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Keywords = cytochrome P450 expression

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21 pages, 2715 KB  
Article
Comparative Transcriptome Analysis of Rhynchophorus ferrugineus (Coleoptera: Curculionidae) Reveals Potential Mechanisms Involved in the Toxication and Detoxification of the External Immune Compound p-Benzoquinone Present in Oral Secretions
by Juan Chen, Yu-Chen Pu, Wen-Qing You, Ya-Nan Ji, Can-Hui Ding, Zong-Wei Zheng, Yi-Fan Wang and You-Ming Hou
Insects 2025, 16(10), 1044; https://doi.org/10.3390/insects16101044 (registering DOI) - 11 Oct 2025
Abstract
p-Benzoquinone (PBQ), a highly toxic compound, is the main active component in larval oral secretions of red palm weevil (RPW), Rhynchophorus ferrugineus, playing critical roles in external immunity and pathogen defense. In this study, we demonstrated that pathogens effectively induce RPW larval [...] Read more.
p-Benzoquinone (PBQ), a highly toxic compound, is the main active component in larval oral secretions of red palm weevil (RPW), Rhynchophorus ferrugineus, playing critical roles in external immunity and pathogen defense. In this study, we demonstrated that pathogens effectively induce RPW larval external immune responses. On this basis, the toxicity of PBQ to third-instar larvae was determined, with poisoning symptoms observed. The differences in gene expression between larvae before and after treatment with PBQ were analyzed by transcriptome sequencing to potentially involve the mechanisms of PBQ toxicity on larvae and the mechanisms of detoxification in the infected larvae. The results indicated that PBQ exposure was associated with altered expression of chitinase (CHI) and phenoloxidase (PO) genes in RPW larvae, which not only affects the digestion and degradation of the old cuticle but also activates phenoloxidase, further oxidizing tyrosine for its conversion into DOPA and dopamine, resulting in the generation of melanin and different degrees of cuticular melanization. The transcriptional changes further suggest that RPW larvae may employ metabolic processes to counteract the external immune-active compound PBQ toxicity by regulating the expression levels of detoxifying enzyme-encoding genes, such as cytochrome P450 (CYP450), glutathione S-transferase (GST), and ATP-binding cassette transporter (ABC). Our research provides potential novel strategies for pest control by targeting insect metabolic detoxification systems. Full article
(This article belongs to the Special Issue Invasive Pests: Bionomics, Damage, and Management)
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14 pages, 4062 KB  
Article
The Cytochrome P450 Enzyme SsCyp64 Mediates γ-linolenyl Alcohol in Regulating Sexual Mating/Filamentation and Pathogenicity of Sporisorium scitamineum
by Enping Cai, Bo Xiong, Qiuping Ling, Xueting Li, Xinglong Chen, Changqing Chang, Jiayun Wu and Nannan Zhang
J. Fungi 2025, 11(10), 729; https://doi.org/10.3390/jof11100729 - 10 Oct 2025
Abstract
Sugarcane smut, caused by Sporisorium scitamineum, is a devastating fungal disease of sugarcane. Sexual mating/filamentation of opposite mating types is a key step in the infection and pathogenicity of S. scitamineum, yet its regulation remains unclear. In this study, we identified [...] Read more.
Sugarcane smut, caused by Sporisorium scitamineum, is a devastating fungal disease of sugarcane. Sexual mating/filamentation of opposite mating types is a key step in the infection and pathogenicity of S. scitamineum, yet its regulation remains unclear. In this study, we identified a cytochrome P450 enzyme-encoding gene, SsCYP64, which plays an important role in oxidative stress and maintaining cell membrane stability in S. scitamineum. Further investigations revealed that deletion of SsCYP64 leads to a decrease in the transcriptional level of SsPRF1, a key transcription factor regulating the sexual mating of S. scitamineum. Subsequently, the constitutive expression of SsPRF1 restored the defect in sexual mating/filamentation of the SsCYP64 deletion mutant, indicating that SsCyp64 regulates the sexual reproduction of S. scitamineum by mediating the transcriptional level of SsPRF1. In addition, metabolomic analysis revealed that the fatty alcohol metabolite γ-linolenyl alcohol significantly decreased in the SsCYP64 deletion mutant, whereas exogenous supplementation with γ-linolenyl alcohol increased the transcriptional level of SsPRF1 and partially restored the sexual mating/filamentation of the SsCYP64 deletion mutant. In conclusion, our results indicated that SsCyp64 mediated the transcription of SsPRF1 by modulating γ-linolenyl alcohol levels, thereby regulating the formation of dikaryotic hyphae in S. scitamineum. These findings provide new insights into the role of cytochrome P450 enzymes in the pathogenic process of plant pathogenic fungi. Full article
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12 pages, 2020 KB  
Article
Molecular-Genetic Research of Rhodococcus rhodochrous IEGM 1362, an Active (–)-Isopulegol Biotransformer
by Polina Y. Maltseva, Natalia A. Plotnitskaya and Irina B. Ivshina
Molecules 2025, 30(19), 3976; https://doi.org/10.3390/molecules30193976 - 3 Oct 2025
Viewed by 280
Abstract
The present study aimed to identify genes encoding enzymes involved in the biotransformation of monoterpenoid (–)-isopulegol by Rhodococcus rhodochrous IEGM 1362. This strain is able to transform (–)-isopulegol with formation of two novel metabolites with promising antitumor and analeptic activities. Cell fractions of [...] Read more.
The present study aimed to identify genes encoding enzymes involved in the biotransformation of monoterpenoid (–)-isopulegol by Rhodococcus rhodochrous IEGM 1362. This strain is able to transform (–)-isopulegol with formation of two novel metabolites with promising antitumor and analeptic activities. Cell fractions of rhodococci and specific inhibitor of cytochrome P450-dependent oxygenase activity were used to establish the localization and type of biotransformation enzymes. The expression of nine CYP450 genes selected by bioinformatics analysis was analyzed by quantitative real-time PCR (qRT-PCR). Selection of optimal reference genes for normalization of qRT-PCR results was performed using BestKeeper, Normfinder, geNorm, Delta CT, and RefFinder algorithms. As a result of these studies, the role of CYP450 enzyme complexes in the biotransformation of (–)-isopulegol was confirmed, and their cytoplasmic localization was established. The genes encoding DNA gyrase subunit B (gyrB) and protein translocase subunit A (secA) were selected as the most stable reference genes. The induced expression of the gene encoding CYP450 hydroxylase in the presence of (–)-isopulegol was determined. The obtained data allow us to identify the specific CYP450 enzyme involved in (–)-isopulegol biotransformation by R. rhodochrous IEGM 1362 and lay the foundation for further studies of molecular and genetic mechanisms of monoterpenoid biotransformation. Full article
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19 pages, 4146 KB  
Article
Ultrastructure and Transcriptome Analysis Reveal Sexual Dimorphism in the Antennal Chemosensory System of Blaptica dubia
by Yu Zhang, Liming Liu, Haiqi Zhao, Jiabin Luo and Lina Guo
Insects 2025, 16(10), 1024; https://doi.org/10.3390/insects16101024 - 3 Oct 2025
Viewed by 396
Abstract
This study distinguished male and female individuals by wing morphology (males with long wings, females with short wings) and investigated sexual dimorphism in the chemosensory system of Blaptica dubia through integrated ultrastructural and transcriptomic analyses. Scanning electron microscopy (SEM) was used to characterize [...] Read more.
This study distinguished male and female individuals by wing morphology (males with long wings, females with short wings) and investigated sexual dimorphism in the chemosensory system of Blaptica dubia through integrated ultrastructural and transcriptomic analyses. Scanning electron microscopy (SEM) was used to characterize the type, number, and distribution of antennal sensilla, while Illumina HiSeq sequencing, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) annotation, and Quantitative Real-time Reverse Transcription Polymerase Chain Reaction (qRT-PCR) validation were employed to analyze sex-specific gene expression profiles. Both sexes exhibited Böhm’s bristles, chaetic, trichoid, and basiconic sensilla. Males showed significantly more chaetic sensilla on the pedicel and longer type I/II chaetic sensilla on the flagellum, whereas females had longer ST2 sensilla. Basiconic sensilla were predominantly flagellar-distributed and more abundant/longer in males. No sexual differences were observed in Böhm’s bristles. Transcriptomics revealed 5664 differentially expressed genes (DEGs) (2541 upregulated; 3123 downregulated), enriched in oxidation-reduction, extracellular space, lysosome, and glutathione metabolism. KEGG analysis identified five key pathways: lysosome, glutathione metabolism, cytochrome P450-mediated xenobiotic/drug metabolism, and ascorbate/aldarate metabolism. Among 11 chemosensory-related DEGs, chemosensory proteins (CSPs) and odorant binding proteins (OBPs) were downregulated in males, while gustatory receptors (GRs), olfactory receptors (Ors), and ionotropic receptors (IRs) were upregulated. These results demonstrate profound sexual dimorphism in both antennal sensilla morphology and chemosensory gene expression, suggesting divergent sex-specific chemical communication strategies in Blaptica dubia, with implications for understanding adaptive evolution in Blattodea. Full article
(This article belongs to the Section Insect Molecular Biology and Genomics)
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18 pages, 1779 KB  
Article
Blackgrass (Alopecurus myosuroides Huds.) Multiple Resistance to ACCase- and ALS-Inhibitors and Its Competition with Winter Wheat
by Aristeidis P. Papapanagiotou, Ioannis Vasilakoglou, Maria V. Alvanou, Ioannis A. Giantsis, Panagiotis Madesis and Ilias G. Eleftherohorinos
Genes 2025, 16(10), 1169; https://doi.org/10.3390/genes16101169 - 3 Oct 2025
Viewed by 230
Abstract
Background/Objectives: The herbicide resistance of blackgrass (Alopecurus myosuroides Huds.) is one of the most serious problems in the winter cereal monoculture in Europe. Recently, Greek farmers expressed complaints of reduced susceptibility of this weed to winter wheat herbicides. Keeping this in mind, [...] Read more.
Background/Objectives: The herbicide resistance of blackgrass (Alopecurus myosuroides Huds.) is one of the most serious problems in the winter cereal monoculture in Europe. Recently, Greek farmers expressed complaints of reduced susceptibility of this weed to winter wheat herbicides. Keeping this in mind, this study focused on the investigation of blackgrass resistance to herbicides at both phenotypic and molecular levels. Methods: Whole-plant rate-response pot assays were conducted to study the possible evolution of resistance (cross- or multiple-resistance) in a blackgrass population to ACCase- and ALS-inhibiting herbicides. Analysis of the ACCase gene sequence, herbicide metabolism study and competition with winter wheat studies were also conducted. Results: High levels of cross-resistance mainly to the ACCase post-emergence clodinafop-propargyl, medium to fenoxaprop-P-ethyl, cycloxydim, pinoxaden, as well as lower levels of resistance to ALS-inhibitors (mesosulfuron-methyl + iodosulfuron-methyl-sodium and pyroxsulam) were confirmed. In addition, the pre-emergence soil-applied herbicides chlorotoluron + diflufenican and prosulfocarb provided excellent control of the S and R blackgrass populations. The analysis of the ACCase gene sequence revealed a point mutation at position 1781, resulting in an amino acid substitution from isoleucine (Ile) to leucine (Leu). Furthermore, the combined application of the herbicides with piperonyl butoxide (PBO, applied 2 h before herbicide application) indicated that there was herbicide metabolism, which may be mediated by cytochrome P450. The R blackgrass population, when grown in competitive interaction with winter wheat, produced more tillers and aboveground fresh weight compared to the S population and caused greater reduction in winter wheat. Conclusions: The results suggest that a blackgrass population has developed multiple resistance to ACCase- and ALS-inhibiting herbicides, due to ACCase gene mutation and herbicide metabolism. No fitness cost and no compromised competitive ability associated with the blackgrass resistance were observed. Full article
(This article belongs to the Special Issue Forage and Grass Genetics and Genomics)
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20 pages, 3824 KB  
Article
Spatial Transcriptomics Reveals Distinct Architectures but Shared Vulnerabilities in Primary and Metastatic Liver Tumors
by Swamy R. Adapa, Sahanama Porshe, Divya Priyanka Talada, Timothy M. Nywening, Mattew L. Anderson, Timothy I. Shaw and Rays H. Y. Jiang
Cancers 2025, 17(19), 3210; https://doi.org/10.3390/cancers17193210 - 1 Oct 2025
Viewed by 569
Abstract
Background: Primary hepatocellular carcinoma (HCC) and liver metastases differ in origin, progression, and therapeutic response, yet a direct high-resolution spatial comparison of their tumor microenvironments (TMEs) within the liver has not previously been performed. Methods: We applied high-definition spatial transcriptomics to [...] Read more.
Background: Primary hepatocellular carcinoma (HCC) and liver metastases differ in origin, progression, and therapeutic response, yet a direct high-resolution spatial comparison of their tumor microenvironments (TMEs) within the liver has not previously been performed. Methods: We applied high-definition spatial transcriptomics to fresh-frozen specimens of one HCC and one liver metastasis (>16,000 genes per sample, >97% mapping rates) as a proof-of-principle two-specimen study, cross-validated in human proteomics and patients’ survival datasets. Transcriptional clustering revealed spatially distinct compartments, rare cell states, and pathway alterations, which were further compared against an independent systemic dataset. Results: HCC displayed an ordered lineage architecture, with transformed hepatocyte-like tumor cells broadly dispersed across the tissue and more differentiated hepatocyte-derived cells restricted to localized zones. By contrast, liver metastases showed two sharply compartmentalized domains: an invasion zone, where proliferative stem-like tumor cells occupied TAM-rich boundaries adjacent to hypoxia-adapted tumor-core cells, and a plasticity zone, which formed a heterogeneous niche of cancer–testis antigen–positive germline-like cells. Across both tumor types, we detected a conserved metabolic program of “porphyrin overdrive,” defined by reduced cytochrome P450 expression, enhanced oxidative phosphorylation gene expression, and upregulation of FLVCR1 and ALOX5, reflecting coordinated rewiring of heme and lipid metabolism. Conclusions: In this pilot study, HCC and liver metastases demonstrated fundamentally different spatial architectures, with metastases uniquely harboring a germline/neural-like plasticity hub. Despite these organizational contrasts, both tumor types converged on a shared program of metabolic rewiring, highlighting potential therapeutic targets that link local tumor niches to systemic host–tumor interactions. Full article
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18 pages, 3197 KB  
Article
Transcriptome Analysis Revealed the Molecular Mechanism of Cyanogenic Glycoside Synthesis in Flax
by Xixia Song, Jinhao Zhang, Lili Tang, Hongmei Yuan, Dandan Yao, Weidong Jiang, Guangwen Wu, Lili Cheng, Dandan Liu, Lie Yang, Zhongyi Sun, Caisheng Qiu, Jian Zhang, Liuxi Yi and Qinghua Kang
Agronomy 2025, 15(10), 2327; https://doi.org/10.3390/agronomy15102327 - 1 Oct 2025
Viewed by 230
Abstract
This study aims to elucidate the molecular mechanisms underlying cyanogenic glycoside accumulation in flax. As an important oil and fiber crop, the nutritional value of flax is compromised by the toxicity of cyanogenic glycoside. To clarify the key genetic regulators and temporal patterns [...] Read more.
This study aims to elucidate the molecular mechanisms underlying cyanogenic glycoside accumulation in flax. As an important oil and fiber crop, the nutritional value of flax is compromised by the toxicity of cyanogenic glycoside. To clarify the key genetic regulators and temporal patterns of cyanogenic glycoside biosynthesis, transcriptomic sequencing was performed on seeds from high- and low-cyanogenic glycoside flax varieties (‘MONTANA16’ and ‘Xilibai’) at three developmental stages: bud stage, full flowering stage, and capsule-setting stage. A total of 127.25 Gb of high-quality data was obtained, with an alignment rate exceeding 87.80%. We identified 31,623 differentially expressed genes (DEGs), which exhibited distinct variety- and stage-specific expression patterns. Principal component analysis (PCA) and hierarchical clustering demonstrated strong reproducibility among biological replicates and revealed the seed pod formation stage as the period with the most significant varietal differences, suggesting it may represent a critical regulatory window for cyanogenic glycoside synthesis. GO and KEGG enrichment analyses indicated that DEGs were primarily involved in metabolic processes (including secondary metabolism and carbohydrate metabolism), oxidoreductase activity, and transmembrane transport functions. Of these, the cytochrome P450 pathway was most significantly enriched at the full bloom stage (H2 vs. L2). A total of 15 LuCYP450 and 13 LuUGT85 family genes were identified, and their expression patterns were closely associated with cyanogenic glycoside accumulation: In high-cyanogenic varieties, LuCYP450-8 was continuously upregulated, and LuUGT85-12 was significantly activated during later stages. Conversely, in low-cyanogenic varieties, high expression of LuCYP450-2/14 may inhibit synthesis. These findings systematically reveal the genetic basis and temporal dynamics of cyanogenic glycoside biosynthesis in flax and highlight the seed pod formation stage as a decisive regulatory window for cyanogenic glycoside synthesis. This study provides new insights into the coordinated regulation of cyanogenic pathways and establishes a molecular foundation for breeding flax varieties with low CNG content without compromising agronomic traits. Full article
(This article belongs to the Section Plant-Crop Biology and Biochemistry)
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23 pages, 10573 KB  
Article
Exposure to Bisphenol B and S Increases the Risk of Male Reproductive Dysfunction in Middle Age
by Sen Zhao, Heliang Ni, Yuan Xiao, Jing Du, Yudong Han, Wenying Wang, Shuang Tang and Mingxi Yu
Int. J. Mol. Sci. 2025, 26(19), 9507; https://doi.org/10.3390/ijms26199507 - 28 Sep 2025
Viewed by 418
Abstract
Accumulating evidence indicates that bisphenol A (BPA) analogs, including bisphenol B (BPB) and bisphenol S (BPS), disrupt testicular function and contribute to male reproductive dysfunction (MRD). However, whether BPA analogs are involved in MRD among middle-aged men remains inconclusive. Therefore, we selected cryptorchidism, [...] Read more.
Accumulating evidence indicates that bisphenol A (BPA) analogs, including bisphenol B (BPB) and bisphenol S (BPS), disrupt testicular function and contribute to male reproductive dysfunction (MRD). However, whether BPA analogs are involved in MRD among middle-aged men remains inconclusive. Therefore, we selected cryptorchidism, erectile dysfunction, premature ejaculation, and testicular tumors as representative MRD conditions in middle-aged individuals, aiming to explore the molecular mechanisms that may be disrupted by bisphenols (BPs). By using GeneCards, STRING and Cytoscape, TP53, AKT1, and MYC were pinpointed as core targets associated with MRD. Enrichment analysis suggested that BPs may induce MRD by disrupting steroidogenesis. UPLC-MS/MS analysis showed that both BPB and BPS exhibit specific accumulation in the testes. Following 20-day exposure to 0.3 or 0.6 mg/kg body weight/day BPB or BPS, testosterone levels and the expression of hub genes were decreased. The molecular docking results demonstrated that both BPB and BPS can directly bind to members of the cytochrome P450 family, potentially interfering with sex hormone biosynthesis. Our study identified the targets and mechanisms through which BPB and BPS induce MRD in middle-aged males, thereby providing insights for the safety assessment of BPs. Full article
(This article belongs to the Special Issue Molecular Biology of Human Reproduction)
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20 pages, 2231 KB  
Article
A Cytochrome P450 Facilitates Polyethylene Metabolism in a Microbial Community
by Madelyn Tarara, Shivani Ahuja and Jay L. Mellies
Int. J. Mol. Sci. 2025, 26(18), 8775; https://doi.org/10.3390/ijms26188775 - 9 Sep 2025
Viewed by 810
Abstract
The synthetic polymer low-density polyethylene (LDPE) is a pervasive pollutant that poses serious environmental concerns and health hazards. PE plastic is rarely recycled, and therefore, biodegradation is a novel approach for managing PE plastic waste. However, few enzymes and organisms that degrade PE [...] Read more.
The synthetic polymer low-density polyethylene (LDPE) is a pervasive pollutant that poses serious environmental concerns and health hazards. PE plastic is rarely recycled, and therefore, biodegradation is a novel approach for managing PE plastic waste. However, few enzymes and organisms that degrade PE plastic have been identified to date. Herein, we demonstrate that a consortium of soil bacteria containing Pseudomonas and Bacillus species can grow on and degrade UV-treated PE film and powder as a sole carbon source, reducing its net mass by 7% and 13%, respectively, in 30 days. Changes in surface functional groups associated with chemical modification of PE were observed via ATR-FTIR analysis, and byproducts associated with PE biodegradation and alkane and carboxylic acid metabolism were observed via GC/MS. Using previously characterized PEases, we identified a gene, CYP102 A5, found in Bacillus thuringiensis strain 9.1, which encodes a cytochrome P450 reductase, whose expression was increased when grown on PE as a sole carbon source. Purified CYP102 A5 protein altered PE surface functional groups, determined by ATR-FTIR, giving evidence of PE oxidation. In sum, we identified a cytochrome P450 reductase that explains, in part, how a consortium of soil bacteria can grow on and degrade PE plastic. Full article
(This article belongs to the Special Issue The Characterization and Application of Enzymes in Bioprocesses)
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40 pages, 543 KB  
Review
Dietary Modulation of CYP3A4 and Its Impact on Statins and Antidiabetic Drugs: A Narrative Review
by Manuel Hernández-Lorca, Isabel M. Timón, Pura Ballester, Paula Henarejos-Escudero, Ana María García-Muñoz, Desirée Victoria-Montesinos and Pablo Barcina-Pérez
Pharmaceuticals 2025, 18(9), 1351; https://doi.org/10.3390/ph18091351 - 9 Sep 2025
Viewed by 1990
Abstract
Cytochrome P450 3A4 (CYP3A4) is a key enzyme involved in the metabolism of nearly half of all clinically used drugs, including widely prescribed statins and antidiabetic agents. Dietary constituents can modulate CYP3A4 expression and activity through various mechanisms, thereby altering drug pharmacokinetics and [...] Read more.
Cytochrome P450 3A4 (CYP3A4) is a key enzyme involved in the metabolism of nearly half of all clinically used drugs, including widely prescribed statins and antidiabetic agents. Dietary constituents can modulate CYP3A4 expression and activity through various mechanisms, thereby altering drug pharmacokinetics and potentially leading to therapeutic failure or toxicity. This narrative review compiles current evidence on dietary modulation of CYP3A4, with a particular focus on pharmacological and clinical implications for lipid-lowering and glucose-lowering drugs. Literature was identified through a comprehensive search in PubMed, Scopus, and Web of Science, including preclinical and clinical studies addressing food–drug interactions involving CYP3A4 substrates. Numerous dietary compounds, such as citrus furanocoumarins, polyphenols, herbal extracts, and vitamins, act as CYP3A4 inhibitors or inducers through competitive, mechanism-based, or nuclear receptor-mediated pathways. Specific examples include simvastatin, atorvastatin, repaglinide, and saxagliptin, whose systemic exposure can be significantly altered by dietary factors. Moreover, interindividual variability in CYP3A4 activity may be shaped by genetic polymorphisms, microbiota-derived metabolites, and epigenetic regulation, further influencing drug response. Understanding these interactions is crucial, especially in polymedicated patients or those receiving drugs with a narrow therapeutic index. Clinicians should remain aware of potential CYP3A4-related food–drug interactions and consider dietary habits and supplement use in therapeutic decision-making. Future research should aim to integrate pharmacogenomics, gut microbiome profiling, and personalized nutrition in order to improve the prediction and prevention of clinically significant interactions. Full article
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29 pages, 464 KB  
Review
Antioxidant Potential of Pollen Polyphenols in Mitigating Environmental Stress in Honeybees (Apis mellifera)
by Ivana Tlak Gajger and Aleksandar Cvetkovikj
Antioxidants 2025, 14(9), 1086; https://doi.org/10.3390/antiox14091086 - 5 Sep 2025
Viewed by 1023
Abstract
Honeybee populations are increasingly threatened by various environmental stressors, including pesticides, pathogens, and climate change. Emerging research highlights the vital role of pollen polyphenols in supporting honeybee health through a network of antioxidants, immune responses, and detoxification mechanisms. This review synthesizes current findings [...] Read more.
Honeybee populations are increasingly threatened by various environmental stressors, including pesticides, pathogens, and climate change. Emerging research highlights the vital role of pollen polyphenols in supporting honeybee health through a network of antioxidants, immune responses, and detoxification mechanisms. This review synthesizes current findings on the chemical diversity, bioactivity, and functional relevance of polyphenolic compounds in honeybee nutrition. Pollen polyphenols, which include flavonoids and phenolic acids, possess remarkably high antioxidant potential, up to 235 times greater than that of nectar. They also significantly increase the expression of antioxidant enzymes, immune system genes, and detoxification pathways such as cytochrome P450s and glutathione-S-transferases. These compounds also demonstrate antimicrobial effects against key pathogens and mitigate the toxic effects of pesticides. The content and composition of polyphenols vary seasonally and geographically, impacting the resilience of honeybee colonies. Field and laboratory studies confirm that polyphenol-rich diets improve survival, gland development, and stress resistance. Advanced analytical techniques, including metabolomics, have expanded our understanding of polyphenol profiles and their effects on honeybee physiology. However, knowledge gaps remain in pharmacokinetics and structure–function relationships. Integrating this evidence into conservation strategies and good beekeeping practices, such as habitat diversification and targeted feed supplementation, is crucial for maintaining honeybee health and ecosystem services in a rapidly changing environment. Full article
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16 pages, 2861 KB  
Article
Comparative Transcriptome Analysis Reveals Epithelial Growth Factor Receptor (EGFR) Pathway and Secreted C-Type Lectins as Essential Drivers of Leg Regeneration in Periplaneta americana
by Xiaoxuan Liu, Nan Sun, Xiaojuan Wu, Jiajia Wu, Shuqi Xian, Dayong Wang and Yechun Pei
Insects 2025, 16(9), 934; https://doi.org/10.3390/insects16090934 - 5 Sep 2025
Viewed by 670
Abstract
The American cockroach (Periplaneta americana) serves as an exemplary model for regeneration research due to its exceptional regenerative capabilities, particularly in appendage regeneration. In this study, regenerated coxa tissue underwent histological analysis through H & E straining. Microscopic examination revealed the [...] Read more.
The American cockroach (Periplaneta americana) serves as an exemplary model for regeneration research due to its exceptional regenerative capabilities, particularly in appendage regeneration. In this study, regenerated coxa tissue underwent histological analysis through H & E straining. Microscopic examination revealed the progression of regeneration. To elucidate the underlying mechanisms, a comparative transcriptomic analysis was conducted between regenerating legs and non-amputated control legs. This analysis identified 2343 differentially expressed genes (DEGs) between 0 days post-amputation (0 dpa) and 7 dpa, 2963 DEGs between 14 dpa and 0 dpa, and 3135 DEGs between 14 dpa and 7 dpa. Significantly, several DEGs are associated with growth- or regeneration-related processes, including extracellular matrix (different collagen, Pro-resilin isoforms, integrin beta (itgb) and matrix metalloproteinase (mmp)), immune-related genes (Toll-like receptor 13 (tlr13), defensin (def), drosomycin-like defensin (dld), Polyphenoloxidases2 (ppo2), cytochrome P450 (p450), peptidoglycan recognition protein (pgrp) and secreted C-type lectin (sClec)), insulin-like growth factor (IGF) and Epidermal Growth Factor Receptor (EGFR). Functional validation through RNA interference (RNAi) further suggested that EGFR and a specific C-type lectin (Regenectin) regulate leg regeneration in Periplaneta americana. These findings enhance our understanding of the molecular mechanisms governing regeneration in this species. Full article
(This article belongs to the Special Issue Insect Transcriptomics)
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29 pages, 7913 KB  
Article
Synthesis, Characterization, and Screening Anticancer—Antibiofilm Activities of Theophylline Derivatives Containing CF3/OCF3 Moiety
by Serpil Demir Düşünceli, Kübra Açıkalın Coşkun, Murat Kaloğlu, Elvan Üstün, Reyhan Çalışkan and Yusuf Tutar
Biology 2025, 14(9), 1180; https://doi.org/10.3390/biology14091180 - 2 Sep 2025
Viewed by 651
Abstract
Background: Theophylline, which is biologically important and found in tea, coffee, and cocoa beans, can be synthesized chemically or by direct extraction and concentration from natural sources. Theophylline derivatives have garnered attention in recent years for their potential therapeutic effects on Mycobacterium tuberculosis [...] Read more.
Background: Theophylline, which is biologically important and found in tea, coffee, and cocoa beans, can be synthesized chemically or by direct extraction and concentration from natural sources. Theophylline derivatives have garnered attention in recent years for their potential therapeutic effects on Mycobacterium tuberculosis, antihistaminic, anti-inflammatory, and anticancer. Also, trifluoromethyl (CF3) group has also been widely used in drug and agrochemical design. Methods: In this study, a series of new theophylline derivatives containing substituted trifluoromethyl and trifluoromethoxy groups were synthesized. The structures of these new compounds were confirmed by NMR, FT-IR, and elemental analyses. Additionally, the anticancer activities of the molecules were analyzed against VEGFR-2, CYP P450, and estrogen receptor by molecular docking method. Furthermore, in vitro biological effects of the compounds were comprehensively evaluated in cancer (A549 and HeLa) and normal (BEAS-2B) cells. Cell viability was assessed by MTT assay, and selectivity index (SI) values were calculated to determine tumor-specific toxicity. Results: N(7)-substituted theophyllines were prepared by the reaction of 1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (theophylline) and trifluoromethyl substituted benzyl halide compounds. The synthesized N(7)-substituted theophyllines were obtained as white powder in high yield. The structure of synthesized compounds was confirmed by various spectroscopic techniques such as 1H, 13C, 19F NMR, and FT-IR spectroscopy, and elemental analysis. The highest interaction was recorded as −5.69 kcal/mol for 3-CF3 substituted against VEGFR-2 structure while the best binding affinity was determined for 4-OCF3 substituted with −6.69 kcal/mol against Human Cytochrome P450 with in silico analysis. The in vitro anticancer activities of the molecules were also evaluated against A549 and HeLa cells, and displayed considerably higher cytotoxicity with 2-CF3, 3-CF3, and 4-CF3 substituted molecules in Hela and A549 cell line. To elucidate the molecular mechanism, apoptosis-related gene expression changes were analyzed by RT-qPCR in A549 and HeLa cells treated with compound 2-CF3. Significant upregulation of pro-apoptotic markers and downregulation of anti-apoptotic genes were observed. Consistently, ELISA-based quantification confirmed increased protein levels of Caspase-3, BAX, and Cytochrome C, and decreased BCL-2, validating the apoptotic mechanism at the protein level. Also, the antibacterial and antibiofilm activity details of the molecules were evaluated against DNA Gyrase, and SarA crystal structures by molecular docking method. The highest interaction was recorded as −5.56 kcal/mol for 2-CF3 substituted with H-bonds with Asn46, Val71, Asp73, and Thr165 against DNA Gyrase crystal structure while 3-CF3 substituted has the best binding affinity against SarA. The in vitro antimicrobial effects of the molecules were also evaluated. Conclusions: The synthesized molecules may provide insight into the development of potential therapeutic agents to the increasing antimicrobial resistance and biofilm-forming capacity of microorganisms. Additionally, compound 2-CF3 substituted exhibited promising and selective anticancer activity through apoptosis induction, supported by gene and protein level evidence. Full article
(This article belongs to the Topic Advances in Anti-Cancer Drugs: 2nd Edition)
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28 pages, 2035 KB  
Review
Molecular Aspects of Geriatric Pharmacotherapy
by Patryk Rzeczycki, Oliwia Pęciak, Martyna Plust and Marek Droździk
Cells 2025, 14(17), 1363; https://doi.org/10.3390/cells14171363 - 1 Sep 2025
Viewed by 973
Abstract
Pharmacotherapy in the geriatric population is one of the greatest challenges in modern medicine. Elderly patients, characterized by multimorbidity and the resulting polypharmacy, are significantly more exposed to adverse drug reactions (ADRs), which often lead to hospitalization and a decline in quality of [...] Read more.
Pharmacotherapy in the geriatric population is one of the greatest challenges in modern medicine. Elderly patients, characterized by multimorbidity and the resulting polypharmacy, are significantly more exposed to adverse drug reactions (ADRs), which often lead to hospitalization and a decline in quality of life. Understanding the reasons for this difference requires an analysis of the physiological changes that occur during the aging process at the molecular level. This article presents a perspective on the molecular aspects of geriatric pharmacotherapy, focusing on the fundamental mechanisms that are modified with age. The analysis covers changes in pharmacokinetics, including the role and regulation of cytochrome P450 (CYP) enzymes, whose activity, especially in phase I reactions, is significantly reduced. The age-dependent dysfunction of drug transporters from the ABC (ATP-binding cassette) and SLC (solute carrier) families in key organs such as the intestines, liver and kidneys is discussed, which affects the absorption, distribution and elimination of xenobiotic compounds, including drugs. The article also provides a comprehensive analysis of the blood–brain barrier (BBB), describing changes in neurovascular integrity, including the dysfunction of tight junctions and a decrease in the activity of P-glycoprotein, sometimes referred to as multidrug resistance protein (MDR). This increases the susceptibility of the central nervous system to the penetration and action of drugs. In the realm of pharmacodynamics, changes in the density and sensitivity of key receptors (serotonergic, dopaminergic, adrenergic) are described based on neuroimaging data, explaining the molecular basis for increased sensitivity to certain drug classes, such as anticholinergics. The paper also explores new research perspectives, such as the role of the gut microbiome in modulating pharmacokinetics by influencing gene expression and the importance of pharmacoepigenetics, which dynamically regulates drug response throughout life via changes in DNA methylation and histone modifications. The clinical implications of these molecular changes are also discussed, emphasizing the potential of personalized medicine, including pharmacogenomics, in optimizing therapy and minimizing the risk of adverse reactions. Such an integrated approach, incorporating data from multiple fields (genomics, epigenomics, microbiomics) combined with a comprehensive geriatric assessment, appears to be the future of safe and effective pharmacotherapy in the aging population. Full article
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Article
In Silico Analysis of Two Hard Tick P450s: Identification, Characterization, and Putative Metabolism of Cymbopogon citratus Essential Oil Constituents
by Caishan Li, Licui Wen, Wenyu Shi, Yuqian Deng, Na Zhou, Xueqing Zhao, Qingyong Guo and Bayinchahan Gailike
Int. J. Mol. Sci. 2025, 26(17), 8489; https://doi.org/10.3390/ijms26178489 - 1 Sep 2025
Viewed by 496
Abstract
The cytochrome p450 gene family is widely involved in various biological processes in arthropods. Tick p450s are often associated with chemical acaricides, but knowledge of their involvement in the metabolism of plant-derived essential oil components is limited. In this study, we identified the [...] Read more.
The cytochrome p450 gene family is widely involved in various biological processes in arthropods. Tick p450s are often associated with chemical acaricides, but knowledge of their involvement in the metabolism of plant-derived essential oil components is limited. In this study, we identified the non-redundant number of p450 transcripts (NRNPTs) from Haemaphysalis longicornis and Hyalomma asiaticum under the Cymbopogon citratus essential oil (CCEO) and terpinolene stress using de novo transcriptome data, respectively. In this study, we identified and characterized the NRNPTs of Ha. longicornis and Hy. asiaticum. Their gene expression patterns and biological functions under CCEO and terpinolene stress were further analyzed. Finally, Hy. asiaticum NRNPTs (87) were more numerous than Ha. longicornis (58). Phylogenetic analyses showed that NRNPTs of both Hy. asiaticum and Ha. longicornis could be categorized in clan 2, clan 3, clan 4, and clan mito, this data comes from the NRNPTs. Phylogenetic analyses showed that NRNPTs of both Hy. asiaticum and Ha. longicornis could be categorized in clan 2, clan 3, clan 4, and clan mito. p450 members of both were most distributed in clan 3. In addition, one Hy. asiaticum NRNPT was identified as belonging to the new classification clan 20 (HyasCYP20A1). The biological functions and pathways of p450 family members enriched in Hy. asiaticum and Ha. longicornis under different exogenous substance stresses were different, and the expression patterns of these genes were inconsistent. Molecular docking results showed that Ha. longicornis p450 members (HaloCYP3A4 and HaloCYP4B1), which were significantly up-regulated under CCEO stress, as well as Hy. asiaticum HyasCYP24A1 and HyasCYP4V2 (the HaloCYP3A4 and HaloCYP4B1 homologous genes), encode proteins that differ in their ability to metabolize CCEO components, but they all bind well to Germacrene D and naphthalene. Our study enriches the knowledge of the involvement of p450 family members of different tick species in the metabolism of essential oil components of plants, and provides a theoretical basis for further in-depth studies on the function of tick p450 enzymes. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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