Applied Biological Chemistry最新文献

The aim of this study was to investigate the protective effects of brown algae, namely Sargassum thunbergii (ST) and Sargassum fusiforme (SF), on memory and cognitive impairment, development of Alzheimer’s disease (AD), oxidative stress, and microglial activation in D-galactose (D-gal)-induced aging rats. Adult male Sprague Dawley rats were administered D-gal (150 mg/kg, i.p.) and a daily dose of hot water extract of ST (150 and 300 mg/kg) or SF (300 mg/kg) or phosphatidylserine [(PS) 30 mg/kg, positive control] for 13 weeks. ST, SF, and PS exhibited improved memory and cognition impairment in both radial arm maze and novel object recognition tests. Administration of ST, SF, and PS attenuated amyloid beta (Aβ) levels by decreasing Aβ production and increasing Aβ clearance-related proteins in the brains of D-gal-induced aging rats. However, only the ST group showed reduced expression of hyper-phosphorylated tau proteins in the brain by suppressing glycogen synthase kinase 3 beta (GSK3β) activities. Moreover, ST, SF, and PS also decreased acetylcholinesterase activity, oxidative stress, microglia activation, and inflammation, and increased the microglial M2 phenotype in the rat brain compared to D-gal-treated control rats. These results indicate that ST and SF could be potential candidates to ameliorate the risk of AD.

Endophytic fungi represent a special and promising microbial resource, known for their ability to promote the growth of host plants and metabolize attractive natural products. In this study, an endophytic fungus identified as Aspergillus keveii XVCY-9 was isolated from fresh tobacco leaves. Chemical purification of its ethyl acetate extracts led to the isolation of nine secondary metabolites. Their structures were elucidated through nuclear magnetic resonance (NMR) and mass spectrometry (MS) data as cinereain (1), carnequinazoline A (2), RES-1149-2 (3), carneamide B (4), carnequinazoline B (5), carneamide A (6), strobilactone A (7), bipolaricin R (8), and 6-epi-ophiobolin N (9). Among them, sesterterpenes 8 and 9 exhibited significant antibacterial effects against seven strains of plant and human pathogenic bacteria, with minimal inhibitory concentrations (MICs) ranging from 0.5 to 3.8 µg/mL, while compounds 1 and 2 showed moderate antimicrobial effects. Furthermore, compounds 2 and 7 could enhance the germination index of wheat seeds, which were even better than that of positive control indole-3-acetic acid. Additionally, compounds 2 and 3 can obviously promote the growth of wheat seedlings. These results suggest endophytic fungus A. keveii XVCY-9 is beneficial for the host plant due to the antibacterial and growth promoting effects of its secondary metabolites.

Greenhouse gas emissions (GHG) are contributing significantly to climate change, particularly from rice paddy fields. However, agricultural management practices such as silicate application can mitigate GHG emissions by altering soil properties and microbial activities. Therefore, the study objective was to analyze the effects of silicate and different fertilizers on GHG emissions in rice paddy fields. The experimental design included five treatments: no fertilizer (NF), inorganic fertilizer (NPK), NPK with rice straw compost (NPKC), NPK with silicate fertilizer (NPKS), and NPK with both rice straw compost and silicate fertilizer (NPKCS). Results demonstrated that the combined application of silicate and compost fertilizers (NPKCS) reduced methane (CH₄) emissions by approximately 14.08% and significantly lowered nitrous oxide (N₂O) (37.15%) emissions compared to NPKC. Additionally, the rice yield increased under all treatments compared to the control (NF), with a greater yield observed under the NPKCS (158.14%). These results underscore the importance of the synergistic use of silicate with compost to mitigate GHG emissions and improve crop productivity.

Faecalibacterium prausnitzii is a predominant anaerobic bacterium in the human gut microbiome, contributing to host intestinal health through butyrate production and anti-inflammatory effects. The L2-6 strain serves as a representative model for genomic and metabolic research, with high potential for therapeutic modulation of the gut microbiota. Butyrate biosynthesis in this organism proceeds through the butyryl-CoA dehydrogenase (BCD) and electron transferring flavoprotein (Etf) system, which is a key enzymatic step linking fatty acid metabolism and redox equilibrium. So far, structural information on F. prausnitzii BCD has been lacking, limiting our mechanistic comprehension of its catalytic cycle. Here, we report the crystal structures of F. prausnitzii L2-6 BCD in both apo and FAD-bound states. The catalytic glutamate is positioned approximately 8.0 Å from the FAD isoalloxazine ring, suggesting that crotonyl-CoA likely enters through the space between E373 and the re-face of FAD. To compare the structure with other species, we obtained a modeling structure of BCD and Etf complexes in the Fp L2-6 strain. Comparative analysis with structurally characterized BCDs and Etf complexes from other butyrate-producing species reveals that F. prausnitzii L2-6 follows a similar electron transfer and catalytic cycle, reinforcing its role in energy conservation and redox balance under anaerobic conditions. These findings deepen our molecular understanding of butyrate metabolism in F. prausnitzii, with broader implications for host-microbiome interactions. Furthermore, the structural framework provided here can serve as a basis for future studies aiming to modulate butyrate production across strains, potentially informing the development of microbiome-based therapeutics.

Background

Ubiquitination, a crucial post-translational modification, plays a vital role in cancer progression. The present research focused on the function of ubiquitin-specific protease 13 (USP13) and its potential mechanism related to leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4) in cisplatin (DDP) resistance and ferroptosis of ovarian cancer (OC).

Methods

Real-time quantitative PCR and Western blotting were used for mRNA and protein detection. The half-maximal inhibitory concentration (IC50) of DDP was determined using CCK-8 assay. Cell proliferation, apoptosis, and migration were assessed through colony formation/EdU assays, flow cytometry, and transwell/wound healing assays, respectively. Ferroptosis was analyzed by detecting reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), Fe²⁺ level and protein marker expression. Co-immunoprecipitation (Co-IP) assay was applied for protein interaction and ubiquitination analysis. Xenograft studies were constructed for in vivo research.

Results

LGR4 expression was increased in DDP-resistant OC tissues and cell lines. After LGR4 was downregulated, chemoresistance and malignant characteristics such as proliferation and migration were suppressed while ferroptosis was promoted in DDP-resistant OC cells. USP13 served as a deubiquitinating enzyme to enhance LGR4 protein stability. USP13 inhibition attenuated DDP resistance and promoted ferroptosis by targeting LGR4. LGR4 knockdown could enhance chemosensitivity of tumor tissues to DDP in mice.

Conclusion

These findings elucidated that USP13 stabilized LGR4 protein to regulate DDP resistance and ferroptosis in OC. Targeting the USP13/LGR4 axis represents a potential therapeutic strategy to overcome DDP resistance in OC.

Highlights

1. 1.

   LGR4 inhibition reduces chemoresistance and promotes ferroptosis in cisplatin-resistant ovarian cancer cells.

2. 2.

   USP13 stabilizes LGR4 protein by deubiquitination.

3. 3.

   LGR4 can reverse the effects of USP13 knockdown on cisplatin resistance and ferroptosis

Food waste contributes significantly to environmental challenges, such as greenhouse gas (GHG) emissions and soil and water contamination through conventional disposal methods. Converting food waste into food waste compost (FWC) offers an alternative that reduces GHG emissions and enriches soil carbon stocks, supporting sustainable agriculture. However, the high sodium (Na) levels in FWC can adversely impact soil health and crop growth. Therefore, the objective was to thoroughly investigate the effect of different amounts of FWC on soil chemical properties, soil carbon stock (SOC), nitrogen use efficiency (NUE), growth, and yield of Chinese cabbage over three crop seasons. The treatments included: ⅰ) No fertilization (NF), ⅱ) inorganic fertilization (NPK, control), ⅲ) NPK + FWC-1 time (FWC1, optimal amount of food waste compost), ⅳ) NPK + FWC-2 times (FWC2), and ⅴ) NPK + FWC-3 times (FWC3). The results showed that excessive FWC application decreased NUE (27.1%) and negatively affected cabbage yield. The FWC3 treatment during second and third crop seasons (CS) increased soil electrical conductivity (EC), Na content, and exchangeable sodium percentage (ESP). Initial FWC applications enhanced SOC stocks by 8.2%; however, continuous use declined SOC stocks. The FWC2 of the second CS increased the NUE and yield of Chinese cabbage, while growth improved in the FWC2 of the first CS. This study provides valuable insights into the balanced use of FWC to improve soil properties, crop growth, and soil carbon sequestration and promote sustainable agriculture.

Sarcopenia starts around age 40, with individuals losing more than 30% of muscle mass by age 70. Due to the absence of approved pharmacological treatments, current management primarily relies on exercise and protein supplementations. Schizonepeta tenuifolia is a medicinal plant commonly found in Korea, China, Japan and is traditionally used for headaches, colds and allergies. However, its preventive effect against sarcopenia have not yet been explored. This study to investigate whether the ethanol extract of Schizonepeta tenuifolia (DKB138) enhances muscle strength in a dexamethasone (DEX)-muscle atrophy mice model. The preventive effects of DKB138 against muscle atrophy were evaluated in DEX-induced models both in vitro and in vivo. In vitro, DEX-induced myotubes were assessed for cell viability to determine cytoprotective effects. In vivo, a DEX-induced muscle atrophy mouse model was used evaluate muscle strength and functional performance. Using UPLC and comparison with reference standards, seven components of DKB138 were identified. DKB138 effectively prevented DEX-induced death in C2C12 skeletal muscle cells. In vivo, mice treated with DKB138 exhibited 28.5% increase in grip strength (***p < 0.001) and a threefold significant increase in running distance (**p < 0.01) compared to the DEX-induced mice. Additionally, DKB138 treatment resulted in downregulation of Murf-1 and Atrogin mRNA while upregulating of MyoD mRNA expression. These finding demonstrate that DKB138 protects against DEX-induced muscle atrophy by suppressing muscle degradation factors and enhancing muscle strength. These results suggest that DKB138 has potential as functional food against muscle dysfunction and atrophy.

Graphical Abstract

This study aimed to investigate the anti-obesity effects of Lactobacillus fermentum TKSN02 and its role in modulating gut microbiota. Biochemical assays, tissue section analysis, and qPCR were employed to evaluate serum and tissue parameters in mice. Additionally, mRNA expression of specific microorganisms in fecal samples was measured to assess changes in gut microbiota composition. The results demonstrated that both L-carnitine and L. fermentum TKSN02 significantly reduced body weight in obese mice. These treatments also decreased liver and epididymal fat organ indices, and lowered serum and hepatic levels of ALT, AST, AKP, TC, TG, and LDL-C. Meanwhile, they increased HDL-C levels, as well as fecal contents of TC, TG, and total protein (TP). H&E staining revealed that L-carnitine and L. fermentum TKSN02 ameliorated obesity-induced liver tissue damage and reduced adipocyte hypertrophy and accumulation. qPCR analysis further indicated that both interventions upregulate the mRNA expression of CPT-1, LPL, PPAR-α, and CYP7A1, while downregulating PPAR-γ and C/EBPα in the liver of high-fat diet-fed mice. Moreover, they promoted the abundance of Bacteroidetes, Lactobacillus, and Bifidobacterium, but suppressed Firmicutes in the gut microbiota. Together, these results suggest that L-carnitine and L. fermentum TKSN02 exert anti-obesity effects, with the high-dose L. fermentum TKSN02 (TKSN02H) showing the most pronounced outcomes. In conclusion, L. fermentum TKSN02 may help control obesity by positively modulating gut microbiota.

Reactive oxygen species (ROS), particularly hydrogen peroxide (H₂O₂), are implicated in oxidative stress and kidney tubular injury. Daphne jejudoensis (DJ), a plant native to Jeju Island, has demonstrated anti-inflammatory properties, but its effects on kidney diseases remain unexplored. This study investigated the impact of DJ extract and its compounds, daphnin and daphnetin, on H₂O₂-induced cell death and ROS production in kidney proximal tubular HK-2 cells. Extracts from the DJ plant parts significantly enhanced cell viability in H₂O₂-exposed cells. The DJ leaf extract significantly reduced levels of superoxide anion and hydroxyl radical and prevented the decrease in superoxide dismutase (SOD) activity. Fractions from 70% ethanol DJ leaf extract exhibited protective effects against H₂O₂-induced injury, with the ethyl acetate fraction standing out for its ability to enhance antioxidant enzyme activities. Daphnin and daphnetin, major bioactive compounds of DJ extract, significantly increased cell viability and reduced ROS production in H₂O₂-exposed cells, restoring SOD and catalase activities. Conclusively, DJ extract and the main compounds, daphnin and daphnetin, protect kidney proximal tubular cells against H₂O₂-induced oxidative stress by reducing ROS production and enhancing antioxidant defenses. These findings suggest the potential therapeutic use of DJ in kidney diseases associated with oxidative stress.

Kale (Brassica oleracea) is a cruciferous vegetable known for health benefits, primarily due to sulforaphane, a compound with notable anticancer properties. Recently, we reported that the application of geraniol can significantly increase sulforaphane content in kale. However, the molecular mechanisms underlying this enhancement remain unexplored. In this study, we aimed to elucidate the metabolic pathways by which geraniol influences sulforaphane biosynthesis. Geraniol was applied as a 500-ppm solution, sprayed on the leaves of kale cultivated in an indoor aeroponic farm, once daily for two consecutive days, one week prior to harvest. As a result, we found that the sulforaphane content in the geraniol-treated group was 2.2 times higher than in the control group. Moreover, gene expression analysis demonstrated significant upregulation of CYP83, SUR1, and UGT, which are key genes involved in sulforaphane biosynthesis, with increases of 1.7, 1.3, and 1.1-fold, respectively, in the geraniol-treated group compared to the control group. These findings suggest that geraniol enhances sulforaphane content by upregulating genes critical to its biosynthesis.