Blood Metabolites Research Articles

Rosa roxburghii trattresidue: A novel feed resource for cattle indicated by the non-deleterious performance and blood metabolites.

Rosa roxburghii tratt residue (RRTR) is a regional and uncommon byproduct in Guizhou. Little information is available on whether RRTR can be used as feed for ruminants. In this study, the feasibility of using RRTR as a new feed resource for cattle was investigated by chemical composition analysis, in vitro gas production (Trial 1) and animal feeding experiments (Trial 2). In trial 1, compared to the commonly used fruit residues, RRTR had a proximate nutrient level; the in vitro gas production curve and dynamics fell within the normal range. In trial 2, 16 cattle were allocated to the control and treatment groups, with 8 replicates of 1 cattle each. Cattle in the control group were fed a basal diet without RRTR, while those in the treatment group were fed a diet containing 30% RRTR to replace 30% whole corn silage in basal diet. Feeding RRTR had little effect on the growth performance of the control and treatment cattle (P > 0.05). The feed-to-gain ratio was greater in the treatment group than in the control group throughout the trial period (P < 0.05). The plasma urea levels in the treatment group were lower (P < 0.05) than that in control group, and the levels of other plasma biochemical metabolites were not different between the two groups of cattle (P > 0.05). The in vivo rumen fermentation parameters did not differ between the control and treatment groups (P > 0.05). Our findings indicate that RRTR has a nutritional profile (crude protein, neutral detergent fiber, acid detergent fiber, and crude fiber) similar to that of commonly used fruit residues (such as apple, pineapple, and citrus residue et al.); improves plasma protein utilization efficiency; and has no negative impact on growth performance, albeit with limited effects on feed conversion; blood metabolites, and rumen fermentation parameters in cattle. Accordingly, we conclude, based on the above-mentioned result, that RRTR can serve as a novel feed alternative resource when considering the affordability and as a practical choice for low-cost diets for cattle.

Effects of varying levels of β-mannanase on growth performance, nutrient digestibility, blood metabolites and diarrhea incidence in weaning pigs

Effects of varying levels of β-mannanase on growth performance, nutrient digestibility, blood metabolites and diarrhea incidence in weaning pigs

The effects of dietary supplementation with red grape pomace treated with ozone gas on ruminal fermentation activities, nutrient digestibility, lactational performance, and blood metabolites in dairy ewes

This study aimed to investigate the effect of red grape pomace (RGP) treated with ozone (O3) gas as a substitute of low-quality alfalfa hay on the ruminal fermentation, nutrient digestibility, and milk production performance of fat-tailed, fed RGP substituted high fibrous alfalfa hay. Present study was performed in two experimental phases: 1) In situ and in vitro phase: Four Ghezel ewes in their third gestation (30 months old; weighing 51 ± 2 kg) with surgically implanted cannulas in their rumen were used to assess the in situ degradability and to obtain ruminal fluid to assay the in vitro gas production; the treatments were RGP not-processed (control; T0), and RGP processed with O3 for 6 (T1), 12 h (T2), and 24 h (T3). Processing RGP with O3 gas reduced (P < 0.05) neutral detergent fiber (NDF) and acid detergent fiber (ADF), although the processing time did not show differences. Ozone-treated RGP caused a reduction (P < 0.02) in total phenolics, total tannins, condensed tannins, protein-bound tannins, and fiber-bound tannins, compared to the control. Processing RGP with O3 for 12 h improved the nutritional value of RGP because of the reduction of the concentration of phenolic compounds, the increase of the in vitro gas production and the dry matter (DM) degradability, and improved fermentation parameters and it was chosen for the second phase of the experiment. 2) In vivo phase: Forty-eight healthy multiparous fat-tailed Ghezel ewes received the control diet (0 % RGP), or diets that substituted 20, 40, and 60 % of the dietary alfalfa hay with RGP processed with O3 for 12 h. Incremental dietary replacement of RGP with alfalfa hay did not influence the ruminal total volatile fatty acids but increased (P < 0.03) propionate. The digestibility coefficients of the DM and the NDF increased (P < 0.001) in diets containing RGP versus the control, but not for the crude protein and ether extract. The ruminal protozoa population exhibited a linear increase with the addition of O3-treated RGP (P < 0.001). Plasma glucose and albumin concentration increased (P < 0.04), and milk production and milk fat, protein, and lactose contents also increased (P < 0.05) with the alfalfa substitution with O3-processed RGP. In conclusion, replacing high-fibrous alfalfa hay with RGP treated with O3 for 12 h improved the apparent digestibility of DM and NDF and maintained the performance of the ewes.

Perturbations in the blood metabolome up to a decade before prostate cancer diagnosis in 4387 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition.

Measuring pre-diagnostic blood metabolites may help identify novel risk factors for prostate cancer. Using data from 4387 matched case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the associations of 148 individual metabolites and three previously defined metabolite patterns with prostate cancer risk. Metabolites were measured by liquid chromatography-mass spectrometry. Multivariable-adjusted conditional logistic regression was used to estimate the odds ratio per standard deviation increase in log metabolite concentration and metabolite patterns (OR1SD) for prostate cancer overall, and for advanced, high-grade, aggressive. We corrected for multiple testing using the Benjamini-Hochberg method. Overall, there were no associations between specific metabolites or metabolite patterns and overall, aggressive, or high-grade prostate cancer that passed the multiple testing threshold (padj <0.05). Six phosphatidylcholines (PCs) were inversely associated with advanced prostate cancer diagnosed at or within 10 years of blood collection. metabolite patterns 1 (64 PCs and three hydroxysphingomyelins) and 2 (two acylcarnitines, glutamate, ornithine, and taurine) were also inversely associated with advanced prostate cancer; when stratified by follow-up time, these associations were observed for diagnoses at or within 10 years of recruitment (OR1SD 0.80, 95% CI 0.66-0.96 and 0.76, 0.59-0.97, respectively) but were weaker after longer follow-up (0.95, 0.82-1.10 and 0.85, 0.67-1.06). Pattern 3 (8 lyso PCs) was associated with prostate cancer death (0.82, 0.68-0.98). Our results suggest that the plasma metabolite profile changes in response to the presence of prostate cancer up to a decade before detection of advanced-stage disease.

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

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. 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. 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. 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.

Investigating the relationship between blood metabolites and diabetic retinopathy using two-sample mendelian randomization and in vivo validation

We addressed fundamental questions about the influence of metabolites on the development of Diabetic retinopathy (DR), and explored the related pathological mechanism. Genome-wide association study (GWAS) database data for metabolites and DR were used to perform Mendelian randomization (MR) studies. The inverse variance weighting (IVW) was chosen as the primary analysis method. Sensitivity analysis was conducted using MR-PRESSO, leave-one-out and Cochran’s Q test. Confounding factors were eliminated to ensure robustness. We also conducted metabolic pathway analysis. In vivo experimental validation was conducted using Sprague Dawley rats. The serum metabolites of the DR group rats and normal group rats were examined to evaluate the MR results. The screen identified eighteen metabolites associated with DR risk, twelve of which were known components. Seven metabolites were positively correlated with DR risk, while five could reduce it. Eight metabolites associated with proliferative DR (PDR) risk were identified, four of which are known components. Three of these were positively associated with PDR risk and one metabolite reduced PDR risk. Additionally, two possible metabolic pathways involved in the biological mechanism of DR were identified. The ELISA results showed that the serum levels of isoleucine and 4-HPA were significantly increased in DR rats, while the level of inosine was decreased. This study offers novel insights into the biological mechanisms underlying DR. Metabolites that are causally linked to DR may serve as promising biomarkers and therapeutic targets.

Genetically predicted 486 blood metabolites in relation to risk of esophageal cancer: a Mendelian randomization study.

Enhancing therapy choices for varying stages of esophageal cancer and improving patient survival depend on timely and precise diagnosis. Blood metabolites may play a role in either causing or preventing esophageal cancer, but further research is needed to determine whether blood metabolites constitute a genetic risk factor for the disease. In order to tackle these problems, we evaluated the causal association between esophageal cancer and 486 blood metabolites that functioned as genetic proxies using a two-sample Mendelian randomization (MR) study. We utilized two-sample MR analyses to evaluate the causal links between blood metabolites and esophageal cancer. For the exposure, we used a genome-wide association study (GWAS) of 486 metabolites, and a GWAS study on esophageal cancer from Sakaue et al. was used for preliminary analyses. Causal analyses employed randomized inverse variance weighted (IVW) as the main method, supplemented by MR-Egger and weighted median (WM) analyses. Sensitivity analyses included the MR-Egger intercept test, Cochran Q test, MR-PRESSO, and leave-one-out analysis. Additionally, independent esophageal cancer GWAS data were utilized for replication and meta-analysis. FDR correction was applied to discern features with causal relationships. For conclusive metabolite identification, we conducted Steiger tests, linkage disequilibrium score regression, and colocalization analyses. Moreover, we utilized the program MetaboAnalyst 5.0 to analyze metabolic pathways. This study found an important association between esophageal cancer and three metabolites: 1-linoleoylglycerophosphoethanolamine* [odds ratio (OR) = 3.21, 95% confidence interval (CI): 1.42-7.26, p < 0.01], pyroglutamine* (OR = 1.92, 95% CI: 1.17-3.17, p < 0.01), and laurate (12:0) (OR = 3.06, 95% CI: 1.38-6.78, p < 0.01). This study establishes a causal link between three defined blood metabolites and esophageal cancer, offering fresh insights into its pathogenesis.

Quantitative Blood Serum IVDr NMR Spectroscopy in Clinical Metabolomics of Cancer, Neurodegeneration, and Internal Medicine.

Despite more than two decades of metabolomics having joined the "omics" scenery, to date only a few novel blood metabolite biomarkers have found their way into the clinic. This is changing now by massive large-scale population metabolic phenotyping for both healthy and disease cohorts. Here, nuclear magnetic resonance (NMR) spectroscopy is a method of choice, as typical blood serum markers can be easily quantified and by knowledge of precise reference concentrations, more and more NMR-amenable biomarkers are established, moving NMR from research to clinical application. Besides customized approaches, to date two major commercial platforms have evolved based on either 600MHz (14.1 Tesla) or 500MHz (11.7 Tesla) high-field NMR systems. This chapter provides an introduction into the field of quantitative in vitro diagnostics research (IVDr) NMR at 600 MHzand its application within clinical research of cancer, neurodegeneration, and internal medicine.

Exploring the Influence of Cheese Consumption on Blood Metabolites: Implications for Disease Pathogenesis, with a Focus on Essential Hypertension

This study examines the causal effects of cheese consumption on blood metabolites and essential hypertension using Mendelian Randomization (MR). GWAS data from the Open GWAS project and FinnGen Biobank were analyzed, focusing on cheese intake, 249 metabolic traits, and hypertension. Instrumental variables were selected based on strict criteria, and causal relationships were assessed using IVW, weighted-median, and MR-Egger methods. Cheese consumption significantly influenced 118 metabolic traits, including amino acids, cholesterol esters, and triglycerides. Notably, it was linked to a reduction in hypertension risk (OR = 0.652, P < 0.0001). Mediation analysis identified 50 metabolic traits as intermediaries, accounting for 0.88% to 8.25% of the total effect. These findings suggest that moderate cheese intake may benefit cardiovascular health by lowering hypertension risk, emphasizing the importance of cheese type and dietary context in health recommendations.

Impact of Silver Nanoparticles (Ag-NPs) as a Dietary Supplement on Growth Performance, Carcass Traits, Blood Metabolites, Digestive Enzymes, and Cecal Microbiota of Growing Rabbits

Abstract The present study investigated the impact of silver nanoparticles (Ag-NPs) on growth performance, carcass traits, liver and kidney functions, immunity and antioxidant indicators, digestive enzymes, and cecum bacteriology of growing rabbits. One hundred 5-week-old New Zealand White (NZW) male rabbits were randomly divided into 5 equal groups and fed for 8 weeks on the basal diet only or on the basal diet supplemented with different levels of Ag-NPs (0.25, 0.50, 0.75, or 1.00 mg/kg diet). Animals in each group were randomly distributed in 10 cages (replicates), with two rabbits each. Different dietary concentrations of Ag-NPs significantly increased live body weight (LBW) and feed conversion ratio (FCR). Also, body weight gain (BWG) increased dramatically during all experimental periods except 11–13 weeks of age. Levels of 0.25 and 1 mg of Ag-NPs/kg diet showed the highest increase in LBW, BWG, and FCR. All studied carcass traits, except liver %, were not affected by Ag-NPs levels. Rabbits fed diet supplemented with 1 mg Ag-NPs had the highest liver %. Serum total protein, albumin, and globulin levels were increased (P&lt;0.05) in groups treated with 0.25 and 0.75 mg Ag-NPs. In contrast, serum values of aspartate transaminase (AST) and alanine transaminase (ALT), urea and creatinine were significantly reduced with the supplementation of Ag-NPs up to 0.75 mg/kg diet. The immunoglobulins M, G, and A (IgM, IgG, and IgA), complement 3 (C3) and lysozyme activity were improved with the inclusion of nano-silver in the rabbit feeds, particularly at the level of 0.25 mg Ag-NPs/kg feed. The inclusion of Ag-NPs in rabbit diets at different concentrations increased the total antioxidant capacity and the activities of superoxide dismutase, catalase, and glutathione peroxidase. Growing rabbits fed on diets supplemented with Ag-NPs had higher levels of digestive enzymes than the control group. The addition of Ag-NPs reduced the load of E. coli, Salmonella spp. and coliform in the rabbit cecum. Overall, the inclusion of 0.25–1 mg Ag-NPs/kg to NZW rabbit diets has shown beneficial effects on health and performance.

Dietary macronutrient composition and partial soybean meal replacement with slow-release urea: Effects on performance, digestibility, rumen fermentation, and nitrogen metabolism in dairy cows

A 2 × 2 factorial arrangement of treatments was used to investigate the interactive effects of dietary macronutrient composition [high-starch, low-fat, low-fiber (HsLFF) than low-starch, high-fat, high-fiber (LsHFF)] and N source [soybean meal (SBM) or partially replaced by slow-release urea (SRU)] on lactation performance, rumen fermentation, N utilization efficiency, nutrient digestibility, blood metabolites, and feeding behavior in cows. A replicated 4 × 4 Latin square design was used involving 12 multiparous Holstein cows (milk yield of 40.5 ± 5.6 kg/d, BW of 590 ± 20 kg; 81 ± 12 d in milk). The HsLFF diet contained 300 g/kg starch, 31.3 g/kg fat, and 301 g/kg NDF, without straw or additional fat. In contrast, the LsHFF diet contained 195.5 g/kg starch, 60.8 g/kg fat, and 367.5 g/kg NDF, enriched with wheat straw (100 g/kg), and additional fat (34 g/kg). The diets were formulated to be iso-nitrogenous and isocaloric. Cows fed the HsLFF diet had greater DM intake, digestibility of DM and CP, milk yield and milk protein %, but lower intakes of NDF, and physically effective NDF, and milk fat % than cows fed the LsHFF diet. Replacing SBM with SRU significantly increased milk solids yield without affecting other lactation performance or BW. Cows fed the LsHFF diet had higher ruminal pH and branched-chain VFA proportions but lower total VFA concentrations compared with the HsLFF diet, while those on the LsHFF-SRU diet had the highest ruminal ammonia levels. Compared with the HsLFF diet, cows fed LsHFF had lower NE intake, milk energy output and energy requirement for maintenance, although energy balances were similar among groups. The HsLFF diet improved N utilization, resulting in higher N content in milk and lower N excretion in feces. Blood metabolite studies showed significant interactions between the main factors, particularly for blood glucose and creatinine, with the lowest levels in cows fed the LsHFF-SRU and LsHFF-SBM diets. In addition, alanine aminotransferase levels were higher in cows fed the LsHFF diet than in cows fed the HsLFF diet. This could indicate early-stage liver stress due to the metabolic imbalance caused by a high-fat, low-starch diet, which can alter energy metabolism. Cows on the HsLFF-SRU diet had the highest glucose levels, indicating possible changes in carbohydrate metabolism or a higher metabolic rate. The concentration of BUN increased steadily after feeding in the LsHFF diet and peaked after 4 h in the LsHFF-SRU diet, with no difference between N sources in the HsLFF diet. Partial replacement of SRU with SBM had no effect on BUN. The interaction between the main factors had a significant effect on MUN content, which was highest in LsHFF-SRU and lowest in HsLFF-SRU, with no difference between the N sources in the HsLFF diets. Overall, while diets with reduced starch and increased fiber and fat compromised lactation performance, partially substituting SRU with SBM helped maintain milk production and milk nitrogen efficiency. However, the LsHFF-SRU diet was less efficient in N utilization, as shown by higher levels of ruminal ammonia, BUN and MUN.

Serum metabolite biomarkers for the early diagnosis and monitoring of age-related macular degeneration

IntroductionAge-related macular degeneration (AMD) is a leading cause of irreversible blindness worldwide, with significant challenges for early diagnosis and treatment. ObjectivesTo identify new biomarkers that are important for the early diagnosis and monitoring of the severity/progression of AMD. MethodsWe investigated the diagnostic and monitoring potential of blood metabolites in a cohort of 547 individuals (167 healthy controls, 240 individuals with other eye diseases as eye disease controls, and 140 individuals with AMD) from 2 centers over three phases: discovery phase 1, discovery phase 2, and an external validation phase. The samples were analyzed via a mass spectrometry-based, widely targeted metabolomic workflow. In discovery phases 1 and 2, we built a machine learning algorithm to predict the probability of AMD. In the external validation phase, we further confirmed the performance of the biomarker panel identified by the algorithm. We subsequently evaluated the performance of the identified biomarker panel in monitoring the progression and severity of AMD. ResultsWe developed a clinically specific three-metabolite panel (hypoxanthine, 2-furoylglycine, and 1-hexadecyl-2-azelaoyl-sn-glycero-3-phosphocholine) via five machine learning models. The random forest model effectively discriminated patients with AMD from patents in the other two groups and showed acceptable calibration (area under the curve (AUC) = 1.0; accuracy = 1.0) in both discovery phases 1 and 2. An independent validation phase confirmed the diagnostic model’s efficacy (AUC = 0.962; accuracy = 0.88). The three-biomarker panel model demonstrated an AUC of 1.0 in differentiating the severity of AMD via RF machine learning, which was consistent across both the discovery and external validation phases. Additionally, the biomarker concentrations remained stable under repeated freeze–thaw cycles (P > 0.05). ConclusionsThis study reveals distinct metabolite variations in the serum of AMD patients, paving the way for the development of the first routine laboratory test for AMD.

Parameters of blood metabolites from Brown Swiss cows in production in the Puno Region. An evaluation according to the number of births

Parameters of blood metabolites from Brown Swiss cows in production in the Puno Region. An evaluation according to the number of births

Assessment of skeletal muscle dynamics and milk production across a 300-day lactation in multiparous dairy cattle

The objective of this study was to evaluate changes in longissimus dorsi muscle depth (LDD) across lactation (0 to 300 DIM) and identify the impact of low versus high muscle reserves immediately after parturition on body weight and body reserve changes as well as production variables across a 300-d lactation. Forty multiparous cows were classified as high muscle (HM; LDD > 5.0 cm; n = 18) or low muscle (LM; LDD ≤ 5.0 cm; n = 22) based on LDD measurements collected within 24 h of parturition. Body weights (BW) and ultrasound scans to assess LDD and back fat depth (BFD) were collected monthly from parturition until 300 DIM. Ultrasound scans captured and measured using available software. Blood samples were taken at 7, 150 and 300 DIM, and plasma was analyzed for markers of metabolic status by measuring insulin, nonesterified fatty acids (NEFA), creatinine, and 3-methylhistidine (3-MH). Milk yield was recorded daily and milk components were analyzed monthly. Data analysis was performed and the statistical models included the fixed effect of muscle group, time, their interaction, and the random effect of cow nested within muscle group with repeated measures using a first-order autoregressive covariance structure. Muscle group was not related with BW or BFD for any of the time points measured. Cows lost BW from 0 to 60 DIM and gained weight from 60 to 300 DIM. Similarly, BFD decreased between 0 to 90 DIM and increased BFD after 90 DIM until 300 DIM. A muscle group by time interaction was observed for LDD. The HM cows had more muscle at 0 DIM, indicative of treatment assignment (1.34 cm more), and 300 DIM (0.78 cm more) and tended to have more muscle at 60 DIM (0.66 cm more) compared with LM. After 240 DIM, both muscle groups began net accretion of muscle reserves until 300 DIM. No differences were observed for blood metabolites measured based on muscle group. However, there were significant time effects for creatinine, 3-MH, and NEFA concentrations, which reflected the observed changes in BFD and LDD measured in ultrasound scans. For statistical analysis of daily milk production, observations were grouped into 3 stages of lactation, early (0-60 DIM), mid (60-240 DIM), and late lactation (240-300 DIM). There was a muscle group by stage of lactation interaction, where in early and mid-lactation, HM cows produced, on average, 1.9 kg more milk/d; however, in late lactation, LM cows produced 1.8 kg more milk/d. Our results indicate that muscle reserves are depleted in early lactation, and accreted in late lactation, whereas BW and BFD started to increase by 90 DIM. Data also supports that cows with more extensive muscle depletion in early lactation had greater milk production, however, substantial muscle accretion in late lactation may result in reduced milk production.

Mediation-adjusted multivariable Mendelian randomisation study identified novel metabolites related to mental health

BackgroundFrom the pathway perspective, metabolites have the potential to improve knowledge about the aetiology of psychiatric diseases. Previous studies suggested a link between specific blood metabolites and mental disorders, but...

Potential causal relationships between blood metabolites, inflammatory cytokines, and venous thromboembolism.

Venous thromboembolism (VTE) is the abnormal coagulation of blood in deep veins, which impairs venous return and includes deep vein thrombosis (DVT) and pulmonary embolism (PE). The incidence of VTE is increasing, leading to severe complications and sequelae. Despite the widespread application of multi-omics analyses in vascular disease research, identifying the specific links between various metabolic products, cytokines, and VTE, as well as their potential mediating roles, requires further validation due to confounding factors. Summary statistics for 1,091 metabolites, 309 metabolite ratios (8,299 individuals), and 41 inflammatory cytokines (8,293 individuals) were obtained from the largest genome-wide association studies (GWAS). Summary statistics for VTE (21,021 cases, 391,160 controls), DVT (6,501 cases, 357,111 controls), and PE (10,046 cases, 401,128 controls) were derived from the FinnGen R10 dataset. We initially examined causal relationships using two-sample MR analysis, followed by Two-step Mendelian Randomization (TSMR) and Multivariable Mendelian Randomization (MVMR) to identify potential mediating mechanisms. We identified causal associations for 78 blood metabolites with VTE, 79 with DVT, and 81 with PE. Among all 41 inflammatory cytokines included, only platelet-derived growth factor BB (PDGF-BB) levels showed a causal relationship with increased risks of VTE, DVT, and PE. MVMR analysis revealed that the associations between glycocholate levels and VTE, DVT, and PE were mediated by PDGF-BB, accounting for 14.54% (p=2.84E-04), 17.10% (p=3.64E-05), and 10.44% (p=1.39E-02), respectively. Furthermore, the associations between dodecanedioate (C12:1-DC) levels and VTE and DVT were also mediated by PDGF-BB, accounting for 12.79% (p=6.10E-04) and 12.17% (p=2.13E-04), respectively. This study reveals significant associations between specific blood metabolites and the risks of VTE, DVT, and PE, with some associations potentially mediated by PDGF-BB.

Lactational performance of dairy buffaloes affected by replacing soybean meal with an alternative microbial protein source

Thirty dairy buffaloes were used for 90 days to evaluate the impact of a novel protein source (HI-PRO®), a feed alternative rich in protein (made from Saccharomyces and Bacillus), on the productivity of nursing buffaloes. The nursing water buffaloes had an average weight of 550 ± 11.2 kg. The treatments consisted of diets containing two distinct protein sources: (1) soybean meal (44 % as the control group); and (2) HI-PRO® product. Throughout the trial, measurements of nutritional digestibility and blood metabolites (total protein, albumin, urea, and creatinine) were conducted. Quantity and composition of the milk were measured to determine the content of milk proteins, lipids, and lactose. The outcome of the results showed insignificant decrease in the buffaloes receiving HI-PRO® feed versus control group. Furthermore, there was enhancement in the fiber digestibility by approximately 2.5 % in the HI-PRO® group compared to the control group. The levels of protein, albumin, globulin, urea, and creatinine fall within the normal range for animals in good health. Using HI-PRO® resulted in a marginal improvement in milk production, increasing it by approximately 4.8 % compared to soybean meal. Furthermore, the buffaloes fed HI-PRO® showed a slightly elevated 4 % fat-corrected milk output and milk composition. To summarize, nursing buffaloes can utilize HI-PRO® as an efficient protein source in their diets, replacing soybean meal.

Relationship of metabolites and metabolic ratios with schizophrenia: a mendelian randomization study

BackgroundThis study aims to investigate the causal relationship of human plasma metabolites and metabolic ratios with schizophrenia (SCZ).MethodsWe employed Mendelian Randomization (MR) approach to comprehensively analyze two large-scale metabolomics and schizophrenia Genome-Wide Association Study (GWAS) datasets, incorporating a total of 1091 metabolites and 309 metabolic ratios, with 52017 schizophrenia patients and 75889 healthy controls. The inverse variance-weighted (IVW) method was utilized to estimate the causal relationship between exposure and outcome. To provide a more comprehensive evaluation, additional Mendelian Randomization (MR) approaches were employed, including MR-Egger regression, weighted median, simple mode, and weighted mode methods. These analyses assessed the causal effects between blood metabolites, metabolic ratios, and schizophrenia. Tests for pleiotropy and heterogeneity were conducted. False Discovery Rate (FDR) correction was applied to account for multiple comparisons and heterogeneity, ensuring the robustness and reliability of our findings. Consistent with previous studies, an FDR threshold of < 0.2 was considered suggestive of a causal relationship, while an FDR of < 0.05 was considered to indicate a significant causal relationship.ResultsThe final results revealed that a significant causal association was found between the levels of two metabolites and schizophrenia, Alliin (OR = 0.915, 95%CI = 0.879–0.953, P = 1.93 × 10− 5, FDR = 0.013) was associated with a decreased risk of schizophrenia, N-actylcitrulline (OR = 1.058, 95%CI = 1.034–1.083, P = 1.4 × 10− 6, FDR = 0.002) was associated with increased risk of schizophrenia. When adjusting FDR to 0.2, the results showed that 4 metabolite levels and 2 metabolite ratios were suggestively causally associated with a reduced risk of schizophrenia including 2-aminooctanoate (OR = 0.904, 95%CI = 0.847–0.964, P = 0.002, FDR = 0.160), N-lactoylvaline (OR = 0.853, 95%CI = 0.775–0.938, P = 0.001,FDR = 0.122), X − 21310 (OR = 0.917, 95%CI = 0.866–0.971, P = 0.003,FDR = 0.195), X − 26111 (OR = 0.932, 95%CI = 0.890–0.976, P = 0.003,FDR = 0.189), Arachidonate (20:4n6) to oleate to vaccenate (18:1) ratio (OR = 0.945, 95%CI = 0.914–0.977, P = 8.2 × 10− 4, FDR = 0.104), and Citrulline to ornithine ratio (OR = 0.924, 95%CI = 0.881–0.969, P = 0.001, FDR = 0.122), while 4 metabolite levels and 2 metabolite ratios were suggestively causally associated with an increased risk of schizophrenia including N2, N5-diacetylornithine (OR = 1.090, 95%CI = 1.031–1.153, P = 0.003, FDR = 0.185), N − acetyl − 2−aminooctanoate (OR = 1.069, 95%CI=(1.027–1.114, P = 0.001, FDR = 0.127), N − acetyl − 2−aminoadipate (OR = 1.081, 95%CI = 1.030–1.133, P = 0.001, FDR = 0.128), X − 13844 (OR = 1.110, 95%CI = 1.036–1.190, P = 0.003, FDR = 0.196), X − 24556 (OR = 1.083, 95%CI = 1.036–1.132, P = 4.5 × 10− 4, FDR = 0.098), X − 24736 (OR = 1.065, 95%CI = 1.028–1.104, P = 5.6 × 10− 4, FDR = 0.098), N − acetylasparagine (OR = 1.048, 95%CI = 1.021–1.075, P = 4.5 × 10− 4, FDR = 0.098), N − acetylarginine (OR = 1.060, 95%CI = 1.028–1.092, P = 1.8 × 10− 4, FDR = 0.083), Cysteine to alanine ratio (OR = 1.086, 95%CI = 1.036–1.138, P = 6.5 × 10− 4, FDR = 0.101), and Benzoate to linoleoyl − arachidonoyl − glycerol (18:2 to 20:4) ratio (OR = 1.070, 95%CI = 1.025–1.117, P = 0.002, FDR = 0.158).ConclusionOur study results provide valuable insights for identifying diagnostic biomarkers related to schizophrenia and offer preliminary research findings for further exploration of the mechanisms linking schizophrenia and metabolism.

Application of a deep-learning marker for morbidity and mortality prediction derived from retinal photographs: a cohort development and validation study

Biological ageing markers are useful to risk stratify morbidity and mortality more precisely than chronological age. In this study, we aimed to develop a novel deep-learning-based biological ageing marker (referred to as RetiPhenoAge hereafter) using retinal images and PhenoAge, a composite biomarker of phenotypic age. We used retinal photographs from the UK Biobank dataset to train a deep-learning algorithm to predict the composite score of PhenoAge. We used a deep convolutional neural network architecture with multiple layers to develop our deep-learning-based biological ageing marker, as RetiPhenoAge, with the aim of identifying patterns and features in the retina associated with variations of blood biomarkers related to renal, immune, liver functions, inflammation, and energy metabolism, and chronological age. We determined the performance of this biological ageing marker for the prediction of morbidity (cardiovascular disease and cancer events) and mortality (all-cause, cardiovascular disease, and cancer) in three independent cohorts (UK Biobank, the Singapore Epidemiology of Eye Diseases [SEED], and the Age-Related Eye Disease Study [AREDS] from the USA). We also compared the performance of RetiPhenoAge with two other known ageing biomarkers (hand grip strength and adjusted leukocyte telomere length) and one lifestyle factor (physical activity) for risk stratification of mortality and morbidity. We explored the underlying biology of RetiPhenoAge by assessing its associations with different systemic characteristics (eg, diabetes or hypertension) and blood metabolite levels. We also did a genome-wide association study to identify genetic variants associated with RetiPhenoAge, followed by expression quantitative trait loci mapping, a gene-based analysis, and a gene-set analysis. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and corresponding 95% CIs for the associations between RetiPhenoAge and the different morbidity and mortality outcomes. Retinal photographs for 34 061UK Biobank participants were used to train the model, and data for 9429participants from the SEED cohort and for 3986participants from the AREDS cohort were included in the study. RetiPhenoAge was associated with all-cause mortality (HR 1·92 [95% CI 1·42-2·61]), cardiovascular disease mortality (1·97 [1·02-3·82]), cancer mortality (2·07 [1·29-3·33]), and cardiovascular disease events (1·70[1·17-2·47]), independent of PhenoAge and other possible confounders. Similar findings were found in the two independent cohorts (HR 1·67 [1·21-2·31] for cardiovascular disease mortality in SEED and 2·07 [1·10-3·92] in AREDS). RetiPhenoAge had stronger associations with mortality and morbidity than did hand grip strength, telomere length, and physical activity. We identified two genetic variants that were significantly associated with RetiPhenoAge (single nucleotide polymorphisms rs3791224 and rs8001273), and were linked to expression quantitative trait locis in various tissues, including the heart, kidneys, and the brain. Our new deep-learning-derived biological ageing marker is a robust predictor of mortality and morbidity outcomes and could be used as a novel non-invasive method to measure ageing. Singapore National Medical Research Council and Agency for Science, Technology and Research, Singapore.

Based on Sportomics: Comparison of Physiological Status of Collegiate Sprinters in Different Pre-Competition Preparation Periods.

This study aimed to assess the impact of pre-competition training by comparing the differences of collegiate sprinters in physiological state between strengthening and tapering training period by sportomics and combining their sport performance. Fifteen collegiate sprinters were investigated or tested on their body composition, dietary habits, energy expenditure, sleep efficiency, heart rate and respiratory rate during training, blood (blood cells, biochemical and immune markers) and urine (urinalysis), gut microbiome distribution, microbiome and blood metabolites, and their functions during the strengthening (Group A) and tapering training period (Group B) prior to competing in the national competitions. We found that 26.67% of sprinters achieved personal bests (PB) after the competition. The limb skeletal muscle mass and lymphocyte ratio of male sprinters in Group B were lower than those in Group A, and the serum creatine kinase (CK) level was higher than Group A (p < 0.05). The levels of serum CK, interleukin-6 (IL-6), interleukin-1β (IL-1β), and urine-specific gravity (SG) of the two groups were higher than the upper limit of the reference value. The detection rates of urine white blood cell (WBC) and protein in Group B were higher than those in Group A. The gut microbiome health index (GMHI) of Group A was higher than that of Group B, and the microbial dysbiosis index was lower than that of Group B. The ratio of Firmicutes/Bacteroidota (F/B) in Group A was higher than that in Group B. There were 65 differential metabolites in the A/B group, and the enriched pathway was mainly the NF-kappa B signaling pathway (up); B/T cell receptor signaling pathway (up); Th1 and Th2 cell differentiation (up); phenylalanine metabolism (up); and growth hormone synthesis, secretion, and action (up). There were significant differences in blood metabolites between the A and B groups, with a total of 89 differential metabolites, and the enriched pathway was mainly the NF-kappa B signaling pathway (up), T cell receptor signaling pathway (up), Th1 and Th2 cell differentiation (up), and glycerophospholipid metabolism (down). In conclusion, the imbalance of the gut microbiome and inflammation and immune-related metabolites of collegiate sprinters during the pre-competition tapering training period may be the cause of their limited sports performance.