PubMed

Allergy. 2024 Aug 19. doi: 10.1111/all.16275. Online ahead of print.ABSTRACTBACKGROUND: Noninvasive biomarkers for diagnosing and monitoring eosinophilic esophagitis (EoE) are currently lacking. This study evaluates 20 biomarkers in serum and saliva, aiming to assess their diagnostic potential in pediatric EoE patients and healthy individuals.METHODS: Blood and saliva from children undergoing upper endoscopy were analyzed for biomarkers, including absolute eosinophil count (AEC), eosinophil-derived neurotoxin (EDN), total and specific IgG4-antibodies (sIgG4), specific IgE-antibodies (sIgE) and 15-hydroxyeicosatetraenoic acid (15(S)-HETE). Some patients participated twice, forming a longitudinal cohort. The ability to use the biomarkers to predict the EoE diagnosis was evaluated.RESULTS: Analysis from 105 children divided into active EoE, remission, and healthy, revealed elevated levels of serum biomarkers (AEC, EDN, 15(S)-HETE, sIgG4, and sIgE) in active EoE compared to healthy individuals. A combination of biomarkers (AEC, EDN, sIgE to egg white and wheat) and symptoms showed an AUC of 0.92 in distinguishing between the three groups. We further showed that optimal cutoff values for these biomarkers could discriminate between active EoE and healthy with a sensitivity of 88% and a specificity of 100% in distinguishing EoE (active and in remission) from healthy. Longitudinally, levels of EDN, sIgG4 to Bos d 4, Bos d 5, Bos d 8, gliadin, and birch, and sIgE to milk decreased in patients progressing from active EoE to remission (p <.05).CONCLUSIONS: This study identified novel biomarkers associated with EoE and proposes a panel, together with symptoms, for effective discrimination between active EoE, EoE in remission, and healthy individuals. The findings may contribute to a less invasive diagnostic method and may be a potential surveillance tool for pediatric EoE patients.PMID:39157867 | DOI:10.1111/all.16275

J Chem Educ. 2024 Jul 16;101(8):3410-3417. doi: 10.1021/acs.jchemed.4c00270. eCollection 2024 Aug 13.ABSTRACTIsotopic labeling is an important tool in medicinal research, metabolomics, and for understanding reaction mechanisms. In this context, transition metal-catalyzed C-H activation has emerged as a key technology for deuterium incorporation via hydrogen isotope exchange. A detailed and easy-to-implement experimental procedure for a nondirected arene deuteration has been developed that exclusively uses commercial equipment and chemicals. The protocol is ideally suited for students and other prospective applicants who are not experts in catalysis. The degree of deuterium incorporation was analyzed via different means like mass spectrometry and 1H and 2H nuclear magnetic resonance (NMR). A hands-on understanding of quantitative NMR, as well as the influence of H/D exchange on experimental spectra, was conveyed by comparative NMR spin simulations. Students were measurably familiarized with the concepts of C-H activation, isotope effects, and basics in experimental catalysis.PMID:39157437 | PMC:PMC11327962 | DOI:10.1021/acs.jchemed.4c00270

J Reprod Infertil. 2024 Jan-Mar;25(1):3-11. doi: 10.18502/jri.v25i1.15193.ABSTRACTBACKGROUND: Testicular cancer (TC) is a relatively rare type of cancer in men. Early diagnosis of TC remains challenging. Metabolomics holds promise in offering valuable insights in this regard. In this study, a metabolic fingerprinting approach was employed to identify potential biomarkers in both serum and seminal plasma of TC patients.METHODS: A total of 9 patients with testicular cancer and 10 controls were included in the study. The metabolic fingerprinting approach was utilized as a rapid diagnostic tool to analyze the metabolome in serum and seminal plasma of TC patients in comparison to fertile men. Raman spectroscopy was applied for the analysis of metabolites in these biological samples.RESULTS: Principal component analysis (PCA) and functional group analysis showed that the differentiation between serum samples from healthy men and TC patients was not possible. However, when analyzing seminal plasma, a significant difference was found between the two groups (p<0.05). Functional group analysis of serum only showed an increase in tryptophan concentration ratio in TC patients as compared to healthy men (p=0.03). In contrast, in seminal plasma of TC patients, this increase was observed in all analyzed compounds, including phenylalanine, tyrosine, lipids, proteins, phenols (p<0.001).CONCLUSION: Our study highlights the potential of metabolic fingerprinting as a fast diagnostic tool for screening TC patients, with seminal plasma serving as a valuable biological sample. Furthermore, several potential biomarkers, particularly phenylalanine, were identified in seminal plasma. This research contributes to our understanding of TC pathogenesis and has the potential to pave the way for early detection and personalized treatment approaches.PMID:39157284 | PMC:PMC11330202 | DOI:10.18502/jri.v25i1.15193

ACS Omega. 2024 Jul 29;9(32):35182-35196. doi: 10.1021/acsomega.4c05688. eCollection 2024 Aug 13.ABSTRACTA realistic exposure to ionizing radiation (IR) from an improvised nuclear device will likely include individuals who are partially shielded from the initial blast delivered at a very high dose rate (VHDR). As different tissues have varying levels of radiosensitivity, e.g., hematopoietic vs gastrointestinal tissues, the effects of shielding on radiation biomarkers need to be addressed. Here, we explore how biofluid (urine and serum) metabolite signatures from male and female C57BL/6 mice exposed to VHDR (5-10 Gy/s) total body irradiation (TBI, 0, 4, and 8 Gy) compare to individuals exposed to partial body irradiation (PBI) (lower body irradiated [LBI] or upper body irradiated [UBI] at an 8 Gy dose) using a data-independent acquisition untargeted metabolomics approach. Although sex differences were observed in the spatial groupings of urine signatures from TBI and PBI mice, a metabolite signature (N6,N6,N6-trimethyllysine, carnitine, propionylcarnitine, hexosamine-valine-isoleucine, taurine, and creatine) previously developed from variable dose rate experiments was able to identify individuals with high sensitivity and specificity, irrespective of radiation shielding. A panel of serum metabolites composed from previous untargeted studies on nonhuman primates had excellent performance for separating irradiated cohorts; however, a multiomic approach to complement the metabolome could increase dose estimation confidence intervals. Overall, these results support the inclusion of small-molecule markers in biodosimetry assays without substantial interference from the upper or lower body shielding.PMID:39157112 | PMC:PMC11325421 | DOI:10.1021/acsomega.4c05688

Front Cell Dev Biol. 2024 Aug 2;12:1421566. doi: 10.3389/fcell.2024.1421566. eCollection 2024.ABSTRACTAmyotrophic lateral sclerosis (ALS) is a fatal disorder characterized by the selective degeneration of upper and lower motor neurons, leading to progressive muscle weakness and atrophy. The mean survival time is two to five years. Although the hunt for drugs has greatly advanced over the past decade, no cure is available for ALS yet. The role of intense physical activity in the etiology of ALS has been debated for several decades without reaching a clear conclusion. The benefits of organized physical activity on fitness and mental health have been widely described. Indeed, by acting on specific mechanisms, physical activity can influence the physiology of several chronic conditions. It was shown to improve skeletal muscle metabolism and regeneration, neurogenesis, mitochondrial biogenesis, and antioxidant defense. Interestingly, all these pathways are involved in ALS pathology. This review will provide a broad overview of the effect of different exercise protocols on the onset and progression of ALS, both in humans and in animal models. Furthermore, we will discuss challenges and opportunities to exploit physiological responses of imposed exercise training for therapeutic purposes.PMID:39156974 | PMC:PMC11327861 | DOI:10.3389/fcell.2024.1421566

World J Gastroenterol. 2024 Aug 7;30(29):3488-3510. doi: 10.3748/wjg.v30.i29.3488.ABSTRACTBACKGROUND: Hyperuricemia (HUA) is a public health concern that needs to be solved urgently. The lyophilized powder of Poecilobdella manillensis has been shown to significantly alleviate HUA; however, its underlying metabolic regulation remains unclear.AIM: To explore the underlying mechanisms of Poecilobdella manillensis in HUA based on modulation of the gut microbiota and host metabolism.METHODS: A mouse model of rapid HUA was established using a high-purine diet and potassium oxonate injections. The mice received oral drugs or saline. Additionally, 16S rRNA sequencing and ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry-based untargeted metabolomics were performed to identify changes in the microbiome and host metabolome, respectively. The levels of uric acid transporters and epithelial tight junction proteins in the renal and intestinal tissues were analyzed using an enzyme-linked immunosorbent assay.RESULTS: The protein extract of Poecilobdella manillensis lyophilized powder (49 mg/kg) showed an enhanced anti-trioxypurine ability than that of allopurinol (5 mg/kg) (P < 0.05). A total of nine bacterial genera were identified to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder, which included the genera of Prevotella, Delftia, Dialister, Akkermansia, Lactococcus, Escherichia_Shigella, Enterococcus, and Bacteroides. Furthermore, 22 metabolites in the serum were found to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder, which correlated to the Kyoto Encyclopedia of Genes and Genomes pathways of cysteine and methionine metabolism, sphingolipid metabolism, galactose metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. Correlation analysis found that changes in the gut microbiota were significantly related to these metabolites.CONCLUSION: The proteins in Poecilobdella manillensis powder were effective for HUA. Mechanistically, they are associated with improvements in gut microbiota dysbiosis and the regulation of sphingolipid and galactose metabolism.PMID:39156502 | PMC:PMC11326090 | DOI:10.3748/wjg.v30.i29.3488

Kidney Int Rep. 2024 May 9;9(8):2559-2562. doi: 10.1016/j.ekir.2024.04.069. eCollection 2024 Aug.NO ABSTRACTPMID:39156147 | PMC:PMC11328555 | DOI:10.1016/j.ekir.2024.04.069

Anal Chem. 2024 Aug 19. doi: 10.1021/acs.analchem.4c01470. Online ahead of print.ABSTRACTThere is growing interest in limiting the use of fungicides and implementing innovative, environmentally friendly strategies, such as the use of beneficial bacteria-triggered immunity, to protect grapevines from natural pathogens. Therefore, we need rapid and innovative ways to translate the knowledge of the molecular mechanisms underlying the activation of grapevine defenses against pathogens to induced resistance. Here, we have implemented an in vivo minimally invasive approach to study the interaction between plants and beneficial bacteria based on metabolic signatures. Paraburkholderia phytofirmans strain PsJN and PsJN-grapevine were used as bacterial and plant-bacterium interaction models, respectively. Using an innovative tool, SpiderMass, based on water-assisted laser desorption ionization with an IR microsampling probe, we simultaneously detect metabolic and lipidomic species. A metabolomic spectrum was thus generated, which was used to build a library and identify the most variable and discriminative peaks between the two conditions. We then showed that caftaric acid (m/z 311.04), caftaric acid dimer (m/z 623.09), derived caftaric acid (m/z 653.15), and quercetin-O-glucuronide tended to accumulate in grapevine leaves after root bacterization with PsJN. In addition, together with these phenolic messengers, we identified lipid biomarkers such as palmitic acid, linoleic acid, and α-linoleic acid as important messengers of enhanced defense mechanisms in Chardonnay plantlets. Taken together, SpiderMass is the next-generation methodology for studying plant-microorganism metabolic interactions with the prospect of in vivo real-time analysis in viticulture.PMID:39155838 | DOI:10.1021/acs.analchem.4c01470

J Agric Food Chem. 2024 Aug 18. doi: 10.1021/acs.jafc.4c04756. Online ahead of print.ABSTRACTNitrogen (N) is a key factor for plant growth and affects anthocyanin synthesis. This study aimed to clarify the potential mechanisms of N levels (LN, 0 kg·ha-1; MN, 150 kg·ha-1; HN, 225 kg·ha-1) in anthocyanin synthesis and grain quality of colored grain wheat. HN increased the yield component traits and grain morphology traits in colored grain wheat while decreasing the processing and nutrient quality traits. Most quality traits were significantly negatively correlated with the yield composition and morphological traits. Anthocyanin was more accumulated under LN conditions, but other related yield and morphological traits of colored grain wheat declined. The anthocyanin content was the highest in blue wheat, followed by that in purple wheat. Cyanidin-3-O-(6-O-malonyl-β-d-glucoside) and cyanidin-3-O-rutinoside were the predominant anthocyanins in blue and purple wheat. The identified anthocyanin-related metabolites were associated with flavonoid biosynthesis, anthocyanin biosynthesis, and secondary metabolite biosynthesis. Therefore, the study provided information for optimizing nitrogen fertilizer management in producing high quality colored wheat and verified the close relationship between anthocyanin and low N condition.PMID:39155472 | DOI:10.1021/acs.jafc.4c04756

Methods Enzymol. 2024;702:317-352. doi: 10.1016/bs.mie.2024.07.001. Epub 2024 Jul 20.ABSTRACTMicroorganisms, plants, and animals alike have specialized acquisition pathways for obtaining metals, with microorganisms and plants biosynthesizing and secreting small molecule natural products called siderophores and metallophores with high affinities and specificities for iron or other non-iron metals, respectively. This chapter details a novel approach to discovering metal-binding molecules, including siderophores and metallophores, from complex samples ranging from microbial supernatants to biological tissue to environmental samples. This approach, called Native Metabolomics, is a mass spectrometry method in which pH adjustment and metal infusion post-liquid chromatography are interfaced with ion identity molecular networking (IIMN). This rule-based data analysis workflow that enables the identification of metal-binding species based on defined mass (m/z) offsets with the same chromatographic profiles and retention times. Ion identity molecular networking connects compounds that are structurally similar by their fragmentation pattern and species that are ion adducts of the same compound by chromatographic shape correlations. This approach has previously revealed new insights into metal binding metabolites, including that yersiniabactin can act as a biological zincophore (in addition to its known role as a siderophore), that the recently elucidated lepotchelin natural products are cyanobacterial metallophores, and that antioxidants in traditional medicine bind iron. Native metabolomics can be conducted on any liquid chromatography-mass spectrometry system to explore the binding of any metal or multiple metals simultaneously, underscoring the potential for this method to become an essential strategy for elucidating biological metal-binding molecules.PMID:39155117 | DOI:10.1016/bs.mie.2024.07.001

Methods Enzymol. 2024;702:215-227. doi: 10.1016/bs.mie.2024.06.005. Epub 2024 Jul 16.ABSTRACTThe sequencing of microbial genomes has far outpaced their functional annotation. Stable isotopic labeling can be used to link biosynthetic genes with their natural products; however, the availability of the required isotopically substituted precursors can limit the accessibility of this approach. Here, we describe a method for using inverse stable isotopic labeling (InverSIL) to link biosynthetic genes with their natural products. With InverSIL, a microbe is grown on an isotopically substituted medium to create a fully substituted culture, and subsequently, the incorporation of precursors of natural isotopic abundance can be tracked by mass spectrometry. This eliminates issues with isotopically substituted precursor availability. We demonstrate the utility of this approach by linking a luxI-type acyl-homoserine lactone synthase gene in a bacterium that grows on methanol with its quorum sensing signal products. In the future, InverSIL can also be used to link biosynthetic gene clusters hypothesized to produce siderophores with their natural products.PMID:39155113 | DOI:10.1016/bs.mie.2024.06.005

Phytochemistry. 2024 Aug 16:114249. doi: 10.1016/j.phytochem.2024.114249. Online ahead of print.ABSTRACTShort rotation coppices (SRCs) represent an important source of biomass. Since they are grown in various mixtures, SRCs represent an excellent opportunity for assessing the effects of local plant neighbourhoods on their performance. We used a common garden experiment consisting of plots that varied in genotype diversity of SRC willows to test for the effects of chemical traits of individual plants and chemical variation in the plots where they grew on insect herbivory. We also explored whether the composition of willows planted in a plot affected their chemistry. To do this, we performed untargeted metabolomics and quantified various chemical traits related to the total set of metabolites we detected, flavonoids, and salicinoids in four willow genotypes. We measured the leaf herbivory that the plants suffered. The genotypes differed in most chemical traits, yet we found only limited effects of individual traits on herbivory damage. Instead, herbivory damage was positively correlated with structural variation in salicinoids in a plot. When analysing the effects of plot chemical variation on herbivory damage separately for each genotype, we found both positive and negative correlations between the two, suggesting both associational resistance and susceptibility. Finally, we also observed a significant effect of the interaction between genotype and plot composition on structural variation in plant chemistry. Overall, our results suggest that high chemical variation in mixed willow SRCs does not necessarily lower the herbivory damage, possibly due to spillover effects of insect herbivores among genotypes. Our results also show that different genotypes respond differently to plot composition in terms of herbivory damage and chemical composition, which may affect their suitability for growing in mixed stands.PMID:39155032 | DOI:10.1016/j.phytochem.2024.114249

Sci Total Environ. 2024 Aug 16:175592. doi: 10.1016/j.scitotenv.2024.175592. Online ahead of print.ABSTRACTN-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), a widely used antioxidant in rubber products, and its corresponding ozone photolysis product N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q), have raised public concerns due to their environmental toxicity. However, there is an existing knowledge gap on the toxicity of 6PPD and 6PPD-Q to aquatic plants. A model aquatic plant, Chlorella vulgaris (C. vulgaris), was subjected to 6PPD and 6PPD-Q at concentrations of 50, 100, 200, and 400 μg/L to investigate their effects on plant growth, photosynthetic, antioxidant system, and metabolic behavior. The results showed that 6PPD-Q enhanced the photosynthetic efficiency of C. vulgaris, promoting growth of C. vulgaris at low concentrations (50, 100, and 200 μg/L) while inhibiting growth at high concentration (400 μg/L). 6PPD-Q induced more oxidative stress than 6PPD, disrupting cell permeability and mitochondrial membrane potential stability. C. vulgaris responded to contaminant-induced oxidative stress by altering antioxidant enzyme activities and active substance levels. Metabolomics further identified fatty acids as the most significantly altered metabolites following exposure to both contaminants. In conclusion, this study compares the toxicity of 6PPD and 6PPD-Q to C. vulgaris, with 6PPD-Q demonstrating higher toxicity. This study provides valuable insight into the risk assessment of tire wear particles (TWPs) derived chemicals in aquatic habitats and plants.PMID:39154997 | DOI:10.1016/j.scitotenv.2024.175592

Sci Total Environ. 2024 Aug 16:175588. doi: 10.1016/j.scitotenv.2024.175588. Online ahead of print.ABSTRACTIn light of increasing concerns about microplastic pollution, it is crucial to understand the biological impacts of biodegradable PHB microplastics on marine organisms. This study included a 96-h exposure experiment to assess acute toxicity at PHB concentrations of 0 mg/L, 100 mg/L, 500 mg/L and 1000 mg/L. Additionally, a 60-day feeding trial was conducted with PHB concentrations of 0, 0.5, 1.0 and 2.0 g/kg to evaluate the long-term effects on growth, physiological health and metabolic responses of Litopenaeus vannamei. Results from the exposure experiment indicated that PHB microplastics up to 100 mg/L were non-toxic to shrimp. However, the 60-day feeding trial revealed that higher concentrations led to slight reductions in survival rates and growth performance, indicating a concentration-dependent response. Analysis of antioxidant and immune enzymes showed minimal changes across most parameters. However, increases in malondialdehyde content and lysozyme activity at higher PHB levels suggested a stress response. Microbial analysis indicated higher species richness and greater community diversity in the PHB group compared to controls, as evidenced by Chao1, ACE, Shannon and Simpson indices. Linear discriminant analysis revealed that Enterobacteriales and related taxa were more prevalent in the PHB group, while Rhodobacteraceae and associated taxa dominated the control group. Pathway analysis highlighted enhanced signal transduction, cell mobility and metabolic resource reallocation in response to PHB-induced stress. Integrated transcriptomic and metabolomic analyses revealed significant regulatory changes, especially in lipid metabolism pathways. These findings suggest that while PHB microplastics trigger adaptive metabolic responses in shrimp, they do not cause acute toxicity. Significant variations in intestinal microbiome composition reflect potential shifts in gut health dynamics due to PHB ingestion. This study enhances our understanding of the ecological impacts of microplastics and underscores the necessity for further research into the environmental safety of biodegradable alternatives.PMID:39154993 | DOI:10.1016/j.scitotenv.2024.175588

Gene. 2024 Aug 16:148826. doi: 10.1016/j.gene.2024.148826. Online ahead of print.ABSTRACTDictamnine(DIC), as the key pharmacological component of the classical Chinese herbal medicine cortex dictamni, possesses multiple pharmacological activities such as anti-microbial, anti-allergic, anti-cancer, and anti-inflammatory activities, however it is also the main toxicant of cortex dictamni induced hepatic damage, yet the underlying molecular mechanisms causing hepatic damage are still largely unknown. With the purpose of explore possibilities hepatotoxicity of dictamnine in zebrafish and to identify the key regulators and metabolites involved in the biological process, we administered zebrafish to dictamnine at a sub-lethal dose (<LC10) for 24 h and performed biochemical index tests, pathological observations, metabolomics, and transcriptomics analyses. The results showed that the liver function indexes such as ALT and AST were affected after the exposure treatment with dictamnine, and the hepatic damage, lipid droplet formation, and increased apoptosis were observed in zebrafish by HE, oil red O(ORO), and Acridine orange hydrochloride(AO)staining. Transcriptome sequencing analysis showed that dictamnine exposure could generate 5696 down-regulated and 4936 up-regulated DEGs(Differential Expressed Genes); metabolomics analysis showed that 36 potential biomarkers were disturbed by dictamnine exposure treatment in juvenile zebrafish. Integration of metabolomics data and transcriptomics data showed that Patatin like phospholipase domain containing 3 Gene Patatin Like Phospholipase Domain Containing 3(PNPLA3), Lactase Gene(LCT), and Galactosidase Beta 1(GLB1) genes were involved in the regulation of 12 key potential biomarkers related to Galactose metabolism and Glycerophospholipid metabolism, such as LysoPC(16:0/0:0) and UDP-4-dehydro-6-deoxy-D-glucose, which in turn regulated pathways of Galactose metabolism and Glycerophospholipid metabolism and consequently induced hepatotoxicity. The comprehensive evaluation of the hepatotoxicity induced by dictamnine was realized from multiple levels, perspectives and indexes by the integrated evaluation method of zebrafish modeling, which supported the applicability of zebrafish in the evaluation of hepatotoxicity of traditional Chinese medicine, and supplied the scientific basis for elucidating the molecular mechanism of the hepatotoxicity induced by dictamnine, as well as guided the development of the toxicity-reducing therapies by dictamnine in the future.PMID:39154970 | DOI:10.1016/j.gene.2024.148826

J Lipid Res. 2024 Aug 16:100622. doi: 10.1016/j.jlr.2024.100622. Online ahead of print.ABSTRACTThis prospective observational study compared the 1H NMR blood lipidomes and metabolomes of 71 community-acquired pneumonia (CAP) patients, 75 COVID-19 pneumonia patients, and 75 healthy controls (matched by age and sex) to identify potential biomarkers and pathways associated with respiratory infections. Both pneumonia groups had comparable severity indices, including mortality, invasive mechanical ventilation, and intensive care unit admission rates. COVID-19 pneumonia patients exhibited more pronounced hypolipidemia, with significantly lower levels of total cholesterol and LDL-c compared to CAP patients. Atherogenic lipoprotein subclasses (VLDL-cholesterol, IDL-cholesterol, IDL-triglyceride, and LDL-triglyceride/LDL-cholesterol) were significantly increased in severe cases of both pneumonia types, while lower HDL-c and small, dense HDL particles were associated with more severe illness. Both infected groups showed decreased esterified cholesterol and increased triglycerides, along with reduced phosphatidylcholine, lysophosphatidylcholine, PUFA, omega-3 fatty acids, and DHA. Additionally, infected patients had elevated levels of glucose, lactate, 3-hydroxybutyrate, and acetone, which are linked to inflammation, hypoxemia, and sepsis. Increased levels of branched-chain amino acids, alanine, glycine, and creatine, which are involved in energy metabolism and protein catabolism, were also observed. Neurotransmitter synthesis metabolites like histidine and glutamate were higher in infected patients, especially those with COVID-19. Notably, severe infections showed a significant decrease in glutamine, essential for lymphocyte and macrophage energy. Severity in COVID-19 pneumonia was also associated with elevated glycoprotein levels (glycoprotein A, glycoprotein B, glycoprotein F), indicating an inflammatory state. These findings suggest that metabolomic and lipidomic changes in pneumonia are connected to bioenergetic pathways regulating the immune response.PMID:39154734 | DOI:10.1016/j.jlr.2024.100622

J Mol Cell Cardiol. 2024 Aug 16:S0022-2828(24)00135-4. doi: 10.1016/j.yjmcc.2024.08.002. Online ahead of print.ABSTRACTIt is still debated whether changes in metabolic flux are cause or consequence of contractile dysfunction in non-ischemic heart disease. We have previously proposed a model of cardiac metabolism grounded in a series of six moiety-conserved, interconnected cycles. In view of a recent interest to augment oxygen availability in heart failure through iron supplementation, we integrated this intervention in terms of moiety conservation. Examining published work from both human and murine models, we argue this strategy restores a mitochondrial cycle of energy transfer by enhancing mitochondrial pyruvate carrier (MPC) expression and providing pyruvate as a substrate for carboxylation and anaplerosis. Metabolomic data from failing heart muscle reveal elevated pyruvate levels with a concomitant decrease in the levels of Krebs cycle intermediates. Additionally, MPC is downregulated in the same failing hearts, as well as under hypoxic conditions. MPC expression increases upon mechanical unloading in the failing human heart, as does contractile function. We note that MPC deficiency also alters expression of enzymes involved in pyruvate carboxylation and decarboxylation, increases intermediates of biosynthetic pathways, and eventually leads to cardiac hypertrophy and dilated cardiomyopathy. Collectively, we propose that an unbroken chain of moiety-conserved cycles facilitates energy transfer in the heart. We refer to the transport and subsequent carboxylation of pyruvate in the mitochondrial matrix as an example and a proposed target for metabolic support to reverse impaired contractile function. Since the days of bed rest, digitalis, and diuresis, the management of heart failure has tested many new ideas. Although big strides have been made to delay, or even reverse altered cardiac structure and function by mechanical and pharmacological interventions, it remains unknown whether the metabolic alterations in the failing heart are a cause or consequence of its compromised state of contraction.PMID:39154711 | DOI:10.1016/j.yjmcc.2024.08.002

Crit Rev Oncol Hematol. 2024 Aug 16:104480. doi: 10.1016/j.critrevonc.2024.104480. Online ahead of print.ABSTRACTGastrointestinal (GI) cancer continues to pose a significant global health challenge. Recent advances in our understanding of the complex relationship between the host and gut microbiota have shed light on the critical role of metabolic interactions in the pathogenesis and progression of GI cancer. In this study, we examined how microbiota interact with the host to influence signalling pathways that impact the formation of GI tumours. Additionally, we investigated the potential therapeutic approach of manipulating GI microbiota for use in clinical settings. Revealing the complex molecular exchanges between the host and gut microbiota facilitates a deeper understanding of the underlying mechanisms that drive cancer development. Metabolic interactions hold promise for the identification of microbial signatures or metabolic pathways associated with specific stages of cancer. Hence, this study provides potential strategies for the diagnosis, treatment and management of GI cancers to improve patient outcomes.PMID:39154670 | DOI:10.1016/j.critrevonc.2024.104480

J Reprod Immunol. 2024 Aug 12;165:104315. doi: 10.1016/j.jri.2024.104315. Online ahead of print.ABSTRACTReproductive diseases and illnesses pose significant challenges in cattle farming, affecting fertility, milk production, and overall herd health. In recent years, the integration of various omics approaches, including transcriptomics, proteomics, metagenomics, miRNAomics, and metabolomics, has revolutionized the study of these conditions. This systematic review summarised the findings from studies that investigated reproductive disease biomarkers in both male and female cattle. After extracting 6137 studies according to exclusion and inclusion criteria, a total of 60 studies were included in this review. All studies identified were associated with female cattle and none were related to reproductive diseases in bulls. The analysis highlights specific biomarkers, metabolic pathways, and microbial compositions associated with bovine reproductive disease conditions, providing valuable insights into the underlying molecular mechanisms of disease. Pro-inflammatory cytokines such as IL-1β, IL-8, IL-4, IL-6, TNFα and acute-phase response proteins such as SAA and HP have been identified as promising biomarkers for bovine reproductive diseases. However, further research is needed to validate these markers clinically and to explore potential strategies for improving cow reproductive health. The role of bulls as carriers of venereal diseases has been underestimated in the current literature and therefore needs more attention to understand their impact on infectious reproductive diseases of female cattle.PMID:39154625 | DOI:10.1016/j.jri.2024.104315

EBioMedicine. 2024 Aug 17;107:105279. doi: 10.1016/j.ebiom.2024.105279. Online ahead of print.ABSTRACTBACKGROUND: 1H-NMR metabolomics and DNA methylation in blood are widely known biomarkers predicting age-related physiological decline and mortality yet exert mutually independent mortality and frailty signals.METHODS: Leveraging multi-omics data in four Dutch population studies (N = 5238, ∼40% of which male) we investigated whether the mortality signal captured by 1H-NMR metabolomics could guide the construction of DNA methylation-based mortality predictors.FINDINGS: We trained DNA methylation-based surrogates for 64 metabolomic analytes and found that analytes marking inflammation, fluid balance, or HDL/VLDL metabolism could be accurately reconstructed using DNA-methylation assays. Interestingly, a previously reported multi-analyte score indicating mortality risk (MetaboHealth) could also be accurately reconstructed. Sixteen of our derived surrogates, including the MetaboHealth surrogate, showed significant associations with mortality, independent of relevant covariates.INTERPRETATION: The addition of our metabolic analyte-derived surrogates to the well-established epigenetic clock GrimAge demonstrates that our surrogates potentially represent valuable mortality signal.FUNDING: BBMRI-NL, X-omics, VOILA, Medical Delta, NWO, ERC.PMID:39154540 | DOI:10.1016/j.ebiom.2024.105279