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

PubMed

Wheat Peptides as Catalysts for Athletic Performance Improvement in Cross-Country Skiers: A Randomized Controlled Trial

Fri, 25/10/2024 - 12:00
Metabolites. 2024 Oct 7;14(10):538. doi: 10.3390/metabo14100538.ABSTRACTOBJECTIVES: This study investigated the efficacy of wheat peptide supplementation compared to regular proteins in elite cross-country skiers, providing insights into the metabolic and performance effects of these supplements in order to guide athletes in selecting optimal energy sources for training and competition.METHODS: Nineteen healthy male cross-country skiers were enrolled and assigned to either the peptide group (PEP, n = 9) or the protein group (PRO, n = 10). A four-week intervention study involving supplementation with wheat peptides/regular proteins was conducted, and pre- and post-intervention assessments were performed to evaluate exercise capacity and metabolic profiles.RESULTS: The study found that the PEP group and the PRO group showed distinct within-group effects on exercise performance. The PEP group demonstrated improved aerobic capacity, including better performance in 10 km roller skating, an increased lactate threshold, and reduced resting blood lactate levels. The PRO group enhanced anaerobic capacity, such as improved sprint time, hexagon test performance, and lactate clearance. Metabolomic analysis revealed specific metabolic pathways affected in each group, with the PEP group showing impacts on the α-linolenic acid pathway and the PRO group on ketone body synthesis and degradation as well as vitamin B6 metabolism.CONCLUSIONS: Our findings indicate that wheat oligopeptides and regular proteins have comparable effects on exercise performance. However, the wheat peptides may offer greater advantages in enhancing aerobic capacity. No significant variations were observed in blood metabolite profiles between the two groups, but distinct metabolic pathways exhibited different responses.PMID:39452919 | DOI:10.3390/metabo14100538

Comparative Impact of Organic Grass-Fed and Conventional Cattle-Feeding Systems on Beef and Human Postprandial Metabolomics-A Randomized Clinical Trial

Fri, 25/10/2024 - 12:00
Metabolites. 2024 Oct 3;14(10):533. doi: 10.3390/metabo14100533.ABSTRACTBACKGROUND/OBJECTIVES: Cattle-feeding systems may have health implications for consumers of beef products. Organic grass-fed (GRA) and conventional (CON) cattle-feeding systems may result in beef products with differing metabolite profiles and therefore could impact the postprandial metabolomic response of consumers. This study aims to measure whole beef metabolomics and postprandial metabolomic response of consumers between GRA and CON beef to elucidate potential health implications.METHODS: This study followed a randomized double-blind crossover design with healthy male and female subjects (n = 10). Plasma samples were taken at fasting (0) and postprandially for four hours after consumption of a steak from each condition. Untargeted metabolomic analysis of whole beef and human plasma samples used LC/MS. Multivariate and pathway enrichment analysis in MetaboAnalyst was used to investigate metabolite and biochemical pathways that distinguished CON and GRA.RESULTS: Cattle-feeding systems impacted both postprandial and whole beef steak metabolomic profiles. Metabolites that contributed to this variation included carnitine species (Proionylcarnitine), fatty acids, amino acids (L-valine), and Calamendiol. These metabolites have been associated with oxidative stress, inflammation, and cardiovascular health. Functional pathway enrichment analysis revealed numerous amino acid degradation pathways, especially branched-chain amino acids, and fatty acid degradation that changed throughout the postprandial time course.CONCLUSIONS: These findings suggest that CON and GRA cattle-feeding systems differentially impact whole beef metabolomics, as well as consumer postprandial metabolic responses and the associated health implications.PMID:39452914 | DOI:10.3390/metabo14100533

Nontargeted Metabolomics to Understand the Impact of Modified Atmospheric Packaging on Metabolite Profiles of Cooked Normal-pH and Atypical Dark-Cutting Beef

Fri, 25/10/2024 - 12:00
Metabolites. 2024 Oct 2;14(10):532. doi: 10.3390/metabo14100532.ABSTRACTBackground: Limited knowledge is currently available on the effects of modified atmospheric packaging (MAP) on the metabolite profiles of cooked beef. The objective was to evaluate the impact of packaging on the cooked color and cooked metabolite profile of normal-pH (normal bright-red color) and atypical-dark-cutting beef (inherently slightly dark-colored) longissimus lumborum muscle. Methods: Normal-pH (pH 5.56) and atypical dark-cutting (pH 5.63) loins (n = 6) were procured from a commercial meat processor. Steaks were randomly assigned to one of three different packaging methods: vacuum packaging, carbon monoxide (CO-MAP), and high oxygen (HiOx-MAP). Following 5 d of retail display, steaks were cooked to 71 °C on a clamshell-style grill, and samples were collected for untargeted metabolites using gas-chromatography mass spectrometry. Results: Raw atypical dark-cutting steaks were less red (p < 0.05) than raw normal-pH steaks. However, there were no differences in internal cooked color between normal-pH and atypical dark-cutting steaks. Steaks packaged in HiOx-MAP steaks had a lower (p < 0.05) cooked redness than vacuum and CO-MAP steaks. A total of 129 metabolite features were identified in the study. Serine and tryptophan were over-abundant in cooked atypical dark-cutting beef compared to raw atypical samples. Citric acid levels were greater in HiOx-MAP packaged beef compared with VP both in normal and atypical dark-cutting beef after cooking, while no differentially abundant metabolites were shared between vacuum and CO-MAP steaks after cooking. Discussion: A slight increase in pH did not influence metabolite profiles in different packaging. However, there were packaging effects within normal and atypical dark-cutting beef. Conclusions: This study suggests that packaging conditions change metabolite profiles, which can influence cooked metabolites. Therefore, the metabolomics approach can be used to better understand cooked color defects such as premature browning.PMID:39452913 | DOI:10.3390/metabo14100532

Comparative Metabolic Profiling in <em>Drosophila suzukii</em> by Combined Treatment of Fumigant Phosphine and Low Temperature

Fri, 25/10/2024 - 12:00
Metabolites. 2024 Sep 28;14(10):526. doi: 10.3390/metabo14100526.ABSTRACTBackground/Objectives: The mechanisms of action of phosphine are diverse and include neurotoxicity, metabolic inhibition, and oxidative stress; however, its efficacy at low temperatures is unclear. Methods: Comparative metabolomics is suitable for investigating the response of the spotted-wing fly Drosophila suzukii to exposure toward a combination of cold stimuli and fumigant PH3. Results: Under this combined exposure, 52 metabolites exhibiting significant differences in stress were identified and their physiological roles were analyzed in the Drosophila metabolic pathway. Most metabolites were involved in amino acids, TCA cycle, and nucleic acids. In addition, the alteration levels of cell membrane lipids, such as glycerophospholipids, sphingolipids, and glycerolipids, clearly showed changes in the combined treatment compared to PH3 and low temperatures alone. Aconitic acid, a component of the TCA cycle, was completely inhibited by the combined treatment. Conclusions: These results suggest that treatment-specific indicators could be useful biomarkers to indicate the synergistic effects of PH3 and low temperature on energy metabolism.PMID:39452907 | DOI:10.3390/metabo14100526

Hyperglycosylation as an Indicator of Aging in the Bone Metabolome of Oryzias latipes

Fri, 25/10/2024 - 12:00
Metabolites. 2024 Sep 27;14(10):525. doi: 10.3390/metabo14100525.ABSTRACTChronological aging of bone tissues is a multi-faceted process that involves a complex interplay of cellular, biochemical, and molecular mechanisms. Metabolites play a crucial role for bone homeostasis, and a changed metabolome is indicative for bone aging, although bone metabolomics are currently understudied. The vertebral bone metabolome of the model fish Japanese medaka (Oryzias latipes) was employed to identify sex-specific markers of bone aging. 265 and 213 metabolites were differently expressed in 8-month-old vs. 3-month-old female and male fish, respectively. The untargeted metabolomics pathway enrichment analysis indicated a sex-independent increased hyperglycosylation in 8-month-old individuals. The upregulated glycosylation pathways included glycosphingolipids, glycosylphosphatidylinositol anchors, O-glycans, and N-glycans. UDP-sugars and sialic acid were found to be major drivers in regulating glycosylation pathways and metabolic flux. The data indicate a disruption of protein processing at the endoplasmic reticulum and changes in O-glycan biosynthesis. Dysregulation of glycosylation, particularly through the hexosamine biosynthetic pathway, may contribute to bone aging and age-related bone loss. The results warrant further investigation into the functional involvement of increased glycosylation in bone aging. The potential of glycan-based biomarkers as early warning systems for bone aging should be explored and would aid in an advanced understanding of the progression of bone diseases such as osteoporosis.PMID:39452906 | DOI:10.3390/metabo14100525

Struggling to Understand the NEC Spectrum-Could the Integration of Metabolomics, Clinical-Laboratory Data, and Other Emerging Technologies Help Diagnosis?

Fri, 25/10/2024 - 12:00
Metabolites. 2024 Sep 26;14(10):521. doi: 10.3390/metabo14100521.ABSTRACTNecrotizing enterocolitis (NEC) is the most prevalent and potentially fatal intestinal injury mainly affecting premature infants, with significant long-term consequences for those who survive. This review explores the scale of the problem, highlighting advancements in epidemiology, the understanding of pathophysiology, and improvements in the prediction and diagnosis of this complex, multifactorial, and multifaced disease. Additionally, we focus on the potential role of metabolomics in distinguishing NEC from other conditions, which could allow for an earlier and more accurate classification of intestinal injuries in infants. By integrating metabolomic data with other diagnostic approaches, it is hoped to enhance our ability to predict outcomes and tailor treatments, ultimately improving care for affected infants.PMID:39452903 | DOI:10.3390/metabo14100521

Ultra-High-Performance Liquid Chromatography-High-Definition Mass Spectrometry-Based Metabolomics to Reveal the Potential Anti-Arthritic Effects of Illicium verum in Cultured Fibroblast-like Synoviocytes Derived from Rheumatoid Arthritis

Fri, 25/10/2024 - 12:00
Metabolites. 2024 Sep 25;14(10):517. doi: 10.3390/metabo14100517.ABSTRACTBACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. The fruits of Illicium verum, which is a medicinal and edible resource, have been shown to have anti-inflammatory properties.METHODS: In this study, we investigated the effects of I. verum extracts (IVEs) on human RA fibroblasts-like synoviocytes (RA-FLS) by using a sensitive and selective ultra-high-performance liquid chromatography with high-definition mass spectrometry (UPLC-HDMS) method. We subsequently analyzed the metabolites produced after the incubation of cultured RA-FLS with IVEs.RESULTS: IVEs inhibited the proliferation and suppressed the migration of RA-FLS, and reduced the levels of inflammatory factors including TNF-α and IL-6. Twenty differential metabolites responsible for the effects of IVEs were screened and annotated based on the UPLC-HDMS data by using a cell metabolomics approach.DISCUSSION: Our findings suggest that treating RA-FLS with IVEs can regulate lipid and amino acid metabolism, indicating that this extract has the potential to modify the metabolic pathways that cause inflammation in RA.CONCLUSIONS: This might lead to novel therapeutic strategies for managing patients with RA.PMID:39452898 | DOI:10.3390/metabo14100517

Global and Targeted Metabolomics for Revealing Metabolomic Alteration in Niemann-Pick Disease Type C Model Cells

Fri, 25/10/2024 - 12:00
Metabolites. 2024 Sep 24;14(10):515. doi: 10.3390/metabo14100515.ABSTRACTBACKGROUND: Niemann-Pick disease type C (NPC) is an inherited disorder characterized by a functional deficiency of cholesterol transport proteins. However, the molecular mechanisms and pathophysiology of the disease remain unknown.METHODS: In this study, we identified several metabolite characteristics of NPC that may fluctuate in a cellular model of the disease, using both global and targeted metabolomic analyses by liquid chromatography/tandem mass spectrometry (LC-MS/MS). Three cell lines, HepG2 cells (wild-type[WT]) and two NPC model HepG2 cell lines in which NPC1 was genetically ablated (knockout [KO]1 and KO2), were used for metabolomic analysis. Data were subjected to enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.RESULTS: The enrichment analysis of global metabolomics revealed that 8 pathways in KO1 and 16 pathways in KO2 cells were notably altered. In targeted metabolomics for 15 metabolites, 4 metabolites in KO1 and 10 metabolites in KO2 exhibited statistically significant quantitative changes in KO1 or KO2 relative to WT. Most of the altered metabolites were related to creatinine synthesis and cysteine metabolism pathways.CONCLUSIONS: In the future, our objective will be to elucidate the relationship between these metabolic alterations and pathophysiology.PMID:39452896 | DOI:10.3390/metabo14100515

Molecular Mechanisms of Drug Resistance in <em>Leishmania</em> spp

Fri, 25/10/2024 - 12:00
Pathogens. 2024 Sep 27;13(10):835. doi: 10.3390/pathogens13100835.ABSTRACTThe protozoan parasite Leishmania causes leishmaniasis, a neglected tropical disease, that disproportionately affects underdeveloped countries. This disease has major health, economic, and social implications, particularly because of the limited treatment options, high cost, the severe side effects associated with available therapeutics, and the high rate of treatment failure caused by the parasites' growing resistance to current medications. In this review, we describe first the common strategies used by pathogens to develop drug resistance and then focus on the arsenal of available drugs to treat leishmaniasis, their modes of action, and the molecular mechanisms contributing to drug resistance in Leishmania spp., including the role of genomic, transcriptional, and translational control. We focus more specifically on our recent discovery of translational reprogramming as a major driver of drug resistance leading to coordinated changes in the translation of transcripts and orchestrating changes in metabolome and lipidome to support drug resistance. A thorough understanding of these mechanisms is essential to identify the key elements needed to combat resistance and improve leishmaniasis treatment methods.PMID:39452707 | DOI:10.3390/pathogens13100835

Recent Advances in Diagnostic Approaches for Mucormycosis

Fri, 25/10/2024 - 12:00
J Fungi (Basel). 2024 Oct 19;10(10):727. doi: 10.3390/jof10100727.ABSTRACTMucormycosis, an invasive fungal infection caused by members of the order Mucorales, often progresses fulminantly if not recognized in a timely manner. This comprehensive review discusses the latest developments in diagnostic approaches for mucormycosis, from traditional histopathology and culture-based methods to advanced and emerging techniques such as molecular assays, imaging, serology, and metabolomics. We discuss challenges in the diagnosis of mucormycosis and emphasize the importance of rapid and accurate identification of this life-threatening infection.PMID:39452679 | DOI:10.3390/jof10100727

Pathogenicity and Metabolomic Characterization of Fusarium graminearum and Fusarium poae Challenge in Barley under Controlled Conditions

Fri, 25/10/2024 - 12:00
J Fungi (Basel). 2024 Sep 26;10(10):670. doi: 10.3390/jof10100670.ABSTRACTBarley is the third most important cereal crop in terms of production in Canada, and Fusarium head blight (FHB) is one of the main fungal diseases of barley. FHB is caused by a species complex of Fusaria, of which Fusarium graminearum Schwabe is the main causal species of FHB epidemics in Canada. Field surveys show that two or more Fusarium species often co-exist within the same field or grain sample, and F. poae is reported as another important species in barley. This study aimed to determine the pathogenicity of F. graminearum, F. poae, and a co-inoculation of both species causing FHB in barley. Two susceptible barley cultivars were spray-inoculated at 10 to 14 days after heading. Phenotypic disease severity was rated on a scale of 0-9 at 4, 7, 14, 21, and 28 days after inoculation. There was a significant difference in FHB severity between F. graminearum and F. poae, where infection with F. graminearum produced more severe disease ratings. F. poae generated lower disease ratings and was not statistically different from the control. When heads were co-inoculated with both Fusarium species, the resulting FHB severity was unchanged relative to heads inoculated with F. graminearum only. The ratio of F. graminearum to F. poae genomic DNA was also no different than when heads were inoculated with F. graminearum alone, as quantified with ddPCR using markers specific to each species. The metabolomic analysis of sample extracts showed that F. graminearum-associated metabolites dominated the mycotoxin profile of co-inoculated samples, which corroborated our other findings where F. graminearum appeared to outcompete F. poae in barley. No significant effect on visual FHB disease ratings or fungal DNA detection was observed between the cultivars tested. However, there were some metabolome differences between cultivars in response to the challenge by both F. graminearum and F. poae.PMID:39452622 | DOI:10.3390/jof10100670

The Potential Use of Targeted Proteomics and Metabolomics for the Identification and Monitoring of Diabetic Kidney Disease

Fri, 25/10/2024 - 12:00
J Pers Med. 2024 Oct 11;14(10):1054. doi: 10.3390/jpm14101054.ABSTRACTDiabetic kidney disease (DKD) is a prevalent microvascular complication of diabetes mellitus and is associated with a significantly worse prognosis compared to diabetic patients without kidney involvement, other microvascular complications, or non-diabetic chronic kidney disease, due to its higher risk of cardiovascular events, faster progression to end-stage kidney disease, and increased mortality. In clinical practice, diagnosis is based on estimated glomerular filtration rate (eGFR) and albuminuria. However, given the limitations of these diagnostic markers, novel biomarkers must be identified. Omics is a new field of study involving the comprehensive analysis of various types of biological data at the molecular level. In different fields, they have shown promising results in (early) detection of diseases, personalized medicine, therapeutic monitoring, and understanding pathogenesis. DKD is primarily utilized in scientific research and has not yet been implemented in routine clinical practice. The aim of this review is to provide an overview of currently available data on targeted omics. After an extensive literature search, 25 different (panels of) omics were withheld and analyzed. Both serum/plasma and urine proteomics and metabolomics have been described with varying degrees of evidence. For all omics, there is still a relative paucity of data from large, prospective, longitudinal cohorts, presumably because of the heterogeneity of DKD and the lack of patient selection in studies, the complexity of omics technologies, and various practical and ethical considerations (e.g., limited accessibility, cost, and privacy concerns).PMID:39452561 | DOI:10.3390/jpm14101054

Combinations of <em>Terminalia bellirica</em> (Gaertn.) Roxb. and <em>Terminalia chebula</em> Retz. Extracts with Selected Antibiotics Against Antibiotic-Resistant Bacteria: Bioactivity and Phytochemistry

Fri, 25/10/2024 - 12:00
Antibiotics (Basel). 2024 Oct 19;13(10):994. doi: 10.3390/antibiotics13100994.ABSTRACTAntimicrobial resistance (AMR) has arisen due to antibiotic overuse and misuse. Antibiotic resistance renders standard treatments less effective, making it difficult to control some infections, thereby increasing morbidity and mortality. Medicinal plants are attracting increased interest as antibiotics lose efficacy. This study evaluates the antibacterial activity of solvent extracts prepared using Terminalia bellirica and Terminalia chebula fruit against six bacterial pathogens using disc diffusion and broth microdilution assays. The aqueous and methanol extracts of T. bellirica and T. chebula showed substantial zones of inhibition (ZOIs) against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). The activity against those bacteria was strong, with minimum inhibitory concentrations (MIC) ranging from 94 µg/mL to 392 µg/mL. Additionally, the T. bellirica methanolic extract showed noteworthy antibacterial activity against Escherichia coli and an extended spectrum β-lactamase (ESBL) E. coli strain (MIC values of 755 µg/mL for both). The aqueous T. bellirica and T. chebula extracts also inhibited Klebsiella pneumoniae growth (MIC values of 784 µg/mL and 556 µg/mL, respectively). The corresponding methanolic extracts also inhibited ESBL K. pneumoniae growth (MIC values of 755 µg/mL and 1509 µg/mL, respectively). Eighteen additive interactions were observed when extracts were combined with reference antibiotics. Strong antagonism occurred when any of the extracts were mixed with polymyxin B. Liquid chromatography-mass spectroscopy (LC-MS) analysis of the extracts revealed several interesting flavonoids and tannins, including 6-galloylglucose, 1,2,6-trigalloyl-β-D-glucopyranose, 6-O-[(2E)-3-phenyl-2-propenoyl]-1-O-(3,4,5-trihydroxybenzoyl)-β-D-glucopyranose, propyl gallate, methyl gallate, sanguiin H4, hamamelitannin, pyrogallol, gallic acid, ellagic acid, chebulic acid, and chebuloside II. All extracts were nontoxic in brine shrimp assays. This lack of toxicity, combined with their antibacterial activities, suggests that these plant species may be promising sources of antibacterial compound(s) that warrant further study.PMID:39452260 | DOI:10.3390/antibiotics13100994

Identifying Potential Natural Antibiotics from Unani Formulas through Machine Learning Approaches

Fri, 25/10/2024 - 12:00
Antibiotics (Basel). 2024 Oct 14;13(10):971. doi: 10.3390/antibiotics13100971.ABSTRACTThe Unani Tibb is a medical system of Greek descent that has undergone substantial dissemination since the 11th century and is currently prevalent in modern South and Central Asia, particularly in primary health care. The ingredients of Unani herbal medicines are primarily derived from plants. Our research aimed to address the pressing issues of antibiotic resistance, multi-drug resistance, and the emergence of superbugs by examining the molecular-level effects of Unani ingredients as potential new natural antibiotic candidates. We utilized a machine learning approach to tackle these challenges, employing decision trees, kernels, neural networks, and probability-based methods. We used 12 machine learning algorithms and several techniques for preprocessing data, such as Synthetic Minority Over-sampling Technique (SMOTE), Feature Selection, and Principal Component Analysis (PCA). To ensure that our model was optimal, we conducted grid-search tuning to tune all the hyperparameters of the machine learning models. The application of Multi-Layer Perceptron (MLP) with SMOTE pre-processing techniques resulted in an impressive accuracy precision and recall values. This analysis identified 20 important metabolites as essential components of the formula, which we predicted as natural antibiotics. In the final stage of our investigation, we verified our prediction by conducting a literature search for journal validation or by analyzing the structural similarity with known antibiotics using asymmetric similarity.PMID:39452237 | DOI:10.3390/antibiotics13100971

Trends in Antimicrobial Resistance of Uropathogens Isolated from Urinary Tract Infections in a Tertiary Care Hospital in Dhaka, Bangladesh

Fri, 25/10/2024 - 12:00
Antibiotics (Basel). 2024 Sep 27;13(10):925. doi: 10.3390/antibiotics13100925.ABSTRACTBackground/Objectives: Urinary tract infection (UTI) is a prevalent microbial infection in medical practise, leading to significant patient morbidity and increased treatment costs, particularly in developing countries. This retrospective study, conducted at a tertiary care hospital in Dhaka, Bangladesh, aims to examine the antimicrobial resistance (AMR) patterns of uropathogens and evaluate whether these patterns are influenced by demographic factors such as gender, age, or patient status. Methods: Standard microbiological techniques were used to identify uropathogens, and AMR patterns were determined using the Kirby-Bauer disc diffusion method. Results: Out of 6549 urine samples, 1001 cultures were positive. The infection was more prevalent in females compared to males. The incidence of UTIs in children aged 0-10 years accounted for 12.59% of the total cases, with this age group also exhibiting the highest rate of polymicrobial infections. Among the bacterial uropathogens, 71.19% of isolates were multidrug resistant (MDR) and 84.27% were resistant to at least one antibiotic. Escherichia coli (n = 544, 73.90% MDR) and Klebsiella species (n = 143, 48.95% MDR) were the most common Gram-negative uropathogens, while Enterococcus species (n = 78, 94.87% MDR) was the predominant Gram-positive isolate in this study. Our results indicate that most uropathogens showed resistance against ceftazidime, followed by cefuroxime, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate, and netilmicin. Moderate levels of resistance were observed against ciprofloxacin, levofloxacin, aztreonam, and cefpodoxime. Conclusions: Amikacin was observed to be effective against Gram-negative uropathogens, whereas cefixime was more active against Gram-positive microorganisms, such as Enterococcus species. Moreover, a principal coordinate analysis (PCoA) depicted no significant influence of gender, patient status, or age on AMR patterns. For the continued usefulness of most antibiotics, periodic analysis of the AMR patterns of uropathogens can help assess the rise of MDR bacteria, and therefore guide the selection of appropriate antibiotic treatment strategies.PMID:39452192 | DOI:10.3390/antibiotics13100925

Effects of Increasing Oral Deoxynivalenol Gavage on Growth Performance, Blood Biochemistry, Metabolism, Histology, and Microbiome in Rats

Fri, 25/10/2024 - 12:00
Biology (Basel). 2024 Oct 18;13(10):836. doi: 10.3390/biology13100836.ABSTRACTMycotoxin-contaminated feed or food can affect physiological responses and cause illnesses in humans and animals. In this study, we evaluated the effects of deoxynivalenol (DON) toxicity on the growth performance, blood biochemistry, histology, microbiome, and metabolism of rats fed with different toxin concentrations. After 1 week of acclimatization, seven-week-old male rats received 0.9% saline as a control, 0.02 mg/kg DON as T1, and 0.2 mg/kg DON as T2 via oral gavage for 4 weeks. The final body weight of the T2 group was significantly lower than that of the control and T1; however, the average daily gain, feed intake, and feed conversion ratio did not differ. Fibrosis and apoptosis were observed in various tissues as DON concentration increased. Creatinine and alkaline phosphatase levels were significantly lower in the DON-treated group than in the control. Firmicutes and Desulfobacterota phyla dominated the cecum, whereas those in the feces were Proteobacteria and Bacteroidetes. Metabolomic profiling showed phenylalanine, tyrosine, and tryptophan biosynthesis as the most prominent pathways. Overall, our results suggest that low-dose and short-term DON exposure can trigger several adverse effects in rats. Dietary toxicants in rats may explain the physiological effects associated with the metabolism commonly reported in animals.PMID:39452144 | DOI:10.3390/biology13100836

Effects of 4.9 GHz Radiofrequency Field Exposure on Brain Metabolomic and Proteomic Characterization in Mice

Fri, 25/10/2024 - 12:00
Biology (Basel). 2024 Oct 10;13(10):806. doi: 10.3390/biology13100806.ABSTRACTElectromagnetic exposure has become increasingly widespread, and its biological effects have received extensive attention. The purpose of this study was to explore changes in the metabolism profile of the brain and serum and to identify differentially expressed proteins in the brain after exposure to the 4.9 GHz radiofrequency (RF) field. C57BL/6 mice were randomly divided into a Sham group and an RF group, which were sham-exposed and continuously exposed to a 4.9 RF field for 35 d, 1 h/d, at an average power density (PD) of 50 W/m2. After exposure, untargeted metabolomics and Tandem Mass Tags (TMT) quantitative proteomics were performed. We found 104 and 153 up- and down-regulated differentially expressed metabolites (DEMs) in the RF_Brain group and RF_Serum group, and the DEMs were significantly enriched in glycerophospholipid metabolism. Moreover, 10 up-regulated and 51 down-regulated differentially expressed proteins (DEPs) were discovered in the RF group. Functional correlation analysis showed that most DEMs and DEPs showed a significant correlation. These results suggested that 4.9 GHz exposure induced disturbance of metabolism in the brain and serum, and caused deregulation of proteins in the brain.PMID:39452115 | DOI:10.3390/biology13100806

Contemporary Update on Clinical and Experimental Prostate Cancer Biomarkers: A Multi-Omics-Focused Approach to Detection and Risk Stratification

Fri, 25/10/2024 - 12:00
Biology (Basel). 2024 Sep 25;13(10):762. doi: 10.3390/biology13100762.ABSTRACTProstate cancer remains a significant health challenge, being the most prevalent non-cutaneous cancer in men worldwide. This review discusses the critical advancements in biomarker discovery using single-omics and multi-omics approaches. Multi-omics, integrating genomic, transcriptomic, proteomic, metabolomic, and epigenomic data, offers a comprehensive understanding of the molecular heterogeneity of prostate cancer, leading to the identification of novel biomarkers and therapeutic targets. This holistic approach not only enhances the specificity and sensitivity of prostate cancer detection but also supports the development of personalized treatment strategies. Key studies highlighted include the identification of novel genes, genetic mutations, peptides, metabolites, and potential biomarkers through multi-omics analyses, which have shown promise in improving prostate cancer management. The integration of multi-omics in clinical practice can potentially revolutionize prostate cancer prognosis and treatment, paving the way for precision medicine. This review underscores the importance of continued research and the application of multi-omics to overcome current challenges in prostate cancer diagnosis and therapy.PMID:39452071 | DOI:10.3390/biology13100762

Novel Biomarkers for Early Detection of Hepatocellular Carcinoma

Fri, 25/10/2024 - 12:00
Diagnostics (Basel). 2024 Oct 13;14(20):2278. doi: 10.3390/diagnostics14202278.ABSTRACTHepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally. Most patients present with late diagnosis, leading to poor prognosis. This narrative review explores novel biomarkers for early HCC detection. We conducted a comprehensive literature review analyzing protein, circulating nucleic acid, metabolite, and quantitative proteomics-based biomarkers, evaluating the advantages and limitations of each approach. While established markers like alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin, and AFP-L3 remain relevant, promising candidates include circulating tumor DNA, microRNAs, long noncoding RNAs, extracellular vesicle, and metabolomic biomarkers. Multi-biomarker panels like the GALAD score, Oncoguard, and Helio liver test show promise for improved diagnostic accuracy. Non-invasive approaches like urine and gut microbiome analysis are also emerging possibilities. Integrating these novel biomarkers with current screening protocols holds significant potential for earlier HCC detection and improved patient outcomes. Future research should explore multi-biomarker panels, omics technologies, and artificial intelligence to further enhance early HCC diagnosis and management.PMID:39451600 | DOI:10.3390/diagnostics14202278

Hepatotoxicity Induced by Methyl Eugenol: Insights from Toxicokinetics, Metabolomics, and Gut Microbiota

Fri, 25/10/2024 - 12:00
Curr Issues Mol Biol. 2024 Oct 11;46(10):11314-11325. doi: 10.3390/cimb46100673.ABSTRACTDue to continuous application as a flavoring agent in the pesticide, pharmaceutical, and food industries, methyl eugenol (ME) persists in the environment and causes deleterious impacts including cytotoxicity, genotoxicity, and liver damage. This study utilized a comprehensive approach, integrating toxicokinetics, metabolomics, and gut microbiota analysis, to explore the mechanisms behind ME-induced hepatotoxicity in mice. The study observed significant rises in ALT and AST levels, along with significant weight loss, indicating severe liver damage. Toxicokinetic data showed delayed Tmax and plasma accumulation after 28 days of repeated ME exposure at doses of 20 mg/kg, 40 mg/kg, and 60 mg/kg. The metabolomic analysis pinpointed four critical pathways-TCA cycle; alanine, aspartate, and glutamate metabolism; arginine biosynthesis; and tyrosine metabolism-linked to 20 potential biomarkers. Gut microbiota analysis revealed that extended ME exposure led to microbial imbalance, particularly altering the populations of Akkermansia, Prevotella, and Ruminococcus, which are key to amino acid metabolism and the TCA cycle, thus contributing to hepatotoxicity. However, the causal relationship between changes in gut microbiota and liver metabolite levels still requires further in-depth research. This study underscores the significant role of liver metabolites and gut microbiota in ME-induced liver damage.PMID:39451553 | DOI:10.3390/cimb46100673

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