Search Results (4,397)

Background: Ginseng oligopeptides (GOPs), small bioactive peptides with potent antioxidant capacity and high bioavailability, have shown promise in promoting healthy aging; however, their underlying molecular mechanisms remain largely unexplored. Methods: Using the model organism Caenorhabditis elegans (C. elegans), we comprehensively evaluated the anti-aging effects of GOPs on lifespan, locomotion, oxidative stress, and gene expression. Integrated phenotypic assays and transcriptomic analyses were conducted to elucidate GOP-mediated molecular mechanisms. The transgenic strain TJ356 (DAF-16::GFP) and the loss-of-function mutant CF1038 [daf-16(mu86)] were employed to functionally validate the role of the DAF-16/FOXO pathway. Results: GOP supplementation significantly extended median lifespan by approximately 11.5% and improved age-related locomotion decline in C. elegans. Transcriptomic profiling identified 1928 differentially expressed genes (DEGs) enriched in metabolic, antioxidant defense, and longevity-regulating pathways. GOPs upregulated key antioxidant and stress-response genes (gst-4, sod-5, mtl-1) and longevity-related regulators (daf-16, lin-31, Y51B9A.9, and daf-12), while downregulating ins-7, an insulin-like peptide. Moreover, GOPs enhanced cytochrome P450–related detoxification and vitamin-dependent (retinol, ascorbate, and riboflavin) metabolic pathways, establishing a multidimensional antioxidant defense network. Phenotypic validation confirmed that GOPs markedly reduced reactive oxygen species (ROS) levels and lipofuscin accumulation (p < 0.001). Notably, GOPs promoted DAF-16 nuclear translocation in TJ356 worms, whereas the lifespan-extending effects were abolished in CF1038 mutants, highlighting the essential role of DAF-16/FOXO in mediating GOP effects. Conclusions: GOPs delay aging in C. elegans by activating the DAF-16/FOXO signaling cascade and reinforcing antioxidant networks, thereby maintaining redox and metabolic homeostasis. These findings provide novel mechanistic evidence supporting GOPs as promising dietary antioxidants for promoting healthy aging through modulation of conserved redox and longevity pathways. Full article

Background: Phylogeographic surveys of obligate freshwater fishes could serve as a pivotal lens through which the biological footprints of historic drainage rearrangements can be deciphered. Methods: Focusing on the headwater-restricted cyprinid Acrossocheilus kreyenbergii in the Pearl, Yangtze, and Huai river basins, we examined variations in mitochondrial cytochrome b gene (Cyt b) to elucidate the phylogeographic architecture and evolutionary history of this stream fish in South–Central China through integrative analyses of phylogeny, ancestral area reconstruction, genetic structure, and population demography. Results: A time-calibrated phylogeny recovered two primary lineages, K-I and K-II, which diverged ca. 2.15 Ma: K-I split into K-Ia (Huai River) and K-Ib (Yangtze–Poyang Lake catchment) at 1.53 Ma, whereas K-II gave rise to K-IIa, K-IIb, and K-IIc through sequential divergences at 1.29 Ma and 0.83 Ma, with K-IIa restricted to the Poyang Lake catchment. K-IIb was shared between the Poyang Lake catchment and the Qiupu River (Yangtze basin), and K-IIc was distributed in the Xijiang River (Pearl basin) as well as the Yangtze–Dongting Lake catchment. Conclusions: Our findings reveal that the phylogeographic architecture of A. kreyenbergii was sculpted by a succession of geologic and anthropocentric events: the Late-Cenozoic collapse of the Zhe–Min Uplift first fractured its range; the intervening Mufu–Lianyun–Luoxiao Mountains then acted as a persistent barrier; the large waters of Poyang and Dongting Lakes served as biological filters; and the 2200-year-old Lingqu Canal—constructed during the Qin dynasty—briefly re-established a corridor for gene flow. Together, these forces disrupted and reorganized the species’ genetic connections, leaving a visible imprint today. Full article

Background: Bisphenol A (BPA) is a widespread environmental endocrine disruptor associated with metabolic dysfunction-associated steatotic liver disease (MASLD). However, its short-term effects at low, environmentally relevant concentrations are still poorly understood. Methods: Adult zebrafish were exposed to 5, 20, or 100 µg/L BPA for 48 h, 7, or 14 days in a pilot test. The lowest effective condition (20 µg/L for 7 days) was selected for a complete experiment. Fish were divided into two groups: control and BPA-exposed (n = 50/group). After exposure, livers were collected for histological (HE, Oil Red O, Nile Red) and molecular (RT-qPCR) analyses. Results: Exposure to 20 µg/L BPA for 7 days induced moderate to severe hepatic steatosis, characterized by vacuolization, hepatocyte ballooning, and lipid accumulation. Gene expression analysis showed upregulation of fasn (fatty acid synthase), acc1 (acetyl-CoA carboxylase 1), srebp-1c (sterol regulatory element-binding protein 1c), nfkb (nuclear factor kappa B), il-6 (interleukin-6), gpx1 (glutathione peroxidase 1), sod (superoxide dismutase), cyp1a (cytochrome P450 1A), and cyp2ad2 (cytochrome P450 2AD2), while adipor2 (adiponectin receptor 2) and gpx4 (glutathione peroxidase 4) were downregulated (decreased activity). Conclusions: Short-term exposure to a low, environmentally relevant concentration of BPA was sufficient to trigger hepatic steatosis in zebrafish. These effects were associated with enhanced lipogenesis, inflammation, oxidative imbalance, and altered xenobiotic metabolism, suggesting that even brief, low-dose BPA exposure may contribute to early events in MASLD pathogenesis. Full article

The American lobster (Homarus americanus) is a non-native species to Europe, but is imported as live seafood and has been identified in European waters. These introductions threaten native populations of the European lobster (Homarus gammarus) via disease introduction, competition, direct predation, and genetic introgression. Differentiating the two species and their hybrids based solely on morphological criteria can be difficult and unreliable. This study presents a real-time PCR assay targeting the cytochrome c oxidase gene 1 (cox1) for rapid detection and identification of H. americanus and H. gammarus. We have also designed a conventional duplex PCR from a previously described nuclear marker (Hgam98), which was sequenced and revealed the presence of a specific H. americanus insert downstream from a variable number tandem repeat region. The combination of these assays resulted in the accurate identification of the two lobster species and F1 hybrid specimens. Full article

The Huainan yellow-feathered chicken is a prized local breed known for its high-quality meat. However, excessive abdominal fat deposition adversely affects feed efficiency and carcass quality. This study aimed to identify genetic markers and candidate genes associated with fat traits to facilitate marker-assisted selection (MAS) using genome-wide association studies (GWAS). A total of 220 chickens were phenotyped for abdominal fat weight (AFW), abdominal fat percentage (AFP), intramuscular fat of pectoral muscle (IFPM), and intramuscular fat of leg muscle (IFLM). GWAS based on whole-genome resequencing revealed significant SNPs for AFW and AFP on chromosomes 1, 2, 7, 10, 13, and 35, annotating genes including GRIA1, CYP1A1, CYP1A2, and SCAMP2. For IFPM and IFLM, significant loci were identified on chromosomes 1, 2, 4, 5, 6, 9, 12, 23, 25, 26, and 28, highlighting genes such as LRP4, FABP3, and ADAMTS9. Functional enrichment analysis showed involvement of steroid hormone biosynthesis, retinol metabolism, and cytochrome P450 pathways in abdominal fat deposition, while Wnt and MAPK signaling pathways regulated intramuscular fat. These findings provide molecular targets for genetic selection to improve fat traits in Huainan chickens. Full article

GV1001, a multifunctional peptide, has shown numerous biomedical activities, including antioxidant, anti-inflammatory, anti-Alzheimer’s, and anti-atherosclerotic effects, and protects mitochondria from cytotoxic agents. Cisplatin is a widely used chemotherapeutic agent against cancers, but its clinical utility is limited by nephrotoxicity driven by mitochondrial dysfunction in renal epithelial cells. Here, we investigated whether GV1001 protected against cisplatin-induced nephrotoxicity (CIN) in vivo and preserved mitochondrial integrity in human renal epithelial cells in vitro. In mice, GV1001 substantially mitigated CIN by significantly reducing histological damage, kidney injury marker expression, macrophage infiltration, endothelial-to-mesenchymal transition, inflammation, and apoptosis. In cultured renal epithelial cells, GV1001 maintained mitochondrial membrane potential, preserved ATP production, and prevented mitochondrial membrane peroxidation possibly by binding to cardiolipin. GV1001 also reduced the level of reactive oxygen species (ROS), suppressed cytochrome c release into the cytosol, and inhibited activation of apoptosis-related pathways elicited by cisplatin. Collectively, these findings demonstrated that GV1001 might protect kidney from cisplatin through maintaining mitochondrial structure and function and suppressing downstream injury cascades in renal epithelial cells. By directly targeting the mitochondrial mechanisms underlying cisplatin toxicity, GV1001 represents as a promising therapeutic strategy to mitigate CIN and improve the safety of cisplatin-based chemotherapy. Full article

Impaired glucose metabolism elevates the risk of neurodegenerative diseases by activating the receptor for advanced glycation end products (RAGE), thereby promoting oxidative and endoplasmic reticulum (ER) stress that leads to neuronal apoptosis. C-phycocyanin (C-PC), a natural pigment–protein complex derived from algae, possesses potent antioxidant and antiglycation properties; however, its capacity to modulate RAGE-mediated neurotoxicity remains to be fully elucidated. In this study, we established a RAGE-driven neuronal injury model by exposing differentiated SH-SY5Y cells to advanced glycation end products (AGEs; 300 μg/mL). Pretreatment with C-PC (15–50 μmol/L) improved cell viability, preserved neuronal morphology, and attenuated AGEs-induced oxidative stress, as indicated by reduced intracellular reactive oxygen species and mitochondrial superoxide levels. Furthermore, C-PC inhibited activation of the PERK-CHOP pathway, and upregulated Bcl-2 while downregulating Bax, thereby preventing cytochrome c release and reducing caspase-9/3 activation as well as apoptotic DNA fragmentation. These neuroprotective effects of C-PC were comparable to those observed with the selective RAGE antagonist FPS-ZM1. In conclusion, our findings demonstrate that C-PC confers robust protection against AGEs-induced neuronal injury by suppressing oxidative and ER stress pathways downstream of RAGE activation, highlighting its potential as a natural modulator of the AGE–RAGE axis for the prevention or treatment of diabetes-associated neurodegeneration. Full article

Pyrenophora tritici-repentis (Ptr), the causal agent of tan spot, is a necrotrophic fungus that represents a significant threat to wheat production worldwide. The development of resistant cultivars is limited by an incomplete understanding of wheat defence responses against Ptr. Here, weighted gene co-expression network analysis (WGCNA) was applied to RNA-seq data from resistant (Robigus) and susceptible (Hereward) wheat lines before and after Ptr infection to identify coordinated host responses. Eight co-expression modules were identified, three of which were linked to either resistance, susceptibility, or Ptr infection. The resistance-associated module was enriched with chloroplast ribosomal machinery genes (e.g., 50S ribosome-binding GTPase, L28, L6), and transcriptional regulators. This suggested that maintaining chloroplast function, coupled with large-scale transcriptional reprogramming, was important for resistance. The susceptibility-associated module indicated the high expression of post-transcriptional modifiers, including SGS3, RBX1, and SENPs. The Ptr-responsive module showed common responses in both genotypes and included several defence-related genes (nucleotide-binding domain leucine-rich repeat R-genes [NLRs], chitinases, beta-1,3-glucanases) and metabolic pathways, such as phenylpropanoid biosynthesis and nitrogen metabolism (phenylpropanoid ammonia lyase [PAL], cytochrome P450s, glutamine synthase, and ammonium transporters). These results define distinct and shared molecular networks that are linked to resistance and susceptibility, providing valuable candidate genes for functional validation that could ultimately be exploited to enhance wheat resilience against necrotrophic fungal pathogens. Full article

The short peptide AlaGluAspLeu (AEDL) stimulates shoot and root development in Nicotiana tabacum. Growing tobacco in the presence of AEDL was found to induce autophagy and programmed cell death, as demonstrated using immunodetection of the autophagy marker ATG8 and cytochrome c in the cytoplasm, as well as the detection of DNA breaks using the TUNEL assay. A detailed study of the ultrastructure of Nicotiana tabacum root cells grown in the presence of AEDL using transmission electron microscopy revealed fundamental structural differences from control cells. Control cells contained only lytic vacuoles, while in the presence of AEDL, tobacco root meristem cells contained predominantly protein-storing vacuoles and amyloplasts with numerous starch granules in the stroma. Characteristic types of phagophores were identified, forming numerous small autophagosomes with cytoplasmic regions, multivesicular bodies, or concentric membranes, possibly with cytoskeletal elements. Expression of autophagy protein genes revealed a decrease in TOR expression, which promoted autophagy activation and prevented ATG13 phosphorylation. ATG8 gene expression significantly increased in the presence of the AEDL peptide. Schematic diagrams of autophagy processes in root cells of control plants and those grown in the presence of AEDL are presented. Based on these data, it was concluded that stimulation of tobacco plant development in the presence of the AEDL peptide at a concentration of 10⁻⁷ M occurs due to the activation of metabolic processes and autophagy. Moreover, the synthesis of metabolites exceeds the required amount of nutrients, which accumulate in vacuoles and leucoplasts. Full article

In this study, for the first time, the genes encoding the mammalian steroidogenesis system—cytochrome P450scc (CYP11A1), and its native redox partners adrenodoxin and adrenodoxin reductase—were successfully expressed in the methylobacterium Methylorubrum extorquens. The advantage of using methylobacteria as an expression chassis is that they grow on inexpensive mineral media, use methanol as a carbon and energy source, and do not possess their own sterol catabolism systems. Using recombinant methylobacteria, the valuable steroid pregnenolone was obtained as a sole metabolite from cholesterol. The effect of media composition, bioconversion conditions such as methanol and N-sources content, modes of substrate addition, detergents, methyl-β-cyclodextrin, biomass, and aeration on pregnenolone accumulation was investigated. Under optimized conditions, its yield exceeded 100 mg/L. The results demonstrate a proof of concept relating to the use of bacteria lacking their own steroid degradation systems as microbial chassis for heterologous steroidogenesis systems, including mammalian cytochrome CYP11A1. Full article

Black soldier flies (Hermetia illucens) are widely used in organic waste bioconversion, and their adaptive capacity to region-specific food waste is critical for efficient application. This study aimed to explore the molecular mechanisms underlying the adaptation of black soldier fly larvae to long-term domestication on regional food waste from Kunming and Qujing. Integrated transcriptomic and metabolomic analyses were performed to identify differences in gene expression and metabolite profiles between the two groups of larvae. The results showed significant divergence in gene expression networks, with key differences in cytochrome P450 detoxification pathways, TOR nutrient-sensing pathways, and zf-C2H2 zinc finger transcription factor families. Metabolomic analysis revealed region-specific metabolic reprogramming, including enhanced branched-chain amino acid degradation in one group and activated sphingolipid signaling pathways with accumulated indole derivatives in the other. Additionally, 13.86% of unannotated metabolites in the metabolome exhibited high connectivity in metabolic networks, suggesting potential roles as “bridge metabolites” in adaptation. These findings demonstrate that long-term domestication on regional food waste drives adaptive differentiation in black soldier fly larvae through regulatory network remodeling, metabolic reprogramming, and activation of hidden metabolic reserves. The study provides a theoretical basis for optimizing the application of black soldier flies in waste treatment and strain breeding and establishes a “substrate-gene-metabolism” multi-omics framework for understanding insect adaptive evolution. Full article

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. The search for effective, new antineoplastic drugs with fewer side effects for the treatment of CRC continues, with marine-derived compounds emerging as promising candidates. Objectives: This study investigates the anticancer potential of Frondanol, a nutraceutical derived from the Atlantic Sea cucumber Cucumaria frondosa, known for its potent anti-inflammatory properties. Methods: Two human CRC cell lines, Caco-2 and HT-29, were used to test the effects of Frondanol using various in vitro approaches. Results: Frondanol significantly inhibited cell viability in a dose- and time-dependent manner. At a 1:10,000 dilution, viability decreased to around 30% in Caco-2 and 20% in HT-29 after 24 h, dropping to nearly 5% at 48 h. Furthermore, a clonogenic assay showed around 50% reduction in colony formation in both cell lines. Flow cytometry-based Annexin V staining revealed that Frondanol increased early apoptosis to ~5.2% in Caco-2 and ~9.4% in HT-29 cells, while cell cycle analysis showed accumulation of the sub G0 (apoptotic) phase increasing from 1.5% to 14.7% (Caco-2) and from 1.9% to 23.8% (HT-29). At the molecular level, Frondanol treatment significantly decreased anti-apoptotic protein B-cell lymphoma (Bcl)-2 expression while increasing the expression of the proapoptotic protein Bcl-2-associated X-protein. Additionally, Frondanol markedly induced cytochrome c release from the mitochondria and activated caspase-9, caspase-7, and caspase-3 after treatment, alongside cleavage of the caspase-3 substrate poly (ADP-ribose) polymerase. Frondanol inhibited 5-lipoxygenase activity, further contributing to its anticancer effects. Conclusions: In conclusion, Frondanol inhibits CRC cell proliferation and induces apoptosis through the mitochondrial pathway in vitro, suggesting that it is a potential nutraceutical for the prevention of human colorectal cancer or a valuable source of anticancer compounds. Full article

Background: The cytochrome P450 family 21 subfamily A member 2 gene (CYP21A2) encodes 21-hydroxylase, a key enzyme in adrenal steroid biosynthesis. Despite its physiological importance, the diversity of CYP21A2 transcript variants and their tissue-specific expression in domestic animals, including cattle, remains largely unexplored. This study aimed to characterize CYP21A2 transcription in adrenal glands and ovaries and assess the potential transcriptional activity of its pseudogene, CYP21A1P. Methods: CYP21A2 transcription was investigated in adrenal and ovarian tissues of 12 healthy cows using semi-quantitative PCR and Sanger sequencing. Real-time PCR was performed to confirm expression levels. Melting curve analysis and electrophoresis were used to validate distinct amplicons corresponding to different transcript variants. Extended amplicons were sequenced to identify transcripts corresponding to reference sequences and potential pseudogene products. Results: A single transcript variant (NM_001013596.1) was consistently detected in adrenal glands, whereas ovaries expressed two variants: NM_001013596.1 and XM_024983378.2. Semi-quantitative analysis showed significantly higher CYP21A2 expression in adrenal glands compared to ovaries (p < 0.01). In ovarian samples, the NM_001013596.1 variant was more abundant than the XM_024983378.2 (p < 0.01). Sanger sequencing revealed two products matching CYP21A2 reference transcripts and an additional, longer product containing sequence motifs specific to the pseudogene CYP21A1P, indicating its transcriptional activity. Conclusions: These results provide the first evidence of tissue-specific expression and differential abundance of CYP21A2 transcript variants in cattle and suggest the transcription of the CYP21A1P pseudogene. The findings reveal the complexity of CYP21A2 expression in steroidogenic tissues and suggest potential regulatory roles for transcript and pseudogene variants in bovine physiology. Full article

Background/Objectives: Molnupiravir (MOV) and nirmatrelvir (NMV) are antiviral drugs that were FDA-approved under the emergency use authorization (EUA) for coronavirus disease-2019 (COVID-19) treatment. MOV and NMV target the viral RNA-dependent RNA polymerase and main protease, respectively. Paxlovid is a combination of NMV and ritonavir (RTV), an inhibitor of the human cytochrome P450-3A4 (hCYP3A4). In this study, the structural consequences in the hCYP3A4 caused by MOV-induced mutations (MIM) were evaluated using in silico tools. Methods: MOV-induced mutations (MIM) were inserted into all the possible hotspots in the active site region of the hCYP3A4 gene, and mutant protein models were built. Structural changes in the heme-porphyrin ring of hCYP3A4 were analyzed in the presence and absence of substrates/inhibitors, including RTV. Molecular dynamics (MD) simulations were performed to analyze the effect of MIM-induced structural changes in hCYP3A4 on drug binding. Results: MD simulations confirm that MIMs, R375G and R440G in hCYP3A4 severely affect the heme-porphyrin ring stability by causing a tilt that in turn affects RTV binding, suggesting a possible inefficiency in the function of hCYP3A4. Similar results were seen for amlodipine, atorvastatin, sildenafil and warfarin, which are substrates of hCYP3A4. Conclusions: The current in silico studies indicate that hCYP3A4 containing MIMs can create complications in the treatment of COVID-19 patients, particularly with co-morbidities due to its functional inefficiency. Hence, clinicians must be vigilant when using MOV in combination with other drugs. Further in vitro studies focused on hCYP3A4 containing MIMs are currently in progress to support our current in silico findings. Full article

Despite advances with novel targeted agents (e.g., BCL-2 or IDH inhibitors) combined with chemotherapy for acute myeloid leukemia (AML), drug resistance persists. We investigated whether blocking Na⁺/H⁺ exchanger 1 (NHE1) could enhance AML cell sensitivity to the BCL-2 inhibitor venetoclax and sought to determine the molecular mechanisms. Our results demonstrated that co-treatment with venetoclax and the NHE1 inhibitor 5-(N,N-hexamethylene) amiloride (HMA) synergistically induced apoptosis in both venetoclax-sensitive and -resistant leukemic cell lines. Specifically, the combination significantly increased apoptosis in venetoclax-resistant THP-1 cells to 72.28% (17.79% with 100 nM venetoclax and 10.15% with 10 μM HMA alone; p < 0.001). Conversely, another venetoclax-resistant line, U-937, showed no significant apoptotic response to the combination. In THP-1 cells, this synergy was mediated via a caspase-dependent programmed cell death pathway, evidenced by an increased BAX/BCL-2 ratio, mitochondrial cytochrome c release, and subsequent caspase-9 and caspase-3 activation. Furthermore, co-treatment downregulated the anti-apoptotic protein MCL-1 and reduced PI3K and Akt phosphorylation, suggesting that inhibition of these survival pathways also contributed to the synergistic effect. Inhibition of NHE1 may substantially enhance venetoclax sensitivity in certain AML models, particularly in venetoclax-resistant THP-1 cells but not in U-937, highlighting biological diversity and the probable involvement of alternative survival pathways. Full article