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Acute liver failure (ALF) is a significant global issue with elevated morbidity and mortality rates. There is an urgent and pressing need for secure and effective treatments. Ferroptosis, a novel iron-dependent regulation of cell death, plays a significant role in multiple pathological processes associated with liver diseases, including ALF. Several studies have demonstrated that mesenchymal stem cells (MSCs) have promising therapeutic potential in the treatment of ALF. This study aims to investigate the positive effects of MSCs against ferroptosis in an ALF model and explore the underlying molecular mechanisms of their therapeutic function. Our results show that intravenously injected MSCs protect against ferroptosis in ALF mouse models. MSCs decrease iron deposition in the liver of ALF mice by downregulating hepcidin level and upregulating FPN1 level. MSCs labelled with Dil are mainly observed in the hepatic sinusoid and exhibit colocalization with the macrophage marker CD11b fluorescence. ELISA demonstrates a high level of IGF1 in the CCL4+MSC group. Suppressing the IGF1 effect by the PPP blocks the therapeutic effect of MSCs against ferroptosis in ALF mice. Furthermore, disruption of IGF1 function results in iron deposition in the liver tissue due to impaired inhibitory effects of MSCs on hepcidin level. Our findings suggest that MSCs alleviate ferroptosis induced by disorders of iron metabolism in ALF mice by elevating IGF1 level. Moreover, MSCs are identified as a promising cell source for ferroptosis treatment in ALF mice.

Neural tube defects (NTDs) represent a developmental disorder of the nervous system that can lead to significant disability in children and impose substantial social burdens. Valproic acid (VPA), a widely prescribed first-line antiepileptic drug for epilepsy and various neurological conditions, has been associated with a 4-fold increase in the risk of NTDs when used during pregnancy. Consequently, urgent efforts are required to identify innovative prevention and treatment approaches for VPA-induced NTDs. Studies have demonstrated that the disruption in the delicate balance between cell proliferation and apoptosis is a crucial factor contributing to NTDs induced by VPA. Encouragingly, our current data reveal that melatonin (MT) significantly inhibits apoptosis while promoting the restoration of neuroepithelial cell proliferation impaired by VPA. Moreover, further investigations demonstrate that MT substantially reduces the incidence of neural tube malformations resulted from VPA exposure, primarily by suppressing apoptosis through the modulation of intracellular reactive oxygen species levels. In addition, the Src/PI3K/ERK signaling pathway appears to play a pivotal role in VPA-induced NTDs, with significant inhibition observed in the affected samples. Notably, MT treatment successfully reinstates Src/PI3K/ERK signaling, thereby offering a potential underlying mechanism for the protective effects of MT against VPA-induced NTDs. In summary, our current study substantiates the considerable protective potential of MT in mitigating VPA-triggered NTDs, thereby offering valuable strategies for the clinical management of VPA-related birth defects.

Vasculogenic mimicry (VM) describes a process by which tumor cells formed a novel microcirculation pattern in an endothelial cell‐free manner. Clinically, VM is associated with aggressive phenotype and poor patient survival. However, the current models for investigating VM include 2D monolayer cultures, Matrigel‐based cultures, and animal models, each of which has limitations. Matrigel‐based models often exhibit batch‐to‐batch variations, while in vivo tumor models currently produce insufficient amounts of VM. There is currently no suitable tumor model to discover new therapeutic targets against VM. Herein, we establish an extracellular matrix (ECM)‐based engineered tumor model in vivo and in vitro. In this study, we demonstrate that matrix proteins enhanced the VM formation in the engineered xenograft model. Furthermore, we also investigated the role of collagen/fibronectin (FN) in melanoma progression and VM formation. Compared with cells cultured on TCPS plates, the B16F10 cells cultured on collagen/FN coated plates showed increased proliferation and stemness, and significantly enhanced invasion and formation of VM networks. Molecular mechanism analysis showed that Integrin/VE‐cadherin/EphA2/PI3K/MMP‐2 signaling pathways are responsible for VM formation. Our results indicate that collagen/FN matrix plays an important role in VM formation in melanoma, suggesting that ECM protein is a potential therapeutic target for anti‐VM therapy for melanoma. [ABSTRACT FROM AUTHOR]

The air pollutant NO2 is one of the major constraints on plant growth, and the ecological value of the ornamental plant Bougainvillea glabra can be weakened by NO2. In this study, an indoor 4 μL·L−1 NO2 simulated fumigation test was conducted with three treatments, CK (normal growth with clean air), T1 (4 μL·L−1 NO2 + 8 h/d), and T2 (4 μL·L−1 NO2 + 24 h/d), which were set up with considerations for time and concentration. The results demonstrated that most of the morphological parameters of B. glabra 'Elizabeth Angus', except for the floral organs, were decreased in the root, stem, leaf, and bract. Continuous fumigation significantly attenuated the growth rate and reduced the water and pigment contents of organs. Excessive NO2 reduced the number and transfer rate of photoelectrons by destroying the photosynthetic reaction center, which in turn weakened photosynthesis, but the plants with intermittent fumigation recovered after fumigation. The Kaplan-Meier (K-M) survival curve displayed median survival periods of 41 and 55.5 h for T1 and T2, respectively, and the morphological structure and most of the indicators of photosynthetic reaction centers changed significantly during stress. Acute injury to B. glabra 'Elizabeth Angus' was caused by 4 μL·L−1 NO2, and B. glabra 'Elizabeth Angus' had limited ability to regulate high concentrations of NO2 acute stress. [ABSTRACT FROM AUTHOR]

Exogenous substances can alleviate plant damage under adverse conditions. In order to explore whether different concentrations of salicylic acid (SA) can play a role in the resistance of Bougainvillea × buttiana 'Miss Manila' to nitrogen dioxide (NO2) stress and the relevant mechanisms of their effects, different concentrations of SA were applied locally under the control experiment condition of 4.0 μL·L−1 NO2, and the role of SA in alleviating injury was studied. The findings noted a significant increase in metabolic adaptations and antioxidant enzyme activities following 0.25–0.75 mM SA application (p < 0.05), except 1 mM. Superoxide dismutase (SOD) and catalase (CAT) in particular increased by 21.88% and 59.71%, respectively. Such an increase led to effective control of the reduction in photosynthetic pigments and the photosynthetic rate and protection of the structural stability of chloroplasts and other organelles. In addition, the activity of nitrate reductase (NR) increased by 83.85%, and the content of nitrate nitrogen (NO3−-N) decreased by 29.23% in nitrogen metabolism. Concurrently, a principal component analysis (PCA) and a membership function analysis further indicated that 0.75 mM SA provided the most notable improvement in NO2 resistance among the different gradients. These findings suggest that 0.25–0.75 mM SA can relieve the stress at 4 μL·L−1 NO2 injury by effectively improving the antioxidant enzyme activity and nitrogen metabolizing enzyme activity, protecting the photosynthetic system and cell structure, but 1 mM SA had the opposite effect. In the future, the specific reasons for inhibition of SA at high concentrations and the comprehensive effects of the application of other exogenous compounds should be further studied. [ABSTRACT FROM AUTHOR]