PubMed

Animals (Basel). 2024 Aug 4;14(15):2264. doi: 10.3390/ani14152264.ABSTRACTBovine mastitis is an inflammatory disease of the mammary glands, and its pathogenesis and diagnosis are complicated. Through qualitative and quantitative analysis of small-molecule metabolites, the metabolomics technique plays an important role in finding biomarkers and studying the metabolic mechanism of bovine mastitis. Therefore, this paper reviews the predictive and diagnostic biomarkers of bovine mastitis that have been identified using metabolomics techniques and that are present in samples such as milk, blood, urine, rumen fluid, feces, and mammary tissue. In addition, the metabolic pathways of mastitis-related biomarkers in milk and blood were analyzed; it was found that the tricarboxylic acid (TCA) cycle was the most significant (FDR = 0.0015767) pathway in milk fluid, and glyoxylate and dicarboxylate metabolism was the most significant (FDR = 0.0081994) pathway in blood. The purpose of this review is to provide useful information for the prediction and early diagnosis of bovine mastitis.PMID:39123790 | DOI:10.3390/ani14152264

Animals (Basel). 2024 Aug 3;14(15):2256. doi: 10.3390/ani14152256.ABSTRACTThe objective of this experiment was to explore the effects of three-way hybridization on rumen microbes and metabolites in sheep using rumen metagenomics and metabolomics. Healthy Hu and CAH (Charolais × Australian White × Hu) male lambs of similar birth weight and age were selected for short-term fattening after intensive weaning to collect rumen fluid for sequencing. Rumen metagenomics diversity showed that Hu and CAH sheep were significantly segregated at the species, KEGG-enzyme, and CAZy-family levels. Moreover, the CAH significantly increased the ACE and Chao1 indices. Further, correlation analysis of the abundance of the top 80 revealed that the microorganisms were interrelated at the species, KEGG-enzyme, and CAZy-family levels. Overall, the microbiome significantly affected metabolites of the top five pathways, with the strongest correlation found with succinic acid. Meanwhile, species-level microbial markers significantly affected rumen differential metabolites. In addition, rumen microbial markers in Hu sheep were overall positively correlated with down-regulated metabolites and negatively correlated with up-regulated metabolites. In contrast, rumen microbial markers in CAH lambs were overall negatively correlated with down-regulated metabolites and positively correlated with up-regulated metabolites. These results suggest that three-way crossbreeding significantly affects rumen microbial community and metabolite composition, and that significant interactions exist between rumen microbes and metabolites.PMID:39123781 | DOI:10.3390/ani14152256

Animals (Basel). 2024 Jul 31;14(15):2225. doi: 10.3390/ani14152225.ABSTRACTThe type of muscle fiber plays a crucial role in the growth, development, and dynamic plasticity of animals' skeletal muscle. Additionally, it is a primary determinant of the quality of both fresh and processed meat. Therefore, understanding the regulatory factors that contribute to muscle fibers' heterogeneity is of paramount importance. Recent advances in sequencing and omics technologies have enabled comprehensive cross-verification of research on the factors affecting the types of muscle fiber across multiple levels, including the genome, transcriptome, proteome, and metabolome. These advancements have facilitated deeper exploration into the related biological questions. This review focused on the impact of individual characteristics, feeding patterns, and genetic regulation on the proportion and interconversion of different muscle fibers. The findings indicated that individual characteristics and feeding patterns significantly influence the type of muscle fiber, which can effectively enhance the type and distribution of muscle fibers in livestock. Furthermore, non-coding RNA, genes and signaling pathways between complicated regulatory mechanisms and interactions have a certain degree of impact on muscle fibers' heterogeneity. This, in turn, changes muscle fiber profile in living animals through genetic selection or environmental factors, and has the potential to modulate the quality of fresh meat. Collectively, we briefly reviewed the structure of skeletal muscle tissue and then attempted to review the inevitable connection between the quality of fresh meat and the type of muscle fiber, with particular attention to potential events involved in regulating muscle fibers' heterogeneity.PMID:39123750 | DOI:10.3390/ani14152225

Animals (Basel). 2024 Jul 28;14(15):2198. doi: 10.3390/ani14152198.ABSTRACTThe addition of glycerin, vitamin C, and niacinamide to pig diets increased the redness of longissimus dorsi; however, it remains unclear how these supplements affect gut microbiota and metabolites. A total of 84 piglets (20.35 ± 2.14 kg) were randomly allotted to groups A (control), B (glycerin-supplemented), C (vitamin C and niacinamide-supplemented), and D (glycerin, vitamin C and niacinamide-supplemented) during a feeding experiment. Metagenomic and metabolomic technologies were used to analyze the fecal compositions of bile acids, metabolites, and microbiota. The results showed that compared to pigs in group A, pigs in group D had lower virulence factor expressions of lipopolysaccharide (p < 0.05), fatty acid resistance system (p < 0.05), and capsule (p < 0.01); higher fecal levels of ferric ion (p < 0.05), allolithocholic acid (p < 0.01), deoxycholic acid (p < 0.05), tauroursodeoxycholic acid dihydrate (p < 0.01), glycodeoxycholic acid (p < 0.05), L-proline (p < 0.01) and calcitriol (p < 0.01); and higher (p < 0.05) abundances of iron-acquiring microbiota (Methanobrevibacter, Clostridium, Clostridiaceae, Clostridium_sp_CAG_1000, Faecalibacterium_sp_CAG_74_58_120, Eubacteriales_Family_XIII_Incertae_Sedis, Alistipes_sp_CAG_435, Alistipes_sp_CAG_514 and Methanobrevibacter_sp_YE315). Supplementation with glycerin, vitamin C, and niacinamide to pigs significantly promoted the growth of iron-acquiring microbiota in feces, reduced the expression of some virulence factor genes of fecal pathogens, and increased the fecal levels of ferric ion, L-proline, and some secondary bile acids. The administration of glycerol, vitamin C, and niacinamide to pigs may serve as an effective measure for muscle redness improvement by altering the compositions of fecal microbiota and metabolites.PMID:39123724 | DOI:10.3390/ani14152198

Animals (Basel). 2024 Jul 25;14(15):2164. doi: 10.3390/ani14152164.ABSTRACTThe intestinal microbiota and its metabolites are essential for the health and growth development of animals. Current research indicates that sex has a certain impact on the structure and function of the intestinal microbiota, but there are few reports on sex differences in intestinal microbiota metabolites, including those of castrated male animals. This study aimed to explore the impact of sex on the intestinal microbial metabolites of Hainan special wild boars (10 entire male pigs, 10 female pigs, and 10 castrated male pigs, denoted EM, FE, and CM, respectively) by employing non-targeted metabolomics and gas chromatography. A total of 1086 metabolites were detected, with the greatest number of differential metabolites observed between EM and FE (54 differential metabolites, including 18 upregulated and 36 downregulated metabolites), the fewest between CM and FE (7 differential metabolites, including 1 upregulated and 6 downregulated metabolites), and an intermediate number between CM and EM (47 differential metabolites, including 35 upregulated and 12 downregulated metabolites). Differential metabolites were involved in more pathways between EM and FE and between CM and EM, including amino acid metabolism and digestive system pathways, whereas differential metabolites were involved in the fewest pathways between CM and FE. Correlation analysis showed Ruminococcaceae UCG-009, uncultured_bacterium_o_SAR324_cladeMarine_group_B, and Candidatus Saccharimonas contributed to the production of metabolites such as trehalose, docosatrienoic acid, D(-)-beta-hydroxy butyric acid, and acetyl-DL-leucine. The levels of acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and isovaleric acid were significantly higher in EM than in FE, with CM falling between the two. Streptococcus, Lachnospiraceae_NK4A136_group and Rikenellaceae_RC9_gut_group showed a significant positive correlation with the production of short-chain fatty acids (SCFAs), while [Eubacterium]_coprostanoligenes_group, uncultured_bacterium_f_p-251-o5 and Ruminococcaceae_UCG-005 showed a significant negative correlation with the generation of SCFAs. This study provides foundational data and significant insights into precision feeding strategies for Hainan special wild boars of different sexes, as well as the study of sex differences in intestinal microbial metabolites in animals.PMID:39123691 | DOI:10.3390/ani14152164

Animals (Basel). 2024 Jul 24;14(15):2149. doi: 10.3390/ani14152149.ABSTRACTThe dietary crude protein level could affect ruminal fermentation parameters and the microflora of ruminants. The present study's aim was to investigate the effects of different protein level diets on ruminal morphology, fermentation parameters, digestive enzyme activity, microflora and metabolites of Tibetan sheep. Ninety weaned lambs (initial weight of 15.40 ± 0.81 kg, 2 months old) were selected and randomly divided into three groups (six pens/treatment, five rams/pen). Dietary treatments were formulated with 13.03% (high protein, HP), 11.58% (moderate protein, MP) and 10.20% (low protein, LP), respectively. Compared with LP, both papillae length and papillae width were significantly promoted in HP and MP (p < 0.05). The concentrations of ammonia nitrogen, total VFAs, propionic acids and butyric acids in HP were significantly increased compared to those in MP and LP (p < 0.05). The activities of protease and α-amylase in HP were significantly greater than those of LP (p < 0.05). For the ruminal microbial community, higher proportions of phylum Prevotella 1 and Succiniclasticum and genus Rikenellaceae RC9 gut group and Ruminococcus 1 were observed in HP (p < 0.05). A total of 60 differential metabolites (DMs) (28 up, 32 down) between HP and MP; 73 DMs (55 up, 18 down) between HP and LP; and 65 DMs (49 up, 16 down) between MP and LP were identified. Furthermore, four pathways of the biosynthesis of unsaturated fatty acids, tryptophan metabolism, bile secretion and ABC transporters were significantly different (p < 0.05). The abundance of phylum Prevotella 1 was negatively associated with stearic acid and palmitic acid but positively associated with the taurine. The abundance of genus Ruminococcus 1 was negatively associated with stearic acid, oleic acid, erucic acid, Indole-3-acetamide and palmitic acid but positively associated with 6-hydroxymelatonin. In conclusion, a 13.03% CP level improved ruminal morphology, fermentation parameters and digestive enzyme activities through modulating the microbial community and regulating metabolism in Tibetan sheep.PMID:39123675 | DOI:10.3390/ani14152149

Foods. 2024 Jul 29;13(15):2399. doi: 10.3390/foods13152399.ABSTRACTFermentation with Bacillus subtilis significantly enhances the physiological activity and bioavailability of soymilk, but the resulting characteristic flavor seriously affects its industrial promotion. The objective of this study was to identify key proteins associated with characteristic flavors in B. subtilis BSNK-5-fermented soymilk using tandem mass tag (TMT) proteomics. The results showed that a total of 765 differentially expressed proteins were identified. Seventy differentially expressed proteins related to characteristic flavor were screened through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. After integrating metabolomics data, fifteen key proteases of characteristic flavor components in BSNK-5-fermented soymilk were further identified, and free ammonia was added. In addition, there were five main formation mechanisms, including the decomposition of urea to produce ammonia; the degradation of glutamate by glutamate dehydrogenase to produce ammonia; the degradation of threonine and non-enzymatic changes to form the derivative 2,5-dimethylpyrazine; the degradation of valine, leucine, and isoleucine to synthesize isovalerate and 2-methylbutyrate; and the metabolism of pyruvate and lactate to synthesize acetate. These results provide a theoretical foundation for the improvement of undesirable flavor in B. subtilis BSNK-5-fermented soy foods.PMID:39123590 | DOI:10.3390/foods13152399

Foods. 2024 Jul 28;13(15):2384. doi: 10.3390/foods13152384.ABSTRACTLycium barbarum L., an important functional food in China, has antioxidant and antiaging activity. However, the exact antioxidant activity mechanism of Lycium barbarum extracts (LBE) is not well understood. Therefore, a carbendazim (CBZ)-induced PC12 cell injury model was constructed and vitrificated to study the antioxidant activity of fresh LBE on the basis of extraction parameter optimization via the full factorial design of experiments (DOE) method. The results showed that the pretreatment of PC12 cells with LBE could reduce the reactive oxygen species (ROS) level by 14.6% and inhibited the mitochondrial membrane potential (MMP) decline by 12.0%. Furthermore, the integrated analysis revealed that LBE played an antioxidant role by activating oxidative phosphorylation (OXPHOS) and restoring MMP, maintaining the tricarboxylic acid (TCA) cycle stability, and regulating the GSH metabolic pathway. The results of the present study provide new ideas for the understanding of the antioxidant function of LBE from a global perspective.PMID:39123576 | DOI:10.3390/foods13152384

Foods. 2024 Jul 27;13(15):2376. doi: 10.3390/foods13152376.ABSTRACTThis study aimed, for the first time, to determine the nutritional composition, beta-glucan and ergosterol contents, phenolic compound composition, and biological and functional activities of a novel mycoprotein produced through a bioconversion process of Durvillaea spp., a brown seaweed. An untargeted metabolomics approach was employed to screen metabolites and annotate molecules with nutraceutical properties. Two products, each representing a distinct consortia of co-cultured fungi, named Myco 1 and Myco 2, were analysed in this study. These consortia demonstrated superior properties compared to those of Durvillaea spp., showing significant increases in total protein (~238%), amino acids (~219%), and β-D-glucans (~112%). The protein contains all essential amino acids, a low fatty acid content, and exhibits high antioxidant activity (21.5-25.5 µmol TE/g). Additionally, Myco 2 exhibited the highest anti-alpha-glucosidase activity (IC50 = 16.5 mg/mL), and Myco 1 exhibited notable anti-lipase activity (IC50 = 10.5 mg/mL). Among the 69 top differentially abundant metabolites screened, 8 nutraceutical compounds were present in relatively high concentrations among the identified mycoproteins. The proteins and polysaccharides in the mycoprotein may play a crucial role in the formation and stabilization of emulsions, identifying it as a potent bioemulsifier. In conclusion, the bioconversion of Durvillaea spp. results in a mycoprotein with high-quality protein, significant nutritional and functional value, and prebiotic and nutraceutical potential due to the production of unique bioactive compounds.PMID:39123566 | DOI:10.3390/foods13152376

Foods. 2024 Jul 26;13(15):2364. doi: 10.3390/foods13152364.ABSTRACTIn order to investigate the composition and differences in volatile organic compounds (VOCs) in yak and cattle-yak meat and determine the key metabolites and metabolic pathways related to flavor formation. In this study, the VOCs and non-volatile metabolites in Longissimus dorsi muscle of two groups of samples were detected and analyzed by gas chromatography-ion migration spectrometry (GC-IMS) and gas chromatography-mass spectrometry (GC-MS). The results showed that 31 VOCs were identified by GC-IMS, including 5 alcohols, 5 ketones, 5 esters, 3 aldehydes, 2 furans, 2 hydrocarbons, 1 amine, 1 acid, 1 thiazole, 1 pyrazine, and 5 others. Most of them were alcohols, ketones, esters, and aldehydes. A total of 75 non-volatile metabolites with significant differences were obtained by GC-MS screening, among which amino acid contents such as serine, glycine, phenylalanine, and aspartic acid were significantly up-regulated in cattle-yak, and glutamic acid and tyrosine were significantly up-regulated in yak. The non-volatile differential metabolites in the two groups were significantly enriched in the metabolic pathways of arginine biosynthesis and oxidative phosphorylation. By combining GC-IMS and GC-MS, this study comprehensively and intuitively reflected the differences in VOCs between yak and cattle-yak meat, and clarified the metabolomic reasons for the differences in VOCs, so as to provide a theoretical basis for meat quality improvement.PMID:39123555 | DOI:10.3390/foods13152364

Foods. 2024 Jul 24;13(15):2327. doi: 10.3390/foods13152327.ABSTRACTThe meat of local livestock breeds often has unique qualities and flavors. In this study, three Shanghai native pig breeds (MSZ, SWT, and SHB) exhibited better meat quality traits than globalized commercial pig breeds (DLY). Subsequently, metabolomic and lipidomic differences in the longissimus dorsi (L) and gluteus (T) muscles of the Shanghai native pig breeds and DLY pig breed were compared using liquid chromatography-mass spectrometry (LC-MS). The results demonstrated that the metabolites mainly consisted of (28.16%) lipids and lipid-like molecules, and (25.87%) organic acids and their derivatives were the two most dominant groups. Hundreds of differential expression metabolites were identified in every compared group, respectively. One-way ANOVA was applied to test the significance between multiple groups. Among the 20 most abundant differential metabolites, L-carnitine was significantly different in the muscles of the four pig breeds (p-value = 7.322 × 10-11). It was significantly higher in the L and T muscles of the two indigenous black pig breeds (MSZ and SWT) than in the DLY pigs (p-value < 0.001). Similarly, lipidomic analysis revealed the PA (18:0/18:2) was significantly more abundant in the muscle of these two black breeds than that in the DLY breed (p-value < 0.001). These specific metabolites and lipids might influence the meat quality and taste properties and lead to customer preferences. Therefore, this study provided insights into the characterization of meat metabolites and lipids in Shanghai native pig breeds.PMID:39123517 | DOI:10.3390/foods13152327

Cancers (Basel). 2024 Jul 30;16(15):2705. doi: 10.3390/cancers16152705.ABSTRACTAberrant metabolism is a hallmark of malignancies including gliomas. Intracranial microdialysis enables the longitudinal collection of extracellular metabolites within CNS tissues including gliomas and can be leveraged to evaluate changes in the CNS microenvironment over a period of days. However, delayed metabolic impacts of CNS injury from catheter placement could represent an important covariate for interpreting the pharmacodynamic impacts of candidate therapies. Intracranial microdialysis was performed in patient-derived glioma xenografts of glioma before and 72 h after systemic treatment with either temozolomide (TMZ) or a vehicle. Microdialysate from GBM164, an IDH-mutant glioma patient-derived xenograft, revealed a distinct metabolic signature relative to the brain that recapitulated the metabolic features observed in human glioma microdialysate. Unexpectedly, catheter insertion into the brains of non-tumor-bearing animals triggered metabolic changes that were significantly enriched for the extracellular metabolome of glioma itself. TMZ administration attenuated this resemblance. The human glioma microdialysate was significantly enriched for both the PDX versus brain signature in mice and the induced metabolome of catheter placement within the murine control brain. These data illustrate the feasibility of microdialysis to identify and monitor the extracellular metabolome of diseased versus relatively normal brains while highlighting the similarity between the extracellular metabolome of human gliomas and that of CNS injury.PMID:39123433 | DOI:10.3390/cancers16152705

Cancers (Basel). 2024 Jul 25;16(15):2643. doi: 10.3390/cancers16152643.ABSTRACTAs of 2022, lung cancer is the most commonly diagnosed cancer worldwide, with the highest mortality rate. There are three main histological types of lung cancer, and it is more important than ever to accurately identify the subtypes since the development of personalized, type-specific targeted therapies that have improved mortality rates. Traditionally, the gold standard for the confirmation of histological subtyping is tissue biopsy and histopathology. This, however, comes with its own challenges, which call for newer sampling techniques and adjunctive tools to assist in and improve upon the existing diagnostic workflow. This review aims to list and describe studies from the last decade (n = 47) that investigate three such potential omics techniques-namely (1) transcriptomics, (2) proteomics, and (3) metabolomics, as well as immunohistochemistry, a tool that has already been adopted as a diagnostic adjunct. The novelty of this review compared to similar comprehensive studies lies with its detailed description of each adjunctive technique exclusively in the context of lung cancer subtyping. Similarities between studies evaluating individual techniques and markers are drawn, and any discrepancies are addressed. The findings of this study indicate that there is promising evidence that supports the successful use of omics methods as adjuncts to the subtyping of lung cancer, thereby directing clinician practice in an economical and less invasive manner.PMID:39123371 | DOI:10.3390/cancers16152643

CNS Neurosci Ther. 2024 Aug;30(8):e14919. doi: 10.1111/cns.14919.ABSTRACTBACKGROUND: Sanfilippo syndrome (mucopolysaccharidosis type IIIA; MPS IIIA) is a childhood dementia caused by inherited mutations in the sulfamidase gene. At present, there is no treatment and children with classical disease generally die in their late teens. Intravenous or intra-cerebrospinal fluid (CSF) injection of AAV9-gene replacement is being examined in human clinical trials; evaluation of the impact on brain disease is an intense focus; however, MPS IIIA patients also experience profound, progressive photoreceptor loss, leading to night blindness.AIM: To compare the relative efficacy of the two therapeutic approaches on retinal degeneration in MPS IIIA mice.METHODS: Neonatal mice received i.v. or intra-CSF AAV9-sulfamidase or vehicle and after 20 weeks, biochemical and histological evaluation of neuroretina integrity was carried out.RESULTS: Both treatments improved central retinal thickness; however, in peripheral retina, outer nuclear layer thickness and photoreceptor cell length were only significantly improved by i.v. gene replacement. Further, normalization of endo-lysosomal compartment size and microglial morphology was only observed following intravenous gene delivery.CONCLUSIONS: Confirmatory studies are needed in adult mice; however, these data indicate that i.v. AAV9-sulfamidase infusion leads to superior outcomes in neuroretina, and cerebrospinal fluid-delivered AAV9 may need to be supplemented with another therapeutic approach for optimal patient quality of life.PMID:39123298 | DOI:10.1111/cns.14919

Genome Med. 2024 Aug 9;16(1):96. doi: 10.1186/s13073-024-01369-6.ABSTRACTBACKGROUND: Immunoglobulin (Ig) glycosylation modulates the immune response and plays a critical role in ageing and diseases. Studies have mainly focused on IgG glycosylation, and little is known about the genetics and epidemiology of IgA glycosylation.METHODS: We generated, using a novel liquid chromatography-mass spectrometry method, the first large-scale IgA glycomics dataset in serum from 2423 twins, encompassing 71 N- and O-glycan species.RESULTS: We showed that, despite the lack of a direct genetic template, glycosylation is highly heritable, and that glycopeptide structures are sex-specific, and undergo substantial changes with ageing. We observe extensive correlations between the IgA and IgG glycomes, and, exploiting the twin design, show that they are predominantly influenced by shared genetic factors. A genome-wide association study identified eight loci associated with both the IgA and IgG glycomes (ST6GAL1, ELL2, B4GALT1, ABCF2, TMEM121, SLC38A10, SMARCB1, and MGAT3) and two novel loci specifically modulating IgA O-glycosylation (C1GALT1 and ST3GAL1). Validation of our findings in an independent cohort of 320 individuals from Qatar showed that the underlying genetic architecture is conserved across ancestries.CONCLUSIONS: Our study delineates the genetic landscape of IgA glycosylation and provides novel potential functional links with the aetiology of complex immune diseases, including genetic factors involved in IgA nephropathy risk.PMID:39123268 | DOI:10.1186/s13073-024-01369-6

Bioresour Technol. 2024 Aug 8;409:131235. doi: 10.1016/j.biortech.2024.131235. Online ahead of print.ABSTRACTManganese(IV) (Mn(IV)) reduction coupled to anaerobic ammonium (NH4+-N) oxidation (Mnammox) is a recently identified metal oxide-mediated nitrogen (N) loss pathway, holding potential value for the efficient removal of NH4+-N from wastewater. However, little is known about the application of Mnammox in wastewater treatment. Here, a novel Mnammox bacterium Aromatoleum evansii (strain MAY27) was screened. Strain MAY27 can utilize MnO2 as an electron acceptor to achieve NH4+-N removal under a low C/N condition (C/N = 0.5). The influencing factors in the Mnammox process and the Mn(IV) reduction driving effect on NH4+-N oxidation were investigated. The physiological characteristics of strain MAY27 and differential metabolic pathways were identified through whole-genome sequencing and metabolomic analyses. A significant up-regulation of several key pathways upon the addition of MnO2, including glycolysis/gluconeogenesis, transmembrane transporter activity, and oxidoreductase activity. This study contributes to the advancement of biotechnological approaches for treating N-containing wastewater.PMID:39121511 | DOI:10.1016/j.biortech.2024.131235

J Community Genet. 2024 Aug 9. doi: 10.1007/s12687-024-00721-y. Online ahead of print.ABSTRACTIndividualised treatment, including genetic services, calls for an increased role of primary healthcare practitioners (pHCPs) in diagnosing and caring for individuals with genetic conditions. PHCPs' genetics knowledge and practices must be current to ensure adequate care. A scoping review was conducted to explore peer-reviewed articles on the knowledge, attitudes, and practices (KAPs) of pHCPs concerning genetics, genetic testing, and genetic services. English-language human genetics/genomics articles published between January 1990 and April 2022 in low- and middle-income countries (LMICs) were included. Twenty-eight articles from 16 LMICs in five World Health Organisation (WHO)-defined regions met the inclusion criteria and showed a steady increase in publications, with varied contributions by region. The Eastern Mediterranean Region (EMR) contributed the most articles (n = 8), while the Western Pacific Region (WPR) had the least (n = 2). Brazil published the most articles (n = 6), while ten countries contributed one article each. Fifteen articles included knowledge, 19 included attitudes towards genetics, and eight included genetic practices. The findings indicate that pHCPs in LMICs lack knowledge of genetics and its applications despite their positive outlook towards genetic services. Barriers such as limited resources, financial constraints, and cultural or religious beliefs hinder access to genetic services. Enhancing pHCPs' genetics education is vital for improving care for those affected by genetic conditions. The scarcity of literature in LMICs emphasises the need for research on educational interventions to improve patient outcomes and family support.PMID:39120782 | DOI:10.1007/s12687-024-00721-y

Cells. 2024 Jul 31;13(15):1288. doi: 10.3390/cells13151288.ABSTRACTThe first objective is to highlight the lack of tools to measure whether a given intervention affords neuroprotection in patients with Alzheimer's or Parkinson's diseases. A second aim is to present the primary outcome measures used in clinical trials in cohorts of patients with neurodegenerative diseases. The final aim is to discuss whether metabolomics using body fluids may lead to the discovery of biomarkers of neuroprotection. Information on the primary outcome measures in clinical trials related to Alzheimer's and Parkinson's disease registered since 2018 was collected. We analysed the type of measures selected to assess efficacy, not in terms of neuroprotection since, as stated in the aims, there is not yet any marker of neuroprotection. Proteomic approaches using plasma or CSF have been proposed. PET could estimate the extent of lesions, but disease progression does not necessarily correlate with a change in tracer uptake. We propose some alternatives based on considering the metabolome. A new opportunity opens with metabolomics because there have been impressive technological advances that allow the detection, among others, of metabolites related to mitochondrial function and mitochondrial structure in serum and/or cerebrospinal fluid; some of the differentially concentrated metabolites can become reliable biomarkers of neuroprotection.PMID:39120318 | DOI:10.3390/cells13151288

Cells. 2024 Jul 31;13(15):1284. doi: 10.3390/cells13151284.ABSTRACTNuclear hormone receptors (NHRs) are a family of ligand-regulated transcription factors that control key aspects of development and physiology. The regulation of NHRs by ligands derived from metabolism or diet makes them excellent pharmacological targets, and the mechanistic understanding of how NHRs interact with their ligands to regulate downstream gene networks, along with the identification of ligands for orphan NHRs, could enable innovative approaches for cellular engineering, disease modeling and regenerative medicine. We review recent discoveries in the identification of physiologic ligands for NHRs. We propose new models of ligand-receptor co-evolution, the emergence of hormonal function and models of regulation of NHR specificity and activity via one-ligand and two-ligand models as well as feedback loops. Lastly, we discuss limitations on the processes for the identification of physiologic NHR ligands and emerging new methodologies that could be used to identify the natural ligands for the remaining 17 orphan NHRs in the human genome.PMID:39120315 | DOI:10.3390/cells13151284

Eur J Heart Fail. 2024 Aug 9. doi: 10.1002/ejhf.3389. Online ahead of print.ABSTRACTAIMS: Heart failure (HF) with preserved ejection fraction (HFpEF) reflects half of all clinical HF yet has few therapies. Obesity and diabetes are now common comorbidities which have focused attention towards underlying myocardial metabolic defects. The profile of a major metabolic pathway, glycolytic intermediates and their regulating enzymes and ancillary pathways, remains unknown.METHODS AND RESULTS: Endomyocardial biopsies from HFpEF (n = 37) and non-failing controls (n = 21) were assayed by non-targeted or targeted metabolomics and immunoblot to determine glycolytic and ancillary pathway metabolites and protein expression of their regulating enzymes. Glucose and GLUT1 expression were higher in HFpEF, but prominent glycolytic metabolites: glucose-6-phosphate, fructose-1,6-biphosphate (F1,6bP), and 3-phosphoglycerate were reduced by -78%, -91%, and -73%, respectively, versus controls. Expression of their corresponding synthesizing enzymes hexokinase, phospho-fructokinase, and phosphoglycerate kinase were also significantly lower (all p < 0.0005). Pentose phosphate and hexosamine biosynthetic pathway metabolites were reduced while glycogen content increased. Despite proximal reduction in key glycolytic intermediates, pyruvate increased but mitochondrial pyruvate transporter (MPC1) expression was reduced. Pyruvate dehydrogenase converting pyruvate to acetyl-CoA was more activated but some Krebs cycle intermediates were reduced. This HFpEF glycolytic profile persisted after adjusting for body mass index (BMI), diabetes, age, and sex, or in subgroup analysis with controls and HFpEF matched for BMI and diabetes/insulin history. In HFpEF, BMI but not glycated haemoglobin negatively correlated with F1,6bP (p = 7e-5, r = -0.61) and phosphoenolpyruvate (p = 0.006, r = -0.46).CONCLUSIONS: Human HFpEF myocardium exhibits reduced glycolytic and ancillary pathway intermediates and expression of their synthesizing proteins. This combines features reported in HF with reduced ejection fraction and obesity/diabetes that likely exacerbate metabolic inflexibility.PMID:39119952 | DOI:10.1002/ejhf.3389