Search Results (10)

Background: Glucocorticoids (GCs) are a key pathogenic factor in steroid-induced avascular necrosis of the femoral head (SANFH). GCs can directly damage bone microvascular endothelial cells (BMECs), leading to impaired intraosseous blood supply. Recent studies suggest the Hippo signaling pathway may be involved in the pathogenesis of SANFH; however, its role in vascular endothelial repair and angiogenesis remains unclear. This study aims to investigate the therapeutic effects of human umbilical cord mesenchymal stem cells (hUC-MSCs) on SANFH, with a particular focus on their protective or reparative mechanisms on BMECs. Methods: In vivo, a SANFH mouse model is established and divided into NC, MPS, and hUC-MSCs groups, followed by Micro-CT imagin, hematoxylin and eosin (HE) staining and immunohistochemistry (IHC) (n = 8 per group). In vitro, BMECs are divided into NC, dexamethasone (Dex), hUC-MSCs, and Fer-1 groups to analyze cellular biological behaviors. Target protein expression is assessed using Western blotting and immunofluorescence microscopy. Ferroptosis-related markers are detected via biochemical assays. Mitochondrial ultrastructural changes are observed using transmission electron microscopy. Results: In vivo, the MPS group exhibited significant bone cavitation, sparse trabeculae, and disrupted trabecular architecture in the femoral head. The hUC-MSCs group showed marked improvement in bone microstructure, HE staining showed a significant decrease in the empty lacunae rate in the femoral head, and IHC results revealed markedly increased expression of cluster of differentiation 31 (CD31) and vascular endothelial growth factor (VEGF). In vitro, Dex stimulation suppressed BMECs proliferation. In Dex-treated cells, levels of intracellular reactive oxygen species (ROS), lipid peroxides, ferrous ion (Fe²⁺), malondialdehyde (MDA), acyl-CoA synthetase long chain family member 4 (ACSL4) and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) were all increased, while expression of glutathione (GSH) and glutathione Peroxidase 4 (GPX4) was reduced. Transmission electron microscopy revealed plasma membrane rupture and reduction or loss of mitochondrial cristae. Furthermore, Dex promoted Hippo-mediated phosphorylation of Yes-associated protein (YAP)/Transcriptional coactivator with PDZ-binding motif (TAZ), upregulated NOX4 expression, and suppressed CD31 and VEGF expression. Following hUC-MSCs treatment, BMECs demonstrated enhanced proliferation, migration, and tube-forming capacity. Cellular GSH and GPX4 levels increased, antioxidant capacity was restored, peroxide accumulation decreased, and cells were protected from ferroptosis-effects comparable to those in the Fer-1 group. Additionally, hUC-MSCs inhibited YAP/TAZ phosphorylation and promoted elevated expression of CD31 and VEGF. Conclusions: These findings suggest that hUC-MSCs may attenuate Dex-induced ferroptosis in BMECs, enhance BMEC migration and angiogenesis, and improve femoral head microstructure in SANFH through modulation of the Hippo-YAP/TAZ signaling pathway. This study provides novel insights into the therapeutic potential of hUC-MSCs for SANFH. Full article

This study investigates the immunomodulatory effects of a well-characterized cannabidiol (CBD)-rich cannabis extract, CAN296, on T lymphocytes (T cells), particularly Cluster of Differentiation 4 (CD4⁺) helper and Cluster of Differentiation 8 (CD8⁺) cytotoxic subsets, by examining T-cell activation, cytokine secretion, and cytotoxic molecule expression in comparison with the conventional treatments dexamethasone (DEX) and tacrolimus (TAC). It addresses key processes involved in the formation of premalignant immune-mediated lesions, such as those seen in oral lichen planus (OLP) and oral manifestations of graft-versus-host disease (oGVHD). CD4⁺ and CD8⁺ T cells were isolated from healthy donors and assessed in vitro for T cell activation via CD69 expression, secreted tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels according to enzyme-linked immunosorbent assay (ELISA), and cytotoxic molecule expression Granzyme B, Perforin, Fas Ligand (Fas-L) quantified by flow cytometry. Cells were treated with different doses of CAN296 (2, 4, 8 µg/mL), DEX (0.4, 4, 40 µg/mL), or TAC (0.1, 1, 10 ng/mL), and all parameters were compared to untreated controls. CAN296 significantly inhibited T cell activation, reducing CD69 expression in CD4⁺ T cells to 2–11% and in CD8⁺ T cells to 5–17%. It also markedly suppressed TNF-α secretion in CD4⁺ T cells at all concentrations (p < 0.0001). In CD8⁺ T cells, CAN296 led to a near-complete reduction in TNF-α and IFN-γ, leaving both cytokines barely detectable at all tested doses (p < 0.0001). The effect of cell inhibition was significantly more pronounced than that observed with DEX or TAC, displaying dose-dependent reductions. TAC inconsistently lowered TNF-α while paradoxically increasing IFN-γ at lower concentrations. Additionally, CAN296 consistently suppressed cytotoxic molecule expression, reducing Granzyme B by 81–82%, Perforin by 40–53%, and Fas-L by 40–44%. DEX showed variable effects on cytotoxic molecule expression. At the same time, TAC demonstrated inconsistent modulation of Perforin and Granzyme B. Overall, CAN296 outperformed DEX and TAC, demonstrating more potent and consistent immunomodulatory effects. CBD-rich cannabis extract, CAN296, exhibits potent immunomodulatory properties by effectively inhibiting T cell activation, lowering pro-inflammatory cytokines, and suppressing cytotoxic molecule expression. Its efficacy surpasses conventional therapies like DEX and TAC, offering a promising novel treatment modality for T cell-mediated disorders, including OLP and oGVHD. These findings support further development of CAN296 formulations to optimize dosing and delivery, followed by clinical trials to validate its therapeutic potential. Full article

Photoperiod is a pivotal regulatory factor in the flowering of Camellia oleifera Abel. (C. oleifera). GIGANTEA (GI) serves as a pivotal regulator, not only orchestrating the intricate circadian rhythm but also governing photoperiod-dependent flowering. In order to explore the function of GI in C. oleifera (CoGI), we obtained a CoGI gene-coding sequence and analyzed a CoGI protein sequence using bioinformatics. Furthermore, we conducted a spatiotemporal expression analysis of CoGI. And a yeast two-hybridization assay was used to screen the interacting proteins of CoGI. Evolutionary analysis revealed high conservation of the CoGI protein, which clustered with the GI protein from Camellia sinensis (CsGI) on a common evolutionary branch. The expression of CoGI was different in each part, and a tissue expression analysis revealed that the relative expression level of the CoGI gene is highest in the leaves of C. oleifera, while it is at its lowest in the seed coats. Transgenic Arabidopsis thaliana (Arabidopsis) overexpressing CoGI exhibited early flowering under long-day conditions. In addition, the yeast two-hybrid library screening revealed interactions between seven C. oleifera proteins and CoGI: CoACR9, CoLAO, CoDExH12-like, CoIT1K-like, CoUPF0481, CoIDM3, and CoAt4g27190-like. The findings demonstrated that CoGI is crucial to C. oleifera’s flowering. Full article

The soil heavy metal pollution around the mine threatens crop growth and human health. Intensively studies of the distribution characteristics and source of soil heavy metals around some typical mines are very crucial for environmental management and green development of mine. A total of eighty-nine soil samples, twenty-one sediment samples, five waste rock samples and two tailing sand samples were sampled to investigate copper (Cu), lead (Pb), zinc (Zn), arsenic (As), cadmium (Cd), chromium (Cr) and mercury (Hg) in soil, sediment, waste rocks and tailings sand around Dexing Copper Mine, Jiangxi Province, China. The concentrations of the seven heavy metals were determined using inductively coupled plasma mass spectrometry ICP-MS/atomic fluorescence spectroscopy (AFS). The I_geo values of soil heavy metal showed that 100% of Cu were at an unpolluted-to-moderately-polluted level (Igeo > 0), more than 50% of Cu were heavily polluted (Igeo > 3), 65.16%, and 22.47%, 7.86% and 7.87% of the soil samples for Cd, Hg, As and Zn were overly moderately polluted (Igeo > 1). A total of 13.48% and 11.24% of the soil samples for Pb and Cr, respectively, were moderately polluted (1 < Igeo < 2). The concentrations of heavy metals in soil were Compared with Risk Screening Values for Contamination of Agricultural Land (RSVCAL), with the concentration of 97.75% soil samples for Cu, and 69.21% of soil samples for Cd were higher than RSVCAL. In Dawu river basin the concentration of 50% soil samples for Pb were higher than RSVCAL. According to I_geo and RSVCAL, the soils around Dexing Copper Mine were polluted by heavy metals to some extent, with especially the Cu pollution of soil being the most serious. These heavy metal concentrations exceeding RSVCAL have threatened the safety of agricultural products. The results of soil profile analysis, principal component analysis (PCA) and cluster analysis (CA) indicated that the mining activities of Dexing copper mine should be the main source of Cu in the soil. High As concentration in soil obviously caused by the copper mine as well. In addition, Dexing Copper Mine should partly account for soil pollution by Zn, Pb, Cd, Hg and Cr around the mine. Full article

In our previous study, we revealed the ameliorative therapeutic effect of dexamethasone (Dex) for Lupus nephritis lesions in the MRL/MpJ-Fas ^lpr/lpr (Lpr) mouse model. The female Lpr mice developed a greater number of mediastinal fat-associated lymphoid clusters (MFALCs) and inflammatory lung lesions compared to the male mice. However, the effect of Dex, an immunosuppressive drug, on both lung lesions and the development of MFALCs in Lpr mice has not been identified yet. Therefore, in this study, we compared the development of lung lesions and MFALCs in female Lpr mice that received either saline (saline group “SG”) or dexamethasone (dexamethasone group “DG”) in drinking water as a daily dose along with weekly intraperitoneal injections for 10 weeks. Compared to the SG group, the DG group showed a significant reduction in the levels of serum anti-dsDNA antibodies, the size of MFALCs, the degree of lung injury, the area of high endothelial venules (HEVs), and the number of proliferating and immune cells in both MFALCs and the lungs. A significant positive correlation was observed between the size of MFALCs and the cellular aggregation in the lungs of Lpr mice. Therefore, this study confirmed the ameliorative effect of Dex on the development of lung injury and MFALCs via their regressive effect on both immune cells’ proliferative activity and the development of HEVs. Furthermore, the reprogramming of MFALCs by targeting immune cells and HEVs may provide a therapeutic strategy for autoimmune-disease-associated lung injury. Full article

In this paper, we make use of data collected for open cluster members by high-resolution spectroscopic surveys and programmes (i.e., APOGEE, Gaia-ESO, GALAH, OCCASO, and SPA). These data have been homogenised and then analysed as a whole. The resulting catalogue contains [Fe/H] and orbital parameters for 251 Galactic open clusters. The slope of the radial metallicity gradient obtained through 175 open clusters with high-quality metallicity determinations is −0.064 ± 0.007 dex kpc${}^{-1}$. The radial metallicity distribution traced by open clusters flattens beyond R${}_{\mathrm{Gal}}$ = 12.1 ± 1.1 kpc. The slope traced by open clusters in the [Fe/H]-L${}_{\mathrm{z}}$ diagram is −0.31 ± 0.02 × 10${}^3$ dex km${}^{-1}$ kpc${}^{-1}$ s, but it flattens beyond L${}_{\mathrm{z}}$ = 2769 ± 177 km kpc s${}^{-1}$. In this paper, we also review some high-priority practical challenges around the study of open clusters that will significantly push our understanding beyond the state-of-the-art. Finally, we compare the shape of the galactic radial metallicity gradient to those of other spiral galaxies. Full article

Heavy metals and As (HMs) pollution in mining areas are a widespread environmental concern. In this study, ground water, surface water, and sediment samples around the Dexing area, one of the largest Cu-polymetallic ore clusters in China, were collected to examine the concentrations and distributions of As, Cd, Cr, Cu, Hg, Pb, and Zn. Pollution indices, geo-accumulation index, and potential ecological risk index were used to estimate the pollution characteristics and ecological risk of HMs. The results show that the major pollutants in the surface water were Cd, Cu, Zn, and Pb, while the dominant ecological risk of HMs in the sediments originated from Cu, As, Hg, and Cd. Moreover, HMs in the surface water and sediments exhibited substantial spatial heterogeneity in the study area, indicating a severely disturbed environment due to mining activities. The proportions of HM pollutions were higher in the Dexing River and its tributaries than in the Le’an River and its tributaries. The surface water pollution was predominant at the tributaries closest to the mine area, while the sediment contamination has been expanded several kilometers downstream of the major rivers. Overall, the ecological risk of HMs was higher in the sediments than in the surface water. Full article

Most current methods for the preparation of tissue spheroids require complex materials, involve tedious physical steps and are generally not scalable. We report a novel alternative, which is both inexpensive and up-scalable, to produce large quantities of viable human keratinocyte cell clusters (clusteroids). The method is based on a two-phase aqueous system of incompatible polymers forming a stable water-in-water (w/w) emulsion, which enabled us to rapidly fabricate cell clusteroids from HaCaT cells. We used w/w Pickering emulsion from aqueous solutions of the polymers dextran (DEX) and polyethylene oxide (PEO) and a particle stabilizer based on whey protein (WP). The HaCaT cells clearly preferred to distribute into the DEX-rich phase and this property was utilized to encapsulate them in the water-in-water (DEX-in-PEO) emulsion drops then osmotically shrank to compress them into clusters. Prepared formulations of HaCaT keratinocyte clusteroids in alginate hydrogel were grown where the cells percolated to mimic 3D tissue. The HaCaT cell clusteroids grew faster in the alginate film compared to the individual cells formulated in the same matrix. This methodology could potentially be utilised in biomedical applications. Full article

Although dexamethasone (DEX) is a widely used immunoregulatory agent, knowledge about its pharmacological properties in farm animals, especially pigs, is insufficient. Previous studies suggest that compared to other species, pigs are less sensitive to the immunosuppression conferred by DEX and more sensitive to the threat of bacterial endotoxins. However, there is a paucity of studies examining DEX immunomodulation in endotoxemia in this species. In this study, a porcine endotoxemia model was established by lipopolysaccharide (LPS) and the effect of DEX-pretreatment on the magnitude and kinetics of neuroendocrine, metabolic, hematologic, inflammatory, and behavioural responses were examined. DEX decreased cortisol, adrenocorticotropic hormone (ACTH), red blood cell, hemoglobin, hematocrit, and lymphocyte whereas glucose concentration was increased under both normal and endotoxemic conditions. By contrast, DEX decreased triglyceride, lactate, and IL-6 concentrations and increased platelet count only under an endotoxemic condition. DEX also reduced the frequency of sickness behaviour following LPS challenge. PCA showed that glucose and triglyceride metabolism together with red blood cell count mainly contributed to the separation of clusters during DEX treatment. Our study demonstrates that DEX protects pigs from inflammation and morbidity in endotoxemia, in spite of their less sensitivity to DEX. Moreover, its considerable role in the regulation of the metabolic and hematologic responses in endotoxemic pigs is revealed for the first time. Full article

Multivariate statistical methods including cluster analysis (CA), discriminant analysis (DA) and component analysis/factor analysis (PCA/FA), were applied to explore the surface water quality datasets including 14 parameters at 28 sites of the Eastern Poyang Lake Basin, Jiangxi Province of China, from January 2012 to April 2015, characterize spatiotemporal variation in pollution and identify potential pollution sources. The 28 sampling stations were divided into two periods (wet season and dry season) and two regions (low pollution and high pollution), respectively, using hierarchical CA method. Four parameters (temperature, pH, ammonia-nitrogen (NH₄-N), and total nitrogen (TN)) were identified using DA to distinguish temporal groups with close to 97.86% correct assignations. Again using DA, five parameters (pH, chemical oxygen demand (COD), TN, Fluoride (F), and Sulphide (S)) led to 93.75% correct assignations for distinguishing spatial groups. Five potential pollution sources including nutrients pollution, oxygen consuming organic pollution, fluorine chemical pollution, heavy metals pollution and natural pollution, were identified using PCA/FA techniques for both the low pollution region and the high pollution region. Heavy metals (Cuprum (Cu), chromium (Cr) and Zinc (Zn)), fluoride and sulfide are of particular concern in the study region because of many open-pit copper mines such as Dexing Copper Mine. Results obtained from this study offer a reasonable classification scheme for low-cost monitoring networks. The results also inform understanding of spatio-temporal variation in water quality as these topics relate to water resources management. Full article