Search Results (175)

Modified biochar can effectively improve the quality and environment of coastal saline–alkali soil, but its effects on the growth and development of halophytes and its mechanism are still unclear. This study systematically evaluated the growth-promoting effects and preliminary mechanisms of H₃PO₄-modified biochar (HBC) and H₃PO₄–kaolinite–biochar composite (HBCK) on the economically important halophyte Kosteletzkya virginica. The results demonstrated that the application of HBC/HBCK significantly enhanced plant growth, resulting in increases of over 55% in plant height and greater than 100% in biomass relative to the control. Multidimensional mechanistic analysis revealed the following: (1) accumulation of nitrogen (N), phosphorus (P), and potassium (K) increased by at least 40%, significantly enhancing nutrient uptake; (2) increases in the activities of superoxide dismutase (SOD) and peroxidase (POD) by over 100% and 70%, respectively, markedly boosting antioxidant capacity and effectively alleviating oxidative stress; (3) molecular regulation via the activation of transcription factor networks (HSP, MYB, TCP, AP2/ERF, bZIP, and NLP) and modulation of key genes in ABA, BR, and JA signaling pathways (CYP707A, CYP90, and OPR2), establishing a multi-layered stress adaptation and growth promotion system. Beyond assessing the growth-promoting effects of modified biochars, this study provides novel insights into the regulatory transcription factor networks and phytohormone signaling pathways, offering theoretical foundations for the molecular design of biochars for saline–alkali soil remediation. Full article

Polycyclic aromatic hydrocarbons (PAHs), prevalent aquatic contaminants, arise from burning fossil fuels, a major source of greenhouse gases driving global warming. PAHs and warmer temperatures individually exert diverse negative effects on aquatic organisms. However, the effects of PAH exposure and/or rising temperature remain largely unknown. Liver in vitro models, like the rainbow trout (Oncorhynchus mykiss) RTL-W1 liver cell line, have been employed to unravel PAH-exposure effects, primarily on cell viability and enzymatic activity. Here, monolayer-cultured (2D) RTL-W1 cells were used to assess the co-exposure effects of temperature (18 and 21 °C) and two PAHs, benzo[a]pyrene (B[a]P) and benzo[k]fluoranthene (B[k]F), at 10 and 100 nM. After a 72 h exposure, the cell density and viability were evaluated using the trypan blue and LDH assays. The mRNA levels of the detoxification-associated genes aryl hydrocarbon receptor (AhR), cytochrome P450 (CYP)1A, CYP3A27, glutathione S-transferase omega 1 (GSTO1), uridine diphosphate–glucuronosyltransferase (UGT), catalase (CAT), and multidrug resistance-associated protein 2 (MRP2) were measured by RT-qPCR. Temperature influenced cell viability and LDH leakage. Both PAHs reduced the cell density and upregulated the mRNA levels of AhR, CYP1A, CYP3A27, and UGT, while GSTO1 and MRP2 were only augmented after the higher B[k]F concentration. Temperature influenced CAT and UGT expression. There was no interaction between temperature and the PAHs. Overall, the results show that B[k]F has more effects on detoxification targets than B[a]P, whereas a temperature increase mildly affects gene expression. The RTL-W1 in 2D seems useful for unravelling not only the liver effects of PAH but also the impact of temperature stress. Full article

Cytochrome P450 (CYP) enzymes are membrane-bound hemoproteins crucial for drug and xenobiotic metabolism. While more than 50 CYPs have been identified in humans, the isoforms from CYP1, 2, and 3 families contribute to the metabolism of about 80% of clinically approved drugs. To evaluate the effects of environmental chemicals on the activities of these important CYP enzyme families, we screened the Tox21 10K compound library to identify chemicals that inhibit CYP1A2, 2C9, 2C19, 2D6, and 3A4 enzymes. The data obtained from these five screenings were analyzed to reveal the structural classes responsible for inhibiting multiple and/or selective CYPs. Some known structural compound classes exhibiting pan-CYP inhibition, such as azole fungicides, along with established clinical inhibitors of CYPs, including erythromycin and verapamil inhibiting CYP3A4 and paroxetine and terbinafine inhibiting CYP2D6, were all confirmed in the current study. In addition, some selective CYP inhibitors, previously unknown but with potent activity (IC₅₀ values < 1 µM), were identified. Examples included yohimbine, an indole alkaloid, and loteprednol, a corticosteroid, which showed inhibitory activity in CYP2D6 and 3A4 assays, respectively. These findings suggest that assessment of a candidate compound’s impact on CYP function may allow pre-emptive mitigation of potential adverse reactions and toxicity during drug development or toxicological characterization of environmental chemicals. Full article

Background/Objectives: Esomeprazole, a proton pump inhibitor (PPI), is commonly prescribed for gastric-acid-related disorders but has been associated with impaired gastrointestinal (GI) motility with long-term use. However, the effect of concurrent antibiotic administration on this dysfunction remains unclear. Therefore, this study aimed to investigate the effects of antibiotics on esomeprazole-induced GI motility dysfunction and explore the underlying mechanisms in a mouse model. Methods: Male C57BL/6 mice were orally administered esomeprazole (160 mg/kg) five times per week for 4 weeks. Three days before initiating esomeprazole treatment, a broad-spectrum antibiotic cocktail (ABX) consisting of ampicillin (1 g/kg), neomycin (1 g/kg), metronidazole (1 g/kg), and vancomycin (0.5 g/kg) was provided in drinking water and maintained throughout the experimental period. Mosapride (3 mg/kg), a prokinetic agent, was used as a positive control. Results: Neither esomeprazole alone nor in combination with ABX affected body weight or food intake. Compared to normal controls, esomeprazole treatment significantly delayed both intestinal transit and gastric emptying. However, ABX co-administration further pronounced intestinal transit time and improved gastric motility. The potential mechanisms may involve interactions among gastric H⁺/K⁺-ATPase, CYP3A11, gastrointestinal hormones (secretin and motilin), and the gut microbiome. Conclusions: Long-term esomeprazole use can impair both gastric and intestinal motility, and ABX co-treatment further exacerbates intestinal transit delay while paradoxically enhancing gastric emptying. These findings highlight the critical role of the gut microbiota in esomeprazole-induced GI motility dysfunction and suggest that antibiotic use should be approached with caution, particularly when combined with PPI therapy. Full article

Phytoalexins are specialized metabolites that are synthesized by plants in response to pathogens. A paradigm in transcription factor (TF) biology is that conserved TFs have dedicated roles across plant lineages in regulating specific branches of specialized metabolism. However, the Arabidopsis (Arabidopsis thaliana) NAC family TF ANAC042 (a.k.a. JUNGBRUNNEN1 or JUB1) regulates the synthesis of camalexin, a Trp-derived phytoalexin specifically produced by several Brassicaceae species, whereas its homolog in soybean (Glycine max) regulates the synthesis of glyceollins, which are Phe-derived phytoalexins specific to soybean. The question addressed by this research is whether ANAC042 broadly regulates phytoalexin biosynthetic pathways in Arabidopsis. Using a novel matrix-assisted laser desorption ionization high-resolution mass spectrometry (MALDI-HRMS) method, we found that the Arabidopsis loss-of-function mutant anac042–1 elicited with bacterial flagellin (Flg22) is deficient in lineage-specific Trp- and conserved Phe-derived phytoalexins—namely camalexin and 4-hydroxyindole-3-carbonyl nitrile (4OH-ICN), and pathogen-inducible monolignols and scopoletin, respectively. Overexpressing ANAC042 in the anac042-1 mutant restored or exceeded wildtype amounts of the metabolites. The expression of phytoalexin biosynthetic genes in mutant and overexpression lines mirrored the accumulation of metabolites. Yeast-one hybrid and promoter-reporter assays in Nicotiana benthamiana found that the ANAC042 protein directly binds and activates the promoters of CYP71B15, CYP71A12, and PAL1 genes for the synthesis of camalexin, 4OH-ICN, and pathogen-inducible monolignol/scopoletin, respectively. Our results demonstrate that ANAC042 regulates conserved and lineage-specific phytoalexin pathways in Arabidopsis. The latter suggests that it is an opportunistic TF that has coopted lineage-specific genes into phytoalexin metabolism, thus providing an exception to the current paradigm. Full article

Polycyclic aromatic hydrocarbons (PAHs) and global warming impact aquatic ecosystems, eventually interacting. Monolayer (2D) cultures of cell lines, such as the rainbow trout liver RTL-W1, are employed for unveiling toxicological effects in fish. Nonetheless, three-dimensional (3D) models constitute an alternate paradigm, better emulating in vivo responses. Here, ultra-low attachment (ULA) plates were used to generate ten-day-old RTL-W1 spheroids for exposure to a control, a solvent control (0.1% DMSO) and the model PAH benzo[k]fluoranthene (BkF) at 10 and 100 nM and at 18 and 23 °C (thermal stress). After a 4-day exposure, spheroids were analyzed for viability (alamarBlue and lactate dehydrogenase), biometry (area, diameter and sphericity), histocytology (optical and electron microscopy), and mRNA levels of the detoxification-related genes cytochrome P450 (CYP)1A, CYP3A27, aryl hydrocarbon receptor (AhR), glutathione S-transferase (GST), uridine diphosphate–glucuronosyltransferase (UGT), catalase (CAT), multidrug resistance-associated protein 2 (MRP2) and bile salt export protein (BSEP). Immunocytochemistry (ICC) was used to assess CYP1A protein expression. Neither temperature nor BkF exposure altered the spheroids’ viability or biometry. BkF modified the cell’s ultrastructure. The expression of CYP1A was augmented with both BkF concentrations, while AhR’s increased at the higher concentration. The CYP1A protein showed a dose-dependent increase. Temperature and BkF concurrently modelled UGT’s expression, which increased in the 100 nM condition at 23 °C. Conversely, CYP3A27, MRP2, and BSEP expressions lowered at 23 °C. CAT and GST mRNA levels were uninfluenced by either stressor. Overall, BkF and temperature impacted independently or interactively in RTL-W1 spheroids. These seem to be useful novel tools for studying the liver-related effects of temperature and PAHs. Full article

Triazoles are important fragments in the development of fungicidal compounds. Fungi have gradually developed drug resistance against traditional fungicides due to long-term overuse. Therefore, there is an urgent need to discover new candidate compounds. A series of 1,2,4-triazole derivatives containing amino acid fragments were designed and synthesized based on mefentrifluconazole. All the target compounds were characterized by ¹H-NMR, ¹³C-NMR, and HRMS techniques. Their antifungal activities against five kinds of phytopathogenic fungi were evaluated in vitro. The results revealed that most compounds had broad-spectrum fungicidal activities at 50 μg/mL and four compounds exhibited better antifungal activity than the control drug mefentrifluconazole. Interestingly, the synthesized compounds 8d and 8k exhibited exceptional antifungal activity against Physalospora piricola, with EC₅₀ values of 10.808 µg/mL and 10.126 µg/mL, respectively. Molecular docking studies demonstrate that the 1,2,4-triazole derivatives 8d and 8k, which incorporate amino acid groups, exhibit strong binding affinity to 14α-demethylase (CYP51). These findings highlight the potential of these compounds as effective antifungal agents. Full article

Wolfberry (Lycium barbarum L.), as a kind of combination of medicine and food, is rich in antioxidant components. However, the deep-processed products of wolfberry need to be developed to improve its added value. This study aimed to investigate the nutrients, active antioxidant ingredients, and liver-protective mechanism of mixed-culture fermented wolfberry vinegar (MFV). The results showed that MFV had significantly higher protein and significantly lower fat content than wolfberry juice before fermentation, indicating that MFV was a healthy product. The active ingredient content, which included total phenolics, total flavonoids, polysaccharides, betaine, and antioxidant activities, was significantly increased in MFV after mixed-culture fermentation. Moreover, MFV improved histopathological changes and reduced liver biochemical indicators in alcohol-treated mice, indicating the improvement of liver function. In addition, MFV effectively alleviated alcohol-induced liver injury by increasing the expression of alcohol metabolizing enzymes and inhibiting CYP2E1 activity. MFV regulated the equilibrium between pro-oxidant and antioxidant levels by downregulating pro-oxidant markers and upregulating antioxidant markers. Furthermore, MFV reduced the levels of inflammatory indexes by inhibiting the PI3K/Akt/NF-κB signaling pathway. These results suggest that MFV is a healthy food for liver protection, which provides a strategy for deep-processed products of wolfberry. Full article

Cyp1b1 substantially affects hepatic vascular and stellate cells (HSC) with linkage to liver fibrosis. Despite minimal hepatocyte expression, Cyp1b1 deletion substantially impacts liver gene expression at birth and weaning. The appreciable Cyp1b1 expression in surrounding embryo mesenchyme, during early organogenesis, provides a likely source for Cyp1b1. Here defined breeder diets established major interconnected effects on neonatal liver of α-linolenic acid (ALA), vitamin A deficiency (VAD) and suboptimal iron fed mice. At birth Cyp1b1 deletion and VAD each activated perinatal HSC, while suppressing iron control by hepcidin. Cyp1b1 deletion also advanced the expression of diverse genes linked to iron regulation. Postnatal stimulations of Srebp-regulated genes in the fatty acid and cholesterol biosynthesis pathways were suppressed by Cyp1b1-deficiency. LncRNA H19 and the neutrophil alarmin S100a9 expression increased due to slower postnatal decline with Cyp1b1 deficiency. VAD reversed each of Cyp1b1 effect, probably due to enhanced HSC release of Apo-Rbp4. At birth, Cyp1b1 deletion enhanced H19 participation. Notably, a suppressor (Cnot3) decreased while an activity partner (Ezh2/H3K methylation) increased H19 expression. ALA elevated hepcidin mRNA and countered the inhibitory effects of Cyp1b1 deletion on hepcidin expression. Oxylipin metabolites of ALA from highly expressed hepatic Cyps are potential mediators. Cyp expression patterns demonstrated female dimorphism for neonatal liver. Mothers followed one of three fetal growth support programs probably linked to maturity at conception. Full article

In this study, Chinese yam polysaccharide (CYP) was fermented by Saccharomyces cerevisiae CICC 32883, and its structural features and antioxidant activities before and after fermentation were analyzed. S. cerevisiae CICC 32883-fermented CYP (CYP-SC) had higher carbohydrate content and lower protein content than the nonfermented CYP (CYP-NF). The monosaccharide composition of CYP-SC was unaffected, but the proportion was changed. Compared with CYP-NF’s molecular weight and polydispersity of 124.774 kDa and 6.58, respectively, those of CYP-SC were reduced to 20.384 kDa and 3.379. Antioxidant results showed that CYP-SC had better effects than CYP-NF in scavenging DPPH, ABTS, hydroxyl, and superoxide radicals. Moreover, CYP-SC showed better activities in enhancing oxidation capacity and protecting HepG2 cells than CYP-NF. Furthermore, the effects of CYP-SC on alleviating and repairing H₂O₂-damaged HepG2 cells are superior to those of CYP-NF. This work offers a green and efficient method for enhancing the antioxidant activity of dietary plant polysaccharides. Full article

The greater amberjack (Seriola dumerili) is an emerging marine fish that is increasingly favored in aquaculture. Currently, there are few studies on the development and regulation of greater amberjack ovaries. In this study, the ovary transcriptome profiles of greater amberjack at three different stages (stage II, III, and IV) were performed, and identified the genes and pathways that may play significant roles in the processes of follicle growth and maturation. A total of 6597, and 1061 differentially expressed genes (DEGs) were detected in FII vs. FIII, FIII vs. FIV, and FII vs. FIV stages, respectively. GO and KEGG enrichment analyses revealed that these DEG_S are primarily involved in steroid hormone biosynthesis (e.g., cyp11a1, cyp17a1, cyp19a1a, hsd3b1, esr1), lipid metabolism (e.g., plpp3, lpl, pld1, and fabp10a), and meiotic arrest and resumption (e.g., pgr, arb, ccnd2, adcy2, adcy9, myl9, calm1). Additionally, several signaling pathways involved in ovarian development have been identified, including the PI3K-Akt, Wnt, TGF-beta, GnRH, and immune-related signaling pathways. qPCR results of nine representative genes related to steroid hormone synthesis and cell growth verified the reliability of the generated RNA-seq data. This research contributes to our comprehension of the molecular processes underlying ovarian growth and maturation in marine fishes and provides a theoretical basis for the investigation of functional genes associated with oogenesis in greater amberjack. Full article

Insects have highly developed olfactory systems in which cytochrome P450s (CYPs) were involved as odor-degrading enzymes throughout the olfactory recognition of odor compounds by insects to avoid continuous stimulation of signaling molecules and thus damage to the olfactory nervous. To understand whether the highly expressed CYPs in the antennae play an olfactory function in Solenopsis invicta worker, in this study, we find six highly expressed antennal CYPs from the transcriptome of S. invicta. Multiple sequence alignment and phylogenetic analysis divided them into two families: the CYP3 family (SinvCYP6K1, SinvCYP6K1-1) and the CYP4 family (SinvCYP4C1, SinvCYP4C1-1, SinvCYP4C1-2, SinvCYP4V2). The expression patterns of these six CYPs were analyzed by RT-qPCR, which revealed that SinvCYP6K1 and SinvCYP4V2 were only highly expressed in the antennae of adult workers. The expression of SinvCYP6K1 and SinvCYP4V2 in workers was markedly diminished after feeding with dsRNA. The electroantennography (EAG) assay demonstrated that the silencing of either SinvCYP6K1 or SinvCYP4V2 resulted in a notable reduction in the EAG response of workers to 2-ethyl-3,6(5)-dimethylpyrazine (EDMP). Furthermore, the trajectory behavior assay showed that the worker’s range and speed of movement in response to EDMP significant decreased after the silencing of SinvCYP6K1 and SinvCYP4V2. The findings indicated that both SinvCYP6K1 and SinvCYP4V2 were implicated in the recognition of EDMP by S. invicta. Full article

Background/Objectives: Pinocembrin is a promising drug candidate for treating ischemic stroke. The interaction of pinocembrin with drug transporters and drug-metabolizing enzymes is not fully revealed. The present study aims to evaluate the interaction potential of pinocembrin with cytochrome P450 (CYP450: CYP2B6, CYP2C9, and CYP2C19) and drug transporters including organic anion transporters (OAT1 and OAT3), organic cation transporters (OCT1 and OCT2), multidrug and toxin extrusion (MATE1 and MATE2, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP). Methods: The interactions of pinocembrin on drug transporters were determined in the Madin–Darby canine kidney (MDCK) cells overexpressing human (h)OAT1 or hOAT3 and in the Chinese hamster ovary (CHO-K1) cells overexpressing hOCT1, hOCT2, hMATE1, or hMATE2. The interactions of pinocembrin with BCRP and P-glycoprotein were determined in Caco-2 cells. The CYP450 enzyme inhibitory activity was assessed by a cell-free CYP450 screening assay. Results: Pinocembrin effectively inhibited the function of OAT1 and OAT3 with a half-inhibitory concentration (IC₅₀) and inhibitory constant (Ki) of ∼2 μM. In addition, it attenuated the toxicity of tenofovir, a substrate of hOAT1, in cells overexpressing hOAT1. Based on the kinetic study and molecular docking, pinocembrin inhibited OAT1 and OAT3 via a competitive inhibition. In contrast to hOAT1 and hOAT3, pinocembrin did not significantly inhibit the function of OCT1, OCT2, MATE1, MATE2, BCRP, and P-glycoprotein. In addition, pinocembrin potently inhibited the activity of CYP2C19, whereas it exhibited low inhibitory potency on CYP2B6 and CYP2C9. Conclusions: The present study reveals the potential drug interaction of pinocembrin on OAT1, OAT3, and CYP2C19. Co-administration with pinocembrin might affect OAT1-, OAT3-, and CYP2C19-mediated drug pharmacokinetic profiles. Full article

It is well known that the function of granulosa cells (GCs) is closely related to follicular development, and FoxO1 and histone methylation have been implicated in follicular development. However, the specific mechanisms by which FoxO1 and histone methylation regulate follicular development are still largely unknown. To explore the specific mechanism of FoxO1 in regulating follicular development, in this study, we showed that the expression of FoxO1 in immature ovaries and small follicles was significantly higher than in mature ovaries and large follicles of sows, respectively. FoxO1 was found to inhibit the secretion of testosterone and proliferation of porcine GCs and promote the secretion of progesterone and apoptosis of porcine GCs. Furthermore, H3K27me3, as a transcriptional inhibitor, can inhibit the transcription of FoxO1. FoxO1 could promote the transcription of CYP1A1, and CYP1A1 was found to inhibit the proliferation and facilitate the ferroptosis of porcine GCs. Collectively, our results revealed that the H3K27me3-FoxO1-CYP1A1 pathway might participate in follicular development, and these findings could provide potential targets for improving follicular development in sows. Full article

Capsaicin and quercitrin have proved to be two major ingredients in fresh chili pepper. However, the effect of these two compounds on hyperlipidemia and the related molecular mechanisms were still unclear. This work was performed to examine the hypolipidemic capacity of capsaicin and quercitrin as well as the related signaling pathways. Hyperlipidemia was induced in mice by feeding them with a high-fat diet for 4 weeks. Both capsaicin and quercitrin were beneficial to inhibit a rise in fasting glucose, total cholesterol, total triglycerides, low-density lipoprotein cholesterol, and total bile acids and to lift the level of high-density lipoprotein cholesterol in the serum. The optimal lipid-lowering data were achieved in the capsaicin and quercitrin/3:1 group. Supplementation with capsaicin and quercitrin both singly and together in the feed caused a significant influence on the metabolite profiles of mouse serum. The signaling pathway for the hypolipidemic effect of capsaicin and quercitrin was related to the down-regulation of epidermal growth factor receptor (EGFR) but the up-regulation of phosphatidylin-ositol-3-kinase (PI3K), protein kinase Bb(Akt), farnesoid X receptor 1 (FXR1), and cholesterol 7α-hydroxylase (CYP7A1). This study confirmed the jointly hypolipidemic effect of capsaicin and quercitrin, which would benefit the valorization of chili pepper resources. Full article