Using the Photo-Piezoelectric Effect of AuPt@BaTiO3 Oxidase Mimetics for Colorimetric Detection of GSH in Serum.

Nanozymes possess major advantages in catalysis and biosensing compared with natural nanozymes. In this study, the AuPt@BaTiO3 bimetallic alloy Schottky junction is prepared to act as oxidase mimetics, and its photo-piezoelectric effect is investigated. The synergy between the photo-piezoelectric effect and the local surface plasmon resonance enhances the directional migration and separation of photogenerated electrons, as well as hot electrons induced by the AuPt bimetallic alloy. This synergy significantly improves the oxidase-like activity. A GSH colorimetric detection platform is developed based on this fading principle. Leveraging the photo-piezoelectric effect allows for highly sensitive detection with a low detection limit (0.225 µM) and reduces the detection time from 10 min to 3 min. The high recovery rate (ranging from 99.91% to 101.8%) in actual serum detection suggests promising potential for practical applications. The development of bimetallic alloy heterojunctions presents new opportunities for creating efficient nanozymes.

Roles of luxS in regulation of probiotic characteristics and inhibition of pathogens in Lacticaseibacillus paracasei S-NB.

Lactic acid bacteria (LAB) have excellent tolerance to the gastrointestinal environment and high adhesion ability to intestinal epithelial cells, which could be closely related to the LuxS/AI-2 Quorum sensing (QS) system. Here, the crucial enzymes involved in the synthesis of AI-2 was analyzed in Lacticaseibacillus paracasei S-NB, and the luxS deletion mutant was constructed by homologous recombination based on the Cre-lox system. Afterwards, the effect of luxS gene on the probiotic activities in L. paracasei S-NB was investigated. Notably, the tolerance of simulated gastrointestinal digestion, AI-2 production, ability of auto-aggregation and biofilm formation significantly decreased (p < 0.05 for all) in the S-NB△luxS mutant. Compared to the wild-type S-NB, the degree of reduction in the relative transcriptional level of the biofilm -related genes in Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923 was diminished when co-cultured with S-NB△luxS. Furthermore, the inhibitory effect of S-NB△luxS on the adhesion (competition, exclusion and displacement) of E. coli ATCC 25922 and S. aureus ATCC 25923 to Caco-2 cells markedly decreased. Therefore, comprehensive analysis of the role by luxS provides an insight into the LuxS/AI-2 QS system of L. paracasei S-NB in the regulation of strain characteristics and inhibition of pathogens.

Sequential flipping: the donor-acceptor exchange mechanism in water trimers.

The donor-acceptor exchange (DAE) is a significant hydrogen bond network rearrangement (HBNR) mechanism because it can lead to the change of the hydrogen bond direction. In this work, we report a new DAE mechanism found in water trimers that is realized by sequential flipping (SF) of all molecules rather than the well-known proton transfer (PT) process. Meanwhile, the SF process has a much smaller potential barrier (0.262 eV) than the previously predicted collective rotation process (about 1.7 eV), implying that the SF process is the main flipping process that can lead to DAE. Importantly, high-precision ab initio calculations show that SF-DAE can make the water ring to show a clear chiral difference from PT-DAE, which brings the prospect of distinguishing the two confusing processes based on circular dichroism spectra. The reaction rate analysis including quantum tunneling indicates an obvious temperature-dependent competitive relationship between the SF and PT processes; specifically, the SF process dominates above 65 K, while the PT process dominates below 65 K. Therefore, in most cases, the contribution for DAE mainly comes from the flipping process, rather than the PT process as previously thought. Our work enriches the understanding of the DAE mechanism in water trimers and provides a piece of the jigsaw that has been sought for the HBNR mechanism.

Sequencing and de novo assembly of 150 genomes from Denmark as a population reference.

Hundreds of thousands of human genomes are now being sequenced to characterize genetic variation and use this information to augment association mapping studies of complex disorders and other phenotypic traits. Genetic variation is identified mainly by mapping short reads to the reference genome or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set of structural variants including many novel insertions and demonstrate how this variant catalogue enables further deciphering of known association mapping signals. We leverage the assemblies to provide 100 completely resolved major histocompatibility complex haplotypes and to resolve major parts of the Y chromosome. Our study provides a regional reference genome that we expect will improve the power of future association mapping studies and hence pave the way for precision medicine initiatives, which now are being launched in many countries including Denmark.

Sophorolipid Suppresses LPS-Induced Inflammation in RAW264.7 Cells through the NF-κB Signaling Pathway.

OBJECTIVES: Biosurfactants with anti-inflammatory activity may alleviate skin irritation caused by synthetic surfactants in cleaning products. Sophorolipid (SL) is a promising alternative to synthetic surfactants. However, there are few reports on the anti-inflammatory activity of SL and the underlying mechanism. The purpose of this work is to verify that lipopolysaccharide (LPS)-induced inflammation could be inhibited through targeting the pathway of nuclear factor-κB (NF-κB) in RAW264.7 cells. METHODS: The influence of SL on cytokine release was investigated by LPS-induced RAW264.7 cells using ELISA. The quantification of the protein expression of corresponding molecular markers was realized by Western blot analysis. Flow cytometry was employed to determine the levels of Ca2+ and reactive oxygen species (ROS). The relative expression of inducible nitric oxide synthase (INOS) and cyclooxygenase-2 (COX-2) was determined by RT-PCR. An immunofluorescence assay and confocal microscope were used to observe the NF-κB/p65 translocation from the cytoplasm into the nucleus. The likely targets of SL were predicted by molecular docking analysis. RESULTS: SL showed anti-inflammatory activity and reduced the release of inflammatory cytokines including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO). The experimental results show that SL suppressed the Ca2+ and ROS levels influx in the LPS-induced RAW264.7 cells and alleviated the LPS-induced expression of iNOS and COX-2, the LPS-induced translocation of NF-κB (p65) from the cytoplasm into the nucleus, and the expression of phosphorylated proteins such as p65 and IκBα. Furthermore, molecular docking analysis showed that SL may inhibit inflammatory signaling by competing with LPS to bind TLR4/MD-2 through hydrophobic interactions and by inhibiting IKKß activation through the hydrogen bonding and hydrophobic interactions. CONCLUSION: This study demonstrated that SL exerted anti-inflammatory activity via the pathway of NF-κB in RAW264.7 cells.

Inhibitory activity of acteoside in melanoma via regulation of the ERß-Ras/Raf1-STAT3 pathway.

BACKGROUND: Melanoma is an aggressive cancer with a rapidly increasing incidence rate worldwide. Acteoside has been shown to have antitumor effects in multiple human cancers; however, the underlying function and mechanisms of acteoside in melanoma remain unclear. PURPOSE: This study explored the inhibitory effect of acteoside on melanoma and the possible mechanisms. METHODS: Acteoside (15 mg/kg, 30 mg/kg) was administered to mice daily for 21 days. ICI182,780 (0.5 mg/kg) was intraperitoneally injected 30 min before acteoside administration three times a week to evaluate whether the effects elicited by acteoside were mediated via the estrogen receptor. Tumor growth and metabolism, cardiac function, ROS and apoptosis levels in the spleen, serum inflammatory factors, and immune cells in the spleen were monitored. STAT3, p-STAT3, CD31, and survivin levels in tumor tissues were measured via immunofluorescence. Ras, Raf1, STAT3, p-STAT3, Bcl-2, Bax, cleaved caspase-3, and cleaved caspase-9 levels in tumor tissues were determined via Western Blotting. RESULTS: The results showed that acteoside inhibited melanoma growth, alleviated inflammation levels in mice, attenuated ROS and apoptosis levels in the spleen, downregulated the levels of CD31, survivin, Ras, Raf1, p-STAT3, and Bcl-2, and upregulated the levels of ERß, Bax, cleaved caspase-3, and cleaved caspase-9. Moreover, the effect of acteoside was blocked by ICI182,780. CONCLUSION: Acteoside may promote the apoptosis of tumor cells by regulating the ERß-Ras/Raf1-STAT3 signaling axis, thus inhibiting the occurrence and development of melanoma.

Physiological Characteristics and Operational Performance of Pilots in the High Temperature and Humidity Fighter Cockpit Environments.

During military operations in high-temperature and relative humidity (RH) conditions, the physiological state and combat capability of pilots are affected severely. In a fighter cockpit, experiments were conducted on thirteen voluntary subjects wearing pilot suits at 21 °C/30%, 30 °C/45%, and 38 °C/60% RH, respectively, in order to examine the physiological changes of pilots in combat thoroughly. The target strike performance, core and skin temperatures, pulse rate, and other parameters were measured and investigated. Significant inter-condition differences were noted in the pulse rate, core temperature, mean skin temperatures, and sweat amount, which increased markedly with elevating temperature and RH. Contrastively, blood oxygen saturation (SpO2) dropped with such elevations. Concerning the skin temperature, the chest and back skin temperatures remained stable, while the temperatures at the hands, feet, and lower arms underwent larger changes with the increasing temperature and humidity. At 38 °C/60% RH, the sweat amount was 3.7 times that at 21 °C/30% RH. The subjects' operational error rates increased as the core temperatures rose, showing high correlations (r2 = 0.81). The results could serve as a theoretical basis for the design of pilot protective equipment and the control of aircraft cockpit temperature.

Protopine Protects Mice against LPS-Induced Acute Kidney Injury by Inhibiting Apoptosis and Inflammation via the TLR4 Signaling Pathway.

Corydalis humosa Migo is a traditional Chinese medicine that clears away damp heat, relieves sore. Protopine (PRO) is an alkaloid component isolated from C. humosa Migo. However, the role of protopine in acute kidney injury (AKI) has not yet been reported. This study aims to investigate the effect and mechanism of protopine isolated from C. humosa Migo on lipopolysaccharide (LPS)-induced AKI in mice. Inflammation accumulation was assessed by small animal living imaging. The blood urea nitrogen (BUN), and serum creatinine (Scr) were measured to assess the effects of protopine on renal function in LPS-induced AKI. The levels of tumor necrosis factor (TNF), interleukin-2 (IL-2), interferon-γ (IFN-γ), and (interleukin-10) IL-10 in serum were detected by cytometric bead array. Flow cytometry was used to detect the levels of reactive oxygen species (ROS) in primary kidney cells. The proportions of granulocytes, neutrophils, and macrophages in peripheral blood were examined to evaluate the effect of protopine on immune cells in mice with AKI. Toll-like receptor (TLR4) and apoptotic signaling pathway were detected by Western blot analysis. The results showed that protopine markedly improved the renal function, relieve inflammation, reversed inflammatory cytokines, transformed apoptosis markers, and regulated the TLR4 signaling pathway in mice with AKI induced by LPS. The protopine isolated from C. humosa Migo protected mice against LPS-induced AKI by inhibiting apoptosis and inflammation via the TLR4 signaling pathway, thus providing a molecular basis for a novel medical treatment of AKI.

Preparation of hollow double-layer Pt@CeO2 nanospheres as oxidase mimetics for the colorimetric-fluorescent-SERS triple-mode detection of glutathione in serum.

Glutathione (GSH) is an essential antioxidant in the human body, but its detection is difficult due to the interference of complex components in serum. Herein, hollow double-layer Pt@CeO2 nanospheres were developed as oxidase mimetics, and the light-assisted oxidase mimetics effects were found. The oxidase activity was enhanced significantly by utilizing the synergistic effect of Schottky junction and the localized surface plasmon resonance (LSPR) of Pt under UV light. A novel GSH colorimetric-fluorescent-SERS sensing platform was established, with the sensing performance notably boosted by using the light-assisted oxidase mimetics effects. This platform boasts an exceptionally low detection limit (LOD) of 0.084 µM, while the detection time was shortened from 10 min to just 2 min. The anti-interference detection with high recovery rate (96.84%-107.4 %) in real serum made it be promising for practical application.

Highly efficient MoS2/MXene aerogel for interfacial solar steam generation and wastewater treatment.

Interfacial solar steam generation using aerogels holds great promise for seawater desalination and wastewater treatment. However, to achieve aerogels with both durable, high-efficiency evaporation performance and excellent salt resistance remains challenging. Here, a molybdenum disulphide (MoS2) and MXene composite aerogel with vertical pore channels is reported, which has outstanding advantages in mechanical properties, water transportation, photothermal conversion, and recycling stability. Benefiting from the plasmon resonance effect of MXene and the excellent photothermal conversion performance of MoS2, the aerogel exhibits excellent light absorption (96.58 %). The aerogel is resistant to deformation and able to rebound after water absorption, because of the support of an ordered vertical structure. Moreover, combined with the low water evaporation enthalpy, low thermal conductivity, and super hydrophilicity, the aerogel achieves an efficient and stable evaporation rate of about 2.75 kg m-2h-1 under one sun and exhibits excellent self-cleaning ability. Notably, the evaporator achieves removal rates of 99.9 % for heavy metal ions and 100 % for organic dyes, which has great potential in applications including seawater desalination and wastewater purification.

Nanocomposites of Conducting Polymers and 2D Materials for Flexible Supercapacitors.

Flexible supercapacitors (FSCs) with high electrochemical and mechanical performance are inevitably necessary for the fabrication of integrated wearable systems. Conducting polymers with intrinsic conductivity and flexibility are ideal active materials for FSCs. However, they suffer from poor cycling stability due to huge volume variations during operation cycles. Two-dimensional (2D) materials play a critical role in FSCs, but restacking and aggregation limit their practical application. Nanocomposites of conducting polymers and 2D materials can mitigate the above-mentioned drawbacks. This review presents the recent progress of those nanocomposites for FSCs. It aims to provide insights into the assembling strategies of the macroscopic structures of those nanocomposites, such as 1D fibers, 2D films, and 3D aerogels/hydrogels, as well as the fabrication methods to convert these macroscopic structures to FSCs with different device configurations. The practical applications of FSCs based on those nanocomposites in integrated self-powered sensing systems and future perspectives are also discussed.

Nanotrench Superfilling Facilitates Embedded Lithium Anode for High-Areal-Capacity Solid-State Batteries.

Solid-state batteries based on lithium metal anodes are expected to meet safety challenges while maintaining a high energy density. One major challenge lies in the fast interface degradation between the electrolyte and the lithium metal. Herein, we propose a quasi-3D interphase on a garnet solid-state electrolyte (SSE) by introducing lithiophilic nanotrenches. The nanotrenches created by the lithiophilic nanowire array can induce the superfilling of lithium metal into the nanotrenches, resulting in a low interfacial resistance (4 Ω cm2). Moreover, the embedded lithium metal anode optimizes the lithium deposition/stripping behavior not limited at the Li-SSE interface (∼1-10 nm) but extended into the bulk lithium anode (∼10 µm), realizing a high critical current density of 1.8-2.0 mA cm-2 at room temperature (RT). The embedded lithium metal anode is further applied in Li||LiFePO4 solid-state batteries, demonstrating a high reversible areal capacity of ∼3.0 mAh cm-2 at RT.

Adaptive generalized super twisting sliding mode control for PMSMs with filtered high-gain observer.

This paper proposes a novel adaptive-gain generalized super twisting algorithm for permanent magnet synchronous motors. The stability of this algorithm is strict proof using the Lyapunov method. Both controllers of the speed-tracking loop and the current regulation loop are designed according to the proposed adaptive-gain generalized super twisting algorithm. Dynamically adjusted gains in the controllers can improve the transient performance and system's robustness while reducing chattering. A filtered high-gain observer is applied in the speed-tracking loop to estimate the lumped disturbances, including parameter uncertainties and external load torque disturbances. The estimates feeding forward to the controller further improve the robustness of the system. Meanwhile, the linear filtering subsystem reduces the sensitivity of the observer to the measurement noise. Finally, experiments are constructed using the adaptive gain generalized super twisting sliding mode algorithm and the fixed gain one, showing the effectiveness and advantages of the proposed control scheme.

Development of Carbon Nanotube/Graphene-Based Alginate Interpenetrating Hydrogels for Removal of Antibiotic Pollutants.

The extensive use of pharmaceutical antibiotics in treatment of human and animal infections has resulted in growing concerns about antibiotic pollution worldwide. In this work a novel interpenetrating polymer network (IPN) hydrogel has been developed to function as an effective and non-selective adsorbent for various antibiotic pollutants in aqueous solution. This IPN hydrogel is made of multiple active components, including carbon nanotube (CNTs), graphene oxide (GO), and urea-modified sodium alginate (SA). It can be readily prepared through efficient carbodiimide-mediated amide coupling reaction followed by calcium chloride-induced alginate cross-linking. The structural properties, swellability, and thermal stability of this hydrogel have been investigated, while its adsorption properties towards an important antibiotic pollutant, tetracycline, was thoroughly characterized based on adsorption kinetic and isotherm analyses. With a BET surface area of 38.7 m2 /g, the IPN hydrogel shows an excellent adsorption capacity of 84.28±4.2 mg/g towards tetracycline in water, while the adsorption capacity is decreased by only 18 % after four cycles of use, demonstrating very good reusability. Adsorptive performance in removing two other antibiotics, neomycin and erythromycin, has also been examined and compared. Overall, our studies disclose that this newly designed hybrid hydrogel is an effective and reusable adsorbent material for treating antibiotic pollution in the environment.

Sophorolipid inhibits histamine-induced itch by decreasing PLC/IP3R signaling pathway activation and modulating TRPV1 activity.

Biosurfactants are attracting much interest due to their potential application as therapeutic agents in the medical and cosmetic field. Previous studies have demonstrated that biosurfactant such as sophorolipid (SL) exhibits immunomodulatory effects. In this article, we found the potential of sophorolipid for inhibiting histamine-induced itch and preliminarily explored its molecular basis. First, behavioral tests indicated that SL can remit the histamine-induced scratching behaviors of mice. Second, SL can suppress the the calcium influx induced by histamine, HTMT and VUF8430 in HaCaT cells. RT-PCR analysis showed that the histamine-induced upregulation of mRNA levels of phospholipase Cγ1, 1,4,5-trisphosphate receptor (IP3R), and protein kinase Cα can be inhibted by SL, suggesting that SL may impede the PLC/IP3R signaling pathway activated by histamine. In further tests, the capsaicin-induced calcium influx can also be inhibited by SL. The immunofluorescence and molecular docking analysis indicated that SL acts as an inhibitor of transient receptor potential vanilloid-1 (TRPV1) activation to decrease calcium influx against stimuli. In summary, these results revealed that SL may inhibit histamine-induced itch by decreasing PLC/IP3R signaling pathway activation and modulating TRPV1 activity. This paper indicates that SL can be a useful treatment for histamine-dependent itch.

Ephedra Herb extract ameliorates adriamycin-induced nephrotic syndrome in rats via the CAMKK2/AMPK/mTOR signaling pathway.

This study aimed to investigate the effect and mechanisms of Ephedra Herb (EH) extract on adriamycin-induced nephrotic syndrome (NS), providing an experimental basis for the clinical treatment of NS. Hematoxylin and eosin staining, creatinine, urea nitrogen, and kidn injury molecule-1 were used to evaluate the activities of EH extract on renal function. The levels of inflammatory factors and oxidative stress were detected by kits. The levels of reactive oxygen species, immune cells, and apoptosis were measured by flow cytometry. A network pharmacological approach was used to predict the potential targets and mechanisms of EH extract in the treatment of NS. The protein levels of apoptosis-related proteins and CAMKK2, p-CAMKK2, AMPK, p-AMPK, mTOR and p-mTOR in the kidneys were detected by Western blot. The effective material basis of EH extract was screened by MTT assay. The AMPK pathway inhibitor (compound C, CC) was added to investigate the effect of the potent material basis on adriamycin-induced cell injury. EH extract significantly improved renal injury and relieve inflammation, oxidative stress, and apoptosis in rats. Network pharmacology and Western blot results showed that the effect of EH extract on NS may be associated with the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine significantly ameliorated adriamycin-induced NRK-52e cell injury. Methylephedrine also significantly improved the phosphorylation of AMPK and mTOR, which were blocked by CC. In sum, EH extract may ameliorate renal injury via the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine may be one of the material bases of EH extract.

MiR-200c-3p and miR-485-5p overexpression elevates cisplatin sensitivity and suppresses the malignant phenotypes of non-small cell lung cancer cells through targeting RRM2.

BACKGROUND: This study intended to investigate the potential mechanism of microRNA-200c-3p (miR-200c-3p) and miR-485-5p in mediating the cisplatin (DDP) resistance in non-small cell lung cancer (NSCLC). METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to measure the expression of miR-200c-3p, miR-485-5p, and ribonucleotide reductase regulatory subunit M2 (RRM2) messenger RNA (mRNA). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to analyze the DDP resistance and the proliferation of NSCLC cells. Colony formation assay was used to assess cell proliferation. Transwell assays were used to evaluate cell migration and invasion. The target relationship between RRM2 and miR-200c-3p or miR-485-5p was verified using dual-luciferase reporter assay. The protein level of RRM2 was measured using Western blot assay. Animal experiments were conducted to analyze the roles of miR-200c-3p and miR-485-5p in the DDP resistance of xenograft tumors in vivo. RESULTS: MiR-200c-3p and miR-485-5p were both downregulated in DDP-resistant NSCLC tissues and cell lines. Overexpressing miR-200c-3p or miR-485-5p suppressed the DDP resistance and malignant behaviors of NSCLC cells. MiR-200c-3p played a synergistic role with miR-485-5p in regulating the chemo-resistance and biological behaviors NSCLC cells. RRM2 was confirmed as a target of miR-200c-3p and miR-485-5p. RRM2 silencing restrained the DDP resistance and progression of NSCLC. RRM2 overexpression partly reversed miR-200c-3p or miR-485-5p-induced influences in NSCLC cells. The overexpression of miR-200c-3p or miR-485-5p aggravated DDP-mediated suppressive effect on tumor growth in vivo. CONCLUSION: MiR-200c-3p or miR-485-5p enhanced the DDP sensitivity and suppressed the malignant behaviors of NSCLC cells partly through targeting RRM2.

Three-Dimensional Artificial Transpiration Structure Based on 1T/2H-MoS2/Activated Carbon Fiber Cloth for Solar Steam Generation.

The rise of solar steam generation is an effective strategy to mitigate clean water shortages. However, achieving further improvements in conversion efficiency and stability remains a challenge. Here, 1T/2H-MoS2 nanosheets were uniformly assembled on activated carbon fiber cloth (A-CFC) through a facial hydrothermal method, and a three-dimensional (3D)-artificial transpiration device (ATD) was prepared using the plant transpiration process. The combination of activated carbon fiber cloth and 1T/2H phase MoS2 exhibits high light absorption (∼97.5%), excellent mechanical stability, large evaporation area, and easy escape of vapor. Additionally, the 3D hollow cone of the MoS2/carbon fiber cloth can effectively reduce radiative and convective energy loss and then achieve the enhancement of energy collection from the environment. An outstanding evaporation rate of 1.61 kg·m-2·h-1 with an optimum conversion efficiency of 97% under one sun is reached. Based on the facile fabrication, excellent stability, and high solar conversion efficiency, this nature-inspired design of 3D 1T/2H-MoS2/A-CFC is expected to facilitate large-scale applications for seawater purification and desalination.

Circ_0011292 knockdown mitigates progression and drug resistance in PTX-resistant non-small-cell lung cancer cells by regulating miR-433-3p/CHEK1 axis.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is one of the most common malignant tumors on earth. Circular RNAs have been disclosed to be vital regulators in the chemoresistance and development of diverse cancers, including NSCLC. Here, we attempted to explore the function of circ_0011292 in paclitaxel (PTX)-resistant NSCLC cells. METHODS: Quantitative real-time polymerase chain reaction or western blot was performed to detect the expression of circ_0011292, microRNA-433-3p (miR-433-3p), and checkpoint kinase 1 (CHEK1). Ribonuclease R (RNase R) assay was performed to assess the stability of circ_0011292. Cell Counting Kit-8 assay was conducted to evaluate the half maximal inhibitory concentration of PTX and cell viability. Cell proliferation was monitored by Edu incorporation and colony formation assays. Cell cycle and apoptosis were detected by flow cytometry. Transwell assay was implemented to assess cell migration and invasion. Western blot assay was utilized to determine the protein levels. Dual-luciferase reporter assay was carried out to verify the targeted interaction between miR-433-3p and circ_0011292 or CHEK1. Xenograft tumor model was constructed for determining the effect of circ_0011292 in NSCLC growth in vivo. RESULTS: Circ_0011292 was upregulated in PTX-resistant NSCLC tissues and cells. Circ_0011292 or CHEK1 knockdown enhanced PTX sensitivity and cell apoptosis, and repressed cell proliferation, migration, and invasion in PTX-resistant NSCLC cells. Mechanistically, circ_0011292 was a sponge of miR-433-3p and miR-433-3p directly targeted CHEK1. Meanwhile, silencing miR-433-3p or overexpressing CHEK1 respectively abrogated the impacts of circ_0011292 deletion or miR-433-3p introduction on PTX resistance and cell progression in PTX-resistant NSCLC cells in vitro. Moreover, circ_0011292 could positively modulate CHEK1 expression through sponging miR-433-3p. In addition, circ_0011292 knockdown retarded tumor growth of NSCLC in vivo. CONCLUSION: Circ_0011292 could accelerate PTX resistance and cell malignant progression of NSCLC cells partially through the regulation of circ_0011292/miR-433-3p/CHEK1 axis.

Extract of Corallodiscus flabellata attenuates renal fibrosis in SAMP8 mice via the Wnt/ß-catenin/RAS signaling pathway.

BACKGROUND: Fibrosis is one of the most common pathological features of the aging process of the kidney, and fibrosis in aging kidneys also aggravates the process of chronic kidney disease (CKD). Corallodiscus flabellata B. L. Burtt (C. flabellata, CF) is a commonly used botanical drug in Chinese folklore. However, few studies have reported its pharmacological effects. This study aimed to explore the effect of CF ethanol extract on renal fibrosis in SAMP8 mice and identify potentially active compounds. METHODS: Senescence-accelerated mouse-prone 8 (SAMP8) were used as animal models, and different doses of CF were given by gavage for one month. To observe the degree of renal aging in mice using ß-galactosidase staining. Masson staining and the expression levels of Col-I, α-SMA, and FN were used to evaluate the renal fibrosis in mice. The protein expression levels of Nrf2 pathway and Wnt/ß-catenin/RAS pathway in the kidney were measured. And ß-galactosidase (ß-gal) induced NRK-52E cells as an in vitro model to screen the active components of CF. RESULTS: The CF ethanol extract significantly inhibited the activity of renal ß-galactosidase and the expression levels of Col-I, α-SMA, and FN in SAMP8 mice, and improved Masson staining in SAMP8 mice. CF remarkably reduced urinary protein, creatinine, urea nitrogen and serum levels of TNF-α and IL-1ß in SAMP8 mice, and significantly increased the levels of SOD and GSH-Px. Moreover, CF activated the Nrf2 pathway and blocked the Wnt/ß-catenin/RAS pathway in the kidneys of mice. Besides, 3,4-dihydroxyphenylethanol (SDC-0-14, 16) and (3,4-dihydroxyphenylethanol-8-O-[4-O-trans-caffeoyl-ß-D-apiofuranosyl-(1→3)-ß-D-glucopyranosyl (1→6)]-ß-D-glucopyranoside (SDC-1-8) were isolated from CF, which reduced the senescence of NRK-52E cells, and maybe the active ingredients of CF playing the anti-aging role. CONCLUSIONS: Our experiments illuminated that CF ethanol extract may ameliorate renal fibrosis in SAMP8 mice via the Wnt/ß-catenin/RAS pathway. And SDC-0-14,16 and SDC-1-8 may be the material basis for CF to exert anti-renal senescence-related effects.