Evodiamine ameliorates intervertebral disc degeneration through the Nrf2 and MAPK pathways.

Degradation of extracellular matrix (ECM), reactive oxygen species (ROS) production, and inflammation are critical players in the pathogenesis of intervertebral disc degeneration (IDD). Evodiamine exerts functions in inhibiting inflammation and maintaining mitochondrial antioxidant functions. However, the biological functions of evodiamine and its related mechanisms in IDD progression remain unknown. The IDD-like conditions in vivo were stimulated via needle puncture. Hematoxylin and eosin staining, Safranin O/Fast Green staining and Alcian staining were performed to determine the degenerative status. The primary nucleus pulposus cells (NPCs) were isolated from Sprague-Dawley rats and then treated with tert-butyl peroxide (TBHP) to induce cellular senescence and oxidative stress. The cell viability was assessed by cell counting kit-8 assays. The mitochondria-derived ROS in NPCs was evaluated by MitoSOX staining. The mitochondrial membrane potential in NPCs was identified by JC-1 staining and flow cytometry. The expression of collagen II in NPCs was measured by immunofluorescence staining. The levels of mRNAs and proteins were measured by RT-qPCR and western blotting. The Nrf2 expression in rat nucleus pulposus tissues was measured by immunohistochemistry staining. Evodiamine alleviated TBHP-induced mitochondrial dysfunctions in NPCs. The enhancing effect of TBHP on the ECM degradation was reversed by evodiamine. The TBHP-stimulated inflammatory response was ameliorated by evodiamine. Evodiamine alleviated the IDD process in the puncture-induced rat model. Evodiamine promoted the activation of Nrf2 pathway and inactivated the MAPK pathway in NPCs. In conclusion, evodiamine ameliorates the progression of IDD by inhibiting mitochondrial dysfunctions, ECM degradation and inflammation via the Nrf2/HO-1 and MAPK pathways.

Three-Dimensional Spiral Evaporator with Side Channels for Efficient Solar-Driven Water Purification.

Solar evaporators have the advantages of not consuming fossil fuels, being environmentally friendly, and nonpolluting, offering a promising sustainable method to obtain fresh water and alleviate the worldwide freshwater shortage crisis. In this work, we report that high-performance solar evaporators can be facilely fabricated by processing a cost-effective polypyrrole (PPy)-coated nonwoven fabric (PCNF) into a three-dimensional (3D) spiral structure and introducing side channels for vapor escape. The coated PPy layer ensures excellent photothermal properties and the chemical stability of the evaporator. Meanwhile, the as-created spiral structure of the evaporator can significantly increase the effective evaporation area and harvest energy from the environment, greatly stimulating the evaporation. The side opening channels can effectively facilitate the escape of vapor generated inside the 3D spiral structure, avoid the internal vapor accumulation, and ultimately promote the evaporation of the inner surface, leading to a boost of the evaporation performance. Combining these features, the resulting evaporator exhibits an ultrahigh evaporation rate of 3.26 kg m-2 h-1 and an energy efficiency of 138% under 1-sun irradiation. More importantly, we show that this evaporator can also be used to collect fresh water from soil and sand, demonstrating its great applicability for obtaining potable water in arid areas.

Simultaneous Solar-Thermal Desalination and Catalytic Degradation of Wastewater Containing Both Salt Ions and Organic Contaminants.

Although solar steam generation is promising in generating clean water by desalinating seawater, it is powerless to totally degrade organic contaminants in the seawater. Herein, solar steam generation and catalytic degradation are integrated to generate clean water by simultaneous solar-driven desalination and catalytic degradation of wastewater containing both salt ions and organic contaminants. Stepwise decoration of three-dimensional nickel foam with polypyrrole, reduced graphene oxide (RGO), and cobalt phosphate is realized to obtain polypyrrole/RGO/cobalt phosphate/nickel foam (PGCN) hybrids for solar-driven desalination and catalytic degradation of wastewater containing antibiotics and salt ions. The oxygen-containing groups of the RGO integrated with the porous nickel foam make the porous PGCN hybrid hydrophilic and ensure the upward transport of water to the evaporation surface, and the oxygen vacancies of the cobalt phosphate allow the PGCN to generate abundant highly active singlet oxygen that could still exhibit excellent catalytic degradation performances in the high salinity and highly alkaline environment of seawater. In addition to the high solar light absorbance and satisfactory solar-thermal conversion efficiency of polypyrrole and RGO, the thermally conductive nickel foam skeleton can effectively transfer the heat generated by the solar-thermal energy conversion to the adjacent cobalt phosphate catalyst and nearby wastewater, achieving a solar-thermal-promoted catalytic degradation of organic contaminants. Therefore, a high pure water evaporation rate of 2.08 kg m-2 h-1 under 1 sun irradiation and 100% catalytic degradation of Norfloxacin and dyes are achieved. The PGCN hybrid is highly efficient in purifying seawater containing 10 ppm Norfloxacin and simultaneously achieves a high purification efficiency of 100 kg m-2 h-1.

Myricetin alleviates H2O2-induced senescence and apoptosis in rat nucleus pulposus-derived mesenchymal stem cells.

INTRODUCTION: Transplantation of mesenchymal stem cells (MSCs) has been reported to be a novel promising target for the regeneration of degenerated intervertebral discs (IVDs). However, the culture and survival limitations of MSCs remain challenging for MSC-based biological therapy. Myricetin, a common natural flavonoid, has been suggested to possess antiaging and antioxidant abilities. Therefore, we investigated the biological function of myricetin, and its related mechanisms involving cell senescence in intervertebral disc degeneration (IDD). MATERIAL AND METHODS: The nucleus pulposus-derived mesenchymal stem cells (NPMSCs) were isolated from 4-month-old Sprague-Dawley (SD) rats and identified by examining surface markers and multipotent differentiation. Rat NPMSCs were cultured in an MSC culture medium or culture medium with different concentrations of H2O2. Myricetin or the combination of myricetin and EX527 were added to the culture medium to investigate the effects of myricetin. Cell viability was evaluated by cell counting kit-8 assays (CCK-8). The apoptosis rate was determined using Annexin V/PI dual staining. The mitochondrial membrane potential (MMP) was analyzed by a fluorescence microscope after JC-1 staining. The cell senescence was determined by SA-ß-Gal staining. MitoSOX green was used to selectively estimate mitochondrial reactive oxygen species (ROS) Apoptosis-associated proteins (Bax, Bcl2, and cleaved caspase-3), senescence markers (p16, p21, and p53), and SIRT1/PGC-1α signaling pathway-related proteins (SIRT1 and PGC-1α) were evaluated by western blotting. RESULTS: The cells isolated from nucleus pulposus (NP) tissues met the criteria for MSCs. Myricetin showed no cytotoxicity up to a concentration of 100 µM in rat NPMSCs cultured for 24 h. Myricetin pretreatment exhibited protective effects against H2O2-induced apoptosis. Myricetin could also alleviate H2O2-induced mitochondrial dysfunctions of increased mitochondrial ROS production and reduced MMP. Moreover, myricetin pretreatment delayed rat NPMSC senescence, as evidenced by decreased exppression of senescence indicators. Pretreatment of NPMSCs with 10 µM EX527, a selective inhibitor of SIRT1, prior to exposure to 100 µM H2O2, reversed the inhibitory effects of myricetin on cell apoptosis. CONCLUSIONS: Myricetin could affect the SIRT1/PGC-1α pathway to protect mitochondrial functions and alleviate cell senescence in H2O2-treated NPMSCs.

Hyperoside ameliorates TNF­α­induced inflammation, ECM degradation and ER stress­mediated apoptosis via the SIRT1/NF­κB and Nrf2/ARE signaling pathways in vitro.

Intervertebral disc degeneration (IDD) is the main pathogenesis of numerous cases of chronic neck and back pain, and has become the leading cause of spinal­related disability worldwide. Hyperoside is an active flavonoid glycoside that exhibits anti­inflammation, anti­oxidation and anti­apoptosis effects. The purpose of the present study was to investigate the effect of hyperoside on tumor necrosis factor (TNF)­α­induced IDD progression in human nucleus pulposus cells (NPCs) and its potential mechanism. The activity and apoptosis of NPCs were detected by Cell Counting Kit­8 and flow cytometry analyses, respectively. The expression of interleukin (IL)­6 and IL­1ß was detected with ELISA kits. Western blotting was used to detect the expression levels of proteins. The results showed that hyperoside effectively alleviated TNF­α­induced NPC apoptosis, and hyperoside treatment inhibited the upregulation of inducible nitric oxide synthase, cyclooxygenase­2, IL­1ß and IL­6 in TNF­α­stimulated NPCs. Compared with the findings in the TNF­α group, the intervention of hyperoside attenuated the upregulated expression of aggrecan and collagen II, and downregulated the expressions of matrix metalloproteinase (MMP) 3, MMP13 and a disintegrin and metalloproteinase with thrombospondin motifs 5. In addition, hyperoside upregulated sirtuin­1 (SIRT1) and nuclear factor E2­related factor 2 (Nrf2) protein expression, and inhibition of SIRT1 or Nrf2 signaling reversed the protective effect of hyperoside on TNF­α­induced NPCs. In summary, hyperoside ameliorated TNF­α­induced inflammation, extracellular matrix degradation, and endoplasmic reticulum stress­mediated apoptosis, which may be associated with the regulation of the SIRT1/NF­κB and Nrf2/antioxidant responsive element signaling pathways by hyperoside.

Luteolin suppresses TNF-α-induced inflammatory injury and senescence of nucleus pulposus cells via the Sirt6/NF-κB pathway.

Luteolin (3',4',5,7-tetrahydroxy flavone) is a flavonoid, which is widely distributed in various plants including flowers, vegetables, and medicinal herbs and spices. Luteolin can be applied in the treatment of various diseases due to its multiple biological activities, such as anti-inflammatory, anticancer, and antioxidative activity. However, its role in intervertebral disc degeneration has not been previously reported. Therefore, the purpose of the present study was to explore the effects of luteolin on Tumor necrosis factor (TNF)-α-induced inflammatory injury and senescence of human nucleus pulposus cells (HNPCs), as well as the underlying mechanisms of action of this compound. Cell viability and apoptosis were assessed by MTT assay and TUNEL staining, respectively. ELISA kits were applied to detect the levels of inflammatory cytokines and the activity of telomerase. Senescence ß-galactosidase staining was used to detect the activity levels of ß-galactosidase in the cells. Cell transfection was performed to achieve interference of sirtuin 6 (Sirt6). The protein expression levels were detected by western blot analysis. TUNEL staining and western blot analysis were performed to assess the expression levels of apoptosis-related proteins. The results indicated that TNF-α induced a significant decrease in HNPC viability and an increase in inflammatory factor levels, while the application of luteolin effectively increased cell viability and decreased intracellular interleukin (IL)-1ß and IL-6 expression levels. Furthermore, luteolin decreased apoptosis compared with the TNF-α groups in a dose-dependent manner. In addition, the results of the detection kits suggested that luteolin reversed TNF-α-induced senescence. Notably, interference with Sirt6 partially reduced the protective effect of luteolin on TNF-α-induced HNPC senescence via the Sirt6/NF-κB pathway. In summary, the data indicated that luteolin suppresses TNF-α-induced inflammatory injury and senescence of HNPCs via the Sirt6/NF-κB pathway.

Effects of three different embryonic exposure modes of 2, 2', 4, 4'-tetrabromodiphenyl ether on the path angle and social activity of zebrafish larvae.

The toxicological research of polybrominated diphenyl ethers (PBDEs) has focused on its neurotoxicity; however, many questions still remain. For example, behavioral effects other than basic locomotion are seldom reported. To further evaluate the neurobehavioral toxicity of 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47), a typical PBDE congener in animal tissues, we employed three different exposure modes, namely, continuous, early pulse, and interval exposure, to investigate the path angle and social activity changes of zebrafish larvae exposed to BDE-47 using automated equipment (Zebrabox). The results showed that different exposure modes might have different effects on the larval path angle and social activity. BDE-47 treatments caused more responsive turns in all exposure modes in the path angle test and more contacts in most of the two-fish social tests, indicating that the neurobehavior of larvae was disturbed by BDE-47. The light condition was also a key impact factor in the effects of BDE-47. The effects of BDE-47 were different during the dark and light conditions. Our study shows a useful neurobehavioral test method for environmental pollutant monitoring and further supports the utility of zebrafish to study neurobehavior, indicating that the path angle has the potential to be a practicable behavioral indicator.

The developmental effects of pentachlorophenol on zebrafish embryos during segmentation: A systematic view.

Pentachlorophenol (PCP) is a typical toxicant and prevailing pollutant whose toxicity has been broadly investigated. However, previous studies did not specifically investigate the underlying mechanisms of its developmental toxicity. Here, we chose zebrafish embryos as the model, exposed them to 2 different concentrations of PCP, and sequenced their entire transcriptomes at 10 and 24 hours post-fertilization (hpf). The sequencing analysis revealed that high concentrations of PCP elicited systematic responses at both time points. By combining the enrichment terms with single genes, the results were further analyzed using three categories: metabolism, transporters, and organogenesis. Hyperactive glycolysis was the most outstanding feature of the transcriptome at 10 hpf. The entire system seemed to be hypoxic, although hypoxia-inducible factor-1α (HIF1α) may have been suppressed by the upregulation of prolyl hydroxylase domain enzymes (PHDs). At 24 hpf, PCP primarily affected somitogenesis and lens formation probably resulting from the disruption of embryonic body plan at earlier stages. The proposed underlying toxicological mechanism of PCP was based on the crosstalk between each clue. Our study attempted to describe the developmental toxicity of environmental pollutants from a systematic view. Meanwhile, some features of gene expression profiling could serve as markers of human health or ecological risk.

[Pollution characteristics and ecological risk assessment of heavy metals in surface sediments of Qingshan Reservoir in Lin' an City, Zhejiang Province of East China].

A total of 8 representative surface sediment sampling sites were collected from the Qingshan Reservoir in Lin'an City of Zhejiang Province to investigate the differences in the total concentrations of As, Cr, Cu, Ni, Mn, Pb, and Zn among the sampling sites. The different forms of the heavy metals, i. e., acid soluble, easily reducible, easily oxidizable, and residual, were determined by BCR sequential extraction method, and the pollution degrees and potential ecological risk, of the heavy metals in the surface sediments at different sampling sites of the Reservoir were assessed by using geo-accumulation index (I(geo)) and Hakanson potential ecological risk index. There existed obvious spatial differences in the total concentrations of the heavy metals in the surface sediments of the Reservoir. The sampling sites nearby the estuaries of the tributaries flowing through downtowns and heavy industrial parks to the Reservoir had obviously higher heavy metals concentrations in surface sediments, as compared to the other sampling sites. In the sediments, Mn was mainly in acid extractable form, Cu and Pb were mainly in reducible form, and As was mainly in residual form. The surface sediments at the sampling sites nearby the estuaries of the tributaries flowing through downtowns to the Reservoir had higher proportions of acid extractable and reducibles forms of the heavy metals, which would have definite potential toxic risk to aquatic organisms. Among the 7 heavy metals in the surface sediments, As showed the highest pollution degree, followed by Cu, Ni, Mn, Pb, and Zn, which were at moderate pollution degree, while Cr was at non-pollution degree, with relatively low potential ecological risk. Through the comparison of the sampling sites, it was observed that the surface sediments at the sites nearby the estuaries of Jinxi River and Hengxi River flowing through downtowns and heavy industrial parks to the Reservoir showed obviously higher heavy metals pollution degree and potential ecological risk.