Licochalcone B (LicB) is a flavonoid derived from the Chinese medicinal herb Glycyrrhiza uralensis Fisch. Several previous studies have demonstrated the wide range of pharmacological activities shown ...by LicB. In this study, we investigated the anticancer effects of LicB in osteosarcoma (OS) tumor cells and its underlying mechanisms. According to the Cell Counting Kit-8 (CCK8) analysis and 5-ethynil-2′-deoxyuridine (EdU) staining results, we found that LicB suppresses OS cells (MG-63 and U2OS) growth depending on its concentration. Furthermore, flow cytometry and Western blot revealed that LicB promoted autophagy and apoptosis in OS cells in a dose-dependent manner. LicB treatment not only decreased the levels of Bcl-2, p62, Caspase-3, and Ki67 protein in MG-63 and U2OS cell lines but also increased the levels of Cleaved Caspase-3, Beclin1, Bax, Atg7, and LC3B. Mechanistically, LicB induced cell apoptosis by promoting the apoptosis-related cleavage of Caspase-3, while suppressing the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway to induce autophagy. The present work is the first to illustrate that LicB can serve as a potential drug candidate for tumor treatment owing to its ability to enhance autophagy and apoptosis, and suppress OS proliferation by inactivating the PI3K/AKT/mTOR pathway.
Removals of Rhodamine B (RhB) and Acid red 1 using the organic modification of bentonite from aqueous phase were optimized. The organobentonite was synthesized by replacing exchangeable Na+ ions in ...Na-bentonite (Na-Bt) with cetyl trimethylammonium bromide (CTAB) and systematically explored for its adsorption behavior as an efficient adsorbent for the removal of dyes. Batch adsorption studies manifested that the maximum adsorption capacity of dyes were found to be 173.5 mg/g and 157.4 mg/g for RhB and Acid red 1 at the initial concentration of 300 mg/L at 30 °C and pH 9 and 8, respectively. The investigations of adsorption isotherm and kinetics model showed that the adsorption isotherm data were fitted well to the Langmuir isotherm and the adsorption kinetic was better by pseudo-second-order kinetic model. Besides, the thermodynamic parameters indicate that the adsorption process is spontaneous and endothermic. Furthermore, the properties of the obtained samples were characterized by X-ray diffraction (XRD), Scanning electronic microscopy (SEM), Brunauer-Emmett-Teller (BET), Fourier transform infrared spectrometry (FT-IR) and zeta potential analysis. The results of the characterization provided evidence of the morphological properties and how well the adsorption process performed.
图 Schematic diagram of organic modified bentonite and adsorption dyes. Display omitted
•Adsorption ability of different types of dyes onto CTAB-bentonite was investigated.•The relationship of structures and adsorption properties of adsorbent was explored.•The influence of different factors on the properties of the adsorbent was revealed.
The dysregulation of circular RNAs (circRNAs) has been identified in various human diseases. Here, we probed into the potential mechanism of circRNA_0092516 in osteoarthritis (OA). The expression of ...circRNA_0092516 was tested by quantitative real-time PCR. MTT, flow cytometry and western blot were applied to confirm the functions of circRNA_0092516 in vitro. Besides, RNA pull-down and dual-luciferase reporter gene experiments were applied to probe into the mechanism. circRNA_0092516 was raised in the tissues of OA patients and chondrocytes stimulated by IL-1β. The potential mechanism analysis expounded that circRNA_0092516 bound to miR-337-3p, and the interference with circRNA_0092516 boosted chondrocyte proliferation and restrained cell apoptosis through the miR-337-3p/phosphatase and tensin homolog (PTEN) axis, thereby improving OA. In-vivo experiments expounded that circRNA_0092516 regulated cartilage production through miR-337-3p. Overall, our data expounded that the interference with circRNA_0092516 boosted chondrocyte proliferation and restrained cell apoptosis through the miR-337-3p/PTEN axis, eventually slowed down the progress of OA.
A healthy immune system is pivotal for the hosts to resist external pathogens and maintain homeostasis; however, the immunosuppressive tumor microenvironment (TME) damages the anti-tumor immunity and ...promotes tumor progression, invasion, and metastasis. Recently, many studies have found that Foxp3+ regulatory T (Treg) cells are the major immunosuppressive cells that facilitate the formation of TME by promoting the development of various tumor-associated cells and suppressing the activity of effector immune cells. Considering the role of Tregs in tumor progression, it is pivotal to identify new therapeutic drugs to target and deplete Tregs in tumors. Although several studies have developed strategies for targeted deletion of Treg to reduce the TME and support the accumulation of effector T cells in tumors, Treg-targeted therapy systematically affects the Treg population and may lead to the progression of autoimmune diseases. It has been understood that, nevertheless, in disease conditions, Foxp3 undergoes several definite post-translational modifications (PTMs), including acetylation, glycosylation, phosphorylation, ubiquitylation, and methylation. These PTMs not only elevate or mitigate the transcriptional activity of Foxp3 but also affect the stability and immunosuppressive function of Tregs. Various studies have shown that pharmacological targeting of enzymes involved in PTMs can significantly influence the PTMs of Foxp3; thus, it may influence the progression of cancers and/or autoimmune diseases. Overall, this review will help researchers to understand the advances in the immune-suppressive mechanisms of Tregs, the post-translational regulations of Foxp3, and the potential therapeutic targets and strategies to target the Tregs in TME to improve anti-tumor immunity.
Osteoarthritis (OA) is a degenerative disease of articular cartilage and its main pathological feature is cartilage destruction, but its specific pathogenesis is still debatable. The aim of this ...study was to explore the role of miR-337-3p in OA pathogenesis.
The expression of miR-337-3p and PTEN in osteoarthritic cartilage tissues was detected using quantitative real time PCR and western blot, respectively. The regulation of miR-337-3p on PTEN was examined by luciferase reporter gene assays. The manipulation of miR-337-3p and PTEN was mediated by siRNA interference technology. The cell viability was analyzed by MTT assays.
MiR-337-3p expression was significantly down-regulated in osteoarthritic cartilage tissues compared with normal cartilage tissues. Further studies confirmed that miR-337-3p overexpression evidently promoted the proliferation and inhibited the apoptosis of OA chondrocytes. PTEN expression was significantly up-regulated in osteoarthritic cartilage tissues and was negatively regulated by miR-337-3p in chondrocytes. PTEN silencing could improve the proliferation of OA chondrocytes and increased pAKT protein expression in OA chondrocytes.
MiR-337-3p regulated OA chondrocytes proliferation through PTEN/AKT axis and thus involved in OA.
YAP (yes-associated protein), a key transcriptional co-factor that is negatively regulated by the Hippo pathway, is crucial for the development and size control of multiple organs, including the ...liver. However, its role in the brain remains unclear. Here, we provide evidence for YAP regulation of mouse neocortical astrocytic differentiation and proliferation. YAP was undetectable in neurons, but selectively expressed in neural stem cells (NSCs) and astrocytes. YAP in NSCs was required for neocortical astrocytic differentiation, with no apparent role in self-renewal or neural differentiation. However, YAP in astrocytes was necessary for astrocytic proliferation. Yap (Yap1) knockout, Yap(nestin) conditional knockout and Yap(GFAP) conditional knockout mice displayed fewer neocortical astrocytes and impaired astrocytic proliferation and, consequently, death of neocortical neurons. Mechanistically, YAP was activated by BMP2, and the active/nuclear YAP was crucial for BMP2 induction and stabilization of SMAD1 and astrocytic differentiation. Expression of SMAD1 in YAP-deficient NSCs partially rescued the astrocytic differentiation deficit in response to BMP2. Taken together, these results identify a novel function of YAP in neocortical astrocytic differentiation and proliferation, and reveal a BMP2-YAP-SMAD1 pathway underlying astrocytic differentiation in the developing mouse neocortex.
Ferroptosis, a new form of programmed cell death, not only promotes the pathological process of various human diseases, but also regulates cancer progression. Current perspectives on the underlying ...mechanisms remain largely unknown. Herein, we report a member of the NEET protein family, CISD3, exerts a regulatory role in cancer progression and ferroptosis both in vivo and in vitro. Pan-cancer analysis from TCGA reveals that expression of CISD3 is generally elevated in various human cancers which are consequently associated with a higher hazard ratio and poorer overall survival. Moreover, knockdown of CISD3 significantly accelerates lipid peroxidation and accentuates free iron accumulation triggered by Xc
inhibition or cystine-deprivation, thus causing ferroptotic cell death. Conversely, ectopic expression of the shRNA-resistant form of CISD3 (CISD3res) efficiently ameliorates the ferroptotic cell death. Mechanistically, CISD3 depletion presents a metabolic reprogramming toward glutaminolysis, which is required for the fuel of mitochondrial oxidative phosphorylation. Both the inhibitors of glutaminolysis and the ETC process were capable of blocking the lipid peroxidation and ferroptotic cell death in the shCISD3 cells. Besides, genetic and pharmacological activation of mitophagy can rescue the CISD3 knockdown-induced ferroptosis by eliminating the damaged mitochondria. Noteworthily, GPX4 acts downstream of CISD3 mediated ferroptosis, which fails to reverse the homeostasis of mitochondria. Collectively, the present work provides novel insights into the regulatory role of CISD3 in ferroptotic cell death and presents a potential target for advanced antitumor activity through ferroptosis.
Yes-associated protein (YAP) transcriptional coactivator is negatively regulated by the Hippo pathway and functions in controlling the size of multiple organs, such as liver during development. ...However, it is not clear whether YAP signaling participates in the process of the formation of glia scars after spinal cord injury (SCI). In this study, we found that YAP was upregulated and activated in astrocytes of C57BL/6 male mice after SCI in a Hippo pathway-dependent manner. Conditional knockout (KO) of
in astrocytes significantly inhibited astrocytic proliferation, impaired the formation of glial scars, inhibited the axonal regeneration, and impaired the behavioral recovery of C57BL/6 male mice after SCI. Mechanistically, the bFGF was upregulated after SCI and induced the activation of YAP through RhoA pathways, thereby promoting the formation of glial scars. Additionally, YAP promoted bFGF-induced proliferation by negatively controlling nuclear distribution of p27
mediated by CRM1. Finally, bFGF or XMU-MP-1 (an inhibitor of Hippo kinase MST1/2 to activate YAP) injection indeed activated YAP signaling and promoted the formation of glial scars and the functional recovery of mice after SCI. These findings suggest that YAP promotes the formation of glial scars and neural regeneration of mice after SCI, and that the bFGF-RhoA-YAP-p27
pathway positively regulates astrocytic proliferation after SCI.
Glial scars play critical roles in neuronal regeneration of CNS injury diseases, such as spinal cord injury (SCI). Here, we provide evidence for the function of Yes-associated protein (YAP) in the formation of glial scars after SCI through regulation of astrocyte proliferation. As a downstream of bFGF (which is upregulated after SCI), YAP promotes the proliferation of astrocytes through negatively controlling nuclear distribution of p27
mediated by CRM1. Activation of YAP by bFGF or XMU-MP-1 injection promotes the formation of glial scar and the functional recovery of mice after SCI. These results suggest that the bFGF-RhoA-YAP-p27
axis for the formation of glial scars may be a potential therapeutic strategy for SCI patients.
Prompt and accurate traffic flow forecasting is a key foundation of urban traffic management. However, the flows in different areas and feature channels (inflow/outflow) may correspond to different ...degrees of importance in forecasting flows. Many forecasting models inadequately consider this heterogeneity, resulting in decreased predictive accuracy. To overcome this problem, an attention-based hybrid spatiotemporal residual model assisted by spatial and channel information is proposed in this study. By assigning different weights (attention levels) to different regions, the spatial attention module selects relatively important locations from all inputs in the modeling process. Similarly, the channel attention module selects relatively important channels from the multichannel feature map in the modeling process by assigning different weights. The proposed model provides effective selection and attention results for key areas and channels, respectively, during the forecasting process, thereby decreasing the computational overhead and increasing the accuracy. In the case involving Beijing, the proposed model exhibits a 3.7% lower prediction error, and its runtime is 60.9% less the model without attention, indicating that the spatial and channel attention modules are instrumental in increasing the forecasting efficiency. Moreover, in the case involving Shanghai, the proposed model outperforms other models in terms of generalizability and practicality.
A previous study has shown that the density of OT receptors in the nucleus accumbens of female prairie voles was positively correlated with alloparental behavior (Olazábal, 2014). ...Feldman and ...colleagues reported that parental sensitive caregiving, including warmth, gaze duration, checking behaviors, responsiveness to child's cues, and engagement, assessed by coding interactive behavior were correlated positively with parental endogenous OT (plasma and salivary OT) in human beings (Feldman et al., 2011). According to a previous report (Kenkel et al., 2017), the alloparenting behaviors such as pup retrieval, licking/grooming, and arched-back huddling, are not qualitatively different from the behavior of parents. The authors also found that the photometric signal increased before the retrieval onset and decreased after retrieval onset. ...PVN activity was closely associated with cortical plasticity in a self-adaption way. ...the relationship between pup retrieval and signaling from virgin PVN to the left auditory cortex was explored.
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