PubMed

Metabolites. 2024 Oct 16;14(10):552. doi: 10.3390/metabo14100552.ABSTRACTBackground/objectives: Ischemic stroke is a major health concern, and nutrition is a modifiable risk factor that can influence recovery outcomes. This study investigated the impact of maternal dietary deficiencies in folic acid (FADD) or choline (ChDD) on the metabolite profiles of offspring after ischemic stroke. Methods: A total of 32 mice (17 males and 15 females) were used to analyze sex-specific differences in response to these deficiencies. Results: At 1-week post-stroke, female offspring from the FADD group showed the greatest number of altered metabolites, including pathways involved in cholesterol metabolism and neuroprotection. At 4 weeks post-stroke, both FADD and ChDD groups exhibited significant disruptions in metabolites linked to inflammation, oxidative stress, and neurotransmission. Conclusions: These alterations were more pronounced in females compared to males, suggesting sex-dependent responses to maternal dietary deficiencies. The practical implications of these findings suggest that ensuring adequate maternal nutrition during pregnancy may be crucial for reducing stroke susceptibility and improving post-stroke recovery in offspring. Nutritional supplementation strategies targeting folic acid and choline intake could potentially mitigate the long-term adverse effects on metabolic pathways and promote better neurological outcomes. Future research should explore these dietary interventions in clinical settings to develop comprehensive guidelines for maternal nutrition and stroke prevention.PMID:39452933 | DOI:10.3390/metabo14100552

Metabolites. 2024 Oct 13;14(10):546. doi: 10.3390/metabo14100546.ABSTRACTBACKGROUND: Clear cell renal cell carcinoma (ccRCC) comprises the majority, approximately 70-80%, of renal cancer cases and often remains asymptomatic until incidentally detected during unrelated abdominal imaging or at advanced stages. Currently, standardized screening tests for renal cancer are lacking, which presents challenges in disease management and improving patient outcomes. This study aimed to identify ccRCC-specific volatile organic compounds (VOCs) in the urine of ccRCC-positive patients and develop a urinary VOC-based diagnostic model.METHODS: This study involved 233 pretreatment ccRCC patients and 43 healthy individuals. VOC analysis utilized stir-bar sorptive extraction coupled with thermal desorption gas chromatography/mass spectrometry (SBSE-TD-GC/MS). A ccRCC diagnostic model was established via logistic regression, trained on 163 ccRCC cases versus 31 controls, and validated with 70 ccRCC cases versus 12 controls, resulting in a ccRCC diagnostic model involving 24 VOC markers.RESULTS: The findings demonstrated promising diagnostic efficacy, with an Area Under the Curve (AUC) of 0.94, 86% sensitivity, and 92% specificity.CONCLUSIONS: This study highlights the feasibility of using urine as a reliable biospecimen for identifying VOC biomarkers in ccRCC. While further validation in larger cohorts is necessary, this study's capability to differentiate between ccRCC and control groups, despite sample size limitations, holds significant promise.PMID:39452927 | DOI:10.3390/metabo14100546

Metabolites. 2024 Oct 13;14(10):545. doi: 10.3390/metabo14100545.ABSTRACTMultiple sclerosis (MS) is a neurodegenerative and inflammatory disease of the central nervous system (CNS) that leads to a loss of myelin. There are three main types of MS: relapsing-remitting MS (RRMS) and primary and secondary progressive disease (PPMS, SPMS). The differentiation in the pathogenesis of these two latter courses is still unclear. The underlying mechanisms of MS are yet to be elucidated, and the treatment relies on immune-modifying agents. Recently, lipidomics and metabolomics studies using human biofluids, mainly plasma and cerebrospinal fluid (CSF), have suggested an important role of lipids and metabolites in the pathophysiology of MS. In this review, the results from studies on metabolomics and lipidomics analyses performed on biological samples of MS patients and MS-like animal models are presented and analyzed. Based on the collected findings, the biochemical pathways in human and animal cohorts involved were investigated and biological mechanisms and the potential role they have in MS are discussed. Limitations and challenges of metabolomics and lipidomics approaches are presented while concluding that metabolomics and lipidomics may provide a more holistic approach and provide biomarkers for early diagnosis of MS disease.PMID:39452926 | DOI:10.3390/metabo14100545

Metabolites. 2024 Oct 11;14(10):543. doi: 10.3390/metabo14100543.ABSTRACTBACKGROUND: The dramatic temperature fluctuations spurred by global warming and the accompanying extreme weather events inhibit mango growth and threaten mango productivity. Particularly, mango flowering is highly sensitive to temperature changes. The mango fruit setting rate was significantly positively correlated with pollen activity, and pollen activity was regulated by different metabolites.METHODS: In this study, the in vitro pollen of two mango varieties ('Renong No.1' and 'Jinhuang'), in which sensitivity to temperature differed significantly, were subjected to different temperature stresses (15 °C, 25 °C and 35 °C), and their metabolomics were analyzed.RESULTS: The present results showed that 775 differential metabolites were screened by liquid chromatography-mass spectrometry and divided into 12 categories. The two varieties had significant differences in metabolite expression under different temperature stresses and the effect of low temperature on 'Renong No.1' mainly focused on amino acid metabolism, while the effect on 'Jinhuang' was mainly related to glycolysis. However, under the 35 °C temperature stress, 'Renong No.1' responded by redistributing riboflavin and betaine in vivo and the most obvious metabolic pathway of 'Jinhuang' enrichment was pyrimidine metabolism, which had undergone complex main body formation and extensive regulatory processes. The changes of metabolites of different varieties under low temperature and high temperature stress were different. Among them, flavonoids or flavonoid derivatives were included in class A (216 metabolites), C (163 metabolites) and D (233 metabolites) metabolites, indicating that flavonoid metabolites had an obvious regulatory effect on mango pollen metabolism under different temperature stress.CONCLUSIONS: The present results provide valuable information for reproductive biology studies and breeding in mango, in particular, the selection and breeding of the most suitable varieties for different production areas.PMID:39452924 | DOI:10.3390/metabo14100543

Metabolites. 2024 Oct 11;14(10):542. doi: 10.3390/metabo14100542.ABSTRACTBACKGROUND/OBJECTIVES: Metabolomics provides insights into the biological underpinnings of disease development and treatment. This systematic review investigated the impact of acupuncture on metabolite levels and associated metabolic pathways using a metabolomic approach.METHODS: Five databases (i.e., PubMed, Embase, Scopus, CINAHL, and Cochrane Central) were searched using terms such as "acupuncture" and "metabolites" to retrieve relevant journal articles published through January 2024. Studies utilizing mass spectrometry or nuclear magnetic resonance were included. Risk of bias was evaluated using the Cochrane Risk of Bias tool and the Newcastle-Ottawa scale. Metabolic pathway analysis was conducted using MetaboAnalyst 6.0 to identify common significant pathways affected by acupuncture. Additionally, subgroup pathway enrichment analysis identified metabolites significantly altered in more than two studies.RESULTS: Among 4019 articles, 22 studies met inclusion criteria, examining changes in metabolomic biomarkers before and after acupuncture for various diseases and symptoms. A total of 226 metabolites showed significant changes, with 14 common metabolites altered in more than two studies (glutamine, androsterone glucuronide, choline, citric acid, decanoylcarnitine, estrone, glutathione, glycine, hypoxanthine, lactic acid, pyruvic acid, serine, proline, and sn-glycero-3-phosphocholine). Common pathways affected by acupuncture were glycine, serine, and threonine metabolism, glutathione metabolism, arginine biosynthesis, and glyoxylate and dicarboxylate metabolism.CONCLUSIONS: This review provides insights of the metabolomic mechanisms underlying acupuncture, highlighting its impact on specific metabolic pathways. Recognizing these changes can enhance acupuncture's effectiveness and support the development of personalized treatments. The findings underscore metabolomics as a valuable tool for understanding and optimizing acupuncture for various diseases and symptoms.PMID:39452923 | DOI:10.3390/metabo14100542

Metabolites. 2024 Oct 9;14(10):539. doi: 10.3390/metabo14100539.ABSTRACTBackground: Pentosidine is an advanced glycation end product that is commonly found in heat-processed foods. Pentosidine has been involved in the occurrence and development of some chronic diseases. It was reported that pentosidine exposure can impair the function of the liver and kidneys. Adipose tissue, as an active endocrine organ, plays an important role in maintaining the normal physiological function of cells. However, the metabolic mechanism that causes pentosidine to induce toxicity in adipose tissue remains unclear. Methods: In the study, thirty male Sprague-Dawley rats were divided into a normal diet group, low dose group, and high dose group. A non-targeted metabolomics approach was used to compare the metabolic profiles of adipose tissue between the pentosidine and normal diet groups. Furthermore, histopathological observation and body weight change analysis were performed to test the results of the metabolomics analysis. Results: A total of forty-two differential metabolites were identified. Pentosidine mainly disturbed twelve metabolic pathways, such as ascorbate and aldarate metabolism, glycine, serine, and threonine metabolism, sulfur metabolism, pyruvate metabolism, etc. Additionally, pyruvic acid was identified as a possible key upregulated metabolite involved in thirty-four metabolic pathways. α-Ketoglutaric acid was named as a probable key downregulated metabolite involved in nineteen metabolic pathways based on enrichment network analysis. In addition, histopathological analysis and body weight changes confirmed the results of the metabolomics analysis. Conclusions: These results provided a new perspective for the molecular mechanisms of adipose tissue toxicity induced by pentosidine.PMID:39452920 | DOI:10.3390/metabo14100539

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

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

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

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

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

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

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

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

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

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

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

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

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

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