Search Results (5,615)

Background: Nymphaea atrans exhibits a gradual flower color transition from nearly white to rose-red during anthesis, yet the molecular mechanisms of this phenomenon remain unclear. In the present study, transcriptomic and metabolomic analyses were performed to systematically investigate anthocyanin accumulation patterns and regulatory mechanisms during the color transition of N. atrans. Methods: Petals were collected at three flowering stages: day 1 (D1), day 3 (D3), and day 5 (D5). Targeted metabolomics was performed using UPLC-ESI-MS/MS to profile anthocyanin and other flavonoid metabolites. Transcriptome analysis was conducted via RNA-seq. Differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) were identified, followed by functional enrichment and integration analysis. Results: The results revealed significant accumulation of seven anthocyanins, including cyanidin-3-O-arabinoside, cyanidin-3-O-glucoside, cyanidin-3-O-galactoside, cyanidin-3-O-(6″-O-acetyl)-glucoside, at stages D3 (day 3 after flowering, light pink petals) and D5 (day 5 after flowering, deep pink petals), accompanied by the upregulation of key enzyme-encoding genes, chalcone synthase, chalcone isomerase, flavanone 3-hydroxylase, di-hydroflavonol 4-reductase, and anthocyanidin synthase in the anthocyanin biosynthetic pathway. Genes involved in JA biosynthesis and key regulatory genes in the JA signaling pathway were significantly up-regulated, indicating that the JA signaling pathway may play an important regulatory role in the synthesis of anthocyanins in N. atrans. Conclusions: This study unravels the metabolic and molecular underpinnings of flower color transition in N. atrans, thereby establishing a theoretical basis for the targeted regulation of floral pigmentation and molecular breeding of ornamental water lilies. Full article

Antimicrobial peptides (AMPs) have re-emerged as promising anti-infective agents, particularly against multidrug-resistant bacteria; however, their therapeutic development remains constrained by proteolytic degradation, host cell toxicity, and rapid systemic clearance. Rather than focusing solely on sequence discovery, recent efforts have shifted toward structural and supramolecular modification strategies aimed at improving stability, selectivity, and pharmacological performance. This review critically analyzes intramolecular modifications—including phosphorylation, glycosylation, acetylation, methylation, and backbone cyclization—that modulate peptide conformation and resistance to enzymatic degradation. In parallel, extramolecular approaches such as PEGylation, lipidation, and conjugation to antibiotics, siderophores, or antibodies are examined in the context of enhanced targeting and prolonged bioavailability. Particular emphasis is placed on localized delivery systems, including hydrogels, polymeric films, and nanofibrous scaffolds, which enable spatially controlled administration and mitigate systemic exposure. By integrating evidence from ex vivo and in vivo infection models, this work delineates the translational potential and remaining bottlenecks of chemically engineered AMP platforms for skin and soft tissue infections. Full article

Background: Gut microbiome-derived metabolites, particularly short-chain fatty acids (SCFA) and tryptophan derivatives, are central mediators of the gut–brain axis. This ex vivo study assessed how nutritional interventions impact such metabolites during early life, a critical period for neurodevelopment. Methods: The effects of galacto-oligosaccharides (GOS), nutrient blends (vitamins, minerals and amino acids) and their combinations were evaluated in the gut microbiomes of infants (2–4 months, n = 6) and young children (2–3 years old, n = 6) using the ex vivo SIFR^® technology. Results: Baseline microbiome composition was age-dependent, with infants displaying lower α-diversity and greater interpersonal variability. After ex vivo incubation, nutrient blends increased the propionate/butyrate ratio and branched-chain fatty acids in young children and elevated several B-vitamins and amino acid-derived metabolites, including indole-3-carboxaldehyde, imidazoleacetic acid and pipecolinic acid. Combining nutrient blends with GOS exhibited potential synergistic effects on propionate (infants) and 2-hydroxyisocaproic acid (HICA, both age groups). GOS strongly stimulated Bifidobacteriaceae and increased metabolites linked to bifidobacterial metabolism like acetate, HICA, N-acetylated amino acids, aromatic lactic acids and acetylagmatine; in young children, butyrate and γ-aminobutyric acid (GABA) also increased. Conclusions: Combinations of GOS with nutrient blends impacted microbiome-derived metabolites associated with the gut–brain axis, with potential synergistic increases of metabolites with emerging roles in neurodevelopment, including GABA, acetylagmatine and HICA. Despite shared bifidogenic effects, differences between age groups indicate that microbiome maturity may influence responses to nutritional intervention. Future clinical studies are needed to determine whether these metabolite changes translate into neurodevelopmental benefits in vivo. Full article

Hydralazine is widely used to treat hypertension during pregnancy and has epigenetic effects in cancer therapy. Cryoplatable human hepatocytes showed concentration-dependent increase in DNA damage response (linear trend p = 0.0069) following 24 h hydralazine treatment. DNA repair-deficient UV5 Chinese hamster ovary (CHO) cell lines expressing human CYP1A2 and either NAT2*4 (reference allele) or NAT2*5 (variant allele) were treated with hydralazine for 24 h. CHO cells expressing NAT2*4 showed a higher acetylation rate than those with NAT2*5 (p < 0.001), whereas CHO cell viability did not differ significantly following hydralazine treatment (p > 0.05). Hydralazine caused a concentration-dependent increase in DNA damage response in the un-transfected UV5 CHO cell line, as well as in each of the UV5 CHO cell lines transfected with human CYP1A2 and/or NAT2 alleles. CHO cells with CYP1A2 only showed higher DNA damage response from hydralazine compared to cells with CYP1A2/NAT2*4 or CYP1A2/NAT2*5 (p < 0.05 and p < 0.0001, respectively), and higher in CYP1A2/NAT2*4 versus CYP1A2/NAT2*5 cells (p = 0.0011). Apurinic/apyrimidinic (AP) sites in CHO cells expressing only CYP1A2 were significantly higher than in the un-transfected UV5 CHO cell line (p < 0.01) and higher in CHO cells expressing CYP1A2/NAT2*4 compared to CYP1A2/NAT2*5, but the difference was not significant (p > 0.05). In contrast, ROS levels were reduced following hydralazine treatment in CHO cells with CYP1A2/NAT2*4 and CYP1A2/NAT2*5 (p < 0.001 and p < 0.05, respectively). The results of the current study document DNA damage responses associated with hydralazine in human hepatocytes and CHO cells. The DNA damage response was increased following N-hydroxylation by CYP1A2, which competes with N-acetylation by NAT2. Full article

Global climate change poses a significant threat to viticulture, primarily due to high temperatures. This study examined temperature-induced changes in phenolic profiles in berries of three wine grape cultivars under 25, 35, and 45 °C for 0–48 h using HPLC-ESI-MS/MS. To investigate the molecular response to severe heat stress, transcriptomic analysis was conducted in Cabernet Sauvignon berries subjected to a 45 °C treatment. Results showed that the 45 °C treatment decreased the levels of anthocyanins (particularly delphinidin-3-O-glucoside and cyanidin-3-O-glucoside) in grape berries. Acylated anthocyanins, such as malvidin-3-O-(6-acetyl)-glucoside, exhibited enhanced stability at elevated temperatures. Additionally, high temperatures increased the levels of protocatechuic and gentisic acids and decreased those of rutin, ferulic acid, and p-coumaric acid. Transcriptomic and qRT-PCR analyses revealed that the expression of OMT, LDOX, GST, F3′5′H, and 3AT was positively correlated with changes in anthocyanin levels under high temperatures, suggesting their roles in the observed phenolic alterations. These findings highlight the molecular responses of winegrapes to heat stress, providing a foundation for future viticulture strategies under changing climatic conditions. Full article

Mitotic catastrophe refers to a complicated mechanism of cell death characterized by failure to complete the processes of mitosis correctly due to aberrant chromosome segregation and abnormal tubulin polymerization. Post-translational modifications (PTMs) play a crucial role in the functional diversity of the proteome by mediating the covalent attachment of functional groups to proteins, which regulates the proteolytic cleavage of subunits, facilitating the degradation of entire proteins. Recent studies suggest that PTMs of key proteins are closely implicated in the occurrence, regulation and potential therapeutic targets of mitotic catastrophe. Here, we summarize how multiple PTMs, including phosphorylation, ubiquitination, acetylation, methylation and other types of PTMs, regulate mitotic catastrophe. In addition, potential therapeutic approaches targeting mitotic catastrophe were also discussed. It is anticipated that the inducement of mitotic catastrophe can serve as a promising new therapeutic approach for various diseases in the future. Full article

A body of evidence suggests that upregulating O-GlcNAcylation, a reversible post-translational modification of serine and threonine residues on target proteins, is beneficial in neurological diseases. However, this phenomenon is currently underexplored in the pharmacotherapy of epilepsy. Therefore, we aimed to explore the potential effects of combining N-acetylglucosamine (GlcNAc), a precursor for O-GlcNAcylation, and a centrally acting benzodiazepine (diazepam) on oxidative stress, a known driver of epilepsy, and some epileptogenesis-associated genes. Mice (n = 10) were randomly assigned to treatment groups and treated with varied oral doses (100, 200, and 400 mg/kg) of GlcNAc in combination with diazepam (1 mg/kg) for 14 days. Following this, seizure was chemically induced with 70 mg/kg pentylenetetrazol intraperitoneally. Brains of treated mice were excised for antioxidant assays and to determine the expression of genes associated with epileptogenesis: potassium chloride co-transporter (KCC4), interleukin (IL-6), tumour necrosis factor-α (TNF-α), and brain-derived neurotrophic factor (BDNF). Our findings suggest that GlcNAc, when concurrently administered with diazepam, prevents oxidative stress and reduces the gene expression of IL-6, a cytokine associated with neuroinflammation and seizures, whilst increasing the gene expression of KCC4, an ion co-transporter that promotes antiepileptogenesis. Full article

Recent studies support the concept of a bidirectional lung–brain axis. While neural, immune, and microbial pathways are increasingly recognized in lung-to-brain communication, the role of matrikines—bioactive peptides generated by extracellular matrix (ECM) proteolysis during remodeling—in this inter-organ communication remains underexplored. This review highlights matrikines originating from the lung, particularly the collagen-derived tripeptide Pro-Gly-Pro (PGP) and the elastin-derived hexapeptide Val-Gly-Val-Ala-Pro-Gly (VGVAPG), as potential mediators linking pulmonary pathology with neurological outcomes. The lung is rich in ECM proteins, and inflammatory conditions such as chronic obstructive pulmonary disease (COPD) and emphysema trigger proteolytic activity by matrix metalloproteinases (MMPs) and neutrophil elastase, releasing matrikines into circulation. Under conditions of blood–brain barrier (BBB) dysfunction, they may access the central nervous system (CNS), where they influence neurons, microglia, and astrocytes, modulating neuroinflammation, autophagy, and synaptic integrity. While PGP can exhibit context-dependent neuroprotective effects, its acetylated form and VGVAPG are associated with neurotoxicity, Tau hyperphosphorylation, and microglial activation. Additional matrikines, including Gly-His-Lys (GHK) and endorepellin, may further modulate CNS homeostasis. Collectively, these findings support lung-derived matrikines as circulating mediators of lung-to-brain signaling, providing a novel mechanistic framework linking chronic pulmonary inflammation to neuropathologies, such as stroke and neurodegenerative disorders, and highlighting potential targets for therapeutic intervention. Full article

Munronia pinnata (Meliaceae), a medicinal plant used in Zhuang traditional medicine, is recognized as a rich source of structurally diverse limonoids. In our continuing investigation of bioactive constituents from Guangxi medicinal plants, four new prieurianin-type limonoids, munropins G–J (1–4), were isolated from their aerial parts. Their structures were determined through comprehensive spectroscopic analysis, including nuclear magnetic resonance and high-resolution mass spectrometry, and further supported by quantum chemical calculations for electronic circular dichroism and statistical probability analysis. Munropins G (1) and H (2) feature an unprecedented C-12 β-D-glucosylated α-methyl-2′-hydroxypentanoate side chain and a C-17 β-substituted furan ring, with 1 being the 7-O-acetyl derivative of 2. Munropins I (3) and J (4) possess a formyl group at C-11, a 3-methyl-2-hydroxypentanoate ester at C-12, and a C-17 γ-hydroxy-α,β-unsaturated γ-lactone unit (21-hydroxy for 3, 23-hydroxy for 4), each existing as an equilibrating mixture of C-21 epimers—a phenomenon observed for the first time within a prieurianin-type framework. The absolute configurations of 1 and 2 were established by quantum chemical electronic circular dichroism calculations, while those of 3 and 4 remain to be assigned. All compounds were evaluated for cytotoxicity against human lung (A549), liver (HepG2), breast (MCF-7), and colon (HCT116) cancer cell lines and for anti-inflammatory activity in lipopolysaccharide-induced RAW 264.7 murine macrophages, but none exhibited significant effects at a concentration of 80 μM. This study expands the chemical diversity of Munronia limonoids and provides new molecular scaffolds for future structure–activity relationship investigations and chemotaxonomic markers for the Meliaceae family. Full article

Oleaginous microorganisms usually accumulate large amounts of lipids under nitrogen limitation and in a carbon-abundant environment. However, how cells sense changes in nitrogen and carbon levels in the culture medium remains a research hotspot. Previous studies have found that the target of rapamycin complex 1 (TORC1) plays a core role in lipid accumulation in oleaginous microorganisms. The results of the Kog1 (the member proteins of TORC1) knockout strain constructed earlier by our group showed that the Kog1 negatively regulated lipid accumulation in the oleaginous fungus Mucor circinelloides. In this study, transcriptomic analysis of the knockout and control strains under nitrogen-limited and nitrogen-sufficient culture was carried out to investigate significant differences in lipid accumulation. Kog1 knockout led to a significant decrease in cell dry weight and an increase in lipid content in M. circinelloides. The transcriptomic results showed that genes encoding the glyoxylic acid cycle and genes encoding acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and Δ9 desaturase in lipid synthesis were upregulated to varying degrees under both conditions, indicating enhanced lipid metabolism that ultimately led to increased lipid accumulation. The knockout of the Kog1 gene also activated the pyruvate–acetaldehyde–acetate metabolic axis and significantly modified the branched-chain amino acid metabolic network, suggesting that Kog1 knockout reprograms the pathway of branched-chain amino acid synthesis and degradation, shifting the carbon flux from amino acid metabolism to acetyl-CoA accumulation. In addition, the gene encoding the SSK1p transcription factor, which participates in the nutrient stress response, was upregulated 41.9- and 51.9-fold in the Kog1 knockout strain compared with the control strain under nitrogen-limited and nitrogen-sufficient conditions, respectively. Full article

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver disease worldwide with complex pathogenesis and no approved specific therapy. Siraitia grosvenorii is a widely used medicinal and edible herb, yet its efficacy and underlying mechanisms against MAFLD remain poorly defined. This study explored the protective effects and potential mechanisms of aqueous extract of Siraitia grosvenorii (AESG) on MAFLD. Based on ultra-high-performance liquid chromatography-linear trap quadrupole orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap-MS) analysis, 38 components in AESG were tentatively assigned, with tetracyclic triterpene saponins being the most abundant. In high-fat diet (HFD)-induced MAFLD mice, AESG significantly attenuated body weight gain, reduced plasma total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C) levels, and dramatically decreased hepatic triglyceride (TG) accumulation from 0.0141 mmol/g in the model group to 0.0063 mmol/g in the low-dose AESG group, corresponding to a reduction of 55.00%. AESG also alleviated plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and improved hepatocyte steatosis. Furthermore, AESG restored HFD-induced gut dysbiosis by enriching beneficial bacteria including Akkermansia and suppressing harmful bacteria such as Ruminococcus. In free fatty acids (FFA) stimulated HepG2 cells, AESG suppressed de novo lipogenesis via downregulating Fatty Acid Synthase (FASN), Acetyl-CoA Carboxylase (ACC) and Sterol Regulatory Element-Binding Protein 1c (SREBP1c), and enhanced antioxidant capacity via activating the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)/Heme Oxygenase 1 (HO-1)/Sirtuin 1 (SIRT1) pathway, thereby attenuating lipid accumulation and oxidative stress. In conclusion, AESG ameliorates MAFLD by inhibiting lipogenesis, improving oxidative stress, and regulating gut microbiota. These findings support Siraitia grosvenorii as a promising natural dietary intervention for MAFLD prevention and adjuvant therapy. Full article

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder with a high incidence of anxiety and depression. However, the underlying mechanisms of these symptoms remain to be fully elucidated. This study investigated the effects and mechanisms of a 20% ethanolic extract of Petasites japonicus leaves (EPJ) on dextran sulfate sodium (DSS)-induced colitis and depression-like behaviors. The physiological compounds identified in the EPJ were citric acid, chlorogenic acid, caffeic acid, fukinolic acid, 3,5-dicaffeoylquinic acid, quercetin 3-O-β-D-glucose-6″-acetate, 4,5-dicaffeoylquinic acid, kaempferol-3-O-(6″-acetyl)-β-glucopyranoside, and pedunculoside. EPJ significantly alleviated DSS-induced colitis, as evidenced by improvements in body weight loss (87.41% vs. 76.02% in the DSS group), colon length (5.75 vs. 4.34 cm), intestinal permeability (52.80 vs. 163.01 μg/mL), and myeloperoxidase (MPO) activity (0.24 vs. 0.67 U/mg) (p < 0.05). Histological analysis further confirmed recovery of goblet cells and attenuation of muscle layer thickening. EPJ also reversed DSS-induced gut microbiota dysbiosis and contributed to the restoration of microbial homeostasis. Behavioral assessments showed that EPJ effectively ameliorated depression-like behaviors. EPJ improved antioxidant systems in colon and brain tissues by modulating malondialdehyde (MDA) levels and reduced glutathione (GSH) and superoxide dismutase (SOD) activity. EPJ further upregulated tight junction protein expression and suppressed TLR4/NF-κB inflammatory pathway activation in both colon and brain tissues. Moreover, EPJ modulated serum stress-related hormones, normalized hypothalamic–pituitary–adrenal (HPA) axis dysregulation, regulated the BDNF/TrkB signaling pathway, and modulated tryptophan–kynurenine metabolism. Collectively, these findings suggest that EPJ exerts protective effects against DSS-induced colitis and depression-like behaviors. Full article

Arsenic induces apoptosis in both cancerous and non-cancerous cells. The mechanism of arsenic-induced apoptosis is complex. We previously demonstrated that the antioxidant acetyl L-carnitine prevented sodium arsenite-induced apoptosis in zebrafish embryos. To gain more insight into the mechanism of arsenic-induced apoptosis, we explored the effect of another antioxidant, N-acetylcysteine (NAC). Co-treatment of sodium arsenite with 1 or 2 mM NAC had no effect on zebrafish development. There was a significant but partial reduction in apoptosis in the embryos co-treated with sodium arsenite and 1 mM NAC, while embryos treated with 1 mM NAC alone showed the loss of normal apoptosis that was observed in the control embryos. Complete abolition of apoptosis occurred in embryos co-treated with sodium arsenite and 2 mM NAC; however, 2 mM NAC alone resulted in 100% mortality, indicating antioxidant toxicity at high doses. NAC (1 mM) did not prevent sodium arsenite-induced increase in motor neurons, suggesting that arsenic-induced apoptosis and supernumerary motor neuron development are mediated via distinct pathways. To determine whether NAC prevented arsenic-induced apoptosis via reactive oxygen species (ROS) signaling, we assessed ROS levels and oxidative modification of proteins (carbonylation) using an OxyBlot assay. Neither sodium arsenite nor NAC altered protein oxidation, ROS levels, or p53, a pro-apoptotic protein, transcript levels. Additionally, dicoumarol, an inducer of p53 protein degradation, did not inhibit sodium arsenite-induced apoptosis. These results indicate that protein oxidation and p53 signaling are not involved in arsenic-induced apoptosis and that NAC prevents arsenic toxicity in zebrafish embryos through a hitherto unknown mechanism. Full article

Mevalonate is a biochemical precursor to a wide range of isoprenoids. Because the mevalonate pathway uses three moles of acetyl–CoA, native pathways which metabolize acetyl–CoA, including citrate synthase, strongly compete with mevalonate synthesis. Our hypothesis is that modifications in citrate synthase, with the aim of reducing this enzyme’s activity, can result in increased mevalonate. Previous research has demonstrated that citrate synthase variants can increase generation of acetyl–CoA-derived products from glucose, but research has not evaluated citrate synthase variants with other common carbon sources like xylose and glycerol. Using five variant strains with chromosomal modifications of citrate synthase, we first compared the growth of these variants with wild-type Escherichia coli on glucose, xylose, or glycerol. In general, any particular modification in citrate synthase (GltA) led to the greatest effect on growth rate in glucose-grown cells. Because the GltA[Y87N D101D* P208L] and GltA[A267T] variants showed the greatest effect on growth using glycerol, we selected these two variants to study the formation of mevalonate from glycerol by E. coli with an introduced mevalonate pathway. Controlled batch processes at the 1.3 L scale demonstrated significantly increased mevalonate production in variants compared to the wild-type background, with the GltA[A267T] attaining 7.3 g/L mevalonate in 16.5 h from 30 g/L glycerol. Nitrogen-limited or phosphorus-limited fed-batch processes using the GltA[A267T] variant performed similarly, and generated over 12 g/L mevalonate in 24–32 h at a yield of 0.24 g/g. This study demonstrates that GltA variants offer a means to generate acetyl–CoA-derived products from glycerol. Full article

Takayasu arteritis (TAK) is a refractory chronic vasculitis of the aorta and its major branches, characterized by unsatisfactory treatment responses and high relapse rates. This review synthesizes current evidence to propose and elaborate a novel pathogenic paradigm: a self-reinforcing “metabolism–epigenetics–inflammation” feedback loop that sustains chronic vascular inflammation in TAK. We detail how immunometabolic reprogramming in immune and vascular wall cells not only meets bioenergetic demands but also generates metabolites (e.g., acetyl-CoA, lactate) that serve as substrates or cofactors for epigenetic modifications. These modifications, in turn, lock in a persistent pro-inflammatory gene expression profile. A central focus is the dissection of the ANK2–MAVS–IL-8 axis, a critical link connecting genetic susceptibility (via ANK2 variants) through mitochondrial dysfunction to sustained, IL-8-driven vascular injury. Building on this mechanistic framework, the review explores the translational potential of emerging biomarker candidates (e.g., IL-8, specific methylation marks) and proposes stratified therapeutic strategies that target distinct nodes within this interactive network, including metabolic drivers, epigenetic stabilizers, and inflammatory effectors. Ultimately, this work provides an integrated conceptual and translational roadmap for advancing precision medicine in TAK. Full article