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International Journal of Molecular... Jun 2024Cytochrome P450 monooxygenases () play a variety of physiological roles, including pesticide resistance, plant allelochemical detoxification, and hormone metabolism... (Comparative Study)
Comparative Study
Cytochrome P450 monooxygenases () play a variety of physiological roles, including pesticide resistance, plant allelochemical detoxification, and hormone metabolism catalysis. However, limited information is available on the classification and expression profiles of the gene family in aphid species. This is the first study to identify the cytochrome P450 gene family in 19 aphid species at the whole genome level. A total of 1100 genes were identified in 19 aphid species. Three hundred genes belonged to six cereal crop aphid species, which were further classified into four subfamilies according to the phylogenetic relationship. The conserved motifs, exon-intron structures, and genomic organization of the same subfamilies were similar. Predictions of subcellular localization revealed that the endoplasmic reticulum harbored the majority of CYP450 proteins. In and , the increase in the gene was primarily caused by segmental duplication events. However, only tandem duplication occurred in the gene family of , , and . Synteny analysis found three continuous colinear gene pairs among six cereal crop aphid species. Furthermore, we obtained the expression profiles of four cereal crop aphids, including , , and . Differential expression analysis provided growth stage specificity genes, tissue specificity genes, organ specificity genes and some detoxification metabolic genes among these four cereal crop aphids. Meanwhile, their expression patterns were showed. The related functions and pathways of were revealed by GO and KEGG enrichment analysis. Above all, we picked the differentially expressed genes from all of the differentially expressed genes (DEGs). These differentially expressed genes provided some new potential candidates for aphid control and management. This work establishes the foundation for further investigations into the regulatory functions of the gene family in aphid species and beyond.
Topics: Aphids; Animals; Cytochrome P-450 Enzyme System; Phylogeny; Multigene Family; Edible Grain; Genome, Insect; Gene Expression Profiling; Synteny; Insect Proteins
PubMed: 38928374
DOI: 10.3390/ijms25126668 -
International Journal of Molecular... Jun 2024Abscisic acid (ABA) plays a crucial role in plant defense mechanisms under adverse environmental conditions, but its metabolism and perception in response to heavy...
Abscisic acid (ABA) plays a crucial role in plant defense mechanisms under adverse environmental conditions, but its metabolism and perception in response to heavy metals are largely unknown. In exposed to CdCl, an accumulation of free ABA was detected in leaves at different developmental stages (A, youngest, unexpanded; B1, youngest, fully expanded; B2, mature; C, old), with the highest content found in A and B1 leaves. In turn, the content of ABA conjugates, which was highest in B2 and C leaves under control conditions, increased only in A leaves and decreased in leaves of later developmental stages after Cd treatment. Based on the expression of , (9-cis-epoxycarotenoid dioxygenase), (aldehyde oxidase) and (ABA-UDP-glucosyltransferase), and the activity of PsAOγ, B2 and C leaves were found to be the main sites of Cd-induced de novo synthesis of ABA from carotenoids and ABA conjugation with glucose. In turn, β-glucosidase activity and the expression of genes encoding ABA receptors (, , , ) suggest that in A and B1 leaves, Cd-induced release of ABA from inactive ABA-glucosyl esters and enhanced ABA perception comes to the forefront when dealing with Cd toxicity. The distinct role of leaves at different developmental stages in defense against the harmful effects of Cd is discussed.
Topics: Abscisic Acid; Pisum sativum; Plant Leaves; Cadmium; Gene Expression Regulation, Plant; Plant Proteins; Dioxygenases; beta-Glucosidase
PubMed: 38928288
DOI: 10.3390/ijms25126582 -
International Journal of Molecular... Jun 2024Genetic variation among inhaled corticosteroid (ICS)-metabolizing enzymes may affect asthma control, but evidence is limited. This study tested the hypothesis that...
Genetic variation among inhaled corticosteroid (ICS)-metabolizing enzymes may affect asthma control, but evidence is limited. This study tested the hypothesis that single-nucleotide polymorphisms (SNPs) in Cytochrome P450 3A5 (CYP3A5) would affect asthma outcomes. Patients aged 2-18 years with persistent asthma were recruited to use the electronic AsthmaTracker (e-AT), a self-monitoring tool that records weekly asthma control, medication use, and asthma outcomes. A subset of patients provided saliva samples for SNP analysis and participated in a pharmacokinetic study. Multivariable regression analysis adjusted for age, sex, race, and ethnicity was used to evaluate the impact of CYP3A5 SNPs on asthma outcomes, including asthma control (measured using the asthma symptom tracker, a modified version of the asthma control test or ACT), exacerbations, and hospital admissions. Plasma corticosteroid and cortisol concentrations post-ICS dosing were also assayed using liquid chromatography-tandem mass spectrometry. Of the 751 patients using the e-AT, 166 (22.1%) provided saliva samples and 16 completed the PK study. The e-AT cohort was 65.1% male, and 89.6% White, 6.0% Native Hawaiian, 1.2% Black, 1.2% Native American, 1.8% of unknown race, and 15.7% Hispanic/Latino; the median age was 8.35 (IQR: 5.51-11.3) years. frequency was 75.8% in White subjects, 50% in Native Hawaiians and 76.9% in Hispanic/Latino subjects. Compared with , the genotype was associated with reduced weekly asthma control (OR: 0.98; 95% CI: 0.97-0.98; < 0.001), increased exacerbations (OR: 6.43; 95% CI: 4.56-9.07; < 0.001), and increased asthma hospitalizations (OR: 1.66; 95% CI: 1.43-1.93; < 0.001); analysis of , and separately showed an allelic copy effect. Finally, PK analysis post-ICS dosing suggested muted changes in cortisol concentrations for patients with the genotype, as opposed to an effect on ICS PK. Detection of , , and could impact inhaled steroid treatment strategies for asthma in the future.
Topics: Humans; Asthma; Child; Male; Female; Polymorphism, Single Nucleotide; Cytochrome P-450 CYP3A; Adolescent; Child, Preschool; Adrenal Cortex Hormones; Genotype; Hydrocortisone; Saliva; Treatment Outcome
PubMed: 38928254
DOI: 10.3390/ijms25126548 -
International Journal of Molecular... Jun 2024The objective of the study was to evaluate the profile and diagnostic significance of serum autoantibodies in infertile patients with premature ovarian insufficiency...
The objective of the study was to evaluate the profile and diagnostic significance of serum autoantibodies in infertile patients with premature ovarian insufficiency (POI). The pilot study included 26 patients of reproductive age with POI and diminished ovarian reserve who received complex treatment using new surgical technologies (Group 1) and 18 patients without POI (Group 2). The profile of serum autoantibodies, including anti-ovarian antibodies, antibodies against thyroid peroxidase (TPO), steroidogenic enzymes, and steroid and gonadotropic hormones, was studied using modified ELISAs and human recombinant steroidogenic enzymes (CYP11A1, CYP19A1, CYP21A2). Patients in Group 1 had higher levels of IgG autoantibodies against steroidogenic enzymes, estradiol, progesterone, and TPO than those in Group 2. Tests for IgG antibodies against CYP11A1, CYP19A1, and CYP21A2 exhibited high sensitivity (65.4-76.9%), specificity (83.3-89.9%), and AUC values (0.842-0.910) for POI, the highest in the first test. Three-antibodies panel screening showed higher diagnostic accuracy (84.1% versus 75-79.6%). The levels of these antibodies correlated with menstrual irregularities and a decrease in the antral follicle count. Thus, antibodies against CYP11A1, CYP19A1, and CYP21A2 have a high diagnostic value for POI. Three-antibody panel screening may improve the accuracy of POI diagnosis and be useful for identifying high-risk groups, early stages of the disease, and predicting POI progression.
Topics: Humans; Female; Autoantibodies; Primary Ovarian Insufficiency; Adult; Infertility, Female; Cholesterol Side-Chain Cleavage Enzyme; Aromatase; Steroid 21-Hydroxylase; Iodide Peroxidase; Pilot Projects; Immunoglobulin G; Biomarkers; Progesterone; Estradiol
PubMed: 38928251
DOI: 10.3390/ijms25126545 -
International Journal of Molecular... Jun 2024Hypoxia-inducible factor 1-alpha (HIF1A) is a key transcription factor aiding tumor cells' adaptation to hypoxia, regulated by the prolyl hydroxylase family (EGLN1-3) by...
Hypoxia-inducible factor 1-alpha (HIF1A) is a key transcription factor aiding tumor cells' adaptation to hypoxia, regulated by the prolyl hydroxylase family (EGLN1-3) by directing toward degradation pathways. DNA methylation potentially influences EGLN and HIF1A levels, impacting cellular responses to hypoxia. We examined 96 HNSCC patients and three cell lines, analyzing gene expression of , , , , and at the mRNA level and EGLN1 protein levels. Methylation levels of and were assessed through high-resolution melting analysis. Bioinformatics tools were employed to characterize associations between and expression and methylation. We found significantly higher mRNA levels of , , , , and ( = 0.021; < 0.0001; < 0.0001; = 0.004, and < 0.0001, respectively) genes in tumor tissues compared to normal ones and downregulation of the mRNA level in tumor tissues ( = 0.0013). In HNSCC patients with hypermethylation of in normal tissue, we noted a reduction in mRNA levels compared to tumor tissue ( = 0.04). In conclusion, the differential expression of and genes in HNSCC tumors compared to normal tissues influences patients' overall survival, highlighting their role in tumor development. Moreover, DNA methylation could be responsible for suppression in the normal tissues of HNSCC patients.
Topics: Humans; DNA Methylation; Hypoxia-Inducible Factor 1, alpha Subunit; Squamous Cell Carcinoma of Head and Neck; Female; Head and Neck Neoplasms; Male; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Hypoxia-Inducible Factor-Proline Dioxygenases; Middle Aged; Prolyl Hydroxylases; Aged; Carcinogenesis; Adult
PubMed: 38928200
DOI: 10.3390/ijms25126495 -
International Journal of Molecular... Jun 2024Physiology and behavior are structured temporally to anticipate daily cycles of light and dark, ensuring fitness and survival. Neuromodulatory systems in the...
Physiology and behavior are structured temporally to anticipate daily cycles of light and dark, ensuring fitness and survival. Neuromodulatory systems in the brain-including those involving serotonin and dopamine-exhibit daily oscillations in neural activity and help shape circadian rhythms. Disrupted neuromodulation can cause circadian abnormalities that are thought to underlie several neuropsychiatric disorders, including bipolar mania and schizophrenia, for which a mechanistic understanding is still lacking. Here, we show that genetically depleting serotonin in knockout mice promotes manic-like behaviors and disrupts daily oscillations of the dopamine biosynthetic enzyme tyrosine hydroxylase (TH) in midbrain dopaminergic nuclei. Specifically, while TH mRNA and protein levels in the Substantia Nigra (SN) and Ventral Tegmental Area (VTA) of wild-type mice doubled between the light and dark phase, TH levels were high throughout the day in knockout mice, suggesting a hyperdopaminergic state. Analysis of TH expression in striatal terminal fields also showed blunted rhythms. Additionally, we found low abundance and blunted rhythmicity of the neuropeptide cholecystokinin (Cck) in the VTA of knockout mice, a neuropeptide whose downregulation has been implicated in manic-like states in both rodents and humans. Altogether, our results point to a previously unappreciated serotonergic control of circadian dopamine signaling and propose serotonergic dysfunction as an upstream mechanism underlying dopaminergic deregulation and ultimately maladaptive behaviors.
Topics: Animals; Serotonin; Mice; Mice, Knockout; Circadian Rhythm; Dopamine; Tyrosine 3-Monooxygenase; Tryptophan Hydroxylase; Ventral Tegmental Area; Cholecystokinin; Dopaminergic Neurons; Male; Substantia Nigra; Mice, Inbred C57BL; Bipolar Disorder
PubMed: 38928178
DOI: 10.3390/ijms25126475 -
International Journal of Molecular... Jun 2024We present a case involving a patient whose clinical phenotype aligns with oculocutaneous albinism (OCA), yet exhibits a complex genotype primarily characterized by...
We present a case involving a patient whose clinical phenotype aligns with oculocutaneous albinism (OCA), yet exhibits a complex genotype primarily characterized by variants of unknown significance (VUS). An 11-year-old boy manifested iris hypopigmentation and translucency, pronounced photophobia, diminished visual acuity and stereopsis, nystagmus, reduced pigmentation of the retina, and foveal hypoplasia. Genetic testing was performed. A heterozygous missense VUS c.230A>G, p.(Gln77Arg), a heterozygous missense VUS c.1307G>C, p.(Gly436Ala), and a heterozygous missense variant c.1205G>A, p.(Arg402Gln) which was classified as a risk factor, were identified. We hypothesized that the c.1307G>C, p.(Gly436Ala) variant is in genetic disequilibrium with the c.1205G>A, p.(Arg402Gln) variant leading to deficient expression of melanogenic enzymes in retinal cells, resulting in the manifestation of mild OCA. Additionally, this study represents the case where we did not detect chiasmal misrouting in visual evoked potentials, nor did we observe a shift in the distribution of ganglion cell thickness from a temporal to a central position. Moreover, our patient's case supports the probable benign nature of the c.230A>G, p.(Gln77Arg) variant.
Topics: Humans; Male; Child; Calpain; Monophenol Monooxygenase; Mutation, Missense; Vitreoretinopathy, Proliferative; Albinism, Oculocutaneous; Phenotype; Pedigree
PubMed: 38928147
DOI: 10.3390/ijms25126442 -
International Journal of Molecular... Jun 2024Leptin regulates lipid metabolism, maximizing insulin sensitivity; however, peripheral leptin resistance is not fully understood, and its contribution to metabolic...
Leptin regulates lipid metabolism, maximizing insulin sensitivity; however, peripheral leptin resistance is not fully understood, and its contribution to metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. This study evaluated the contribution of the leptin axis to MASLD in humans. Forty-three participants, mostly female (86.04%), who underwent cholecystectomy were biopsied. Of the participants, 24 were healthy controls, 8 had MASLD, and 11 had metabolic dysfunction-associated steatohepatitis (MASH). Clinical and biochemical data and the gene expression of leptin, leptin receptor (), suppressor of cytokine signaling 3 (), sterol regulatory element-binding transcription factor 1 (), stearoyl-CoA desaturase-1 (), and patatin-like phospholipase domain-containing protein 2 (), were determined from liver and adipose tissue. Higher serum leptin and levels in the omental adipose tissue (OAT) and liver with MASH were found. In the liver, was positively correlated with leptin expression in adipose tissue, and was correlated with . In OAT, was correlated with insulin resistance and transaminase enzymes ( < 0.05 for all. In conclusion, we evidenced the correlation between the peripheral leptin resistance axis in OAT-liver crosstalk and the complications of MASLD in humans.
Topics: Humans; Leptin; Female; Male; Liver; Middle Aged; Omentum; Adipose Tissue; Adult; Fatty Liver; Receptors, Leptin; Suppressor of Cytokine Signaling 3 Protein; Insulin Resistance; Sterol Regulatory Element Binding Protein 1; Stearoyl-CoA Desaturase
PubMed: 38928125
DOI: 10.3390/ijms25126420 -
International Journal of Molecular... Jun 2024and , bacterial degraders of the herbicide glyphosate, were found to induce phosphonatase (phosphonoacetaldehyde hydrolase, EC 3.11.1.1) when grown on minimal media...
and , bacterial degraders of the herbicide glyphosate, were found to induce phosphonatase (phosphonoacetaldehyde hydrolase, EC 3.11.1.1) when grown on minimal media with glyphosate as the sole source of phosphorus. The phosphonatases of the strains were purified to an electrophoretically homogeneous state and characterized. The enzymes differed in their kinetic characteristics and some other parameters from the previously described phosphonatases. The phosphonatase of was first revealed to separate into two stable forms, which had similar kinetic characteristics but interacted differently with affinity and ion-exchange resins. The genomes of the investigated bacteria were sequenced. The phosphonatase genes were identified, and their context was determined: the bacteria were shown to have gene clusters, which, besides the phosphonatase operon, included genes for LysR-type transcription activator (substrate sensor) and putative iron-containing oxygenase PhnHD homologous to monooxygenases PhnY and TmpB of marine organophosphonate degraders. Genes of 2-aminoethylphosphonate aminotransferase (PhnW, EC 2.6.1.37) were absent in the achromobacterial phosphonatase operons; instead, we revealed the presence of genes encoding the putative flavin oxidase HpnW. In silico simulation showed 1-hydroxy-2-aminoethylphosphonate to be the most likely substrate of the new monooxygenase, and a number of glycine derivatives structurally similar to glyphosate to be substrates of flavin oxidase.
Topics: Glyphosate; Glycine; Achromobacter; Operon; Soil Microbiology; Bacterial Proteins; Herbicides; Multigene Family; Kinetics; Gene Expression Regulation, Bacterial
PubMed: 38928116
DOI: 10.3390/ijms25126409 -
International Journal of Molecular... Jun 2024Schizophrenia spectrum disorders (SSD) are a group of diseases characterized by one or more abnormal features in perception, thought processing and behavior. Patients...
Schizophrenia spectrum disorders (SSD) are a group of diseases characterized by one or more abnormal features in perception, thought processing and behavior. Patients suffering from SSD are at risk of developing life-threatening complications. Pharmacogenetic studies have shown promising results on personalized treatment of psychosis. In the current study, 103 patients diagnosed with SSD treated with risperidone as antipsychotic monotherapy were enrolled. Socio-demographics and clinical data were recorded, and laboratory tests and genotyping standard procedure for cytochrome P450 (CYP) 2D6*4 were performed. Patients were evaluated by the Positive and Negative Syndrome Scale (PANSS) on admission and at discharge. Based on the reduction in the PANSS total score, subjects were divided into non-responders, partial responders and full responders. Only 11 subjects had a full response to risperidone (10.67%), 53 subjects (51.45%) had a partial response, and 39 participants (37.86%) were non-responders. Patients at first episode psychosis showed significantly higher levels of blood glucose and prolactin levels, while chronic patients showed significantly higher LDL levels. Adverse drug reactions (ADR) such as tremor and stiffness significantly correlated with genetic phenotypes ( = 0.0145). While CYP2D6 showed no impact on treatment response, ADR were significantly more frequent among poor and intermediate metabolizers.
Topics: Humans; Cytochrome P-450 CYP2D6; Risperidone; Male; Female; Schizophrenia; Adult; Antipsychotic Agents; Middle Aged; Genotype; Young Adult
PubMed: 38928058
DOI: 10.3390/ijms25126350