Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Unveiling Lipidomic Alterations in Metabolic Syndrome: A Study of Plasma, Liver, and Adipose Tissues in a Dietary-Induced Rat Model

Sat, 26/10/2024 - 12:00
Nutrients. 2024 Oct 13;16(20):3466. doi: 10.3390/nu16203466.ABSTRACTMetabolic syndrome (MetS) is a complex condition characterized by fat accumulation, dyslipidemia, impaired glucose control and hypertension. In this study, rats were fed a high-fat high-fructose (HFF) diet in order to develop MetS. After ten weeks, the dietary-induced MetS was confirmed by higher body fat percentage, lower HDL-cholesterol and increased blood pressure in the HFF-fed rats compared to the normal-fed control animals. However, the effect of MetS development on the lipidomic signature of the dietary-challenged rats remains to be investigated. To reveal the contribution of specific lipids to the development of MetS, the lipid profiling of rat tissues particularly susceptible to MetS was performed using untargeted UHPLC-QTOF-MS/MS lipidomic analysis. A total of 37 lipid species (mainly phospholipids, triglycerides, sphingolipids, cholesterol esters, and diglycerides) in plasma, 43 lipid species in liver, and 11 lipid species in adipose tissue were identified as dysregulated between the control and MetS groups. Changes in the lipid signature of selected tissues additionally revealed systemic changes in the dietary-induced rat model of MetS.PMID:39458462 | DOI:10.3390/nu16203466

The Effects of <em>swnH1</em> Gene Function of Endophytic Fungus <em>Alternaria oxytropis</em> OW 7.8 on Its Swainsonine Biosynthesis

Sat, 26/10/2024 - 12:00
Microorganisms. 2024 Oct 17;12(10):2081. doi: 10.3390/microorganisms12102081.ABSTRACTThe swnH1 gene in the endophytic fungus Alternaria oxytropis OW 7.8 isolated from Oxytropis glabra was identified, and the gene knockout mutant ΔswnH1 was first constructed in this study. Compared with A. oxytropis OW 7.8, the ΔswnH1 mutant exhibited altered colony and mycelium morphology, slower growth rate, and no swainsonine (SW) in mycelia, indicating that the function of the swnH1 gene promoted SW biosynthesis. Five differential expressed genes (DEGs) closely associated with SW synthesis were identified by transcriptomic analysis of A. oxytropis OW 7.8 and ΔswnH1, with sac, swnR, swnK, swnN, and swnH2 down-regulating. Six differential metabolites (DEMs) closely associated with SW synthesis were identified by metabolomic analysis, with P450, PKS-NRPS, saccharopine, lipopolysaccharide kinase, L-PA, α-aminoadipic, and L-stachydrine down-regulated, while L-proline was up-regulated. The SW biosynthetic pathways in A. oxytropis OW 7.8 were predicted and refined. The results lay the foundation for in-depth exploration of the molecular mechanisms and metabolic pathways of SW synthesis in fungi and provide reference for future control of SW in locoweeds, which would benefit the development of animal husbandry and the sustainable use of grassland ecosystems.PMID:39458390 | DOI:10.3390/microorganisms12102081

Fecal Microbiota Transplantation for Recurrent <em>Clostridioides difficile</em> Infections in a Cystic Fibrosis Child Previously Screen Positive, Inconclusive Diagnosis (CFSPID): A Case Report

Sat, 26/10/2024 - 12:00
Microorganisms. 2024 Oct 12;12(10):2059. doi: 10.3390/microorganisms12102059.ABSTRACTClostridioides difficile infection (CDI) is generally treated with vancomycin, metronidazole or fidaxomicin, although fecal microbiota transplantation (FMT) represents a promising therapeutic option for antibiotic-resistant recurrent C. difficile infections (rCDIs) in adults. In pediatric cystic fibrosis (CF) patients, CDIs are generally asymptomatic and respond to treatment. Here, we present the case of an 8-year-old female, initially diagnosed as "CFTR-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis" (CMRS/CFSPID), who then progressed to CF at 12 months. In the absence of CF-related symptoms, she presented multiple and disabling episodes of bloody diarrhoea with positive tests for C. difficile antigen and A/B toxin. After conventional treatments failed and several CDI relapses, FMT was proposed. Donor screening and GM donor-receiver matching identified her mother as a donor. Metataxonomy and targeted metabolomics provided, through a pre- and post-FMT time course, gut microbiota (GM) profiling to assess GM engraftment. At first, the GM map revealed severe dysbiosis, with a prevalence of Bacteroidetes and Proteobacteria (i.e., Klebsiella spp., Escherichia coli), a reduction in Firmicutes, a GM nearly entirely composed of Enterococcaceae (i.e., Enterococcus) and an almost complete depletion of Verrucomicrobia and Actinobacteria, mostly represented by Veillonella dispar. Post FMT, an increment in Bifidobacterium spp. and Collinsella spp. with a decrease in V. dispar restored intestinal eubiosis. Consistently, four weeks after FMT treatment, the child's gut symptoms cleared, without CDI recurrence.PMID:39458368 | DOI:10.3390/microorganisms12102059

Multi-Omics Analysis Unravels the Impact of Stool Sample Logistics on Metabolites and Microbial Composition

Sat, 26/10/2024 - 12:00
Microorganisms. 2024 Sep 30;12(10):1998. doi: 10.3390/microorganisms12101998.ABSTRACTHuman health and the human microbiome are inevitably intertwined, increasing their relevance in clinical research. However, the collection, transportation and storage of faecal samples may introduce bias due to methodological differences, especially since postal shipping is a common practise in large-scale clinical cohort studies. Using four different Omics layer, we determined the structural (16S rRNA sequencing, cytometric microbiota profiling) and functional integrity (SCFAs, global metabolome) of the microbiota in relation to different easy-to-handle conditions. These conditions were storage at -20 °C, -20 °C as glycerol stock, 4 °C and room temperature with and without oxygen exposure for a maximum of one week. Storage time affected the microbiota on all Omics levels. However, the magnitude was donor-dependent, highlighting the need for purpose-optimized sample collection in clinical multi-donor studies. The effects of oxygen exposure were negligible for all analyses. At ambient temperature, SCFA and compositional profiles were stable for 24 h and 48 h, respectively, while at 4 °C, SCFA profiles were maintained for 48 h. The global metabolome was highly susceptible, already changing at 24 h in non-frozen conditions. Thus, faecal microbiota was best preserved on all levels when transported as a native sample frozen within 24 h, leading to the least biased outcomes in the analysis. We conclude that the immediate freezing of native stool samples for transportation to the lab is best suited for planned multi-Omics analyses that include metabolomics to extend standard sequencing approaches.PMID:39458307 | DOI:10.3390/microorganisms12101998

Comparative Study on Growth and Metabolomic Profiles of Six Lactobacilli Strains by Sodium Selenite

Sat, 26/10/2024 - 12:00
Microorganisms. 2024 Sep 24;12(10):1937. doi: 10.3390/microorganisms12101937.ABSTRACTSelenium (Se) has garnered increasing attention in the field of nutrition, as it is essential for both humans and animals. Certain microorganisms can enrich inorganic selenium and convert it into organic selenium. The growth and metabolomic profiles of six lactobacilli strains exposed to 50 μg/mL of sodium selenite were performed using gas chromatography tandem time-off light mass spectrometry (GC-TOF-MS) analysis. The addition of selenium significantly increased both the population and weight of the Lacticaseibacillus rhamnosus PS5, Lbs. rhamnosus RT-B, Limosilactobacillus reuteri 3630, and Lmb. reuteri 1663 strains, while those of the other two strains decreased. A total of 271 metabolites were determined, with their concentrations ranked from highest to lowest as follows: organic acids and derivatives, oxygen compounds, lipids and lipid-like molecules, and benzenoids. In certain groups, the concentrations of serine, aspartic acid, trehalose, palmitic acid, methylthreonine, and melibiose increased significantly, whereas glucuronic acid, ribose, ornithine, and methionine were downregulated. The metabolic pathways were significantly associated with ABC transporters, glycine, serine, threonine metabolism, and aminobenzoate degradation and other pathways. Based on these findings, we concluded that the transport, absorption, assimilation, and stress response to selenium by lactobacilli in metabolomic changed. Furthermore, the metabolomic alterations among different types of lactobacilli varied primarily due to their distinct properties.PMID:39458247 | DOI:10.3390/microorganisms12101937

The mTOR Pathway: A Common Link Between Alzheimer's Disease and Down Syndrome

Sat, 26/10/2024 - 12:00
J Clin Med. 2024 Oct 17;13(20):6183. doi: 10.3390/jcm13206183.ABSTRACTDown syndrome (DS) is a chromosomal condition that causes many systemic dysregulations, leading to several possible age-related diseases including Alzheimer's disease (AD). This may be due to the triplication of the Amyloid precursor protein (APP) gene or other alterations in mechanistic pathways, such as the mTOR pathway. Impairments to upstream regulators of mTOR, such as insulin, PI3K/AKT, AMPK, and amino acid signaling, have been linked to amyloid beta plaques (Aβ) and neurofibrillary tangles (NFT), the most common AD pathologies. However, the mechanisms involved in the progression of pathology in human DS-related AD (DS-AD) are not fully investigated to date. Recent advancements in omics platforms are uncovering new insights into neurodegeneration. Genomics, spatial transcriptomics, proteomics, and metabolomics are novel methodologies that provide more data in greater detail than ever before; however, these methods have not been used to analyze the mTOR pathways in connection to DS-AD. Using these new techniques can unveil unexpected insights into pathological cellular mechanisms through an unbiased approach.PMID:39458132 | DOI:10.3390/jcm13206183

Effects of Methionine on Milk Performance and Milk Constituents of Lactating Donkeys

Sat, 26/10/2024 - 12:00
Animals (Basel). 2024 Oct 19;14(20):3027. doi: 10.3390/ani14203027.ABSTRACTThis study investigated the effects of adding methionine (Met) in milk production and the milk and blood metabolites of lactating donkeys. Eighteen healthy multiparous donkeys in early-stage lactation were selected for this study. The donkeys were randomly divided into three groups and fed diets with different levels of Met: control group (C, Met 0 g/d), Met group I (M1, Met 5 g/d), and Met group II (M2, Met 15 g/d). The total duration of the experiment was 5 weeks. Donkey milk and blood samples were collected at the end of the experiment. The milk yield and composition, milk, and serum metabolites were analyzed. The results showed that the addition of 5 g of Met significantly increased milk yield as well as the milk composition contents of protein, fat, lactoferrin, polyunsaturated fatty acid (PFA), solids, and solids-not-fat (SNF) (p < 0.05). Significant differences in metabolites were detected among the different samples of milk (p < 0.05). The addition of Met increased the levels of milk metabolites, such as myristic acid, d-glutamine, l-aspartic acid, and LPS 16:0. A total of 753 metabolites were detected in the serum, including 17 differential metabolites between C and M1 and 48 differential metabolites between C and M2. The levels of serum metabolites, such as l-ascorbate, inositol, and l-lysine, were up-regulated by the addition of Met (p < 0.05). The above results indicated that Met increased donkey milk production and milk composition yield and improved milk metabolites by regulating serum metabolites. These results provide a foundation for improving the nutritional needs of lactating donkeys and the nutritional regulation of donkey milk synthesis.PMID:39457957 | DOI:10.3390/ani14203027

Nitidine Chloride Alleviates Hypoxic Stress via PINK1-Parkin-Mediated Mitophagy in the Mammary Epithelial Cells of Milk Buffalo

Sat, 26/10/2024 - 12:00
Animals (Basel). 2024 Oct 18;14(20):3016. doi: 10.3390/ani14203016.ABSTRACTHypoxia in the mammary gland epithelial cells of milk buffalo (BMECs) can affect milk yield and composition, and it can even cause metabolic diseases. Nitidine chloride (NC) is a natural alkaloid with antioxidant properties that can scavenge excessive reactive oxygen species (ROS). However, the effect of NC on the hypoxic injury of BMECs and its molecular mechanisms are still unknown. Here, an immunofluorescence assay, transmission electron microscopy (TEM), and flow cytometry, combined with untargeted metabolomics, were used to investigate the protective effect of NC on hypoxic stress injury in BMECs. It was found that NC can significantly reduce cell activity (p < 0.05) and inhibit cellular oxidative stress (p < 0.05) and cell apoptosis (p < 0.05). A significant decrease in mitophagy mediated by the PINK1-Parkin pathway was observed after NC pretreatment (p < 0.05). In addition, a metabolic pathway enrichment analysis demonstrated that the mechanisms of NC against hypoxic stress may be related to the downregulation of pathways involving aminoacyl tRNA biosynthesis; arginine and proline metabolism; glycine, serine, and threonine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; and phenylalanine metabolism. Thus, NC has a protective effect on hypoxic mitochondria, and it can regulate amino acid metabolism in response to hypoxic stress. The present study provides a reference for the application of nitidine chloride to regulate the mammary lactation function of milk buffalo.PMID:39457946 | DOI:10.3390/ani14203016

GnRH Immunocastration in Male Xizang Sheep: Impacts on Rumen Microbiome and Metabolite Profiles for Enhanced Health and Productivity

Sat, 26/10/2024 - 12:00
Animals (Basel). 2024 Oct 11;14(20):2942. doi: 10.3390/ani14202942.ABSTRACTCastration is a prevalent and indispensable practice in sheep husbandry, aiding in enhancing meat quality, mitigating aggressive behavior, and managing unwanted reproduction. Nevertheless, the conventional surgical castration procedure poses several challenges, including heightened stress and pain, detrimental impacts on animal welfare, and diminished economic efficacy in farming operations. Consequently, immunocastration methods, serving as substitutes for surgical castration, are progressively finding application in livestock. The rumen, an essential and distinctive digestive and absorptive organ in ruminants, has been associated with enhanced meat quality and productive performance following castration in previous research studies, albeit fewer investigations have explored the potential impacts of GnRH immunization on the rumen's internal milieu in sheep post-de-escalation. Hence, the present study delved into evaluating the impact of GnRH immunocastration on the rumen microbiome and metabolomics in male Xizang sheep. This was achieved through the establishment of a GnRH immunocastration animal model and the collection of rumen fluid for microbiological and comprehensive metabolomics investigations. The outcomes of this investigation unveiled that the impact of GnRH immunocastration on body weight gain was more pronounced during the achievement of the castration objective. In addition, the Firmicutes-to-Bacteroidota ratio in the immune male (IM) group exceeded that of the control group (EM), suggesting that GnRH immunodeficiency may enhance the digestion and absorption of feed in male Xizang sheep. At the taxonomic level, the elevated presence of Prevotella and Quinella bacteria in the IM group compared to the EM group indicated that castration influenced a segment of the rumen microbiota in male Xizang sheep, thereby bolstering the digestive and metabolic efficacy of the rumen concerning nutrient utilization, particularly in the breakdown and absorption of proteins, carbohydrates, and lipids, ultimately expediting the fattening process and weight gain in male Xizang sheep following castration. Moreover, analysis of ruminal fluid metabolomics revealed that GnRH immunization had notable impacts on certain metabolites in the ruminal fluid of male Xizang sheep, with metabolites like 5-hydroxyindole acetic acid and 3-hydroxyindole acetic acid showing significant downregulation in the IM group compared to the EM group, while niacin and tyramine exhibited significant upregulation. These findings indicate a profound influence of GnRH immunization on the maintenance of ruminal equilibrium and ruminal health (including the health of ruminal epithelial cells). This study validates that GnRH immunocastration not only achieves the objectives of castration but also enhances ruminal health in male Xizang sheep, thus laying a foundational theoretical basis for the application and dissemination of GnRH immunocastration technology.PMID:39457871 | DOI:10.3390/ani14202942

Pterin-Based Red Coloration Predicts the Outcome of Male-Male Competition in Guinan Toad-Headed Lizard

Sat, 26/10/2024 - 12:00
Animals (Basel). 2024 Oct 11;14(20):2923. doi: 10.3390/ani14202923.ABSTRACTAnimal coloration offers a unique opportunity to explore the evolutionary mechanisms underlying phenotypic diversity. Conspicuous coloration caused by pigments plays a crucial role in social signaling across multiple species by conveying information about individual quality, social ranks, or reproductive condition. Nevertheless, most previous studies have focused predominantly on colors produced by the exogenous pigments-carotenoids. Pterins are another prevalent group of conspicuous pigments, which can be produced endogenously and have received comparatively little attention. Whether pterin-based colors represent reliable signals remains elusive. The remarkable red ventrolateral coloration exhibited by males of the Guinan toad-headed lizard (Phrynocephalus guinanensis) in the Mugetan Desert presents an ideal model for investigating pterin-based coloration. Through electron microscopy and metabolomic identification, we discovered three types of pterin pigments within xanthophores. Integrating a series of morphological measurements and behavioral experiments, we found that this red coloration was not correlated with body size, bite force, and testosterone level, nor did females show a preference bias toward it. However, the red intensity predicted male-male competition outcomes, with deeper red males being more likely to emerge as winners. Our results indicated that the pterin-based coloration could convey information about male quality, suggesting its potential role in honest signaling, given the vital importance of pterin metabolism in physiological processes. This study provides a novel case into the understanding of pterin-based colors in animals.PMID:39457853 | DOI:10.3390/ani14202923

From Genomics to Metabolomics: Molecular Insights into Osteoporosis for Enhanced Diagnostic and Therapeutic Approaches

Sat, 26/10/2024 - 12:00
Biomedicines. 2024 Oct 18;12(10):2389. doi: 10.3390/biomedicines12102389.ABSTRACTOsteoporosis (OP) is a prevalent skeletal disorder characterized by decreased bone mineral density (BMD) and increased fracture risk. The advancements in omics technologies-genomics, transcriptomics, proteomics, and metabolomics-have provided significant insights into the molecular mechanisms driving OP. These technologies offer critical perspectives on genetic predispositions, gene expression regulation, protein signatures, and metabolic alterations, enabling the identification of novel biomarkers for diagnosis and therapeutic targets. This review underscores the potential of these multi-omics approaches to bridge the gap between basic research and clinical applications, paving the way for precision medicine in OP management. By integrating these technologies, researchers can contribute to improved diagnostics, preventative strategies, and treatments for patients suffering from OP and related conditions.PMID:39457701 | DOI:10.3390/biomedicines12102389

Preliminary Metabolomics Study Suggests Favorable Metabolic Changes in the Plasma of Breast Cancer Patients after Surgery and Adjuvant Treatment

Sat, 26/10/2024 - 12:00
Biomedicines. 2024 Sep 26;12(10):2196. doi: 10.3390/biomedicines12102196.ABSTRACTBackground/Objectives: The management of early breast cancer (BC) includes surgery, followed by adjuvant radiotherapy, chemotherapy, hormone therapy, or immunotherapy. However, the influence of these interventions in metabolic reprogramming remains unknown. This study explored alterations in the plasma metabolome of BC patients following distinct treatments to deepen our understanding of BC pathophysiology, outcomes, and the identification of potential biomarkers. Methods: We included 52 women diagnosed with BC and candidates for surgery as primary oncological treatment. Blood samples were collected at diagnosis, two weeks post-surgery, and one month post-radiotherapy. Plasma samples from 49 healthy women served as controls. Targeted metabolomics assessed 74 metabolites spanning carbohydrates, amino acids, lipids, nucleotide pathways, energy metabolism, and xenobiotic biodegradation. Results: Before treatment, the BC patients exhibited notable changes in carbohydrate, nucleotide, lipid, and amino acid metabolism. We noticed a gradual restoration of specific metabolite levels (hypoxanthine, 3-phosphoglyceric acid, xylonic acid, and maltose) throughout different treatments, suggesting a normalization of the nucleotide and carbohydrate metabolic pathways. Moreover, we observed increased dodecanoic acid concentrations, a metabolite associated with cancer protection. These variations distinguished patients from controls with high specificity and sensitivity. Conclusions: Our preliminary study suggests that oncological treatments modify the metabolism of patients towards a favorable profile with a decrease in the pathways that favor cell proliferation and an increase in the levels of anticancer molecules. These findings emphasize the pivotal role of metabolomics in recognizing the biological pathways influenced by each cancer treatment and the resulting metabolic consequences. Furthermore, it aids in identifying potential biomarkers for disease onset and progression.PMID:39457508 | DOI:10.3390/biomedicines12102196

Research Progress on Genomic Regions and Candidate Genes Related to Milk Composition Traits of Dairy Goats Based on Functional Genomics: A Narrative Review

Sat, 26/10/2024 - 12:00
Genes (Basel). 2024 Oct 19;15(10):1341. doi: 10.3390/genes15101341.ABSTRACTBACKGROUND: Goat milk has gained global attention for its unique nutritional properties and potential health benefits. Advancements in functional genomic technologies have significantly progressed genetic research on milk composition traits in dairy goats.RESULTS: This review summarizes various research methodologies applied in this field. Genome-wide association studies (GWAS) have identified genomic regions associated with major milk components, with the diacylglycerol acyltransferase 1 (DGAT1) gene and casein gene cluster consistently linked to milk composition traits. Transcriptomics has revealed gene expression patterns in mammary tissue across lactation stages, while the role of non-coding RNAs (such as miRNAs and circRNAs) in regulating milk composition has been confirmed. Proteomic and metabolomic studies have not only helped us gain a more comprehensive understanding of goat milk composition characteristics but have also provided crucial support for the functional validation of genes related to milk components. The integration of multi-omics data has emerged as an effective strategy for elucidating complex regulatory networks from a systems biology perspective.CONCLUSIONS: Despite progress, challenges remain, including refining reference genomes, collecting large-scale phenotypic data, and conducting functional validations. Future research should focus on improving reference genomes, expanding study populations, investigating functional milk components, exploring epigenetic regulation and non-coding RNAs, and studying microbiome-host genome interactions. These efforts will inform more precise genomic and marker-assisted selection strategies, advancing genetic improvements in milk composition traits in dairy goats.PMID:39457465 | DOI:10.3390/genes15101341

Integrated Transcriptional and Metabolomic Analysis of Factors Influencing Root Tuber Enlargement during Early Sweet Potato Development

Sat, 26/10/2024 - 12:00
Genes (Basel). 2024 Oct 14;15(10):1319. doi: 10.3390/genes15101319.ABSTRACTBACKGROUND: Sweet potato (Ipomoea batatas (L.) Lam.) is widely cultivated as an important food crop. However, the molecular regulatory mechanisms affecting root tuber development are not well understood.METHODS: The aim of this study was to systematically reveal the regulatory network of sweet potato root enlargement through transcriptomic and metabolomic analysis in different early stages of sweet potato root development, combined with phenotypic and anatomical observations.RESULTS: Using RNA-seq, we found that the differential genes of the S1 vs. S2, S3 vs. S4, and S4 vs. S5 comparison groups were enriched in the phenylpropane biosynthesis pathway during five developmental stages and identified 67 differentially expressed transcription factors, including AP2, NAC, bHLH, MYB, and C2H2 families. Based on the metabolome, K-means cluster analysis showed that lipids, organic acids, organic oxides, and other substances accumulated differentially in different growth stages. Transcriptome, metabolome, and prophetypic data indicate that the S3-S4 stage is the key stage of root development of sweet potato. Weighted gene co-expression network analysis (WGCNA) showed that transcriptome differential genes were mainly enriched in fructose and mannose metabolism, pentose phosphate, selenium compound metabolism, glycolysis/gluconogenesis, carbon metabolism, and other pathways. The metabolites of different metabolites are mainly concentrated in amino sugar and nucleotide sugar metabolism, flavonoid biosynthesis, alkaloid biosynthesis, pantothenic acid, and coenzyme A biosynthesis. Based on WGCNA analysis of gene-metabolite correlation, 44 differential genes and 31 differential metabolites with high correlation were identified.CONCLUSIONS: This study revealed key gene and metabolite changes in early development of sweet potato root tuber and pointed out potential regulatory networks, providing new insights into sweet potato root tuber development and valuable reference for future genetic improvement.PMID:39457443 | DOI:10.3390/genes15101319

Multi-Omics Revealed Regulatory Mechanisms Underlying the Flowering of <em>Ferula sinkiangensis</em> across Three Dimensions

Sat, 26/10/2024 - 12:00
Genes (Basel). 2024 Sep 28;15(10):1275. doi: 10.3390/genes15101275.ABSTRACTBackgroud/Objectives: Ferula spp. is an essential crop in Central Asia with pronounced economic benefits governed by its flowering process. However, the mechanisms of the flowering phenotype remain unclear. Methods: In this study, using F. sinkiangensis as a model plant, we integrated transcriptome, proteome, and metabolome analyses to compare the multilayer differences in leaves and roots of plants with flowering and unflowering phenotypes. Results: We found that several variations in the transcriptome, proteome, and metabolome were closely associated with flowering. The Photosynthesis and Phenylpropanoid biosynthesis pathways in plants with the flowering phenotype were more active. Additionally, three flowering genes, named FL2-FL4, were upregulated in the leaves of flowering plants. Notably, six transcription factors were potentially responsible for regulating the expression of FL2-FL4 in the leaves to mediate flowering process of F. sinkiangensis. Moreover, genes relevant to Photosynthesis and Phenylpropanoid biosynthesis were also involved in regulating the expression of FL2-FL4 in flowering plants. Conclusions: The active regulation network together with Photosynthesis and Phenylpropanoid biosynthesis were essential for inducing the expression of flowering-related genes in leaves to promote the flowering process of F. sinkiangensis.PMID:39457399 | DOI:10.3390/genes15101275

Metabolomic Changes Associated with AGXT2 Genotype Variants and Stone Formation in a Colony of Cats

Sat, 26/10/2024 - 12:00
Genes (Basel). 2024 Sep 27;15(10):1264. doi: 10.3390/genes15101264.ABSTRACTOBJECTIVE: The objective of this study was to assess serum chemistries and metabolomic parameters in cats with genetic variants of the alanine-glyoxylate aminotransferase 2 (AGXT2) gene to determine abnormalities associated with urolith formation and better understand effective approaches for the treatment of cats with uroliths.METHODS: AGXT2 genotypes of 445 cats in the colony at Hill's Pet Nutrition, Inc. (Topeka, KS, USA) were assessed in a genome-wide association study. Additionally, the serum chemistries and metabolic profiles of each cat were determined, along with their lifetime history of stone incidence. Factor analysis was used as a data-reduction method for metabolites in order to perform statistical hypothesis testing and to select significant metabolites from the more than 600 serum metabolites identified.RESULTS: Of the 82 cats forming stones in the colony (18.4%), the majority were calcium oxalate. Results showed that approximately one third of the cats with the AA variant of the AGXT2 gene have stones, that chronic kidney disease (CKD) is more common in cats with stones, and that having stones results in a shorter lifespan. A discriminant variable selection process was performed to determine the complete blood count, serum biochemistries, and serum metabolomic factors that best discriminated among the three genotypes (AA, AG, GG) and between cats forming stones and non-stone formers. Several of the highly ranked discriminating factors included metabolites related to decreased aminotransferase activity in cats with the AA variant of the AGXT2 gene. Another factor that ranked highly for discriminating between stone formers and non-stone formers contained lipid metabolites, consisting of multiple sphingomyelin species and cholesterol.CONCLUSIONS: These findings support the results of feeding studies in cats, whereby CKD cats fed food supplemented with betaine and prebiotics have experienced an increase in total body mass, reduced uremic toxins, and altered sphingomyelin concentrations.PMID:39457388 | DOI:10.3390/genes15101264

The Association of the Oral Microbiota with Cognitive Functioning in Adolescence

Sat, 26/10/2024 - 12:00
Genes (Basel). 2024 Sep 27;15(10):1263. doi: 10.3390/genes15101263.ABSTRACTBackground: A growing body of research supports the role of the microbial communities residing in the digestive system in the host's cognitive functioning. Most of these studies have been focused on the gut microbiome and its association with clinical phenotypes in middle-aged and older adults. There is an insufficiency of population-based research exploring the association of normative cognitive functioning with the microbiome particularly with the oral microbiota. Methods: In this study, using metagenomics and metabolomics, we characterized the salivary microbiome diversity in a sample of 51 males of Hispanic and African American origin aged 12-18 years and explored the associations between the microbiome and the youths' cognitive performance captured with the Kaufman Assessment Battery for Children II (KABC-II). Results: Several bacterial species of the oral microbiota and related metabolic pathways were associated with cognitive function. In particular, we found negative associations between indicators of general intelligence and the relative abundance of Bacteroidetes and Lachnospiraceae and positive associations with Bifidobacteriaceae and Prevotella histicola sp. Among metabolic pathways, the super pathways related to bacterial cell division and GABA metabolism were linked to cognitive function. Conclusions: The results of our work are consistent with the literature reporting on the association between microbiota and cognitive function and support further population work to elucidate the potential for a healthy oral microbiome to improve cognitive health.PMID:39457387 | DOI:10.3390/genes15101263

Transcriptome and Metabolome Analysis of BmFAMeT6 Overexpression in Bombyx mori

Sat, 26/10/2024 - 12:00
Genes (Basel). 2024 Sep 27;15(10):1261. doi: 10.3390/genes15101261.ABSTRACTBackground/Objectives: The gene-encoding farnesyl diphosphate O-methyltransferase 6 (FAMeT 6) is a member of the farnesyl diphosphate O-methyltransferase family. Our previous studies have demonstrated its influence on juvenile hormone levels in third instar silkworm larvae. Methods: we utilized transcriptomic and metabolomic techniques to investigate the changes in third instar larvae at 0, 12, and 24 h following BmFAMeT6 overexpression. Results: (1) The differentially expressed homologous genes were enriched in detoxification-related pathways at all three time points. (2) Transcription factor analysis of DEGs indicated a predominant presence of ZF-C2H2. (3) The metabolite-related network suggested that BmFAMeT6 may influence the metabolism of silkworm larvae through the ABC transporters, purine metabolism, and tyrosine metabolism pathways. (4) The differential gene count, differential metabolite count, and types of metabolites at the three time points indicated a shift in the regulatory focus within the larvae as time progresses, with the inflection point of regulation occurring at the third instar larval stage, 12 h. Conclusion: In summary, our research indicates that the regulatory role of BmFAMeT6 occurs within the context of the domestic silkworm's own growth and development regulation.PMID:39457386 | DOI:10.3390/genes15101261

Integrated Transcriptomics and Metabolomics Reveal Key Insights into Iridoid Biosynthesis in Gentiana crassicaulis Seeds during Germination

Sat, 26/10/2024 - 12:00
Genes (Basel). 2024 Sep 26;15(10):1255. doi: 10.3390/genes15101255.ABSTRACTBackground:Gentiana crassicaulis Duthie ex Burk., a key species used in traditional Chinese medicine for treating rheumatic pain and stroke, contains iridoids as its primary active component. However, the biosynthetic mechanisms underlying iridoid production are not fully understood. Methods: This study focused on iridoid biosynthesis during the germination of G. crassicaulis seeds, integrating metabolomic and transcriptomic analyses to uncover the underlying pathways and key candidate genes. Results: 196,132 unigenes and 10 iridoid compounds were identified through RNA-seq and ultra performance liquid chromatography-quadrupole time of flight-mass spectrometer (UPLC-Q-TOF-MS), respectively. The intersection of results from Pearson correlation analysis and weighted gene co-expression network analysis (WGCNA) revealed a significant correlation between 26 genes and iridoid levels, suggesting their potential role in the iridoid metabolism. Notably, six highly expressed candidate genes (DL7H, SLS, CYP76, CYP72A2, CYP84A1, and 13-LOX3) and five iridoids (loganic acid, sweroside, swertiamarin, gentiopicroside, and 6'-O-β-D-glucosyl-gentiopicroside) responded to methyl jasmonate stimulation in G. crassicaulis seedlings. Conclusions: by combining the known functions of candidate gene families, It is hypothesized that the CYP716 and LOX families exert indirect influences on iridoid metabolism, while the CYP71, CYP81, CYP72, CYP76, CYP710 families, 2OG-FeII family, and the glucosyltransferase family are likely to play direct roles in the biosynthetic transformations of the five iridoids. This study provides a theoretical basis for further functional gene validation and metabolic engineering aimed at enhancing iridoid production. The insights gained could lead to improved iridoid production efficiency in medicinal plants, ultimately benefiting the quality and efficacy of medicinal materials.PMID:39457379 | DOI:10.3390/genes15101255

An Analysis of the Mechanism About CO<sub>2</sub> Enrichment Promoting Carbohydrate Metabolism in Cucumber (<em>Cucumis sativus</em> L.) Leaves

Sat, 26/10/2024 - 12:00
Int J Mol Sci. 2024 Oct 21;25(20):11309. doi: 10.3390/ijms252011309.ABSTRACTElevated CO2 can affect the synthesis and distribution of photosynthetic assimilates. However, the carbohydrate metabolism molecular mechanism of cucumber leaves in response to CO2 enrichment is unclear. Therefore, it is of great significance to investigate the key functional regulatory genes in cucumber. In this study, the growth of cucumber leaves under different CO2 conditions was compared. The results showed that under CO2 enrichment, leaf area increased, the number of mesophyll cells increased, stomata enlarged, and more starch grains accumulated in the chloroplasts. Compared with the control, the starch and soluble sugar content of leaves were maximally increased by 194.1% and 55.94%, respectively; the activities of fructose-1,6-bisphosphatase (FBPase), ADPG pyrophosphorylase (AGPase), starch synthase (SSS), sucrose phosphate synthase (SPS), sucrose synthase (SS) and invertase (Inv) were maximally increased by 36.91%, 66.13%, 33.18%, 21.7%, 54.11%, and 46.01%, respectively. Through transcriptome analysis, a total of 1,582 differential expressed genes (DEGs) were identified, in which the starch and sucrose metabolism pathway was significantly enriched, and 23 genes of carbon metabolism were screened. Through metabolome analysis, a total of 22 differential accumulation metabolites (DAMs) were identified. Moreover, D-glucose and D(+)-glucose were significantly accumulated, showing upregulation 2.4-fold and 2.6-fold, respectively. Through combined analysis of transcriptome and metabolome, it was revealed that seven genes were highly related to D-glucose, and Csa6G153460 (AGPase), Csa5G612840 (β-glucosidase), and Csa4G420150 (4-α-glucanotransferase) were significantly correlated to the carbohydrate regulatory network. Furthermore, the mechanism of CO2 enrichment that promotes carbohydrate metabolism in leaves at the molecular level was revealed. This mechanism advances the development of the cell wall and leaf morphology by activating the expression of key genes and improving enzyme activity.PMID:39457091 | DOI:10.3390/ijms252011309

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