Although the ubiquitin-editing enzyme A20 is a key player in inflammation and autoimmunity, its role in cancer metastasis remains unknown. Here we show that A20 monoubiquitylates Snail1 at three ...lysine residues and thereby promotes metastasis of aggressive basal-like breast cancers. A20 is significantly upregulated in human basal-like breast cancers and its expression level is inversely correlated with metastasis-free patient survival. A20 facilitates TGF-β1-induced epithelial-mesenchymal transition (EMT) of breast cancer cells through multi-monoubiquitylation of Snail1. Monoubiquitylated Snail1 has reduced affinity for glycogen synthase kinase 3β (GSK3β), and is thus stabilized in the nucleus through decreased phosphorylation. Knockdown of A20 or overexpression of Snail1 with mutation of the monoubiquitylated lysine residues into arginine abolishes lung metastasis in mouse xenograft and orthotopic breast cancer models, indicating that A20 and monoubiquitylated Snail1 are required for metastasis. Our findings uncover an essential role of the A20-Snail1 axis in TGF-β1-induced EMT and metastasis of basal-like breast cancers.
Gut dysbiosis is closely associated with the occurrence of inflammatory bowel disease (IBD) and psychiatric disorder. Here, to understand the difference of gut microbiota composition and ...physiological effect between IBD patients with (IBD/D
) or without depression (IBD/D
), we analyzed the fecal microbiota composition of patients with IBD with (/D
) or without depression (/D
) and healthy volunteers (HVs) and examined the effects of these fecal microbiota transplantations (FMTs) on the occurrence of systemic inflammation and anxiety/depression in mice. FMTs from patients with IBD/D
or IBD/D
caused IBD-like colitis in the transplanted mice: they increased the myeloperoxidase activity, IL-1β and IL-6 expression, and NF-κB
/CD11c
cell population in the colon. Transplantation of the IBD/D
patient feces (IBD/D
-F) caused IBD-like colitis more strongly than that of IBD/D
-F. FMTs from patients with IBD/D
also caused anxiety-/depression-like behaviors, increased the NF-κB
/Iba1
and lipopolysaccharide (LPS)
/Iba1
cell populations, and decreased the BDNF
/NeuN
cell population in the hippocampus. They increased LPS levels in the blood. FMTs from patients with IBD/D
caused anxiety-like, but not depression-like, behaviors. α-/β-diversities and composition of gut microbiota in IBD-F were different from those of HV feces (HV-F). The Enterobacteriaceae and Enterococcaceae populations and LPS levels were higher in the IBD-F than in the HV-F. The Enterococcaceae population was higher in IBD/D
-F vs. IBD/D
-F. However, the transplantation of HV-F into mice previously transplanted with IBD/D
-F significantly reduced depression-like behaviors, NF-κB
/Iba1
and LPS
/Iba1
cell populations in the hippocampus, LPS levels in the feces and blood, and IL-1β expression in the colon. These findings suggest that the outbreak of depression/anxiety may be dependent on the systemic inflammation with a leaky gut through the gut dysbiosis-attributable overproduction of bacterial LPS and suppression of tight junction protein expression in patients with IBD.
Lactobacillus paracasei is a major probiotic and is well known for its anti-inflammatory properties. Thus, we investigated the effects of L. paracasei-derived extracellular vesicles (LpEVs) on ...LPS-induced inflammation in HT29 human colorectal cancer cells and dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice. ER stress inhibitors (salubrinal or 4-PBA) or CHOP siRNA were utilized to investigate the relationship between LpEV-induced endoplasmic reticulum (ER) stress and the inhibitory effect of LpEVs against LPS-induced inflammation. DSS (2%) was administered to male C57BL/6 mice to induce inflammatory bowel disease, and disease activity was measured by determining colon length, disease activity index, and survival ratio. In in vitro experiments, LpEVs reduced the expression of the LPS-induced pro-inflammatory cytokines IL-1α, IL-1β, IL-2, and TNFα and increased the expression of the anti-inflammatory cytokines IL-10 and TGFβ. LpEVs reduced LPS-induced inflammation in HT29 cells and decreased the activation of inflammation-associated proteins, such as COX-2, iNOS and NFκB, as well as nitric oxide. In in vivo mouse experiments, the oral administration of LpEVs also protected against DSS-induced colitis by reducing weight loss, maintaining colon length, and decreasing the disease activity index (DAI). In addition, LpEVs induced the expression of endoplasmic reticulum (ER) stress-associated proteins, while the inhibition of these proteins blocked the anti-inflammatory effects of LpEVs in LPS-treated HT29 cells, restoring the pro-inflammatory effects of LPS. This study found that LpEVs attenuate LPS-induced inflammation in the intestine through ER stress activation. Our results suggest that LpEVs have a significant effect in maintaining colorectal homeostasis in inflammation-mediated pathogenesis.
Incidences of heat stress due to the changing global climate can negatively affect the growth and yield of temperature-sensitive crops such as soybean variety, Pungsannamul. Increased temperatures ...decrease crop productivity by affecting biochemical, physiological, molecular, and morphological factors either individually or in combination with other abiotic stresses. The application of plant growth-promoting endophytic bacteria (PGPEB) offers an ecofriendly approach for improving agriculture crop production and counteracting the negative effects of heat stress.
We isolated, screened and identified thermotolerant B. cereus SA1 as a bacterium that could produce biologically active metabolites, such as gibberellin, indole-3-acetic acid, and organic acids. SA1 inoculation improved the biomass, chlorophyll content, and chlorophyll fluorescence of soybean plants under normal and heat stress conditions for 5 and 10 days. Heat stress increased abscisic acid (ABA) and reduced salicylic acid (SA); however, SA1 inoculation markedly reduced ABA and increased SA. Antioxidant analysis results showed that SA1 increased the ascorbic acid peroxidase, superoxide dismutase, and glutathione contents in soybean plants. In addition, heat stress markedly decreased amino acid contents; however, they were increased with SA1 inoculation. Heat stress for 5 days increased heat shock protein (HSP) expression, and a decrease in GmHSP expression was observed after 10 days; however, SA1 inoculation augmented the heat stress response and increased HSP expression. The stress-responsive GmLAX3 and GmAKT2 were overexpressed in SA1-inoculated plants and may be associated with decreased reactive oxygen species generation, altered auxin and ABA stimuli, and enhanced potassium gradients, which are critical in plants under heat stress.
The current findings suggest that B. cereus SA1 could be used as a thermotolerant bacterium for the mitigation of heat stress damage in soybean plants and could be commercialized as a biofertilizer only in case found non-pathogenic.
Salinity is a major threat to the agriculture industry due to the negative impact of salinity stress on crop productivity. In the present study, we isolated rhizobacteria and evaluated their ...capacities to promote crop growth under salt stress conditions.
We isolated rhizospheric bacteria from sand dune flora of Pohang beach, Korea, and screened them for plant growth-promoting (PGP) traits. Among 55 bacterial isolates, 14 produced indole-3-acetic acid (IAA), 10 produced siderophores, and 12 produced extracellular polymeric and phosphate solubilization. Based on these PGP traits, we selected 11 isolates to assess for salinity tolerance. Among them, ALT29 and ALT43 showed the highest tolerance to salinity stress. Next, we tested the culture filtrate of isolates ALT29 and ALT43 for IAA and organic acids to confirm the presence of these PGP products. To investigate the effects of ALT29 and ALT43 on salt tolerance in soybean, we grew seedlings in 0 mM, 80 mM, 160 mM, and 240 mM NaCl treatments, inoculating half with the bacterial isolates. Inoculation with ALT29 and ALT43 significantly increased shoot length (13%), root length (21%), shoot fresh and dry weight (44 and 35%), root fresh and dry weight (9%), chlorophyll content (16-24%), Chl a (8-43%), Chl b (13-46%), and carotenoid (14-39%) content of soybean grown under salt stress. Inoculation with ALT29 and ALT43 also significantly decreased endogenous ABA levels (0.77-fold) and increased endogenous SA contents (6-16%), increased total protein (10-20%) and glutathione contents, and reduced lipid peroxidation (0.8-5-fold), superoxide anion (21-68%), peroxidase (12.14-17.97%), and polyphenol oxidase (11.76-27.06%) contents in soybean under salinity stress. In addition, soybean treated with ALT29 and ALT43 exhibited higher K
uptake (9.34-67.03%) and reduced Na
content (2-4.5-fold). Genes involved in salt tolerance, GmFLD19 and GmNARK, were upregulated under NaCl stress; however, significant decreases in GmFLD19 (3-12-fold) and GmNARK (1.8-3.7-fold) expression were observed in bacterial inoculated plants.
In conclusion, bacterial isolates ALT29 and ALT43 can mitigate salinity stress and increase plant growth, providing an eco-friendly approach for addressing saline conditions in agricultural production systems.
Heat stress is one of the major abiotic stresses that impair plant growth and crop productivity. Plant growth-promoting endophytic bacteria (PGPEB) and humic acid (HA) are used as bio-stimulants and ...ecofriendly approaches to improve agriculture crop production and counteract the negative effects of heat stress. Current study aimed to analyze the effect of thermotolerant SA1 an isolate of Bacillus cereus and HA on tomato seedlings. The results showed that combine application of SA1+HA significantly improved the biomass and chlorophyll fluorescence of tomato plants under normal and heat stress conditions. Heat stress increased abscisic acid (ABA) and reduced salicylic acid (SA) content; however, combined application of SA1+HA markedly reduced ABA and increased SA. Antioxidant enzymes activities revealed that SA1 and HA treated plants exhibited increased levels of ascorbate peroxidase (APX), superoxide dismutase (SOD), and reduced glutathione (GSH). In addition, heat stress markedly reduced the amino acid contents; however, the amino acids were increased with co-application of SA1+HA. Similarly, inductively-coupled plasma mass-spectrometry results showed that plants treated with SA1+HA exhibited significantly higher iron (Fe+), phosphorus (P), and potassium (K+) uptake during heat stress. Heat stress increased the relative expression of SlWRKY33b and autophagy-related (SlATG5) genes, whereas co-application of SA1+HA augmented the heat stress response and reduced SlWRKY33b and SlATG5 expression. The heat stress-responsive transcription factor (SlHsfA1a) and high-affinity potassium transporter (SlHKT1) were upregulated in SA1+HA-treated plants. In conclusion, current findings suggest that co-application with SA1+HA can be used for the mitigation of heat stress damage in tomato plants and can be commercialized as a biofertilizer.
Despite the excellent sorption ability of biochar for heavy metals, it is difficult to separate and reuse after adsorption when applied to wastewater treatment process. To overcome these drawbacks, ...we developed an engineered magnetic biochar by pyrolyzing waste marine macro-algae as a feedstock, and we doped iron oxide particles (e.g., magnetite, maghemite) to impart magnetism. The physicochemical characteristics and adsorption properties of the biochar were evaluated. When compared to conventional pinewood sawdust biochar, the waste marine algae-based magnetic biochar exhibited a greater potential to remove heavy metals despite having a lower surface area (0.97m2/g for kelp magnetic biochar and 63.33m2/g for hijikia magnetic biochar). Although magnetic biochar could be effectively separated from the solution, however, the magnetization of the biochar partially reduced its heavy metal adsorption efficiency due to the biochar's surface pores becoming plugged with iron oxide particles. Therefore, it is vital to determine the optimum amount of iron doping that maximizes the biochar's separation without sacrificing its heavy metal adsorption efficiency. The optimum concentration of the iron loading solution for the magnetic biochar was determined to be 0.025–0.05mol/L. The magnetic biochar's heavy metal adsorption capability is considerably higher than that of other types of biochar reported previously. Further, it demonstrated a high selectivity for copper, showing two-fold greater removal (69.37mg/g for kelp magnetic biochar and 63.52mg/g for hijikia magnetic biochar) than zinc and cadmium. This high heavy metal removal performance can likely be attributed to the abundant presence of various oxygen-containing functional groups (COOH and OH) on the magnetic biochar, which serve as potential adsorption sites for heavy metals. The unique features of its high heavy metal removal performance and easy separation suggest that the magnetic algae biochar can potentially be applied in diverse areas that require biosorbents for pollutant removal.
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•Magnetic biochar derived from marine macro-algae was made for heavy metal adsorption.•Physicochemical properties and isotherms were characterized using various techniques.•Iron-loaded condition was optimized for Cd, Cu, and Zn removal and magnetic separation simultaneously.•Magnetic macro-algae biochar had high selectivity for Cu with plentiful O-containing groups.•Adsorption and recovery ability showed an opposite tendency as iron doping increased.
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•Combined inoculated endophytic LHL10 and LHL06 exhibited significant resistance to combined abiotic stress.•LHL10 and LHL06 synergism significantly ameliorated impacts of metals, ...high temperature and PED induced stress in soybean.•Synergistic association of endophytes down-regulated endogenous hormones of soybean.•Co-inoculated soybean presented reduced metals accumulation and enhanced antioxidant level under combined abiotic stress.•Co-inoculation down-regulating heavy metal ATPase genes and enhanced heat shock protein 90 genes expression.
Recently, the use of endophytic fungi for promoting growth and alleviating abiotic stress has gained considerable attention. However, the association of compatible endophytic fungi with crop plants under simultaneous effects of abiotic stresses is less explored. The current study elucidated the interactive effects of hormone (gibberellins and indole-3-acetic acid)-producing and combined multi-abiotic stresses (heavy metals; Ni, Cd, and Al, drought resistant, high temperature) resistant Paecilomyces formosus LHL10 and Penicillium funiculosum LHL06 on Glycine max L. under heavy metals (Ni, Cd, and Al), high temperature and drought (HTD) stress. Results revealed that the co-inoculation of LHL10 and LHL06 promoted plant growth attributes and photosynthetic activity as well as glutathione, catalase, and SOD activities and decreased lipid peroxidation by enhancing macronutrient uptake under HTD stress. Additionally, the co-inoculation reduced metal accumulation and translocation in plants by down-regulating heavy metal ATPase gene (GmHMA13, GmHMA14, and GmHMA18) expression. Furthermore, the regulation of drought-related GmDREB2, GmDREB1B, GmERD1, GmRD20, and heat shock protein 90 (GmHsp90A2 and GmHsp90A1) gene expression in co-inoculated plants reduced endogenous abscisic acid and jasmonic acid levels and positively affected plant development under HTD stress. The duo of LHL10 and LHL06 proved to be a vital strategy for the development of G. max in metal-contaminated soil in semiarid and high-temperature conditions for sustainable agriculture.
Gangliosides have been known to play a role in the regulation of apoptosis in cancer cells. This study has employed disialyl-ganglioside GD1b to apoptosis in human breast cancer MCF-7 cells using ...exogenous treatment of the cells with GD1b and endogenous expression of GD1b in MCF-7 cells. First, apoptosis in MCF-7 cells was observed after treatment of GD1b. Treatment of MCF-7 cells with GD1b reduced cell growth rates in a dose and time dependent manner during GD1b treatment, as determined by XTT assay. Among the various gangliosides, GD1b specifically induced apoptosis of the MCF-7 cells. Flow cytometry and immunofluorescence assays showed that GD1b specifically induces apoptosis in the MCF-7 cells with Annexin V binding for apoptotic actions in early stage and propidium iodide (PI) staining the nucleus of the MCF-7 cells. Treatment of MCF-7 cells with GD1b activated apoptotic molecules such as processed forms of caspase-8, -7 and PARP (Poly(ADP-ribose) polymerase), without any change in the expression of mitochondria-mediated apoptosis molecules such as Bax and Bcl-2. Second, to investigate the effect of endogenously produced GD1b on the regulation of cell function, UDP-gal: β1,3-galactosyltransferase-2 (GD1b synthase, Gal-T2) gene has been transfected into the MCF-7 cells. Using the GD1b synthase-transfectants, apoptosis-related signal proteins linked to phenotype changes were examined. Similar to the exogenous GD1b treatment, the cell growth of the GD1b synthase gene-transfectants was significantly suppressed compared with the vector-transfectant cell lines and transfection activated the apoptotic molecules such as processed forms of caspase-8, -7 and PARP, but not the levels of expression of Bax and Bcl-2. GD1b-induced apoptosis was blocked by caspase inhibitor, Z-VAD. Therefore, taken together, it was concluded that GD1b could play an important role in the regulation of breast cancer apoptosis.
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