搜索结果：Bioscience, biotechnology, and biochemistry

Soluble epoxide hydrolase (sEH) is a key enzyme in epoxy fatty acid (EpFA) metabolism, significantly affecting the balance of lipid mediators and the health of the central nervous system (CNS). This review explains the molecular biology, enzymatic activity, and clinical importance of sEH, emphasizing its role in converting anti-inflammatory epoxygenase metabolites into less active diols. Blocking sEH increases EpFA availability, leading to protective effects in experimental models of neuroinflammation, oxidative stress, and vascular failure linked to Alzheimer's, Parkinson's, and traumatic brain injury. The pharmacokinetics and chemistry of urea- and amide-based sEH inhibitors are also reviewed to highlight their development as potential CNS-targeted treatments. Recent preclinical and early clinical studies indicate that sEH inhibition may slow neurodegeneration and improve synaptic plasticity, thereby enhancing cognitive and behavioral functions. Overall, this review combines biochemical and pharmacological insights to support sEH as a promising target for treating neuroinflammation and neurodegenerative diseases characterized by disrupted lipid mediator signaling.

Barley and rye are major cereals worldwide and contain proteinaceous α-amylase inhibitors for biological defence against insects. Inhibiting mammalian α-amylase could potentially be a promising functional food characteristic for suppressing postprandial blood glucose levels. This study examined in vitro mammalian α-amylase inhibitory effects and the physicochemical and functional properties of barley and rye albumins, including thermal stability, solubility, emulsifying and foaming properties, to evaluate their potential applications in various foods. Both barley and rye albumins inhibited mammalian α-amylase and maintained their activity even after heating. High solubility was observed at pH 3.0-6.0, which was maintained after heating at 80 °C for 20 min. Furthermore, barley and rye albumins exhibited high emulsifying and foaming properties at pH 3.0-6.0. These findings suggest that barley and rye albumins are promising materials for suppressing postprandial blood glucose elevation and can be used in various functional foods.

Xanthan gum is commonly used in the food industry to adjust food consistency and to improve the safety of swallowing liquids and food in people with dysphagia. The pro-inflammatory effect of xanthan gum is acknowledged in the literature. This study aimed to examine the effect of chronic xanthan gum supplementation in the diet on intestinal inflammatory processes in adult Wistar rats at three different doses. After the tenth week of treatment, white adipose tissue (epididymal, retroperitoneal, and mesenteric) was collected, and the distal colon was dissected and processed for cytokine and immunohistochemical analysis. Fecal matter from the colon was used for microbiota analysis. In general, the addition of xanthan gum at all doses promoted an inflammatory state as demonstrated by the high presence of lymphocytes. Also, it modified the content of the pro-inflammatory cytokines IL-1β and TNF-α compared to the control group. Regarding the colon barrier markers, xanthan gum increased the Claudin 2 and ZO-1 levels. The α diversity and relative abundance of Bacterioidetes (B), Firmicutes (F), F/B ratio were similar among the groups. Elusimicrobiota was increased. Our research, using an experimental model, confirmed the clinical assumption that xanthan gum is associated with the development of necrotizing enterocolitis in neonates. We validated the biological mechanism and metabolic pathway in the intestine of the deleterious effect of continuous use of xanthan gum. In conclusion, dietary xanthan gum induced moderate-grade inflammation and modified the colon gut barrier. Recent advances in the study of xanthan gum underscore the need for translational research bridging experimental findings and clinical practice.

Understanding how host gene regulation responds to viral infection is essential for developing effective antiviral strategies. Emerging evidence suggests that host transcripts undergo dynamic chemical modifications to counteract viral invasion. Conversely, viruses that rely on nuclear transcription exploit host RNA methyltransferases to enhance mRNA export and translation. Orthopoxviruses, however, complete their entire replication cycle within compartmentalized cytoplasmic "factories" utilizing enzymes encoded by their large double-stranded viral DNA genomes. The dynamic interplay between host and poxviral epitranscriptome remains poorly characterized. Using a temporally resolved model of Vaccinia virus (VV) infection, we investigated host-virus interactions through transcriptome and N6-methyladenosine (m⁶A) epitranscriptome whole genome sequencing. We found that host m⁶A modifications respond rapidly to VV infection, preceding the delayed transcriptional changes that emerge at later stages. Early m⁶A signatures included key innate immunity factors as well as host genes involved in transcriptional regulation, post-transcriptional modification, and protein ubiquitination. Functional assays validated two host factors with early m⁶A modification changes that are essential for VV infection: a m⁶A reader, YTHDF1, and a component of the SCF E3 ubiquitin ligase complex, FBXO31. The m⁶A gain on YTHDF1 enhanced its protein expression and promoted efficient VV replication. In addition, we identified previously unrecognized roles of FBXO31 and the SCF E3 ligase complex in supporting VV infection. Temporal profiling of the m⁶A epitranscriptome reveals how VV exploits host post-transcriptional regulatory pathways, specifically m⁶A RNA modification and protein ubiquitination. These findings highlight critical host factors co-opted during poxvirus infection and identify potential targets for therapeutic intervention.

The silkworm (Bombyx mori L., Thai strain Nanglai) is an important lepidopteran insect whose physiology is influenced by diet. This study compared artificial diet and mulberry leaves in larval performance, digestive enzyme activity, and gut microbiota using 16S rRNA gene sequencing. Survival was reduced in artificial diet-fed larvae at all instars. Mulberry leaf-fed larvae-maintained survival (97.33%-94.33%), whereas artificial diet-fed larvae declined from 84.33% in the first instar to 56.67% in the fifth instar, with survival 31.0% and 37.7% lower during the fourth and fifth instars, respectively. Total larval duration was longer under artificial diet feeding (34.0 vs. 27.67 days), while body weight did not differ significantly. Amylase activity was higher in mulberry leaf-fed larvae (3rd: 1,293; 5th: 2,394 U/mL) than in artificial diet-fed larvae (931 and 603 U/mL). Protease activity was lower in artificial diet-fed larvae at the third instar (779 vs. 886 U/mL) but higher at the fifth instar (462 vs. 352 U/mL). Microbial analyses revealed diet- and stage-dependent differences. At the fifth instar, alpha diversity was higher in mulberry leaf-fed larvae, with greater Chao1 richness, Shannon diversity, and Pielou's evenness. Principal coordinate analysis (PCoA) explained 91.11% of variation and showed clustering by diet and stage. Artificial diet feeding enriched Lactiplantibacillus and Saccharopolyspora, whereas mulberry leaf feeding supported greater taxonomic complexity. These findings indicate that artificial diet reshapes gut microbiota and digestive physiology, which may be associated with the observed reduction in larval survival during late development.

Plant polysaccharides can exert immunomodulatory activities. In this study we provided chemical characterization of wheat cell culture-derived polysaccharides (WCCPS) and assessed their capacity to modulate inflammatory responses in mouse macrophages. The total sample (T-010) contained arabinogalactans, arabinans, glucans and xyloglucans. Fractionation by anion-exchange chromatography rendered a bound acidic fraction (B-010) and an unbound neutral fraction (UB-010). The B-010 fraction was enriched in arabinogalactans and arabinans, with some galactans, homogalacturonans, and arabinoxylans. The neutral UB-010 fraction was composed of glucans and xyloglucans. None of the WCCPS preparations triggered cytokine production on their own, but each potentiated different macrophage responses to bacterial lipopolysaccharide (LPS). The total WCCPS in T-010 increased LPS-induced tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 secretion, whereas the acidic arabinogalactan-rich fraction B-010 boosted IL-6 release and selectively upregulated nitric oxide synthase 2 (Nos2) and cholesterol 25-hydroxylase (Ch25h) expression in response to LPS. In contrast, the neutral UB-010 fraction enhanced IL-6 levels and induced Nos2 expression without altering Ch25h expression. These results suggest that WCCPS can modulate distinct aspects of the inflammatory response, with their effects shaped by their composition and structural features. Future research will focus on elucidating the molecular mechanisms underlying the immunomodulatory activity of WCCPS.

Regulation of lipid homeostasis requires coordinated control of fatty acid (FA) oxidation, lipogenesis, and adipocyte differentiation. Cordyanhydride A (CA) was isolated from Cordyceps militaris (CM) extract cultivated on germinated soybean through bioactivity-guided fractionation and structurally characterized using nuclear magnetic resonance (NMR) spectroscopy. The effect of CA was examined in mouse hepatocytes and adipocytes using gene expression analysis, immunoblotting, and lipid accumulation assays. In AML12 hepatocytes, CA upregulated the expression of enzymes and transcriptional regulators involved in FA oxidation and suppressed the lipogenic enzymes. In 3T3-L1 adipocytes, it markedly reduced lipid accumulation and downregulated the expression of transcription factors required for adipocyte differentiation. Molecular docking and dynamics simulations supported stable interactions between CA and key proteins involved in lipid metabolism. These results demonstrate that CA modulates lipid metabolism at the cellular level and underscore the value of integrated experimental and computational approaches in characterizing functional metabolites derived from fermented microorganisms.

In this study, beta glucan nanoparticles were fabricated and encapsulated with Doxorubicin for an effective drug delivery for triple negative breast cancer treatment. The synthesized nanoparticles were characterized by FTIR, TEM, SEM, DLS and zeta potential analysis. A drug encapsulation rate of 80% was achieved and drug release studies displayed a better release of drug from encapsulated glucan nanoparticles in acidic media. In vitro cytotoxicity and cellular uptake were evaluated by MTT and fluorescence microscopy, respectively where the IC50 concentrations for Dox and Dox loaded nano glucans were found to be 2.5 and 1µg/ml respectively. SEM, TEM and DLS results showed that beta glucan nanoparticles have a size distribution between 30-100 nm. FTIR and zeta potential analysis confirmed the loading of Dox. The results over MDA-MB-231 cells showed that Dox loaded beta glucan nanoparticles were effectively internalized and had more cytotoxic activity with respect to free drug.

LPS-induced inflammation triggers metabolic reprogramming and nutritional decline. This study aimed to identify biomarkers for inflammatory and nutritional stress using GC-MS/MS-based metabolomic profiling. Male mice received LPS to induce systemic inflammation. Evaluations included liver histology (H&E, Gr-1), blood biochemistry, and metabolomic analysis of liver and plasma. LPS administration significantly increased hepatic neutrophil infiltration and liver enzymes, while decreasing nutritional markers (total protein, albumin, LDL-cholesterol). In the liver, LPS increased glycolytic and TCA cycle intermediates (e.g. 3-phosphoglycerate, citric acid) but decreased amino acids, including glutamine and tryptophan. Plasma analysis showed significant decreases in tryptophan, glucose, and succinic acid. Notably, tryptophan was significantly reduced in both compartments. Our findings demonstrate that tryptophan serves as a robust biomarker for monitoring the intersection of inflammatory response and nutritional status, reflecting synchronized metabolic shifts in the liver and plasma.

Despite decades of biochemical and structural studies of the nucleosome1, researchers lack genome-scale methods to determine variability in nucleosome structure along individual chromatin fibres. To address this, here we present Iteratively Defined Lengths of Inaccessibility (IDLI), a computational method that maps the single-molecule co-occupancy of structurally distinct nucleosomes, subnucleosomes and other protein-DNA interactions through long-read single-molecule footprinting2,3. IDLI classifies methylase-inaccessible footprints on individual chromatin fibres into (i) linker-histone-associated nucleosomes; (ii) nucleosomes with focal DNA accessibility along the nucleosome wrap; (iii) unwrapped nucleosomes; and (iv) subnucleosomal species such as hexasomes, tetrasomes and other short DNA protections. Applying IDLI to chromatin from mouse embryonic stem cells, we discover that more than 85% of nucleosomes exhibit intranucleosomally accessible DNA (nucleosome 'distortion'). We observe epigenomic-domain- and expression-level-specific patterns of distortion, including at promoters and mouse satellite repeat sequences. Transcription factor (TF) motif occurrence correlates significantly with distinct types of distortion, and degron experiments provide evidence of direct regulation by TFs. We apply IDLI to in vitro endoderm differentiation in human induced pluripotent stem cells and primary mouse hepatocytes. In both cases, we observe distortion at pioneer TF FOXA2 binding sites, demonstrating that distortion is developmentally encoded and present in vivo. Finally, genetic experiments in mice show that a nucleosome-binding domain of FOXA2 directly affects nucleosome structure in vivo, implicating these protein-nucleosome interactions as direct mediators of distortion. Our work suggests extreme but regulated nucleosome structural variability at the single-molecule level. Furthermore, our approach offers opportunities to model TF binding, nucleosome remodelling and cell-type-specific chromatin regulation across biological contexts.

Mammalian orthoreoviruses (MRVs), commonly known as reoviruses, are an emerging zoonotic threat that are known for their broad host tropism and potential for causing severe clinical pathology in both humans and animals. Despite this epidemic risk, currently, there are no approved therapeutic agents that are able to disrupt MRV transmission. The viral attachment protein sigma1 (σ1), mediating the entry of the virus into the host cells is a critical target for antiviral intervention. This study used an in silico structure-based drug design strategy to screen for bioactive phytochemicals that are capable of inhibiting the function of σ1. We screened a library of 376 bioactive phytochemicals with known antiviral potential against the σ1 receptor binding domain using molecular docking. Among the candidates, catechin gallate was the most potent inhibitor, possessing a superior binding affinity of -8.1 kcal/mol followed by bilobetin, which also showed a favorable binding affinity of -7.8 kcal/mol. Structural interaction analysis showed that catechin gallate and bilobetin occupies the active JAM-A binding pocket, forming stable interactions with some of the residues, including Gly381, Glu384, and Arg316, which are essential for the reovirus in the cellular attachment process. Subsequent pharmacokinetic and toxicity profiling proved that catechin gallate possessed favorable safety and drug-like characteristics, whereas bilobetin exhibited an unfavorable toxicity profile. In addition, molecular dynamics (MD) simulations supported the stability of σ1-catechin gallate complex relative to the σ1-bilobetin complex. Extensive post-trajectory analyses including RMSD, RMSF, Rg, SASA, and H-bond, showed that the binding of the catechin gallate significantly increases the rigidity and compactness of the protein. PCA indicated that the first three principal components (PC1-PC3) accounted for 74.1% and 76.2% of the total variance for catechin gallate and bilobetin, respectively, with the σ1-catechin gallate complex displaying a more compact conformational cluster consistent with greater stability. MM-GBSA analysis also showed favorable binding for both complexes, with estimated binding energies of -15.6097 ± 3.21 kcal/mol and -13.7327 ± 5.44 kcal/mol for the σ1-catechin gallate and σ1-bilobetin complexes, respectively, with catechin gallate showing comparatively stronger binding. Our results reveal a precise mechanism by which the lead compound catechin gallate sterically occludes the σ1 receptor-binding pocket, thereby likely abrogating viral attachment to the host cell. This comprehensive preclinical evaluation provides supporting evidence for the further development of catechin gallate using in vivo models and clinical trials as a promising antiviral candidate against reovirus infection.

Bifidobacterium psychraerophilum was isolated from Kishu-Narezushi, marking the first discovery of the Bifidobacterium species originating from a spontaneously fermented traditional Japanese food. Kishu-Narezushi is a traditional Japanese spontaneously fermented food composed of fish, rice, and salt. Typically, Bifidobacterium species are isolated from milk-related fermented foods or human intestines. The isolated strain was identified as B. psychraerophilum and named the Yasuke strain. B. psychraerophilum are closely related with Bifidobacterium aquikeferi and Bifidobacterium crudilactis. The Yasuke strain and Bifidobacterium psychraerophilum DSM 22366 exhibited greater resistant to salt and oxygen compared to other Bifidobacterium species. Draft genome analysis of the Yasuke strain and four other B. psychraerophilum strains indicates the presence of stress tolerance-related genes. Superoxide dismutase [Mn] and glutathione peroxidase genes are observed in this species. Genes involved in phage interactions, proline metabolism, and sugar and amino acid transport were uniquely identified in the Yasuke strain.

Cacti are xerophytic plants characterized by water-storing cladodes, thick cuticles, and CAM photosynthesis, enabling high productivity under harsh conditions. They accumulate ascorbate (AsA) at levels comparable to those of leafy vegetables, potentially contributing to stress tolerance and nutritional value. However, the regulation of AsA accumulation in cacti remains poorly understood. Here, we used the dwarf prickly pear cactus Nopalea cochenillifera to investigate the tissue-specific distribution and environmental responses of AsA. AsA preferentially accumulated in the cortex, exhibited light-dependent increases, and was maintained or even increased under high-light, drought, and low-temperature stress conditions. Supplementation experiments with AsA and its precursors suggest the presence of multiple biosynthetic pathways and inter-cladode transport mechanisms. These results provide insights into mechanisms specific to the cactus N. cochenillifera for maintaining AsA homeostasis under adverse environmental conditions. This study provides the first evidence of tissue-specific and stress-responsive regulation of AsA metabolism in cactus cladodes.

Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, regulates the metabolism of exogenous compounds. Pharmacological inhibition of AhR reduces lipid droplet (LD) accumulation and suppresses hepatitis C virus (HCV) proliferation. Recent evidence implicates AhR in the propagation of viruses such as herpes simplex virus type 1 (HSV-1), making it a host factor regulating the proliferation of diverse viruses and an attractive target for broad-spectrum antivirals. To identify AhR ligands with antiviral activity, we screened secondary metabolites derived from fungi isolated from various animals. We identified roquefortine C, an indole alkaloid obtained from quail-derived fungi, as an AhR antagonist. Roquefortine C suppressed LD formation and HCV production in human hepatoma cells. Additionally, it showed anti-HSV-1 and anti-pseudorabies virus (PRV) activities. Notably, our study demonstrated the relationship between AhR and PRV for the first time. AhR ligands could represent potential lead compounds with broad-spectrum antiviral properties.

Acute lung injury (ALI) is characterized by excessive inflammation, oxidative stress, and impaired resolution responses, partly driven by dysregulated macrophage activation. In this study, a defined mixture of eicosapentaenoic acid (EPA)-derived dihydroxyeicosapentaenoic acids (diHEPAs), comprising 5,15-diHEPA and 8,15-diHEPA at an equimolar ratio, was generated using soybean lipoxygenase and its protective effects on lipopolysaccharide (LPS)-induced ALI were investigated. Mice were orally administered 5,15-diHEPA (40 μg/kg), 8,15-diHEPA (40 μg/kg), or the diHEPA mixture (20 μg/kg each) for 7 days before LPS challenge. LPS exposure induced severe lung injury, as evidenced by an increased lung wet/dry ratio, inflammatory cell infiltration, and oxidative stress. Treatment with diHEPAs attenuated lung pathological damage, reduced proinflammatory cytokine production, and restored redox homeostasis. Consistently, in vitro studies in RAW264.7 macrophages showed that the diHEPA mixture suppressed LPS-induced inflammatory responses through the inhibition of NF-κB signaling and rebalanced oxidative stress via modulation of the NOX2/Nrf2/HO-1/ROS axis. Altogether, these results indicate that EPA-derived diHEPAs confer protection against ALI by suppressing inflammation and restoring redox balance, emphasizing their potential as therapeutic agents for ALI.

To investigate the influence of genome editing on the taste and odor of fish meat, we conducted a comparative analysis of taste components, odor components and lipid oxidation index, in the dorsal muscle of mc4r-deficient red sea bream compared to the unedited control. In terms of taste components, only some free amino acids were significantly difference in the mc4r-deficient group compared with the unedited control group. Differences were also noted in non-protein nitrogen, equivalent umami concentration, and some taste-active value between the mc4r-deficient and unedited control groups. Regarding odor components, some volatile organic compounds were significantly difference in the mc4r-deficient group. However, no differences were observed in other taste and odor components, or the lipid oxidation index between these groups. These findings suggest that the effect of mc4r deficiency on taste and odor-related components and lipid oxidation in red sea bream muscle is minor.

Periodontal disease is a major oral infectious condition that leads to the degradation of alveolar bone and subsequent tooth loss. Porphyromonas gingivalis, a keystone pathogen in periodontitis, plays a critical role in disease initiation and progression. In a previous study, we demonstrated the anti-P. gingivalis activity of epimedokoreanin B, a prenylated flavonoid derived from Epimedium species. However, its in vivo efficacy against periodontitis remains unclear. Oral administration of epimedokoreanin B attenuated P. gingivalis-induced alveolar bone resorption in murine periodontitis models and suppressed infection-induced antibody production Furthermore, epimedokoreanin B compromised bacterial membrane integrity and virulent gene expressions. In this preclinical study, in vitro and in vivo analyses indicate that epimedokoreanin B suppressed both bacterial viability and virulence, thereby attenuating alveolar bone loss caused by periodontitis. These findings suggest that epimedokoreanin B is a promising candidate for the development of novel therapeutics targeting periodontal pathogens.

Vitamin D (VD) and Wnt signaling both play important roles in bone metabolism and are targeted in osteoporosis therapy. Combination treatment with VD derivatives and anti-sclerostin antibodies that activate Wnt signaling improves clinical outcomes, although the molecular basis of this cooperative effect remains unclear. Because β-catenin functions as a transcriptional co-regulator in canonical Wnt signaling, we examined whether β-catenin modulates vitamin D receptor (VDR)-mediated transcription. Reporter assays were performed in Saos-2 osteoblastic cells using vitamin D response element (VDRE) and TCF/LEF-responsive reporters. Activation of Wnt signaling by CHIR99021 or expression of constitutively active β-catenin did not enhance VDR transcriptional activity but modestly suppressed VD-induced transcription. Similar results were obtained in HCT116 and COS-1 cells. These findings indicate that VDR and Wnt/β-catenin signalings are not cross-talked at the transcriptional level.

Diphenylmethylene serine methyl ester is an important precursor for the synthesis of O-glycoprotein mimics; however, it exists as an equilibrium mixture of imine and oxazolidine forms due to intramolecular cyclization. Upon crystallization from ether/hexane, the oxazolidine form is typically obtained as the predominant species, and the pure imine form has not been isolated to date. In this study, diphenylmethylene serine methyl ester was synthesized from serine methyl ester and benzophenone imine, purified by chromatography, and subsequently recrystallized from methanol to selectively afford the imine form in high purity. The structure was confirmed by nuclear magnetic resonance spectroscopy and single-crystal X-ray diffraction analysis. Tautomeric interconversion was investigated in deuterated chloroform at various temperatures, revealing a gradual conversion of the imine into the oxazolidine form until equilibrium was established. These findings clarify the tautomeric behavior of this compound and provide an effective strategy for the selective isolation of tautomers of serine derivatives.