The complex pathogenesis of preeclampsia (PE), a significant contributor to maternal and neonatal mortality globally, is poorly understood despite substantial research. This review explores the ...involvement of exosomal microRNAs (exomiRs) in PE, focusing on their impact on the protein kinase B (AKT)/hypoxia-inducible factor 1-α (HIF1α)/vascular endothelial growth factor (VEGF) signaling pathway as well as endothelial cell proliferation and migration. Specifically, this article amalgamates existing evidence to reveal the pivotal role of exomiRs in regulating mesenchymal stem cell and trophoblast function, placental angiogenesis, the renin-angiotensin system, and nitric oxide production, which may contribute to PE etiology. This review emphasizes the limited knowledge regarding the role of exomiRs in PE while underscoring the potential of exomiRs as non-invasive biomarkers for PE diagnosis, prediction, and treatment. Further, it provides valuable insights into the mechanisms of PE, highlighting exomiRs as key players with clinical implications, warranting further exploration to enhance the current understanding and the development of novel therapeutic interventions.
Tongue coating has been used as an effective signature of health in traditional Chinese medicine (TCM). The level of greasy coating closely relates to the strength of dampness or pathogenic qi in TCM ...theory. Previous empirical studies and our systematic review have shown the relation between greasy coating and various diseases, including gastroenteropathy, coronary heart disease, and coronavirus disease 2019 (COVID-19). However, the objective and intelligent greasy coating and related diseases recognition methods are still lacking. The construction of the artificial intelligent tongue recognition models may provide important syndrome diagnosis and efficacy evaluation methods, and contribute to the understanding of ethnopharmacological mechanisms based on TCM theory.
The present study aimed to develop an artificial intelligent model for greasy tongue coating recognition and explore its application in COVID-19.
Herein, we developed greasy tongue coating recognition networks (GreasyCoatNet) using convolutional neural network technique and a relatively large (N = 1486) set of tongue images from standard devices. Tests were performed using both cross-validation procedures and a new dataset (N = 50) captured by common cameras. Besides, the accuracy and time efficiency comparisons between the GreasyCoatNet and doctors were also conducted. Finally, the model was transferred to recognize the greasy coating level of COVID-19.
The overall accuracy in 3-level greasy coating classification with cross-validation was 88.8% and accuracy on new dataset was 82.0%, indicating that GreasyCoatNet can obtain robust greasy coating estimates from diverse datasets. In addition, we conducted user study to confirm that our GreasyCoatNet outperforms TCM practitioners, yet only consuming roughly 1% of doctors’ examination time. Critically, we demonstrated that GreasyCoatNet, along with transfer learning, can construct more proper classifier of COVID-19, compared to directly training classifier on patient versus control datasets. We, therefore, derived a disease-specific deep learning network by finetuning the generic GreasyCoatNet.
Our framework may provide an important research paradigm for differentiating tongue characteristics, diagnosing TCM syndrome, tracking disease progression, and evaluating intervention efficacy, exhibiting its unique potential in clinical applications.
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•Meta-analysis is used to review the relation between tongue and COVID-19.•Developing and testing datasets for greasy coating recognition are constructed.•The GreasyCoatNet obtains robust greasy coating classifications from diverse datasets.•Expectation of greasy coating is proposed to evaluate the continuous greasy level.•A COVID-specific deep network is derived by finetuning the GreasyCoatNet.
Abstract
Background
Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), are devastating clinical disorders with high mortality, and for which more effective ...therapies are urgently needed. FGF1, the prototype member of the FGF family, is shown to exert protective effects against injurious stimuli in multiple disease models. Here we aimed to evaluate whether FGF1 pretreatment is protective against LPS-induced ALI and elucidate the potential underlying mechanisms.
Methods
For drug-treated groups, C57B/6 mice received a single i.p. injection of FGF1 (1 mg/kg) 1 h before the LPS challenge or not. To induce the ALI model, the mice were treated by intratracheal instillation of LPS (5 mg/kg). Then, histopathological changes in lung tissues were assessed by hematoxylin and eosin staining and transmission electron microscopy. ELISA and qPCR assays were used to detect pro-inflammatory cytokine levels in BALF and lung tissues, respectively. The total number of inflammatory cells (neutrophils and macrophages) in BALF were counted using the Wright-Giemsa method. The expressions of reactive oxygen species (ROS) and malondialdehyde (MDA) were measured using their respective kits. Western blot and immunostaining were used to evaluate the expressions of antioxidants (Nrf-2, HO-1, SOD2, GPX4, and Catalase), as well as the inflammatory and/or apoptosis-related factors (TLR4, NF-κB, and Cleaved- caspase 3).
Results
FGF1 pretreatment significantly ameliorated the LPS-induced histopathological changes, reduced lung wet/dry ratios, ROS and MDA levels, total BALF protein, inflammatory cell infiltration, proinflammatory cytokine levels, and significantly increased the expression of antioxidant proteins (Nrf-2, HO-1, Catalase, and SOD2). In addition, FGF1 pretreatment significantly reduced the expression of TLR4 and cleaved- caspase 3, inhibited NF-κB activation, and reduced LPS-induced cell apoptosis.
Conclusions
Altogether, our results suggest that FGF1 pretreatment is protective against LPS-induced ALI through mediating anti-inflammatory and antioxidant effects, which may be attributed to the downregulation of TLR4 expression and inhibition of NF-κB activation, as well as promotion of antioxidant defenses. Therefore, FGF1 administration may prove beneficial in preventative strategies for ALI/ARDS.
Abstract
Practical electrochemical CO
2
-to-CO conversion requires a non-precious catalyst to react at high selectivity and high rate. Atomically dispersed, coordinatively unsaturated metal-nitrogen ...sites have shown great performance in CO
2
electroreduction; however, their controllable and large-scale fabrication still remains a challenge. Herein, we report a general method to fabricate coordinatively unsaturated metal-nitrogen sites doped within carbon nanotubes, among which cobalt single-atom catalysts can mediate efficient CO
2
-to-CO formation in a membrane flow configuration, achieving a current density of 200 mA cm
−2
with CO selectivity of 95.4% and high full-cell energy efficiency of 54.1%, outperforming most of CO
2
-to-CO conversion electrolyzers. By expanding the cell area to 100 cm
2
, this catalyst sustains a high-current electrolysis at 10 A with 86.8% CO selectivity and the single-pass conversion can reach 40.4% at a high CO
2
flow rate of 150 sccm. This fabrication method can be scaled up with negligible decay in CO
2
-to-CO activity. In situ spectroscopy and theoretical results reveal the crucial role of coordinatively unsaturated metal-nitrogen sites, which facilitate CO
2
adsorption and key *COOH intermediate formation.
Tunable and enhanced low‐field magnetoresistance (LFMR) is observed in epitaxial (La0.7Sr0.3MnO3)0.5:(ZnO)0.5 (LSMO:ZnO) self‐assembled vertically aligned nanocomposite (VAN) thin films, which have ...been grown on SrTiO3 (001) substrates by pulsed laser deposition (PLD). The enhanced LFMR properties of the VAN films reach values as high as 17.5% at 40 K and 30% at 154 K. They can be attributed to the spin‐polarized tunneling across the artificial vertical grain boundaries (GBs) introduced by the secondary ZnO nanocolumns and the enhancement of spin fluctuation depression at the spin‐disordered phase boundary regions. More interestingly, the vertical residual strain and the LFMR peak position of the VAN films can be systematically tuned by changing the deposition frequency. The tunability of the physical properties is associated with the vertical phase boundaries that change as a function of the deposition frequency. The results suggest that the tunable artificial vertical GB and spin‐disordered phase boundary in the unique VAN system with vertical ferromagnetic‐insulating‐ferromagnetic (FM‐I‐FM) structure provides a viable route to manipulate the low‐field magnetotransport properties in VAN films with favorable epitaxial quality.
Self‐assembled (La0.7Sr0.3MnO3)0.5:(ZnO)0.5 vertically aligned nanocomposite (VAN) thin films are epitaxially grown on SrTiO3 (001) substrates by pulsed laser deposition (PLD). The unique VAN system with a vertical ferromagnetic–insulating–ferromagnetic structure exhibits tunable and enhanced low‐field magnetoresistance that is associated with the tunable vertical phase boundaries.
Impact of ferroptosis on preeclampsia: A review Shan, Yuping; Guan, Chengcheng; Wang, Jingli ...
Biomedicine & pharmacotherapy,
November 2023, 2023-11-00, 20231101, 2023-11-01, Letnik:
167
Journal Article
Recenzirano
Odprti dostop
Preeclampsia (PE) is usually associated with the accumulation of reactive oxygen species (ROS) resulting from heightened oxidative stress (OS). Ferroptosis is a unique type of lipid ...peroxidation-induced iron-dependent cell death distinct from traditional apoptosis, necroptosis, and pyroptosis and most likely contributes considerable to PE pathogenesis. At approximately 10–12 weeks of gestation, trophoblasts create an environment rich in oxygen and iron. In patients with PE, ferroptosis-related genes such as HIF1 and MAPK8 are downregulated, whereas PLIN2 is upregulated. Furthermore, miR-30b-5p overexpression inhibits solute carrier family 11 member 2, resulting in a decrease in glutathione levels and an increase in the labile iron pool. At the maternal-fetal interface, physiological hypoxia/reperfusion and excessive iron result in lipid peroxidation and ROS production. Owing to the high expression of Fpn and polyunsaturated fatty acid-containing phospholipid-related enzymes, including acyl-CoA synthetase long-chain family member 4, lysophosphatidylcholine acyl-transferase 3, and spermidine/spermine N1-acetyltransferase 1, trophoblasts become more susceptible to OS and ROS damage. In stage 1, the injured trophoblasts exhibit poor invasion and incomplete uterine spiral artery remodeling caused by ferroptosis, leading to placental ischemia and hypoxia. Subsequently, ferroptosis marked by OS occurs in stage 2, eventually causing PE. We aimed to explore the new therapeutic target of PE through OS in ferroptosis.
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•Trophoblasts are more vulnerable to ferroptosis.•Ferroptosis may participate in two stages of preeclampsia.•The key pathways of ferroptosis may be useful in PE prevention and treatment.
Reprogrammed metabolism and redox homeostasis are potential targets of cancer therapy. Our previous study demonstrated that the kidney form of glutaminase (GLS1) is highly expressed in hepatocellular ...carcinoma (HCC) cells and can be used as a target for effective anticancer therapy. Dihydroartemisinin (DHA) increases intracellular reactive oxygen species (ROS) levels leading to cytotoxicity in cancer cells. However, the heterogeneity of cancer cells often leads to differing responses to oxidative lesions. For instance, cancer cells with high ratio of GSH/GSSG, a critical ROS scavenger, are resistant to ROS-induced cytotoxicity. We postulate that a combinatorial strategy firstly disrupting redox homeostasis followed by DHA might yield a profound antitumor efficacy. In this study, when HCC cells were treated with a GLS1 inhibitor 968, the ROS elimination capacity was significantly reduced in HCC cells, which rendered HCC cells but not normal endothelial cells more sensitive to DHA-mediated cytotoxicity. We further confirmed that this synergistic antitumor efficacy was mediated by excessive ROS generation in HCC cells. NAC, a ROS inhibitor, partly rescued the combinatorial cytotoxic effect of 968 and DHA. Given that GLS1 is a potential antitumor target and DHA has been safely used in clinic, our findings provide new insight into liver cancer therapy targeting glutamine metabolism combined with the ROS generator DHA, which can be readily translated into cancer clinical trials.
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