The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) is continuously rising, evolving into a global health challenge. Concurrently, cases of hepatocellular carcinoma ...(HCC) associated with MASLD are also on the increase. Although traditional risk factors such as age, gender, and metabolic factors play significant roles in the development of HCC, it cannot be overlooked that MASLD, triggered by changes in modern lifestyle and dietary habits, may also exacerbate the risk of HCC, and this phenomenon is common even among non-obese individuals. Regrettably, MASLD often fails to receive timely diagnosis, resulting in a limited number of patients receiving HCC surveillance. Moreover, there is currently a lack of clear definition for the target population for surveillance beyond patients with cirrhosis. Consequently, MASLD-related HCC is often detected at a late stage, precluding the optimal timing for curative treatment. However, our understanding of the pathogenesis and progression of HCC remains limited. Therefore, this paper reviews relevant literature from recent years, delving into multiple dimensions such as pathogenesis, surveillance and diagnosis, prevention, and treatment, aiming to provide new ideas and directions for the prevention and treatment of MASLD-related HCC.
Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Autophagy is associated with NAFLD. Ghrelin is a gut hormone with various functions ...including energy metabolism and inflammation inhibition. We investigated the therapeutic effect of ghrelin on NAFLD and its association with autophagy. Methods: C57bl/6 mice were fed a high-fat diet for 8 weeks to induce a model of chronic NAFLD, with ghrelin (10 µg/kg) administrated subcutaneously twice weekly from weeks 6 to 8. LO2 cells were pretreated with ghrelin (10-8 M) before stimulation with free fatty acid (palmitic and oleic acids; 1 mM). Lipid droplets were identified by hematoxylin and eosin and Red O staining and quantified by triglyceride test kits. LC3I/II, an important biomarker protein of autophagy was detected by western blotting, real-time polymerase chain reaction, immunohistochemistry and immunofluorescence. Tumor necrosis factor (TNF)-a and interleukin (IL)-6 were detected by ELISA and immunohistochemistry. Nuclear factor (NF)-κB p65 was detected by western blotting and immunofluorescence. AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) were detected by western blotting. Results: Ghrelin reduced the triglyceride content in high fat diet (HFD) group in vivo and free fatty acid (FFA) group in vitro. TNF-a and IL-6 were significantly reduced in the ghrelin-treated mice compared with the control group. Autophagy induction was accompanied with intracellular lipid reduction in ghrelin-treated mice. Ghrelin upregulated autophagy via AMPK/mTOR restoration and inhibited translocation of NF-κB into the nucleus. Conclusions: The results indicate that ghrelin attenuates lipotoxicity by autophagy stimulation and NF-κB inhibition.
The addition of nanomaterials to polymers can result not only in significant material property improvements, but also assist in creating entirely new composite functionalities. By dispersing graphene ...nanoplatelets (GNPs) within a polydimethylsiloxane matrix, we show that efficient light absorption by GNPs and subsequent energy transduction to the polymeric chains can be used to controllably produce significant amounts of motion through entropic elasticity of the pre-strained composite. Using dual actuators, a two-axis sub-micron resolution stage was developed, and allowed for two-axis photo-thermal positioning (~100 μm per axis) with 120 nm resolution (feedback sensor limitation), and ~5 μm/s actuation speeds. A PID control loop automatically stabilizes the stage against thermal drift, as well as random thermal-induced position fluctuations (up to the bandwidth of the feedback and position sensor). Maximum actuator efficiency values of ~0.03% were measured, approximately 1000 times greater than recently reported for light-driven polymer systems.
The Na/K-ATPase is an important membrane ion transporter and a signaling receptor that is essential for maintaining normal cell function. The current study examined the role of Na/K-ATPase signaling ...in regulating miR-29b-3p, an anti-fibrotic microRNA, in a mouse chronic kidney disease (CKD) model (5/6th partial nephrectomy or PNx). The results showed that CKD induced significant reduction of miR-29b-3p expression in the heart tissue by activation of Src and NFκB signaling in these animals. To demonstrate the role of Na/K-ATPase signaling, we also performed the PNx surgery on Na/K-ATPase α1 heterozygous (α1+/-) mice, which expresses ~40% less Na/K-ATPase α1 compared to their wild type littermates (WT) and exhibits deficiency in Na/K-ATPase signaling. We found that CKD did not significantly change the miR-29b-3p expression in heart tissue from the α1+/- animals. We also found that CKD failed to activate Src and NFκB signaling in these animals. Using isolated cardiac fibroblasts from α1+/- mice and their WT littermates, we showed that ouabain, a specific Na/K-ATPase ligand, induces decreased miR-29b-3p expression in fibroblasts isolated from WT mice, but had no effect in cells from α1+/- mice. Inhibition of NFκB by Bay11-7082 prevented ouabain-induced miR-29b-3p reduction in WT fibroblasts. To further confirm the in vivo effect of Na/K-ATPase signaling in regulation of miR-29b-3p and cardiac fibrosis in CKD animals, we used pNaKtide, a Src inhibiting peptide derived from the sequence of Na/K-ATPase, to block the activation of Na/K-ATPase signaling. The result showed that pNaKtide injection significantly increased miR-29b-3p expression and mitigated the CKD-induced cardiac fibrosis in these animals. These results clearly demonstrated that Na/K-ATPase signaling is an important mediator in CKD that regulates miR-29b-3p expression and cardiac fibrosis, which provides a novel target for regulation of miR-29b-3p in CKD. We also demonstrate that antagonizing Na/K-ATPase signaling by pNaKtide can reduce organ fibrosis through the stimulation of tissue miR-29b-3p expression.
It’s significant to find an atom-economic way to prepare graphene-manganese oxide nanocomposites for supercapacitors. Herein, a highly atom-efficient strategy is reported to synthesize reduced ...graphene oxide (rGO)-Mn3O4 nanoparticles composite for supercapacitors. First, rGO/MnSO4 suspension is obtained by hydrothermal reduction of graphene oxide (GO)/MnSO4 suspension, which is directly produced via Hummers method, and then rGO-Mn3O4 nanoparticles composites are prepared by precipitation of Mn3O4 nanoparticles anchored in-situ on rGO sheets. The as-prepared rGO-Mn3O4 nanocomposites with 86.96% Mn3O4 exhibit high specific capacitance of 258.6 F g−1 and 186.2 F g−1 at 0.25 A g−1, when using 2 M KOH and 1 M Na2SO4 solution as electrolyte, respectively. More importantly, with the wastewater recovered in the preparation process as electrolyte, the rGO-Mn3O4 composites can deliver a high specific capacitance of 221.6 F g−1 at 50 mA g−1 and 97.1% of the initial capacitance is retained after 1000 cycles at 1 A g−1. In addition, the rGO-MnO2 nanosheets composites can also be obtained via a similar strategy. Obviously, this work provides an atom-efficient way for preparation of rGO-manganese oxide nanocomposites for supercapacitors by fully utilizing effective components of the reaction system, including the wastewater.
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•rGO-Mn3O4 composites are prepared by a highly atom-economic strategy.•The wastewater from the process is utilized as electrolyte for supercapacitor.•The rGO-Mn3O4 composites show good supercapacitive performance in the wastewater.•rGO-MnO2 nanosheets composites can also be synthesized in the process.
Liquid biopsies have advanced rapidly in recent years for use in diagnostic and prognostic applications. One important aspect of this advancement is the growth in our understanding of microRNA ...(miRNA) biology. The measurement of miRNAs packaged within exosomes, which are constantly released into the blood stream, may reflect pathological changes within the body. The current study performed miRNA profiling using plasma and plasma-derived exosome samples from two animal models of kidney disease, the 5/6th partial nephrectomy (PNx) and two-kidney-one-clip (2K1C) models. The RT-qPCR-based profiling results revealed that the overall miRNA expression level was much higher in plasma than in plasma-derived exosomes. With 200μl of either plasma or exosomes derived from the same volume of plasma, 629 out of 665 total miRNAs analyzed were detectable in plasma samples from sham-operated rats, while only 403 were detectable in exosomes with a cutoff value set at 35cycles. Moreover, the average miRNA expression level in plasma was about 16-fold higher than that in exosomes. We also found a select subset of miRNAs that were enriched within exosomes. The number of detectable miRNAs from plasma-derived exosomes was increased in rats subjected to PNx or 2K1C surgery compared to sham-operated animals. Importantly, we found that the changes of individual miRNAs measured in plasma had very poor concordance with that measured in plasma-derived exosomes in both animal models, suggesting that miRNAs in plasma and plasma-derived exosomes are differentially regulated in these disease conditions. Interestingly, PNx and 2K1C surgeries induced similar changes in miRNA expression, implying that common pathways were activated in these two disease models. Pathway analyses using DIANA-miRPath v3.0 showed that significantly changed exosomal miRNAs were associated with extracellular matrix (ECM) receptor interaction and mucin type-O-glycan synthesis pathways, which are related with tissue fibrosis and kidney injury, respectively. In conclusion, our results demonstrated that due to the differential changes in miRNAs, the measurement of exosomal miRNAs cannot be replaced by the measurement of miRNAs in plasma, or vice versa. We also showed that a set of miRNAs related with kidney injury and organ fibrosis were dysregulated in plasma-derived exosomes from animal models of kidney disease.
•Changes in miRNAs can be detected in both plasma and plasma-derived exosomes.•Measurements of miRNAs in plasma and exosomes are not necessarily interchangeable.•Exosomal miRNAs measurement in CKD animals suggests activation of pro-fibrotic pathways.
Improving catalytic activity and durabilty through the structural and compositional development of bifunctional electrocatalysts with low cost, high activity and stability is a challenging issue in ...electrochemical water splitting. Herein, we report the fabrication of heterostructured P-CoMoO4@NiCoP on a Ni foam substrate through interface engineering, by adjusting its composition and architecture. Benefitting from the tailored electronic structure and exposed active sites, the heterostructured P-CoMoO4@NiCoP/NF arrays can be coordinated to boost the overall water splitting. In addition, the superhydrophilic and superaerophobic properties of P-CoMoO4@NiCoP/NF make it conducive to water dissociation and bubble separation in the electrocatalytic process. The heterostructured P-CoMoO4@NiCoP/NF exhibits excellent bifunctional electrocatalysis activity with a low overpotential of 66 mV at 10 mA cm−2 for HER and 252 mV at 100 mA cm−2 for OER. Only 1.62 V potential is required to deliver 20 mA cm−2 in a two-electrode electrolysis system, providing a decent overall water splitting performance. The rational construction of the heterostructure makes it possible to regulate the electronic structures and active sites of the electrocatalysts to promote their catalytic activity.
Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that occurs in the lining of the rectum and colon. Apoptosis of the intestinal epithelial cells (IECs) is common in active UC ...patients. Ghrelin is reported to be downregulated in apoptosis of IECs induced by tumor necrosis factor-α (TNF-α). Therefore, we hypothesized that ghrelin might play an antiapoptotic role in UC progression, which was investigated using
and
studies. The TNF-α-treated Caco-2 cell model and mouse colitis model induced by dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS) were established and employed. We found that ghrelin could inhibit the apoptosis of Caco-2 cells induced by TNF-α, which could be disturbed by D-lys3-GHRP-6, the antagonist of ghrelin receptor GHS-R1a. Similarly, in the DSS- and TNBS-induced mouse colitis models, ghrelin could also protect intestinal tissues from apoptosis in DSS- and TNBS-induced colitis depending on GHS-R1a. Furthermore, ghrelin modulated the unfolded protein response (UPR) pathway and regulated the expressions of caspase-3, BAX, and Bcl-2, which contributed to the inhibition of cell apoptosis. In conclusion, ghrelin protects IECs from apoptosis during the pathogenesis of colitis by regulating the UPR pathway.
Hierarchical structures are very common in knowledge graphs, and semantic hierarchy-preserved knowledge graph embeddings have achieved promising results in the knowledge graph link prediction task. ...However, handling one-to-many, many-to-one, and many-to-many relations that can provide hierarchical information is challenging and brings entity indistinguishability issues. To address this limitation, this paper proposes a novel knowledge graph embedding model, namely Entity-context and Relation-context combined Knowledge Graph Embeddings (ERKE), in which each relation is defined as a rotation with variable moduli from the source entity to the target entity in the polar coordinate system. It can be seen as a combination of two spaces—modulus space and phase space. In the modulus space, modulus information is used to model semantic hierarchies, and entity-context information is adopted to make node representations more expressive. Besides, based on the design of the propagation rule of Graph Convolution Network (GCN), a new GCN model suitable for processing semantic hierarchies in knowledge graphs is proposed. In the phase space, relation-context information is used to make entities easier to distinguish. Specifically, a rotation operation in the polar coordinate system is transformed to the addition operation in the rectangular coordinate system, and relations between entities are mapped into their entity-specific hyperplanes. The proposed method is verified by the experiments on three benchmark datasets, and experimental results demonstrate that the proposed method can learn the semantic hierarchies in knowledge graphs and improve the prediction accuracy of complex one-to-many, many-to-one, and many-to-many cases simultaneously.
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