Analysis of causal relationship between blood metabolites and prostate cancer by two-sample Mendelian randomization

Objective:To investigate the causal relationship between blood metabolite levels and the occurrence of prostate cancer by using two-sample Mendelian randomization method.Methods:Pooled data from public databases for genome-wide association analyses of blood metabolites and prostate cancer were selected,and inverse variance weighting(IVW)was used as the primary method for estimating the causal effects,while heterogeneity tests,gene multiplicity tests and sensitivity analyses were performed to assess the stability and reliability of the results.Results:A total of six known metabolites were found to potentially increase the risk of prostate cancer development(P<0.05),namely fructose,allantoin,5-hydroxytryptophan,potassium ketoisocaproate,glycyltryptophan,and 1-heptadecanoyl-glycerol-3-phosphorylcholine,with no heterogeneity or genetic pleiotropy found.Conclusion:Six known blood metabolites may be potential risk factors for prostate cancer development in European populations.

The effect of the ratio of standardized ileal digestible lysine to metabolizable energy on growth performance,blood metabolites and hormones of lactating sows

A total of 335 lactating sows （Landrace x Large White） were used in two experiments to determine the optimum ratio of standardized ileal digestible lysine （SID-Lys） to metabolizable energy （ME） for mixed parity sows during lactation. In Exp. 1, 185 sows （weighing an average of 256.2 ± 6.5 kg and having an average parity of 3.4 ± 0.3） were allocated to one of six experimental diets in a completely randomized block design within parity groups （1, 2, and 3＋）. The experimental diets were formulated to contain 3.06, 3.16, 3.20, 3.25, 3.30 or 3.40 Mcal/kg of ME and each diet was fed to the sows throughout a 28 day lactation. All diets provided a similar SID-lysine level （0.86%）. As a result, the diets provided a SID-Lys：ME ratio of 2.81, 2.72, 2.69, 2.65, 2.61 or 2.53 g/Mcal ME. Sow feed intake was significantly （P 〈 0.01） affected by the energy content of the diet as well as by sow parity. Using regression analysis, feed intake was shown to be maximized at 3.25, 3.21, 3.21 and 3.21 Mcal/kg of ME for parity 1, 2, 3＋ sows and the entire cohort of sows respectively （quadratic; P 〈 0.01）. In addition, the result of feed intake can be expressed as 2.65, 2.69, 2.69 and 2.68 g/Mcal based on analysis of SID-Lys：ME ratio. Litter weight gain was affected by dietary treatment for parity 3＋ sows and the entire cohort （P 〈 0.01）. Based on regression analysis, litter weight gain was maximized at 3.25 and 3.24 Mcal/kg of ME for parity 3＋ （quadratic; P 〈 0.01） and the entire cohort （quadratic; P 〈 0.01）. Similarly, the result of litter weight gain could be expressed as 2.65 and 2.66 g/Mcal of SID- Lys：ME ratio. Therefore, 3.25 Mcal/kg of ME was selected for Exp. 2 in which 150 sows （weighing 254.6 ± 7.3 kg and having an average parity of 3.4 ± 0.4） were allocated to one of five treatments in a completely randomized block design within parity （1, 2, and 3＋）. The experimental diets were formulated to contain 2.1, 2.4, 2.7, 3.0 or 3.3 g/Mcal of SID-Lys：ME ratio with all diets providing 3.25 Mcal/kg of ME. The diets were fed to the sows throughout a 28 day lactation. Sow body weight loss was affected by dietary treatment （parity 3＋ sows, P = 0.02; entire cohort, P 〈 0.01） and by sow parity （P 〈 0.01）. Litter weight at weaning and litter weight gain were affected by dietary treatment for parity 1, 2, 3＋ sows and the entire cohort （P 〈 0.01） as well as by sow parity （P 〈 0.01）. Plasma urea nitrogen （P 〈 0.01）, creatinine （P 〈 0.01） and non-esterifide fatty acids （P = 0.04） were decreased as the SID-Lys：ME ratio of the diet increased. Insulin-like growth factor-1 （P = 0.02）, estradiol （P 〈 0.01） and luteinizing hormone （P = 0.02） were increased as the SID-Lys：ME ratio in diet increased. Based on a broken-line model, the estimated SID-Lys： ME ratio to maximize litter weight gain was estimated to be 3.05 g/Mcal.

Evaluating the causal relationship between human blood metabolites and gastroesophageal reflux disease

BACKGROUND Gastroesophageal reflux disease(GERD)affects approximately 13% of the global population.However,the pathogenesis of GERD has not been fully elucidated.The development of metabolomics as a branch of systems biology in recent years has opened up new avenues for the investigation of disease processes.As a powerful statistical tool,Mendelian randomization(MR)is widely used to explore the causal relationship between exposure and outcome.AIM To analyze of the relationship between 486 blood metabolites and GERD.METHODS Two-sample MR analysis was used to assess the causal relationship between blood metabolites and GERD.A genome-wide association study(GWAS)of 486 metabolites was the exposure,and two different GWAS datasets of GERD were used as endpoints for the base analysis and replication and meta-analysis.Bonferroni correction is used to determine causal correlation features(P<1.03×10^(-4)).The results were subjected to sensitivity analysis to assess heterogeneity and pleiotropy.Using the MR Steiger filtration method to detect whether there is a reverse causal relationship between metabolites and GERD.In addition,metabolic pathway analysis was conducted using the online database based MetaboAnalyst 5.0 software.RESULTS In MR analysis,four blood metabolites are negatively correlated with GERD:Levulinate(4-oxovalerate),stearate(18:0),adrenate(22:4n6)and p-acetamidophenylglucuronide.However,we also found a positive correlation between four blood metabolites and GERD:Kynurenine,1-linoleoylglycerophosphoethanolamine,butyrylcarnitine and guanosine.And bonferroni correction showed that butyrylcarnitine(odd ratio 1.10,95% confidence interval:1.05-1.16,P=7.71×10^(-5))was the most reliable causal metabolite.In addition,one significant pathways,the"glycerophospholipid metabolism"pathway,can be involved in the pathogenesis of GERD.CONCLUSION Our study found through the integration of genomics and metabolomics that butyrylcarnitine may be a potential biomarker for GERD,which will help further elucidate the pathogenesis of GERD and better guide its treatment.At the same time,this also contributes to early screening and prevention of GERD.However,the results of this study require further confirmation from both basic and clinical real-world studies.

Effects of biochanin A on lactational performance,nitrogen metabolism,and blood metabolites in dairy cows

Optimizing nitrogen utilization efficiency and mitigating nitrogen losses in cows plays a pivotal role in fostering economic sustainability within contemporary agricultural systems.Biochanin A(BCA),a natural component in red clover,has the potential to improve nitrogen metabolism in dairy cows.The primary objective of this study was to probe the impact of biochanin A supplementation on lactational performance,nitrogen metabolism,and blood metabolites in dairy cows.A complete randomized block design experiment was conducted over 28 d,involving 36 multiparous Holstein cows(comparable milk yield=37.1±2.90 kg,BW=642±70.0 kg,days in milk=92±8.0 d,and parity=2.4±0.50),which were allocated to three treatment groups:the Control group(with 0 g/d BCA),the Low group(with 10 g/d per cow BCA),and the High group(with 40 g/d per cow BCA).Biochanin A supplementation improved the lactational performance of cows by increasing milk yield by 6.3%(P=0.007)and feed efficiency by 12.7%(P=0.009).Total intestinal apparent digestibility was unaffected by BCA supplementation(P>0.05),but microbial nitrogen was increased by 30.0%(P=0.002)for promoting nitrogen utilization efficiency by 20.7%(P=0.004).Milk competent yields(protein,lactose,and non-fat milk solid)were increased with increasing BCA supplementation(P 0.05).BCA did not affect body health of dairy cows.Additionally,none of the plasma endocrine hormones were affected(P>0.05).A total of 95 significantly different metabolites were screened from the plasma metabolites of cows in the BCA-added and non-added groups.After performing an enrichment analysis of the metabolic pathways associated with the different metabolites,six specific pathways were identified:bile acid biosynthesis,aspartate metabolism,pyrimidine metabolism,arginine and proline metabolism,the urea cycle,and ammonia recycling.The inclusion of BCA is suggested to enhance milk yield and modulate nitrogen metabolism by influencing relevant metabolites within the metabolic pathways.

Effects of Bupleurum extract on blood metabolism, antioxidant status and immune function in heat-stressed dairy cows

This experiment was conducted to evaluate the effects of Bupleurum extract （BE） on blood metabolites, antioxidant status, and immune function in dairy cows under heat stress. Forty lactating Holstein cows were randomly assigned to 1 of 4 treatments. The treatments consisted of 0, 0.25, 0.5, and 1.0 g of BE kg-1 dry matter. Supplementation with BE decreased （P〈0.05） blood urea nitrogen （BUN） contents and increased blood total protein （TP） and albumin （ALB） levels compared with control cows, but it had no effects （P〉0.05） on blood glucose （GLU）, nonesterified fatty acid （NEFA）, total triglycedde （TG）, low-density lipoprotein cholesterol （LDL-C）, and high density lipoprotein cholesterol （HDL-C）. Compared with control cows, cows fed BE had higher （P〈0.05） superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） activity. However, supplementation with BE had no effect （P〉0.05） on total antioxidant capacity （T-AOC） or malondialdehyde （MDA） levels. The immunoglobulin （Ig） A and G contents increased （P〈0.05） in cows fed 0.25 or 0.5 g of BE kg-1. Interleukin （IL）-2 and IL-4 levels were higher （P〈0.05） in cows fed 0.5 and 1.0 g of BE kg-1, and IL-6 was significantly elevated （P〈0.05） in cows fed 0.5 g of BE kg-1. There were no treatment effects （P〉0.05） on the CD4＋ and CD8＋ T lymphocyte ratios, CD4＋/CD8＋ratio, or tumor necrosis factor-α （TNF-α） level among the groups. These findings suggest that BE supplementation may improve protein metabolism, in addition to enhancing antioxidant activity and immune function in heat-stressed dairy cows.

Performance and plasma concentration of metabolites in transition dairy cows supplemented with vitamin E and fat

The objective of this study was to evaluate the effects of vitamin E（VE; 1 500 or 3 000 international units（IU） d^（-1）） and fat（2% of dry matter calcium salt of soybean oil） supplementation during the transition period on feed intake, milk yield and composition and blood metabolites of dairy cows. 48 multiparous Holstein cows were randomly assigned into one of four treatments in a 2×2 factorial arrangement of vitamin E and supplemental dietary fat during the transition period. Treatments were： 1） 1 500 IU d^（-1） vitamin E without fat supplementation（1 500VE-F）; 2） 1 500 IU d^（-1） vitamin E with fat supplement（1 500VE＋F）; 3） 3 000 IU d^（-1） vitamin E without fat supplementation（3 000VE-F）; and 4） 3 000 IU d^（-1） vitamin E with fat supplement（3 000VE＋F）. Dietary treatments were initiated at approximately 28 d before expected calving dates and continued through 28 d postpartum. Dry matter intake（DMI） was unaffected（P〉0.05） by prepartum treatment. Regardless of vitamin E supplementation, DMI was greater（P〈0.01） in fat-supplemented cows compared with un-supplemented cows（19.60 vs. 18.45 kg d^（-1）; SEM=0.42） during the postpartum period. Energy balance and body weight were not affected（P〉0.05） by treatments. Postpartum diets had no significant effect on milk yield or milk composition. Plasma concentrations of non-esterified fatty acids, glucose, and insulin were not affected（P〉0.05） by treatments. Regardless of vitamin E supplementation, plasma β-hydroxybutyrate concentration was greater（P〈0.05） in fat-supplemented cows compared with un-supplemented cows during the postpartum period. These results showed no indication of positive effects on lactation performance associated with vitamin E and dietary fat supplement in transition cows.

Exploratory Study on Relationship among Body Weight, Body Condition Score and Some Blood Biochemical Parameters of Non-Descriptive Goats in Mzimvubu Local Municipality: A Case of Santombe Village

Body weight is a crucial trait that aids farmers in decision-making regarding vaccinations, feeding, marketing and selection during the breeding programs. The study was conducted to investigate the effect of sex and age on body weight (BW), body condition score (BCS) and some blood biochemical parameters (BBP) and to determine the correlation amongst BW, BCS and BBP of non-descriptive goats at Santombe communal farming system. Blood samples were collected from 33 apparently healthy goats (27 females and 6 males) aged 6 - 8 tooth with a mean BW (32.62 ± 11.39 kg) while BCS (3.17 ± 0.39) was taken by means of palpating the lumbar area, sternum and the ribs. The BCS was rated on a scale of 1 to 5 with 1 being emaciated and 5 being extremely fat. The blood samples were analyzed using Cobas intergra 400 plus chemistry analyzer, Roche for biochemical parameters such as total protein (TP), urea, cholesterol (Chol), magnesium (Mg), phosphorous (P) and calcium (Ca) with mean values of 72.79 ± 5.84 mg/l, 2.76 ± 1.16 mmol/l, 2.08 ± 0.40 mmol/l, 1.09 ± 0.09 mmol/l, 2.30 ± 0.49 mmol/l and 2.45 ± 0.12 mmol/l respectively. Sex and age had significant effects on BW, BCS and some biochemical parameters. The BW and BCS for males were significantly higher than for females. Correlation results indicated that BW had a positive relationship with BCS (r = 0.677), TP and BW (r = 0.400), Chol and BCS (r = 0.4025) and Mg and TP (r = -0.075). Age and sex had significant influences on BW, BCS and some blood biochemical parameters. Consideration of the factors can aid in determining the accurate diagnosis of the nutritional status of goats.

Effects of Rumen-protected Methionine on Rumen Fermentation, lactation Performance and Plasma Characteristics in Dairy Cows

The objective was to evaluate effects of rumen-protected methionine （RP-Met） supplementation on rumen fermentation, lactation performance and plasma characteristics in dairy cows. Twenty-four multiparous （2.2 - 0.40 parity） Holstein dairy cows, averaged 620 ± 12.3 kg of BW, 68 ± 2.5 day in milk and daily milk production averaged 26.0 ±0.3 kg/cow were used in a replicated 4 × 4 Latin square experiment. The treatments were： control （without RP-Met）, LRP-Met, MRP-Met and HRP-Met with 20, 40 and 60 g RP-Met per cow per day, respectively. RP-Met was hand-mixed into the top one-third of the daily ration. Experimental periods were 30 days with 15 d of adaptation and 15 d of sampling. Dry matter （DM） intake and milk yields were not affected （P 〉 0.05） with increasing RP-Met supplementation. Yields of 4%FCM, ECM, milk fat and milk protein were higher （P 〈 0.03） for RP-Met supplementation than control and were quadratically （P 〈 0.05） changed due to the higher percentage of milk fat and protein for RP-Met supplementation than control （P 〈 0.03）. Ruminal pH tended to be lower （P = 0.071） for RP-Met supplementation than control, whereas total VFA concentration tended to be higher （P = 0.086） for RP-Met supplementation than control. Ratio of acetate to propionate decreased linearly （P = 0.001） from 4.01 to 3.57 as RP-Met supplementation increased due to the increase in propionate production. Digestibilities of DM, OM, CP, NDF and ADF in the total tract were higher （P 〈 0.05） for RP-Met supplementation than control and were quadratically （P 〈 0.05） increased with increasing RP-Met supplementation. Plasma concentrations of glucose not affected （P 〉 0.05） with RP-Met supplementation, Plasma concentrations of non-esterified fatty acids （NEFA） were significantly lower （P = 0.017） for RP-Met supplementation than control and were linearly （P = 0.011） changed. Plasma concentrations of beta-hydroxybutyrate tended to be lower （P = 0.068） for RP-Met supplementation than control and were linearly （P = 0.001） changed. The present results indicate that supplementation of diet with RP-Met improved the content of milk fat and protein, rumen fermentation and feed digestion, decreased plasma concentrations of NEFA. It was suggested that the RP-Met stimulated the digestive microorganisms or enzymes in a dose-dependent manner. In the experimental conditions of this trial, the optimum RP-Met dose was about 25 g RP-Met per cow per day.

Involvement of Quebracho tannins in diet alters productive and reproductive efficiency of postpartum buffalo cows

This study was conducted to investigate the effects of 10 weeks supplementation of Quebracho tannins(QT; 0 [control], 100 [QT100] or 200 g/[cow$d] [QT_(200)]) to 30 multiparous postpartum buffalo cows(10 cows per group) on milk yield and composition, blood metabolites and reproductive performance.Supplementation of QT100 had no significant effect on milk yield, whereas QT_(200) decreased(P < 0.05) this trait. Compared with the control group, both QT levels decreased(P < 0.05) fat-corrected milk(FCM)yield, but no significant effects were found on percentages of milk fat and protein. Contrariwise, yields of milk fat, lactose and milk protein were decreased(P < 0.05) when QT_(200) was supplemented. The solids nonfat(SNF) percentage and yield were decreased(P < 0.05) with QT100 supplementation. Moreover, QT tended to numerically reduce total number of ovarian follicles, number of small follicles, peripheral progesterone concentration and conception rate. Supplementation of QT_(200) numerically increased number of large follicles, mean diameter of large follicle, number and diameters of corpora lutea. The inclusion of QT_(200) shortened days open(DO) and decreased number of services per conception.Contrariwise, QT did not show significant effects on serum total protein, albumin, globulin, glucose,cholesterol and triglycerides concentrations. Supplementation of QT100 caused an increase(P < 0.05) of serum urea compared with that in control and QT_(200) groups. Generally, QT decreased(P < 0.05) serum creatinine concentration. Therefore, the supplementation of a commercial QT to early lactating Egyptian buffalo cows displayed negative consequences on their productive and reproductive performances.