins , Zearalenone , Humans , Female , Animals , Sheep , Zearalenone/metabolism , Reactive Oxygen Species/metabolism , Heme Oxygenase-1/metabolism , Oxidative Stress , Granulosa Cells/metabolism , Antioxidants/pharmacology , Mycotoxins/metabolism , Apoptosis
7.
Clin Chim Acta ; 555: 117827, 2024 Mar 01.
Article En | MEDLINE | ID: mdl-38346531

BACKGROUND: Aberrant sialylation is closely associated with the tumorigenesis, progression, and metastasis, and may be of importance for disease diagnosis. However, the analysis of altered expression of sialylated glycans (SGs) in blood is particularly challenging due to the low content and poor ionization efficiency of sialylated glycans in mass spectrometry. METHODS: An analytical strategy based on enrichment of SGs, liquid chromatography-high resolution mass spectrometric detection, and automatic glycan annotation was developed to profile the sialylated N-glycome in serum. The enrichment of sialylated glycans was accomplished using cationic cotton via electrostatic and hydrogen interaction. Using partial least squares-discriminant analysis (PLS-DA), the approach was applied for nontarget screening and profiling of aberrant sialylated N-glycans in hepatocellular carcinoma (HCC). RESULTS: 55 SGs were identified in human serum, and three important SGs (SG35, SG45, and SG46) were screened to have good diagnostic specificity for HCC. Their areas under the receiver operating characteristic (ROC) curve (AUC) were higher than α-fetoprotein (AFP)'s (AUC = 0.85), at 0.88, 0.87, and 0.91, respectively. When three SGs are combined, the diagnostic specificity for HCC may increase to 94 %. The fact that SGs biomarkers are sensitive to AFP-Negative HCC is very noteworthy. CONCLUSIONS: The method significantly advanced the search for sialylated glycan-based cancer biomarkers. In comparison to traditional indicators like AFP and imaging tools, SGs showed a higher diagnostic sensitivity for HCC.


Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnosis , alpha-Fetoproteins , Liquid Chromatography-Mass Spectrometry , Liver Neoplasms/diagnosis , Polysaccharides/analysis , Biomarkers, Tumor
8.
Food Chem ; 445: 138691, 2024 Jul 01.
Article En | MEDLINE | ID: mdl-38354646

Milk fat globule membrane proteins (MFGMP) in human milks have positive effects on infant's health. As gestational diabetes mellitus (GDM) causes variations in MFGMP, it is essential to understand the effects of GDMon MFGMP. This study aims to investigate and compare the MFGMP (>3 months postpartum) of GDM and non-GDM (NGDM) women using four-dimensional-data-independent-acquisition proteomics technology. Principal component analysis shows significant differences in the MFGMP of GDM and NGDM women. A total of 4747 MFGMP were identified in maturehuman milk of GDM and NGDM women. Among these proteins, 174 differentially expressed proteins (DEPs) were identified in MFGM of GDM and NGDM women. Albumin (FC = 7.96) and transthyretin (FC = 2.57) which are related to insulin resistance and involved in thyroid hormone synthesis, are significantly up-regulated in MFGMP of GDM mothers indicating insulin resistance, imbalance of glucose homeostasis and poor glucose metabolism might persist in postpartum period.


Diabetes, Gestational , Glycolipids , Glycoproteins , Insulin Resistance , Lipid Droplets , Pregnancy , Female , Humans , Milk, Human/metabolism , Diabetes, Gestational/genetics , Diabetes, Gestational/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , Proteomics , Milk Proteins/metabolism
9.
Environ Res ; 248: 118250, 2024 May 01.
Article En | MEDLINE | ID: mdl-38244964

The persistent O3 pollution in the Beijing-Tianjin-Hebei (BTH) region remains unresolved, largely due to limited comprehension of O3-precursor relationship and photochemistry drivers. In this work, intraday O3 sensitivity evolution from VOC-limited (volatile organic compound) regime in the forenoon to transition regime in the late afternoon was inferred by relative incremental reactivity (RIR) in summer 2019 at Xianghe, a suburban site in BTH region, suggesting that VOC-focused control policy could combine with stringent afternoon NOx control. Then detailed impacts of VOC subgroups on O3 formation were further comprehensively quantified by parametric OH reactivity (KOH), O3 formation potential (OFP), as well as RIR weighted value and O3 formation path tracing (OFPT) approach based on photochemical box model. O3 episode days corresponded to stronger O3 formation, depicted by higher KOH (10.4 s-1), OFP (331.7 µg m-3), RIR weighted value (1.2), and F(O3)-OFPT (15.5 ppbv h-1). High proportions of isoprene and OVOCs (oxygenated VOCs) to the total KOH and the OFPT method were demonstrated whereas results of OFP and RIR-weighted presented extra great impacts of aromatics on O3 formation. The OFPT approach captured the process that has already happened and included final O3 response to the original VOC, thus reliable for replicating VOC impacts. The comparison results of the four methods showed similarities when utilizing KOH and OFPT methods, which reveals that the potential applicability of simple KOH for contingency VOC control and more complex OFPT method for detailed VOC- and source-oriented control during policy-making. To investigate propulsion of VOC-involved O3 photochemistry, atmospheric oxidation capacity (AOC) was quantified by two atmospheric oxidation indexes (AOI). Both AOIp_G (7.0 × 107 molec cm-3 s-1, potential AOC calculated by oxidation reaction rates) and AOIe_G (8.5 µmol m-3, estimated AOC given redox electron transfer for oxidation products) were stronger on O3 episode days, indicating that AOC promoted the radical cycling initiated from VOC oxidation and subsequent O3 production. Result-oriented AOIe_G reasonably characterized actual AOC inferred by good linear correlation between AOIe_G and O3 concentrations compared to process-oriented AOIp_G. Therefore, with continuous NOx abatement, AOIe_G should be considered to represent actual AOC, also O3-inducing ability.


Air Pollutants , Ozone , Volatile Organic Compounds , Air Pollutants/analysis , Ozone/analysis , Volatile Organic Compounds/analysis , Environmental Monitoring , China , Oxidation-Reduction
10.
Comput Biol Med ; 168: 107744, 2024 01.
Article En | MEDLINE | ID: mdl-38006826

Data augmentation is widely applied to medical image analysis tasks in limited datasets with imbalanced classes and insufficient annotations. However, traditional augmentation techniques cannot supply extra information, making the performance of diagnosis unsatisfactory. GAN-based generative methods have thus been proposed to obtain additional useful information to realize more effective data augmentation; but existing generative data augmentation techniques mainly encounter two problems: (i) Current generative data augmentation lacks of the capability in using cross-domain differential information to extend limited datasets. (ii) The existing generative methods cannot provide effective supervised information in medical image segmentation tasks. To solve these problems, we propose an attention-guided cross-domain tumor image generation model (CDA-GAN) with an information enhancement strategy. The CDA-GAN can generate diverse samples to expand the scale of datasets, improving the performance of medical image diagnosis and treatment tasks. In particular, we incorporate channel attention into a CycleGAN-based cross-domain generation network that captures inter-domain information and generates positive or negative samples of brain tumors. In addition, we propose a semi-supervised spatial attention strategy to guide spatial information of features at the pixel level in tumor generation. Furthermore, we add spectral normalization to prevent the discriminator from mode collapse and stabilize the training procedure. Finally, to resolve an inapplicability problem in the segmentation task, we further propose an application strategy of using this data augmentation model to achieve more accurate medical image segmentation with limited data. Experimental studies on two public brain tumor datasets (BraTS and TCIA) show that the proposed CDA-GAN model greatly outperforms the state-of-the-art generative data augmentation in both practical medical image classification tasks and segmentation tasks; e.g. CDA-GAN is 0.50%, 1.72%, 2.05%, and 0.21% better than the best SOTA baseline in terms of ACC, AUC, Recall, and F1, respectively, in the classification task of BraTS, while its improvements w.r.t. the best SOTA baseline in terms of Dice, Sens, HD95, and mIOU, in the segmentation task of TCIA are 2.50%, 0.90%, 14.96%, and 4.18%, respectively.


Brain Neoplasms , Humans , Image Processing, Computer-Assisted
11.
Appl Opt ; 62(33): 8869-8881, 2023 Nov 20.
Article En | MEDLINE | ID: mdl-38038033

A lens defect is a common quality issue that has seriously harmed the scattering characteristics and performance of optical elements, reducing the quality consistency of the finished products. Furthermore, the energy hotspots coming from the high-energy laser through diffraction of optical component defects are amplified step by step in multi-level laser conduction, causing serious damage to the optical system. Traditional manual detection mainly relies on experienced workers under a special light source environment with high labor intensity, low efficiency, and accuracy. The common machine vision techniques are incapable of detecting low contrast and complex morphological defects. To address these challenges, a deep learning-based method, named STMask R-CNN, is proposed to detect defects on the surface and inside of a lens in complex environments. A Swin Transformer, which focuses on improving the modeling and representation capability of the features in order to improve the detection performance, is incorporated into the Mask R-CNN in this case. A challenge dataset containing more than 3800 images (18000 defect sample targets) with five different types of optical lens defects was created to verify the proposed approach. According to our experiments, the presented STMask R-CNN reached a precision value of 98.2%, recall value of 97.7%, F1 score of 97.9%, mAP@0.5 value of 98.1%, and FPS value of 24 f/s, which outperformed the SSD, Faster R-CNN, and YOLOv5. The experimental results demonstrated that the proposed STMask R-CNN outperformed other popular methods for multiscale targets, low contrast target detection and nesting, stacking, and intersecting defects sample detection, exhibiting good generalizability and robustness, as well as detection speed to meet mechanical equipment production efficiency requirements. In general, this research offers a favorable deep learning-based method for real-time automatic detection of optical lens defects.

12.
Stroke Vasc Neurol ; 2023 Nov 10.
Article En | MEDLINE | ID: mdl-37949481

BACKGROUND AND PURPOSE: Cortical superficial siderosis (cSS) and cerebral microbleed (CMB) have distinct effects on intracerebral haemorrhage (ICH). We aim to investigate the combined effect of cSS and CMB on outcomes after ICH. METHODS: Based on a single-centre stroke registry database, patients with spontaneous ICH who had CT scan within 48 hours after ictus and MRI subsequently were identified. Eligible patients were divided into four groups (cSS-CMB-, cSS-CMB+, cSS+CMB-, cSS+CMB+) according to cSS and CMB on susceptibility-weighted image of MRI. Primary outcomes were haematoma volume on admission and unfavourable outcome defined as modified Rankin Scale scores ≥3 at 3 months. Secondary outcomes were all-cause death, recurrence of stroke and ICH during follow-up (median follow-up 2.0 years, IQR 1.0-3.0 years). RESULTS: A total of 673 patients were identified from 1044 patients with spontaneous ICH. 131 (19.5%) had cSS and 468 (69.5%) had CMB. Patients with cSS+CMB+ had the highest rate of poor outcome at 3 months, as well as all-cause death, recurrent stroke and ICH during follow-up. In cSS- patients, CMB was associated with smaller haematoma (ß -0.13; 95% CI -0.22 to -0.03; p=0.009), but it still increased risks of recurrent ICH (OR 4.6; 95% CI 1.3 to 15.6; p=0.015) and stroke (OR 2.0; 95% CI 1.0 to 4.0; p=0.049). These effects of CMB became unremarkable in the context of cSS+. CONCLUSIONS: Patients with different combinations of cSS and CMB have distinct patterns of short-term and long-term outcomes. Although CMB is related to restrained haematoma, it does not improve long-term outcomes. TRIAL REGISTRATION NUMBER: NCT04803292.

13.
Histol Histopathol ; : 18678, 2023 Nov 22.
Article En | MEDLINE | ID: mdl-38018874

Lysosomal-associated transmembrane protein 5 (LAPTM5) has been associated with poor prognosis in cancer patients. Its role in regulating metastasis in pancreatic ductal adenocarcinoma (PDAC), however, remains vague. The study here aimed to expound the metastasis-promoting properties of LAPTM5 in PDAC and the detailed mechanism. LAPTM5 was overexpressed in metastatic PDAC cells and was related to the dismal prognosis of patients in GEO datasets. By using lentiviral vectors harboring short hairpin RNA, we found that LAPTM5 downregulation reduced PDAC cell viability, proliferation, and aggressiveness in vitro and liver metastasis in vivo. Zinc finger with KRAB and SCAN domains 5 (ZKSCAN5) was predicted and verified to mediate LAPTM5 transcription in PDAC cells. Both ZKSCAN5 and SET domains, containing lysine methyltransferase 7 (SETD7) bound to the LAPTM5 promoter, and ZKSCAN5 recruited SETD7 to form a complex promoting LAPTM5 transcription. LAPTM5 knockdown reversed the promoting effect of ZKSCAN5 on the metastasis of PDAC cells. Thus, our findings on the ZKSCAN5/SETD7/LAPTM5 axis provide insights into the underlying mechanism of liver metastasis dissemination in PDAC.

14.
Geriatr Nurs ; 54: 219-228, 2023.
Article En | MEDLINE | ID: mdl-37844538

BACKGROUND: Xerosis cutis in older adults is a geriatric public health issue that severely affects healthy aging, associated with adverse outcomes and increased nursing burden. Skin care plays a significant role in the management of xerosis cutis. AIM: To assess the pooled prevalence and interventions of xerosis cutis among older adults. METHODS: We searched ten databases systematically from inception to August 29, 2023. We estimated pooled prevalence of xerosis cutis using Stata 15.0. RESULTS: 28 articles were included in this review. The pooled prevalence of xerosis cutis was 53 %(95 %CI:36-69 %). We found the prevalence of xerosis cutis was highest in nursing homes and developed countries. The prevalence of xerosis cutis was similar in males and females. The prevalence of mild xerosis cutis and xerosis cutis at lower limbs was relatively high. Regular use of humectant-containing leave-on skin care products and structured skin care regimens were helpful in alleviating xerosis cutis. CONCLUSION: Older adults are at high risk for xerosis cutis. The research provides health professionals with a basic framework for the prevention and management of xerosis cutis.


Skin Diseases , Male , Female , Humans , Aged , Prevalence , Skin Diseases/epidemiology , Skin Diseases/therapy , Nursing Homes , Skin Care
15.
Mol Pharm ; 20(12): 6429-6440, 2023 Dec 04.
Article En | MEDLINE | ID: mdl-37903292

Endothelial cell damage is an important feature of preeclampsia (PE). Human umbilical mesenchymal stem-cell-derived extracellular vesicles (HUMSCs-derived EVs) have been shown to have therapeutic effects on a variety of diseases and tissue damage. However, the therapeutic effect of HUMSCs-derived EVs on endothelial injury in PE remains unclear. This study explored the possible mechanism of HUMSCs-derived EVs in the treatment of endothelial cell injury. Tumor necrosis factor α- and lipopolysaccharide-induced endothelial dysfunction models were used to evaluate the therapeutic effect of HUMSCs-derived EVs on endothelial injury. We further constructed PE mouse models to explore the function of HUMSCs-derived EVs in vivo. The changes of metabolites in endothelial cells after HUMSCs-derived EVs treatment were analyzed by metabolomics analysis and further validated by cell experiments. HUMSCs-derived EVs treatment can alleviate endothelial cell injury in PE, involving cell proliferation, migration, angiogenesis, and anti-inflammatory. Importantly, administration of HUMSCs-derived EVs improves hypertension and proteinuria in PE mice, alleviates kidney damage, and promotes vascularization in the placenta. Furthermore, metabolomics analysis found that the arginine metabolic pathway is activated after HUMSCs-derived EVs treatment. We also observed increased arginine level, nitric oxide content, and nitric oxide synthase activity, and further experiments proved that activating the arginine metabolic pathway could alleviate endothelial dysfunction. Our results reveal that HUMSCs-derived EVs could ameliorate PE endothelial dysfunction by activating the arginine metabolic pathway and may serve as a therapeutic method for treating PE.


Extracellular Vesicles , Pre-Eclampsia , Pregnancy , Female , Humans , Mice , Animals , Pre-Eclampsia/therapy , Pre-Eclampsia/metabolism , Endothelial Cells , Extracellular Vesicles/metabolism , Umbilical Cord , Arginine
17.
Drug Des Devel Ther ; 17: 2593-2611, 2023.
Article En | MEDLINE | ID: mdl-37664450

Background: Psoriasis is a complex autoimmune disease. Frequent interactions between epidermal and immune cells are likely to be responsible for the strong heterogeneity of psoriasis. Therefore, our work aims to build on current knowledge and further search for new molecular mechanisms related to psoriasis pathogenesis in order to develop new targeted drugs. Methods: Data from psoriasis samples were obtained from the Gene Expression Omnibus (GEO) database, and batch effects were corrected using the "Combat" algorithm in the "SVA" package. Functional annotation of differential genes in psoriasis was performed by Gene set enrichment analysis (GSEA). Core functional modules were identified using the Multiscale Embedded Gene Co-Expression Network Analysis (MEGENA) algorithm for selection from the differential gene interaction network. The expression and potential function of Rh Family C Glycoprotein (RHCG) was predicted in single cell data by the "Seurat" package and validated in psoriasis samples by multiplex immunofluorescence. In addition, the regulatory function of HOP Homeobox (HOPX) on RHCG in keratinocytes was confirmed using RNA interference. Using immune infiltration analysis, RHCG and DC cells were analyzed for their association. Finally, the molecular mechanisms of treatment of psoriasis using Tripterygii Radix (TR) and Cinnamomi Ramulus (CR) were explored through network pharmacology and experimental validation. Results: Immune response (represented by C1_2) and collagen matrix formation (represented by C1_3) were identified as two important pathogenic factors in psoriasis and helped to define new biological subtypes of psoriasis. One important psoriasis hub gene, RHCG, was obtained and found to be closely associated with keratinocyte differentiation as well as DC cell maturation. And RHCG was regulated by HOPX in keratinocytes. In addition, the mechanism of action of CR and TR in the treatment of psoriasis was tentatively confirmed to be related to TRPV3, NFKB2, and YAP1. Conclusions: Our study identifies a new causal disease gene (RHCG) and offers potential alternatives for the treatment of psoriasis.


Autoimmune Diseases , Cation Transport Proteins , Humans , Algorithms , Cell Differentiation , Databases, Factual , Glycoproteins , Membrane Glycoproteins
18.
Opt Express ; 31(16): 26610-26625, 2023 Jul 31.
Article En | MEDLINE | ID: mdl-37710518

This paper outlines an experimental demonstration of a Bayesian image reconstruction approach to achieve rapid single-photon color imaging of moving objects. The capacity to extract the color of objects is important in a variety of target identification and computer vision applications. Nonetheless, it remains challenging to achieve high-speed color imaging of moving objects in low-photon flux environments. The low-photon regime presents particular challenges for efficient spectral separation and identification, while unsupervised image reconstruction algorithms are often slow and computationally expensive. In this paper, we address both of these difficulties using a combination of hardware and computational solutions. We demonstrate color imaging using a Single-Photon Avalanche Diode (SPAD) detector array for rapid, low-light-level data acquisition, with an integrated color filter array (CFA) for efficient spectral unmixing. High-speed image reconstruction is achieved using a bespoke Bayesian algorithm to produce high-fidelity color videos. The analysis is conducted first on simulated data allowing different pixel formats and photon flux scenarios to be investigated. Experiments are then performed using a plasmonic metasurface-based CFA, integrated with a 64 × 64 pixel format SPAD array. Passive imaging is conducted using white-light illumination of multi-colored, moving targets. Intensity information is recorded in a series of 2D photon-counting SPAD frames, from which accurate color information is extracted using the fast Bayesian method introduced herein. The per-frame reconstruction rate proves to be hundreds of times faster than the previous computational method. Furthermore, this approach yields additional information in the form of uncertainty measures, which can be used to assist with imaging system optimization and decision-making in real-world applications. The techniques demonstrated point the way towards rapid video-rate single-photon color imaging. The developed Bayesian algorithm, along with more advanced SPAD technology and utilization of time-correlated single-photon counting (TCSPC) will permit live 3D, color videography in extremely low-photon flux environments.

19.
Front Plant Sci ; 14: 1247707, 2023.
Article En | MEDLINE | ID: mdl-37711287

Soybean [Glycine max (Linn.) Merr] is a source of plant-based proteins and an essential oilseed crop and industrial raw material. The increase in the demand for soybeans due to societal changes has coincided with the increase in the breeding of soybean varieties with enhanced traits. Earlier gene editing technologies involved zinc finger nucleases and transcription activator-like effector nucleases, but the third-generation gene editing technology uses clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9). The rapid development of CRISPR/Cas9 technology has made it one of the most effective, straightforward, affordable, and user-friendly technologies for targeted gene editing. This review summarizes the application of CRISPR/Cas9 technology in soybean molecular breeding. More specifically, it provides an overview of the genes that have been targeted, the type of editing that occurs, the mechanism of action, and the efficiency of gene editing. Furthermore, suggestions for enhancing and accelerating the molecular breeding of novel soybean varieties with ideal traits (e.g., high yield, high quality, and durable disease resistance) are included.

20.
Crit Rev Food Sci Nutr ; : 1-16, 2023 Aug 26.
Article En | MEDLINE | ID: mdl-37632418

Milk fat globule membrane (MFGM) is a complex trilayer structure present in mammalian milk and is mainly composed of phospholipids and proteins (>90%). Many studies revealed MFGM has positive effects on the immune system, brain development, and cognitive function of infants. Probiotics are live microorganisms that have been found to improve mental health and insulin sensitivity, regulate immunity, and prevent allergies. Probiotics are unstable and prone to degradation by environmental, processing, and storage conditions. In this review, the processes used for encapsulation of probiotics particularly the potential of MFGM and its constituents as encapsulating materials for probiotics are described. This study analyzes the importance of MFGM in encapsulating bioactive substances and emphasizes the interaction with probiotics and the gut as well as its resistance to adverse environmental factors in the digestive system when used as a probiotic embedding material. MFGM can enhance the gastric acid resistance and bile resistance of probiotics, mainly manifested in the survival rate of probiotics. Due to the role of digestion, MFGM-coated probiotics can be released in the intestine, and due to the biocompatibility of the membrane, it can promote the binding of probiotics to intestinal epithelial cells, and promote the colonization of some probiotics in the intestine.

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