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Fungi belonging to the genus Neosartorya (teleomorph of Aspergillus spp.) are of great concern in the production and storage of berries and fruit-based products, mainly due to the production of thermoresistant ascospores that cause food spoilage and possible secretion of mycotoxins. We initially tested the antifungal effect of six natural extracts against 20 isolates of Neosartorya spp. using a traditional inhibition test on Petri dishes. Tested isolates did not respond uniformly, creating 5 groups of descending sensitivity. Ten isolates best representing of the established sensitivity clusters were chosen for further investigation using a Biolog™ MT2 microplate assay with the same 6 natural extracts. Additionally, to test for metabolic profile changes, we used a Biolog™ FF microplate assay after pre-incubation with marigold extract. All natural extracts had an inhibitory effect on Neosartorya spp. growth and impacted its metabolism. Lavender and tea tree oil extracts at a concentration of 1000 µg mL−1 presented the strongest antifungal effect during the inhibition test, however all extracts exhibited inhibitory properties at even the lowest dose (5 µg mL−1). The fungal stress response in the presence of marigold extract was characterized by a decrease of amino acids and carbohydrates consumption and an uptake of carboxylic acids on the FF microplates, where the 10 studied isolates also presented differences in their innate resilience, creating 3 distinctive sensitivity groups of high, average and low sensitivity. The results confirm that natural plant extracts and essential oils inhibit and alter the growth and metabolism of Neosartorya spp. suggesting a possible future use in sustainable agriculture as an alternative to chemical fungicides used in traditional crop protection. [ABSTRACT FROM AUTHOR]

The current research was conducted during May-October, 2023 aimed to assess the haemato-biochemical parameters in cattle affected with S. aureus affected subclinical mastitis. Mastitis in dairy cattle is the persistent, inflammatory reaction of the udder tissue. Financial losses due to mastitis occur in the case of both sub-clinically and clinically affected animals. Subclinical mastitis exhibits no clinical signs and mostly remains unnoticed by the farmer and can be detected if specific tests are performed in milk samples. Sub-clinical mastitis has an erosive effect on the economy of dairy farmers as it effect directly on the milk quality and quantity. In India prevalence of sub-clinical mastitis was found to be more in cows when compared to clinical mastitis. Blood samples were collected from the jugular vein of 10 healthy and 10 subclinical mastitis affected cattle. Blood samples were analyzed for Hb, PCV, TEC, TLC, while serum samples were examined for ALT, AST, ALP, Glucose, Total protein, Albumin, Cholesterol and Calcium. Haematology report showed significantly (p<0.01) decrease in Hb, PCV and TEC in subclinical affected cattle when compared to healthy animals. TLC was significantly increased in (p<0.01) subclinical affected animal than healthy animal. Biochemical estimate revealed significantly (p<0.05) higher average values of AST, ALP and Ca in subclinical mastitis affected animals compared to healthy animals. Glucose, total protein, albumin, cholesterol and ALT levels are significantly (p<0.05) decrease in subclinical mastitis affected animals when compared to healthy cows. Haemato-biochemical parameters can be used as important for pathological state of subclinical mastitis animals. [ABSTRACT FROM AUTHOR]

Chimaeribacter arupi (heterotypic synonym: "Nissabacter archeti") is a facultative anaerobic, newly described Gram-negative rod and belongs to the Yersineacea family. Here, we report the case of a 19-month-old female infant patient who presented to the emergency unit with somnolence and fever. C. arupi was isolated from a positive blood culture, taken via an implanted Broviac catheter, proving a bloodstream infection by the pathogen. The objective of this study was to utilize whole genome sequencing to assess the genes encoding potential virulence associated factors, which may play a role in host tropism, tissue invasion and the subsequent stages in the pathogenesis of a bloodstream infection with C. arupi. The genome of the isolate was completely sequenced employing Illumina MiSeq and Nanopore MinION sequencing and the presumptive virulence associated factors and antimicrobial resistance genes were investigated in more detail. Additionally, we performed metabolic profiling and susceptibility testing by microdilution. The presence of predicted TcfC-like α-Pili suggests that C. arupi is highly adapted to humans as a host. It utilizes flagellar and type IV pili-mediated motility, as well as a number of γ1-pili and a s-pilus, which may be used to facilitate biofilm formation and adherence to host epithelia. Additionally, long polar fimbriae may aid in tissue invasion. The bacterium possesses antioxidant factors, which may enable temporary survival in phagolysosomes, and a capsule that potentially provides protection from phagocytosis. It may acquire iron ions from erythrocytes through the type 6 secretion system and hemolysins. Furthermore, the isolate exhibits betalactamase- mediated penicillin and aminopenicillin resistance. Based on the analysis of the whole genome, we conclude that C. arupi possesses virulence factors associated with tissue invasion and may thus be a potential opportunistic pathogen of bloodstream infections. [ABSTRACT FROM AUTHOR]

.037Kidney stone risk identified at donor workup, n (%) Past history of kidney stones2 While urine metabolic testing appears to be limited in its ability to predict future recurrent stone formation [[6]], at least six different transplant guidelines have recommended urine metabolic profile testing for potential kidney donors with stone risk [[7]]. While larger and longer follow-up studies are needed to confirm the low risk of subsequent kidney stones in higher-risk donor candidates, those with an acceptable amount of stone risk should be considered viable donor candidates. [Extracted from the article]

The aims of this study were to evaluate metabolic profiles obtained at -14, 14, and 28 days in milk (DIM), and to identify potential predictive biomarkers of Holstein dairy cows with purulent vaginal discharge (PVD) at 28 DIM. The body condition score (BCS) and hematocrit (Hct) were evaluated, and a metabolic profile test (MPT) was performed at -14, 14, and 28 DIM using serum samples. Cows at 28 DIM were classified using a vaginoscopy and divided into groups of healthy cows (n=89) and cows with PVD (n=31). Albumin (Alb), total cholesterol (TCho), calcium (Ca) and, magnesium (Mg) levels were lower in cows with PVD than in healthy cows at 14 DIM. At 28 DIM, levels of Alb, TCho, Ca, blood urea nitrogen (BUN), Mg, and Hct were lower in cows with PVD. A multivariate stepwise logistic regression analysis showed that higher non-esterified fatty acids (NEFA; odds ratios; OR=4.47; P<0.01), lower Alb (OR=0.07; P<0.01) and lower TCho (OR=0.99; P=0.08) at 14 DIM, and lower Hct (OR=0.83; P=0.05), lower Alb (OR=0.12; P<0.01), and lower BUN (OR=0.74; P=0.02) at 28 DIM were significantly associated with PVD. In conclusion, serum Alb levels was a potential indicator associated with PVD, reflecting dietary protein deficiency preceding disease. Our findings suggest that MPT should be considered to monitor health status during the postpartum period for early diagnosis of PVD. [ABSTRACT FROM AUTHOR]

Simple Summary: Withers height and chest girth in calves were significantly correlated with carcass weight and body weight, regardless of sex. Meanwhile, the relationship between blood metabolites and carcass weight differed according to sex. Body measurements and blood metabolites measured during the growing period could be used to determine the nutritional and physiological status of cattle and predict the final carcass weight, but the animal factor, such as sex, should be considered. This study aimed to identify the growth performance and blood factors associated with carcass weight in Japanese Black calves based on 675 performance tests and field carcass records. We measured the body weight, withers height, and chest girth at the start of fattening age (approximately 8–10 months) and analyzed eight blood factors, including vitamins and metabolites. Single- and two-trait animal models were used to estimate the heritability and genetic correlations. The heritability estimates for growth performance were moderate to high (ranging from 0.48 to 0.74), and those for blood metabolites were low to moderate (ranging from 0.19 to 0.51). Estimates for genetic correlations of carcass or body weight with body weight, withers height, and chest girth were high (ranging from 0.42 to 0.80). The body weight and withers height at 8 months of age are possibly closely related to the final carcass weight. The blood metabolites associated with body weight were vitamin E in steers (castrated males) and β-carotene in heifers. Our findings indicate that body measurements and blood metabolites measured during the growing period could be used to determine the nutritional and physiological status of cattle as well as predict carcass weight. [ABSTRACT FROM AUTHOR]

Winnie, a mouse carrying a missense mutation in the MUC2 mucin gene, is a valuable model for inflammatory bowel disease (IBD) with signs and symptoms that have multiple similarities with those observed in patients with ulcerative colitis. MUC2 mucin is present in Winnie, but is not firmly compacted in a tight inner layer. Indeed, these mice develop chronic intestinal inflammation due to the primary epithelial defect with signs of mucosal damage, including thickening of muscle and mucosal layers, goblet cell loss, increased intestinal permeability, enhanced susceptibility to luminal inflammation-inducing toxins, and alteration of innervation in the distal colon. In this study, we show that the intestinal environment of the Winnie mouse, genetically determined by MUC2 mutation, selects an intestinal microbial community characterized by specific pro-inflammatory, genotoxic, and metabolic features that could imply a direct involvement in the pathogenesis of chronic intestinal inflammation. We report results obtained by using a variety of in vitro approaches for fecal microbiota functional characterization. These approaches include Caco-2 cell cultures and Caco-2/THP-1 cell co-culture models for evaluation of geno-cytotoxic and pro-inflammatory properties using a panel of 43 marker RNAs assayed by RT-qPCR, and cell-based phenotypic testing for metabolic profiling of the intestinal microbial communities by Biolog EcoPlates. While adding a further step towards understanding the etiopathogenetic mechanisms underlying IBD, the results of this study provide a reliable method for phenotyping gut microbial communities, which can complement their structural characterization by providing novel functional information. [ABSTRACT FROM AUTHOR]

The present study aimed to compare serum amyloid A (SAA) concentrations of Japanese Black (JB) breeding cows in both clinically normal and diseased cows diagnosed by veterinarians using modified latex agglutination turbidimetric immunoassay (LATIA) to determine the cut-off values for healthy and diseased JB cows. For the comparison, a total of 289 serum samples of healthy cows without any clinical symptoms intended for the metabolic profile test and 66 serums from diseased cows clinically diagnosed by veterinarians were measured for the SAA concentrations. A significant difference (p-value = 6.68 × 10−29) was observed in the mean SAA concentrations between the healthy (2.8 ± 3.2 mg/L) and diseased (54.8 ± 76.8 mg/L) groups, and the median concentrations of the healthy and diseased groups were 1.5 mg/L and 31.2 mg/L, respectively. Finally, the cut-off SAA concentrations at each probability were 2.9 mg/L (p = 0.05), 5.7 mg/L (p = 0.1), 13.7 mg/L (p = 0.5), and 21.8 mg/L (p = 0.9), respectively, and 6.5 mg/L (p = 0.122) based on evaluation performed using the receiver operating characteristic curve. The results indicated that, with the practical application of the obtained cut-off value, the measurement of SAA concentrations for JB breeding cows with LATIA could be potentially beneficial in the early evaluation of inflammatory diseases in JB breeding cows and possibly useful in the prevention of not only metabolic diseases but also non-nutritional diseases during the perinatal period of JB breeding cows. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to evaluate distinct performance indicators and energy system contributions in 3 different, new sport-specific finger flexor muscle exercise tests. Methods: The tests included the maximal strength test, the all-out test (30 s) as well as the continuous and intermittent muscle endurance test at an intensity equaling 60% of maximal force, which were performed until target force could not be maintained. Gas exchange and blood lactate were measured in 13 experienced climbers during, as well as pre and post the test. The energy contribution (anaerobic alactic, anaerobic lactic, and aerobic) was determined for each test. Results: The contribution of aerobic metabolism was highest during the intermittent test (59.9 ± 12.0%). During continuous exercise, this was 28.1 ± 15.6%, and in the all-out test, this was 19.4 ± 8.1%. The contribution of anaerobic alactic energy was 27.2 ± 10.0% (intermittent), 54.2 ± 18.3% (continuous), and 62.4 ± 11.3% (all-out), while anaerobic lactic contribution equaled 12.9 ± 6.4, 17.7 ± 8.9, and 18.2 ± 9.9%, respectively. Conclusion: The combined analysis of performance predictors and metabolic profiles of the climbing test battery indicated that not only maximal grip force, but also all-out isometric contractions are equally decisive physical performance indices of climbing performance. Maximal grip force reflects maximal anaerobic power, while all-out average force and force time integral of constant isometric contraction at 60% of maximal force are functional measures of anaerobic capacity. Aerobic energy demand for the intermittent exercise is dominated aerobic re-phosphorylation of high-energy phosphates. The force-time integral from the intermittent test was not decisive for climbing performance. [ABSTRACT FROM AUTHOR]

"Western diet" containing high concentrations of sugar and fat consumed during pregnancy contributes to development of obesity and diabetes type 2 in offspring. To mimic effects of this diet in animals, a cafeteria (CAF) diet is used. We hypothesized that CAF diet given to rats before, and during pregnancy and lactation differently influences fat content, metabolic and inflammation profiles in offspring. Females were exposed to CAF or control diets before pregnancy, during pregnancy and lactation. At postnatal day 25 (PND 25), body composition, fat contents were measured, and blood was collected for assessment of metabolic and inflammation profiles. We have found that CAF diet lead to sex-specific alterations in offspring. At PND25, CAF offspring had: (1) higher percentage of fat content, and were lighter; (2) sex-specific differences in levels of glucose; (3) higher levels of interleukin 6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor (TNF-α); (4) sex-specific differences in concentration of IL-6 and TNF-α, with an increase in CAF females; (5) higher level of IL-10 in both sexes, with a more pronounced increase in females. We concluded that maternal CAF diet affects fat content, metabolic profiles, and inflammation parameters in offspring. Above effects are sex-specific, with female offspring being more susceptible to the diet. [ABSTRACT FROM AUTHOR]

Captive primates require environmental enrichment to minimize physical and mental stress. However, only a few objective evaluations have been performed to assess environment-induced physiological variations in these animals. In this study, we evaluated the usage of the metabolic profile test (MPT) to assess the influences of the housing environment on the physiology of Japanese macaques. Five male macaques were housed in an old type of cage (old cage group), in which the macaques were exposed to wind (except for a shelter box), and four males were in a new -type of cage (new cage group), which had a sub-room with a waterer that was surrounded by insulating panels. Blood samples were collected bimonthly for a year from the two groups to determine the complete blood count and blood biochemistry. The increase in the body weight of the macaques in both groups was suppressed during the cold season. Furthermore, this suppression was more pronounced in the old cage group, suggesting that the energy expenditure was higher in the old cage group than in the new cage group. Moreover, the red blood cell count and hematocrit values were higher during the cold season in both cages than during the warm season, suggesting that macaques were dehydrated during the cold season. Dehydration tendency was more pronounced in the macaques from the old cage group than in those from the new cage group, suggesting that their water intake decreased during the cold season. Our results suggest that the MPT can be used to evaluate environment-induced physiological variations in Japanese macaques. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to explore the individual and combined effects of obesity and metabolic profile on the impairment of glomerular function among hypertensive subjects. Methods: This is a cross‐sectional study enrolling 499 hypertensive subjects. Based on body mass index values and metabolic profile, they were assigned to one of four metabolic phenotype groups: MHNO: metabolically healthy non‐obese, MHO: metabolically healthy but obese, MUHNO: metabolically unhealthy but non‐obese, and MUHO: metabolically unhealthy and obese. The effect of the interaction between obesity and metabolic profile was tested on an additive scale, for both microalbuminuria and reduced estimated glomerular filtration rate (eGFR). Results: After adjustment for confounding factors, the highest risk of both microalbuminuria and decreased eGFR was found among patients of the MUHO group (OR = 6.0 [2.13], p < 0.0001, OR = 5.4 [1.26], p = 0.03, respectively). Analysis of the additive interaction indicates that 51% and 53% of the risk of microalbuminuria and its combination with low eGFR respectively is explained by the co‐occurrence of obesity and metabolic disorder. The mechanism of this interaction is synergistic (synergy index = 2.6, [1.5.3]). Conclusion: The decline of glomerular function in hypertensive subjects is significantly exacerbated by the interaction between obesity and metabolic disorders. The management of such high‐risk subjects requires, in addition to the therapeutic regimen, an adequate dietary and physical program in order to preserve glomerular function. SUMMARY AT A GLANCE: This cross‐sectional study explored the individual and combined effects of obesity and metabolic profile on kidney function among 499 hypertensive subjects, and found that the odds of microalbuminuria and low eGFR was highest in patients with metabolically unhealthy obesity. The co‐exsitence of obesity and metabolic disorder showed a synergistic interaction for this association. [ABSTRACT FROM AUTHOR]

Background: Copper supplementation in ruminants deserves special attention because of the narrow margin between deficiency and toxicity. The aim of the study was to analyse the relationship between the Cu concentration and other blood parameter values having taken into consideration their physiological limits based on the variation of copper concentration in the three different sheep breeds. Methods: Sixty sheep (35±5 kg) kept on the same farm were studied: the Suffolk (n = 20), the Merino (n = 20) and the Lithuanian blackhead (n = 20). The sheep were selected according to the following parameters: 3.5±0.3 years old, not pregnant during the entire investigation period, clinically healthy. All sheep were kept under the same conditions and throughout the year, were fed at the same time the same ration balanced according to their physiological needs. Individual blood samples were collected on the same day, on monthly basis for the period of one year (April 2018 to May 2019). Blood biochemical parameters as well blood haematology and cortisol concentration were analysed. Result: The highest average value of copper concentration was found in the Merino breed. The study has shown that the lowest number of blood samples with the levels of copper meeting the physiological limit values was found in the native Lithuanian blackhead sheep at the end of the grazing period and in the Merino and the Suffolk breeds - during the coldest winter months. The increase in copper concentration could be related to the stress caused due to the changes in dietary conditions, the variations of ambient temperature and different breed response to these factors. [ABSTRACT FROM AUTHOR]

Environmental metabolomics has the potential to facilitate the establishment of a new suite of tools for assessing the physiological status of important wildlife species. A first step in developing such tools is to evaluate the impacts of various capture techniques on metabolic profiles as capture is necessary to obtain the biological samples required for assays. This study employed 1H nuclear magnetic resonance (NMR)-based metabolite profiling of 562 blood serum samples from wild bighorn sheep to identify characteristic molecular serum makers of three capture techniques (dart, dropnet, and helicopter-based captures) to inform future sampling protocols for metabolomics studies, and to provide insights into the physiological impacts of capture. We found that different capture techniques induce distinct changes in amino acid serum profiles, the urea cycle, and glycolysis, and attribute the differences in metabolic patterns to differences in physical activity and stress caused by the different capture methods. These results suggest that when designing experiments involving the capture of wild animals, it may be prudent to employ a single capture technique to reduce confounding factors. Our results also supports administration of tranquilizers as soon as animals are restrained to mitigate short-term physiological and metabolic responses when using pursuit and physical restraint capture techniques. [ABSTRACT FROM AUTHOR]

Every year individuals experience symptoms that remain undiagnosed by healthcare providers. In the United States, these rare diseases are defined as a condition that affects fewer than 200,000 individuals. However, there are an estimated 7000 rare diseases, and there are an estimated 25–30 million Americans in total (7.6–9.2% of the population as of 2018) affected by such disorders. The NIH Common Fund Undiagnosed Diseases Network (UDN) seeks to provide diagnoses for individuals with undiagnosed disease. Mass spectrometry-based metabolomics and lipidomics analyses could advance the collective understanding of individual symptoms and advance diagnoses for individuals with heretofore undiagnosed disease. Here, we report the mass spectrometry-based metabolomics and lipidomics analyses of blood plasma, urine, and cerebrospinal fluid from 148 patients within the UDN and their families, as well as from a reference population of over 100 individuals with no known metabolic diseases. The raw and processed data are available to the research community so that they might be useful in the diagnoses of current or future patients suffering from undiagnosed disorders. Measurement(s) Metabolomics • Lipidomics Technology Type(s) gas chromatography-mass spectrometry • Ultra High-performance Liquid Chromatography/Tandem Mass Spectrometry Factor Type(s) age group • sex Sample Characteristic - Organism Homo sapiens Sample Characteristic - Environment blood plasma material • urine material • cerebrospinal fluid material Sample Characteristic - Location United States of America Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13656581 [ABSTRACT FROM AUTHOR]

Idiopathic forms of Focal Segmental Glomerulosclerosis (FSGS) are caused by circulating permeability factors, which can lead to early recurrence of FSGS and kidney failure after kidney transplantation. In the past three decades, many research endeavors were undertaken to identify these unknown factors. Even though some potential candidates have been recently discussed in the literature, "the" actual factor remains elusive. Therefore, there is an increased demand in FSGS research for the use of novel technologies that allow us to study FSGS from a yet unexplored angle. Here, we report the successful treatment of recurrent FSGS in a patient after living-related kidney transplantation by removal of circulating factors with CytoSorb apheresis. Interestingly, the classical published circulating factors were all in normal range in this patient but early disease recurrence in the transplant kidney and immediate response to CytoSorb apheresis were still suggestive for pathogenic circulating factors. To proof the functional effects of the patient's serum on podocytes and the glomerular filtration barrier we used a podocyte cell culture model and a proteinuria model in zebrafish to detect pathogenic effects on the podocytes actin cytoskeleton inducing a functional phenotype and podocyte effacement. We then performed Raman spectroscopy in the < 50 kDa serum fraction, on cultured podocytes treated with the FSGS serum and in kidney biopsies of the same patient at the time of transplantation and at the time of disease recurrence. The analysis revealed changes in podocyte metabolome induced by the FSGS serum as well as in focal glomerular and parietal epithelial cell regions in the FSGS biopsy. Several altered Raman spectra were identified in the fractionated serum and metabolome analysis by mass spectrometry detected lipid profiles in the FSGS serum, which were supported by disturbances in the Raman spectra. Our novel innovative analysis reveals changed lipid metabolome profiles associated with idiopathic FSGS that might reflect a new subtype of the disease. [ABSTRACT FROM AUTHOR]

Background: Spinal cord injury (SCI) patients display disruption of gut microbiome, and gut dysbiosis exacerbate neurological impairment in SCI models. Cumulative data support an important role of gut microbiome in SCI. Here, we investigated the hypothesis that fecal microbiota transplantation (FMT) from healthy uninjured mice into SCI mice may exert a neuroprotective effect. Results: FMT facilitated functional recovery, promoted neuronal axonal regeneration, improved animal weight gain and metabolic profiling, and enhanced intestinal barrier integrity and GI motility in SCI mice. High-throughput sequencing revealed that levels of phylum Firmicutes, family Christensenellaceae, and genus Butyricimonas were reduced in fecal samples of SCI mice, and FMT remarkably reshaped gut microbiome. Also, FMT-treated SCI mice showed increased amount of fecal short-chain fatty acids (SCFAs), which correlated with alteration of intestinal permeability and locomotor recovery. Furthermore, FMT downregulated IL-1β/NF-κB signaling in spinal cord and NF-κB signaling in gut following SCI. Conclusion: Our study demonstrates that reprogramming of gut microbiota by FMT improves locomotor and GI functions in SCI mice, possibly through the anti-inflammatory functions of SCFAs. 4wtf5ApZ8ToEwi5YEe-D32 Video Abstract [ABSTRACT FROM AUTHOR]

Bovine isoleucyl-tRNA synthetase (IARS) disorder, a major cause of weak calf syndrome, is caused by a homozygous missense (c.235G>C) mutation in the bovine IARS gene of Japanese Black (JB) cattle, which was identified in 2013. However, the extent to which the carrier rate has changed at Kagoshima prefecture, Japan, and whether the carrier status is associated with any clinical or reproductive problems, have yet to be ascertained. In this study, using a real-time polymerase chain reaction-based genotyping assay, we determined the carrier rate in a regional JB cow population at Kagoshima prefecture. Comparative analyses were performed on the metabolic profile test (MPT) results and reproductive performance data obtained for heterozygous carrier and homozygous wild-type cows. In 2009 and 2018, DNA samples were collected from 130 and 462 clinically healthy JB cows, respectively, in Kagoshima prefecture. MPT results and reproductive performance data were evaluated for 62 cows, comprising four heterozygous carriers and 58 wild-type cows. Genotyping revealed that the carrier rate was 6.9% in 2009 and 1.5% in 2018, the difference of which was statistically significant (P<0.005). There were no statistically significant differences between the carrier and wild-type cows with respect to either MPT results or reproductive performance, indicating that the carrier cows have necessary IARS activity to maintain minimal health and reproductive potential. [ABSTRACT FROM AUTHOR]

The metabolic profile test in animals is used to assess their nutritional status, to diagnose disease and assess fertility. The aim of this paper was to investigate the metabolic profile in buffalo cows. Forty buffaloes from the Research and Development Station for Buffaloes Secaia -Romania, were divided into two groups (20 heads/group). Estrus induction protocols were applied to the first group (G1), while the second group consisted of buffalo cows that express natural oestrus (G2). When the artificial insemination was performed, blood samples were taken and the following parameters were determined: hemoglobin, total serum protein, phosphorus, calcium, magnesium, alkaline phosphatase, cholesterol, glucose, lipase, urea. G2buffalocows had significantly higher concentrations of hemoglobin, serum protein, glucose and inorganic phosphorus, while the serum calcium levels were lower in the group. The concentration of magnesium, alkaline phosphatase, cholesterol, lipase and urea did not differ significantly between the buffalo groups (p>0.05). The Ca:P ratio for G2buffaloes was lower (1.94:1) compared to G1buffaloes (2.89:1). It can be concluded that the level of hemoglobin, serum protein, glucose, calcium and inorganic phosphorus plays a major role in the reproduction of buffaloes. [ABSTRACT FROM AUTHOR]

In the present paper, the metabolic profile was analysed in a group of adult Rhode Island hens extensively required for the production of IgY antibodies against bacterial entities. The results reveal changes in the leukocyte formula dominated by an increase in the percentage of heterophils and a decrease in the percentage of lymphocytes in the blood. An increase in the level of serum proteins with predominance of globulins is added to this. Increased uric acid levels were found also. Increased levels of GOT and GPT transaminases and -GT indicated an intensification of the protein metabolism, LDH and PA were not significantly modified. Regarding carbohydrate metabolism, it was found that serum glucose and lactate were maintained within physiological limits. The lipid profile was characterized by maintaining serum triglycerides and cholesterol within normal limits. Significant decrease in HDL and increase in LDL were interpreted as a decrease in the proteosynthetic capacity of the liver. The mineral profile was dominated by the increase of the level of sodium, iron, magnesium and calcium but by the decrease of the level of chlorine, potassium and phosphorus. [ABSTRACT FROM AUTHOR]

Context: The significance of an early diagnosis of gestational diabetes mellitus (GDM) with oral glucose tolerance test (OGTT) has not been determined.Objective: The objective of this work is to investigate GDM diagnosed by early and standard OGTTs and determine adverse maternal and neonatal outcomes associated with early GDM diagnosis.Research Design and Methods: The Early Diagnosis of Gestational Diabetes Mellitus study is a prospective cohort study. Each participant in the study underwent 2 OGTTs, an early OGTT at 18 to 20 gestational weeks (gws) and a standard OGTT at 24 to 28 gws. The reproduciblity between early and standard OGTT were analyzed. Maternal and neonatal metabolic disorders and pregnancy outcomes were compared across groups.Results: A total of 522 participants completed both the early and standard OGTTs. The glucose values in the early OGTT were not significantly different from those in the standard OGTT (fasting: 4.31 ± 0.41 mmol/L vs 4.29 ± 0.37 mmol/L, P = .360; 1-hour: 7.68 ± 1.71 mmol/L vs 7.66 ± 1.59 mmol/L, P = .826; 2-hour: 6.69 ± 1.47 mmol/L vs 6.71 ± 1.39 mmol/L, P = .800). The reproducibility of early and standard OGTT results was 74.9%. Pregnant women in the GDM group had higher glycated hemoglobin, C-peptide, and homeostasis model assessment of insulin resistance in the late gestational period. Neonates born to mothers in the GDM group were at a higher risk of being large for gestational age (odds ratio [OR]: 3.665; 95% CI, 1.006-11.91) and were also more prone to neonatal hyperinsulinemia (OR: 3.652; 95% CI, 1.152-10.533).Conclusion: Early-onset GDM diagnosed by OGTT at 18 to 20 gws is associated with maternal and neonatal metabolic disorders and adverse pregnancy outcomes. Further randomized controlled trials on the therapeutic efficacy for early-onset GDM will confirm the significance of early screening for GDM. [ABSTRACT FROM AUTHOR]

The effects of feeding, fasting, and re-feeding on the metabolic profile of growing cattle were studied. Blood and urine samples were obtained from 12 crossbred steers weighing approximately 300 kg during the following periods: 11 h of normal feeding (postprandial period), 48 consecutive hours of fasting, followed by 48 h of re-feeding. Compared with the postprandial period, fasting caused the following modifications: moderate hypoglycemia accompanied by remarkable lipolysis detected by the increase in plasma levels of free fatty acids (FFAs); absence of hepatic lipidosis, as there were no changes in aspartate aminotransferase activity or serum cholesterol levels; mild ketogenesis, confirmed by the slight increase of β-hydroxybutyrate (βHB); increased amino acid burn for energy production, verified by the increase in serum urea contents. There were strong positive correlations between the plasma levels of FFAs and βHB (r = 0.68; p < 0.001), fasting duration and FFA concentration (r = 0.92; p < 0.00001), and fasting duration and serum urea (r = 0.52; p < 0.001); there was a negative correlation between fasting duration and blood glucose (r =-0.52; p < 0.0001). During this same period, mild hypovolemia characterized by an increase in intravascular volume deficit was observed. The metabolic condition observed during fasting was completely reversed during re-feeding, except for the temporarily higher proteolysis [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the differences in the metabolic profile and body composition of monozygotic (MZ) twins concordant and discordant for the practice of physical exercise. The sample consisted of 92 MZ twins (72.5% female and 27.5% male, mean age 25.4 ± 5.69 years), registered with the Brazilian Registry of Twins, residing in Natal, Brazil. Data collection was carried out between the years 2016 and 2018. On day 1, subjects underwent a whole-body fitness evaluation, including measures of weight, height, body composition by Dual-Energy X-ray Absorptiometry and the Cardiorespiratory Exercise Test. On day 2, 10 ml blood samples were collected (overnight fasting) to determine the lipid profile and fasting glucose. The sample was separated into three groups: Active Concordant twins (Concordant A, n = 44 subjects), Inactive Concordant twins (Concordant I, n = 22 subjects) and Discordant pairs for Physical Exercise (Discordant PE, n = 26 subjects). The results demonstrated a difference between the discordant twins for exercise and also between the active versus sedentary groups, indicating a causal effect of exercise on the fat percentage, maximum oxygen consumption (VO2max) and second ventilatory threshold variables. Between groups, a difference was also observed between the groups in ventilatory threshold, very low-density lipoprotein and triglycerides. We concluded that, regardless of genetics, the practice of physical exercise was sufficient to generate alterations in body composition and VO2max in MZ twins, but not in the lipid profile or fasting glucose. [ABSTRACT FROM AUTHOR]

We conducted comprehensive (untargeted) metabolic profiling of volatile organic compounds (VOCs) emitted in culture by bacterial taxa Francisella tularensis (F. tularensis) subspecies novicida and Bacillus anthracis (B. anthracis) Sterne, surrogates for potential bacterial bioterrorism agents, as well as selective measurements of VOCs from their fully virulent counterparts, F. tularensis subspecies tularensis strain SCHU S4 and B. anthracis Ames. F. tularensis and B. anthracis were grown in liquid broth for time periods that covered logarithmic growth, stationary, and decline phases. VOCs emitted over the course of the growth phases were collected from the headspace above the cultures using solid phase microextraction (SPME) and were analyzed using gas chromatography-mass spectrometry (GC-MS). We developed criteria for distinguishing VOCs originating from bacteria versus background VOCs (originating from growth media only controls or sampling devices). Analyses of collected VOCs revealed methyl ketones, alcohols, esters, carboxylic acids, and nitrogen- and sulfur-containing compounds that were present in the bacterial cultures and absent (or present at only low abundance) in control samples indicating that these compounds originated from the bacteria. Distinct VOC profiles where observed for F. tularensis when compared with B. anthracis while the observed profiles of each of the two F. tularensis and B. anthracis strains exhibited some similarities. Furthermore, the relative abundance of VOCs was influenced by bacterial growth phase. These data illustrate the potential for VOC profiles to distinguish pathogens at the genus and species-level and to discriminate bacterial growth phases. The determination of VOC profiles lays the groundwork for non-invasive probes of bacterial metabolism and offers prospects for detection of microbe-specific VOC biomarkers from two potential biowarfare agents. [ABSTRACT FROM AUTHOR]

Liriodendron tulipifera, also known as tuliptree, is a popular ornamental horticultural plant with extraordinary tulip-shaped flowers characterized by an orange band near their base. The mechanisms underlying petal band-specific pigmentation during L. tulipifera flower development are unclear. Here, we combined nontargeted and targeted metabolomics and transcriptomics to identify a pathway cascade leading to carotenoid biosynthesis that is specifically activated in the petal band. The comparative analysis of carotenoid metabolites between L. tulipifera and Liriodendron hybrids indicates that γ-carotene, a rare carotene in plants, is the most likely orange pigment responsible for the coloration of the petal band. Phenotypic and transcriptomic analyses of developing petals reveal that the band area is first predefined by the loss of green color. Later, the band is maintained by locally activating and repressing carotenoid and chlorophyll biosynthesis genes, respectively. Two rate-limiting genes of carotene biosynthesis, carotenoid isomerase (CRTISO) and epsilon lycopene cyclase (ε-LCY), encode the core enzymes responsible for petal band-specific orange pigmentation in L. tulipifera. In particular, a putative additional ε-LCY copy specific to L. tulipifera may contribute to the distinct petal coloration pattern, compared with L. chinense. Taken together, our work provides a first glimpse of the metabolome and transcriptome dynamics in tuliptree flower coloration and provides a valuable resource for flower breeding or metabolic engineering as well as for understanding flower evolution in an early woody angiosperm. [ABSTRACT FROM AUTHOR]

As a complex microbial ecosystem, wine is a particularly interesting model for studying interactions between microorganisms as fermentation can be done by microbial consortia, a unique strain or mixed culture. The effect of a specific yeast strain on its environments is unique and characterized by its metabolites and their concentration. With its great resolution and excellent mass accuracy, ultrahigh resolution mass spectrometry (uHRMS) is the perfect tool to analyze the yeast metabolome at the end of alcoholic fermentation. This work reports the change in wine chemical composition from pure and mixed culture fermentation with Lachancea thermotolerans, Starmerella bacillaris, Metschnikowia pulcherrima and S. cerevisiae. We could clearly differentiate wines according to the yeast strain used in single cultures and markers, which reflect important differences between the yeast species, were extracted and annotated. Moreover, uHRMS revealed underlining intra species metabolomics differences, showing differences at the strain level between the two Starmerella bacillaris. Non volatile metabolomics analysis of single and sequential fermentations confirmed that mixed fermentations lead to a different composition. Distinct metabolites appeared in wines from sequential fermentation compared to single fermentation. This suggests that interactions between yeasts are not neutral. [ABSTRACT FROM AUTHOR]

Objective(s): Unstable angina (UA) is a form of the acute coronary syndrome (ACS) that affects more than a third of the population before age 70. Due to the limitations of diagnostic tests, appropriate identification of UA is difficult. In this study, we proceeded to investigate metabolite profiling in UA patients compared with controls to determine potential candidate biomarkers. Materials and Methods: Ninety-four plasma samples from UA and 32 samples from controls were analyzed based on 1H NMR spectroscopy. The raw data were processed, analyzed, and subjected to partial least squares-discrimination analysis (PLS-DA), a supervised classification method with a good separation of control and UA patients was observed. The most important variables (VIP) .1 were selected and submitted to MetaboAnalyst pathway enrichment to identify the most important ones. Results: We identified 17 disturbed metabolites in UA patients in comparison with the controls. These metabolites are involved in various biochemical pathways such as steroid hormone biosynthesis, aminoacyl-tRNA biosynthesis, and lysine degradation. Some of the metabolites were deoxycorticosterone, 17-hydroxyprogesterone, androstenedione, androstanedione, etiocholanolone, estradiol, 2-hydroxyestradiol, 2-hydroxyestrone, 2-methoxyestradiol, and 2-methoxyestrone. In order to determine test applicability in diagnosing UA, a diagnostic model was further created using the receiver operator characteristic (ROC) curve. The areas under the curve (AUC), sensitivity, specificity, and precision were 0.87, 90%, 65%, and 91%, respectively, for diagnosing of UA. Conclusion: These metabolites could not only be useful for the diagnosis of UA patients but also provide more information for further deciphering of the biological processes of UA. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate PET/FDG metabolic parameters in locally advanced GEJC and correlate it with molecular pathological profiles. Methods: We retrospectively analyzed data from 66 patients with a histopathological diagnosis of GEJC who had undergone 18F-FDG PET/CT before surgical resection. Maximum standardized uptake (SUVmax), mean standardized uptake (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor were measured and calculated using the region of interest (ROI) technique. The relationship between metabolic parameters and the Lauren's classification, histologic differentiation, Ki-67 staining and positivity for human epidermal growth factor receptor 2 (HER2), c-Met, and epidermal growth factor receptor (EGFR) were investigated through immunohistochemical (IHC) analyses. Results: Of the total 66 patients, significant differences were observed between intestinal and non-intestinal (mixed and diffuse) adenocarcinomas in SUVmax (8.23 ± 2.83 vs. 6.29 ± 2.41, P = 0.008), SUVmean (4.85 ± 1.47 vs. 3.93 ± 1.22, P = 0.017), MTV (24.96 cm3 vs. 8.90 cm3; P = 0.004), and TLG (97.38 cm3 vs. 37.09 cm3, P = 0.005) values. SUVmax, MTV, and TLG of moderately differentiated adenocarcinomas were significantly higher than those of the poorly differentiated ones. SUVmax was significantly higher in tissues with a higher Ki-67 index or in the c-MET-negative group (P = 0.045, P = 0.036). No significant correlation was found between metabolic parameters and the expression of HER2 or EGFR in GEJC. Conclusion: 18F-FDG PET/CT may be useful for predicting the molecular pathological profiles of GEJC and for determining appropriate therapeutic strategy. [ABSTRACT FROM AUTHOR]

Kidney stone is a chronic metabolic disease that caused by many factors, especially by the metabolic disturbances of urine compositions, but the metabolic profiling of the urine from kidney stone patients remains poorly explored. In the present study, 1H NMR spectroscopy and multivariate pattern recognition analytical techniques were combined to explore the metabolic profiling of the urine from kidney stone patients. A total of 216 urine samples obtained from kidney stone patients (n = 110) and healthy controls (n = 106) were investigated. The results indicated that principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) models were capable of distinguishing kidney stone patients from healthy controls. In addition, a total of 15 metabolites was obviously different in concentration between the two groups. Furthermore, four metabolic pathways, including glyoxylate and dicarboxylate metabolism, glycine, serine and threonine metabolism, phenylalanine metabolism and citrate cycle (TCA cycle), were closely associated with kidney stone. Together, our results established a preliminary metabolic profiling of the urine from kidney stone patients via using 1H NMR-based analytical techniques for the first time and provided a novel method for recognizing and observing the kidney stone disease. [ABSTRACT FROM AUTHOR]

1. Docetaxel (DTX) liposome powder was stable over three months, and the liposome suspension was stable within 8 h. 2. Rabbits, rats and mice were intravenously treated with DTX-LP or with a DTX injection (DTX-IN). Four major metabolites of DTX were identified in feces: M1, M2, M3 and M4. However, M4 was not found in the bile. 3. The most abundant metabolite in the feces was M2 followed by M1/M3, with only a small amount of M4 observed. The most abundant metabolite in bile was also M2, followed by M1/M3. 4. The liposomal delivery of DTX did not alter the in vivo drug metabolism, and there were no significant differences among the three species tested. This suggested that this formulation is pharmaceutically safe for clinical use. In contrast to the traditional injected formula, DTX-LP administration significantly delayed drug metabolism, as observed in feces and bile. This property will greatly enhance the DTX therapeutic efficacy and reduce the systemic side effects of NSCLC treatment. [ABSTRACT FROM AUTHOR]

Background: Evidence suggests the pivotal contribution of nutrition as a modifiable risk factor for sarcopenia. The present cross-sectional study characterized the nutritional and metabolic profile of sarcopenia through an extensive exploration of a wide array of blood biomarkers related to muscle protein metabolism and transcriptomic signatures in community-dwelling elderly adults.Methods: Among 189 older individuals with a mean age of 73.2 years, sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia criteria based on appendicular lean mass measured by dual-energy X-ray absorptiometry scan, muscle strength, and gait speed. Nutritional status was evaluated using the mini-nutritional assessment (MNA). In addition, we assessed specific blood biomarkers of nutritional status (plasma essential amino acids [EAAs], vitamins), nicotine-derived metabolites, and an extensive microarray analysis from peripheral blood mononuclear cells.Results: Malnutrition defined by low MNA score was independently associated with sarcopenia (p < .001). Sarcopenic elderly showed lower body mass index and leptin and higher adiponectin and high-density lipoproteins. Levels of EAAs including lysine, methionine, phenylalanine, threonine, as well as branched-chain AAs and choline, were inversely associated with sarcopenia. Furthermore, nicotine metabolites (cotinine and trans-3'-hydroxycotine) and vitamin B6 status were linked to one or more clinical and functional measures of sarcopenia. Differentially expressed genes and ingenuity pathway analysis supported the association of nutrition with sarcopenia.Conclusions: Herein, the characterization of a nutritional and metabolic signature of sarcopenia provides a firm basis and potential identification of specific targets and directions for the nutritional approach to the prevention and treatment of sarcopenia in aging populations. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the Jurinea macrocephala roots afforded six compounds namely β-sitosterol (1), lupenone (2), physcion (3), ptiloepoxide (4), 20, 21α-epoxytaraxastan-3β-ol (5) and chlorogenic acid (6). All the compounds were isolated for the first time in roots. The structures of the compounds were established by analysis of their spectroscopic (1H and 13C NMR) and spectrometric (MS) data, as well as by comparison of these with those reported in the literature. Metabolic profiling of chloroform and ethyl acetate fractions were also accomplished using NMR. In NMR analysis, ERETIC (electronic reference to access in-vivo concentration) 2 method was used for the quantification of identified metabolites. High quantity of chlorogenic acid (6, 130 mg/g) lupenone (2, 33.4 mg/g) and amyrins (α, β) (170.6 mg/g) were detected in ethyl acetate and chloroform fractions. Further studies on the biological evaluation of phenolic-rich and chloroform fractions could be beneficial to explore its pharmaceutical potential. [ABSTRACT FROM AUTHOR]

Background: Previous individual studies have shown the differences in inflammatory cytokines and gray matter volumes between bipolar disorder (BD) and unipolar depression (UD). However, few studies have investigated the association between pro-inflammatory cytokines and differences in brain gray matter volumes between BD and UD.Methods: In this study, 72 BD patients and 64 UD patients were enrolled, with comparable gender and age distributions (33.8% males and an average age of 39.3 ± 13.7 years). Each participant underwent metabolic profiling (including body mass index (BMI), glucose, triglyceride, high-density lipoprotein (HDL), leptin, insulin, adiponectin), pro-inflammatory cytokine (including soluble interleukin-6 receptor (sIL-6R), soluble interleukin-2 receptor (sIL-2R), C-reactive protein (CRP), soluble tumor necrosis factor receptor type 1 (sTNF-R1) examinations, and structural magnetic resonance imaging exams. Voxel-based morphometry was performed to investigate the gray matter volume differences between BD and UD patients. Correlations between pro-inflammatory cytokines and the gray matter volume difference were analyzed.Results: Compared to UD patients, the BD group had significantly higher BMI, and higher levels of sIL-6R and sTNF-R1 than the UD patients. The BMI significantly correlated with the level of pro-inflammatory cytokines. Adjusted for age, sex, BMI, duration of illness and total intracranial volume, the BD individuals had significantly more reduced gray matter volumes over 12 areas: R. cerebellar lobule VIII, R. putamen, L. putamen, R. superior frontal gyrus, L. lingual gyrus, L. precentral gyrus, R. fusiform gyrus, L. calcarine, R. precuneus, L. inferior temporal gyrus, L. hippocampus, and L. superior frontal gyrus. These 12 gray matter volume differences between BP and UD patients negatively correlated with sIL-6R and sTNF-R1 levels.Conclusions: Our results suggested that BD patients had higher BMI and pro-inflammatory cytokine levels in comparison to UD patients, especially IL-6 and sTNF-R1, which may contribute to greater gray matter reductions in BD patients in comparison to UD patients. The results support the neuro-inflammation pathophysiology mechanism in mood disorder. It is clinically important to monitor BMI, which, in this investigation, positively correlated with levels of inflammatory cytokines. [ABSTRACT FROM AUTHOR]

External secretions play a vital role in external immune defense. However, the functions and components of these exudates are largely unknown in the red palm weevil, Rhynchophorus ferrugineus (Olivier) (Coleoptera: Curculionidae). In order to determine their role in external immunity, the immunosuppressive efficacy of the secretions in vitro against microbes, including bacteria and fungi, was clarified. In the present study, we found that these secretions had antimicrobial activity in vitro , implying external immunizing potency against pathogens. Surprisingly, all liquid phases of secretions could not significantly inhibit the growth of microbes in vitro compared to solid phases. To explain this phenomenon, the composition and emission differentia of secretions from the exocrine glands associated with different developmental stages, secretory regions, and phases were identified and analyzed based on metabonomics techniques. A total of more than 200 compounds, including quinines, phenols, aldehydes, acids, alcohols, saccharides, ketones, esters, amines, salts, ureas, and heterocycles, were identified in the secretions of larvae and adults. The liquid phase shared a number of metabolites with the solid phase, but the emission types and amounts were significantly different in the two phases, resulting in differences in external immunological activity. Tyrosine and p -benzoquinone were the dominant metabolites in all of the secretions, accounting for approximately 11.29% of emissions, with the portion in the solid phase being generally higher than that in the liquid phase. Moreover, only p -benzoquinone was entirely significantly upregulated in the solid phase compared to the liquid phase. Therefore, metabolome analysis suggested that p -benzoquinone, which may potentially be developed to be a valuable marker for determining external immunity, was considered to be the main substance responsible for external immune functions. This hypothesis was further demonstrated by the antimicrobial activity of p -benzoquinone. [ABSTRACT FROM AUTHOR]

Leigh Syndrome (OMIM 256000) is a heterogeneous neurologic disorder due to damage in mitochondrial energy production that usually starts in early childhood. The first description given by Leigh pointed out neurological symptoms in children under 2 years and premature death. Following cases brought some hypothesis to explain the cause due to similarity to other neurological diseases and led to further investigation for metabolic diseases. Biochemical evaluation and specific metabolic profile suggested impairment in energy production (OXPHOS) in mitochondria. As direct approach to involved tissues is not always possible or safe, molecular analysis is a great cost-effective option and, besides biochemical results, is required to confirm the underlying cause of this syndrome face to clinical suspicion. The Next Generation Sequencing (NGS) advance represented a breakthrough in molecular biology allowing simultaneous gene analysis giving short-time results and increasing the variants underlying this syndrome, counting over 75 monogenic causes related so far. NGS provided confirmation of emerging cases and brought up diagnosis in atypical presentations as late-onset cases, which turned Leigh into a heterogeneous syndrome with variable outcomes. This review highlights clinical presentation in both classic and atypical phenotypes, the investigation pathway throughout confirmation emphasizing the underlying genetic heterogeneity and increasing number of genes assigned to this syndrome as well as available treatment. [ABSTRACT FROM AUTHOR]

There continues to be a significant shortage of donor livers for transplantation. One impediment is the discard rate of fatty, or steatotic, livers because of their poor post-transplant function. Steatotic livers are prone to significant ischemia-reperfusion injury (IRI) and data regarding how best to improve the quality of steatotic livers is lacking. Herein, we use normothermic (37°C) machine perfusion in combination with metabolic and lipidomic profiling to elucidate deficiencies in metabolic pathways in steatotic livers, and to inform strategies for improving their function. During perfusion, energy cofactors increased in steatotic livers to a similar extent as non-steatotic livers, but there were significant deficits in anti-oxidant capacity, efficient energy utilization, and lipid metabolism. Steatotic livers appeared to oxidize fatty acids at a higher rate but favored ketone body production rather than energy regeneration via the tricyclic acid cycle. As a result, lactate clearance was slower and transaminase levels were higher in steatotic livers. Lipidomic profiling revealed ω-3 polyunsaturated fatty acids increased in non-steatotic livers to a greater extent than in steatotic livers. The novel use of metabolic and lipidomic profiling during ex situ normothermic machine perfusion has the potential to guide the resuscitation and rehabilitation of steatotic livers for transplantation. [ABSTRACT FROM AUTHOR]

Background: Autosomal recessive bestrophinopathy (ARB) is a retinal degenerative disorder caused by BEST1 mutations with autosomal recessive inheritance. We aim to map a comprehensive genomic and metabolomic profile of a consanguineous Chinese family with ARB. Methods: Ophthalmic examinations were performed on the affected patients with ARB. The proband was screened for potential causative mutations in a panel with 256 known retinal disease genes by using target capture sequencing. The related mutation was further validated and segregated in the family members by Sanger sequencing. In silico prediction tools were used for pathogenicity assessment. A UHPLC-MS/MS metabolomic analysis was performed to explore the disease-associated metabolic feature. Results: The affected patients from this family were characterized by low vision, the presence of subretinal fluid, macular edema, and hyperopia with coincidental angle closure. DNA sequencing identified a novel missense mutation in the BEST1 gene c.646G > A (p.Val216Ile) of the proband. Sanger sequencing further confirmed the mutation. The missense mutation was co-segregation across the pedigree and predicted to be deleterious by SIFT (0.017). The blood metabolic profiles were highly similar among all family members probably because of the same lifestyle, habitat and genomic background. However, ARB patients presented a significant deregulation of metabolites, such as citric acid, L-Threonic acid, and eicosapentaenoic acid. Conclusions: We identified a novel disease-associated variant in the BEST1 gene as well as a disease-specific metabolic feature in familial ARB. Our findings helped improve the understanding of ARB mechanisms. [ABSTRACT FROM AUTHOR]

In a prospective, randomized, three-arms, controlled clinical study, Chinese Herbal Medicine MaZiRenWan (MZRW, also known as Hemp Seed Pill) demonstrates comparable efficacy with Senna for functional constipation (FC) during an 8-week treatment period. Both MZRW and Senna are better than a placebo; relative to Senna and a placebo, MZRW displayed a more sustained effect during the 8-week follow-up period. The characteristic pharmacological mechanism responsible for this observation is still unclear. To explore this, we collected pre- and post-treatment serum samples of 85 FC patients from MZRW/Senna/placebo treatment groups for pharmacometabolomic analysis. An ultrahigh-performance liquid chromatography-mass spectrometer (UPLC-MS) was used for metabolic profiling and quantification. In vivo studies were conducted in constipated C57BL/6J mice to verify the effects and corresponding mechanism(s) of the action of MZRW. Pearson correlation analysis, paired t-test, one-way ANOVA analysis, χ2 test, and Student t-test were used to interpret the clinical and preclinical data. Changes in levels of circulating oleamide and its derivatives negatively correlate with improvement in complete spontaneous bowel movement (CSBM) in the MZRW group (Pearson r = -0.59, p = 0.00057). The same did not hold true for either Senna or placebo groups. Oleamide is a known regulator of intestinal motility. MZRW treatment resulted in reduced levels of circulating oleamide in FC patients. Experimental verification showed that MZRW attenuated oleamide-induced slow intestinal motility in mice. MZRW decreased oleamide levels in serum, ileum, and colon in normal mice, but increased expression of colonic fatty acid amide hydrolase (FAAH). In conclusion, MZRW improved bowel movement in FC by down-regulating oleamide, possibly by enhancing FAAH-mediated degradation. Our findings suggest a novel therapeutic strategy for FC. [ABSTRACT FROM AUTHOR]

Aim: Guanidinoacetate N -methyltransferase (GAMT) is the second essential enzyme in creatine (Cr) biosynthesis. Short-term Cr deficiency is metabolically well tolerated as GAMT–/– mice exhibit normal exercise capacity and response to ischemic heart failure. However, we hypothesized long-term consequences of Cr deficiency and/or accumulation of the Cr precursor guanidinoacetate (GA). Methods: Cardiac function and metabolic profile were studied in GAMT–/– mice >1 year. Results: In vivo LV catheterization revealed lower heart rate and developed pressure in aging GAMT–/– but normal lung weight and survival versus age-matched controls. Electron microscopy indicated reduced mitochondrial volume density in GAMT–/– hearts (P < 0.001), corroborated by lower mtDNA copy number (P < 0.004), and citrate synthase activity (P < 0.05), however, without impaired mitochondrial respiration. Furthermore, myocardial energy stores and key ATP homeostatic enzymes were barely altered, while pathology was unrelated to oxidative stress since superoxide production and protein carbonylation were unaffected. Gene expression of PGC-1α was 2.5-fold higher in GAMT–/– hearts while downstream genes were not activated, implicating a dysfunction in mitochondrial biogenesis signaling. This was normalized by 10 days of dietary Cr supplementation, as were all in vivo functional parameters, however, it was not possible to differentiate whether relief from Cr deficiency or GA toxicity was causative. Conclusion: Long-term Cr deficiency in GAMT–/– mice reduces mitochondrial volume without affecting respiratory function, most likely due to impaired biogenesis. This is associated with hemodynamic changes without evidence of heart failure, which may represent an acceptable functional compromise in return for reduced energy demand in aging mice. [ABSTRACT FROM AUTHOR]

Elucidating the metabolite profiles during the growth of Streptococcus thermophilus is beneficial for understanding its growth characteristics. The changes in the intracellular and extracellular concentrations of carbohydrates, nucleotides, amino sugars, nucleoside sugars, fatty acids, and amino acids, as well as their metabolites over time, were investigated by metabolomics technology. Most metabolites of nucleotides were highly accumulated in the intracellular environment after the mid-exponential phase. Increases in the intracellular unsaturated fatty acids and N-acetyl-glucosamine and N-acetyl-muramoate recycling provided potential evidence that cell envelope remodeling occurred after the mid-exponential phase. At the later fermentation stages, potentially functional metabolite produced by glycine was highly accumulated in the intracellular environment. Additionally, potential toxic metabolites produced by phenylalanine and tyrosine could not be excreted into the extracellular environment in a timely basis. The accumulation of large amounts of these metabolites might be the primary cause of the overconsumption of amino acids and influence the growth of S. thermophilus. [ABSTRACT FROM AUTHOR]

Background: Rootstock has a significant impact on plant growth and development, including fruit maturation. However, the existence of mutual interaction between scion and rootstock is often neglected. To explore the origin of different fruit quality traits in citrus, we studied the effect of rootstock and the reciprocal interaction between scion and rootstock of nine combinations; three mandarin varieties grafted on three different rootstocks. We analyzed the metabolic profile of juice via gas and liquid chromatography-mass spectrometry (GC-MS and LC-MS, respectively). Additionally, we profiled phloem sap composition in the scion and the rootstock. Quality traits of fruit and their physio-chemical characteristics were also evaluated. Results: For all three cultivars, rootstock was found to affect fruit yield and biochemical fruit quality parameters (sugar and acidity) in interactions with the scions. In mandarin juice, eight of 48 compounds (two primary and six secondary) were related directly to the rootstock, and another seven (one primary and six secondary) were interactively affected by scion and rootstock. In scion and rootstock sap, six and 14 of 53 and 55 primary metabolites, respectively, were directly affected by the rootstock, while 42 and 33 were affected by rootstock interactively with scion, respectively. Conclusion: In this work, we show for the first time a reciprocal effect between rootstock and scion. Based on our results, the scion and rootstock interaction might be organ, distance or time dependent. [ABSTRACT FROM AUTHOR]

Late onset Alzheimer's disease (LOAD) is a progressive neurodegenerative disease with four well-established risk factors: age, APOE4 genotype, female chromosomal sex, and maternal history of AD. Each risk factor impacts multiple systems, making LOAD a complex systems biology challenge. To investigate interactions between LOAD risk factors, we performed multiple scale analyses, including metabolomics, transcriptomics, brain magnetic resonance imaging (MRI), and beta-amyloid assessment, in 16 months old male and female mice with humanized human APOE3 (hAPOE3) or APOE4 (hAPOE4) genes. Metabolomic analyses indicated a sex difference in plasma profile whereas APOE genotype determined brain metabolic profile. Consistent with the brain metabolome, gene and pathway-based RNA-Seq analyses of the hippocampus indicated increased expression of fatty acid/lipid metabolism related genes and pathways in both hAPOE4 males and females. Further, female transcription of fatty acid and amino acids pathways were significantly different from males. MRI based imaging analyses indicated that in multiple white matter tracts, hAPOE4 males and females exhibited lower fractional anisotropy than their hAPOE3 counterparts, suggesting a lower level of white matter integrity in hAPOE4 mice. Consistent with the brain metabolomic and transcriptomic profile of hAPOE4 carriers, beta-amyloid generation was detectable in 16-month-old male and female brains. These data provide therapeutic targets based on chromosomal sex and APOE genotype. Collectively, these data provide a framework for developing precision medicine interventions during the prodromal phase of LOAD, when the potential to reverse, prevent and delay LOAD progression is greatest. [ABSTRACT FROM AUTHOR]

Background: Metabolomics time-course experiments provide the opportunity to understand the changes to an organism by observing the evolution of metabolic profiles in response to internal or external stimuli. Along with other omic longitudinal profiling technologies, these techniques have great potential to uncover complex relations between variations across diverse omic variables and provide unique insights into the underlying biology of the system. However, many statistical methods currently used to analyse short time-series omic data are i) prone to overfitting, ii) do not fully take into account the experimental design or iii) do not make full use of the multivariate information intrinsic to the data or iv) are unable to uncover multiple associations between different omic data. The model we propose is an attempt to i) overcome overfitting by using a weakly informative Bayesian model, ii) capture experimental design conditions through a mixed-effects model, iii) model interdependencies between variables by augmenting the mixed-effects model with a conditional auto-regressive (CAR) component and iv) identify potential associations between heterogeneous omic variables by using a horseshoe prior. Results: We assess the performance of our model on synthetic and real datasets and show that it can outperform comparable models for metabolomic longitudinal data analysis. In addition, our proposed method provides the analyst with new insights on the data as it is able to identify metabolic biomarkers related to treatment, infer perturbed pathways as a result of treatment and find significant associations with additional omic variables. We also show through simulation that our model is fairly robust against inaccuracies in metabolite assignments. On real data, we demonstrate that the number of profiled metabolites slightly affects the predictive ability of the model. Conclusions: Our single model approach to longitudinal analysis of metabolomics data provides an approach simultaneously for integrative analysis and biomarker discovery. In addition, it lends better interpretation by allowing analysis at the pathway level. An accompanying R package for the model has been developed using the probabilistic programming language Stan. The package offers user-friendly functions for simulating data, fitting the model, assessing model fit and postprocessing the results. The main aim of the R package is to offer freely accessible resources for integrative longitudinal analysis for metabolomics scientists and various visualization functions easy-to-use for applied researchers to interpret results. [ABSTRACT FROM AUTHOR]

Background: Reliable biomarkers for gestational diabetes mellitus (GDM) would be beneficial in the early prevention of adverse metabolic outcomes during pregnancy and beyond.Objectives: The objective of this study was to investigate whether the early pregnancy serum metabolic profile differs in women developing GDM from those remaining healthy. Furthermore, we evaluated the potential of these metabolites to act as predictive markers for GDM.Methods: This was a prospective study investigating overweight and obese [prepregnancy BMI (in kg/m2) ≥25 and >30, respectively] pregnant women (prepregnancy median BMI: 28.5; IQR: 26.4-31.5; n = 357). Fasting serum samples were analyzed with a targeted NMR approach in early pregnancy (median: 14.3 weeks of gestation). GDM was diagnosed on the basis of a 2-h, 75-g oral-glucose-tolerance test at a median of 25.7 weeks of gestation.Results: In early pregnancy, 78 lipid metabolites differed in women who later developed GDM (n = 82) compared with those who remained healthy (n = 275) (ANCOVA, adjusted for confounding factors and corrected for multiple comparisons; false discovery rate <0.05). Higher concentrations of several-sized VLDL particles and medium- and small-sized HDL particles, and lower concentrations of very large-sized HDL particles, were detected in women developing GDM. Furthermore, concentrations of amino acids including 2 branched-chain amino acids, isoleucine and leucine, and GlycA, a marker for low-grade inflammation, were higher in women who developed GDM. Receiver operating characteristic analysis revealed that the most predictive marker for GDM was a higher concentration of small-sized HDL particles (AUC: 0.71; 95% CI: 0.67, 0.77; P < 0.001).Conclusions: We identified a distinct early pregnancy metabolomic profile especially attributable to small HDL particles in women developing GDM. The aberrant metabolic profile could represent a novel way to allow early identification of this most common medical condition affecting pregnant women. This trial was registered at clinicaltrials.gov as NCT01922791. [ABSTRACT FROM AUTHOR]

Idiosyncratic drug-induced liver injury (IDILI) is a rare but potentially severe adverse drug reaction. To date, identifying individuals at risk for IDILI remains challenging. This is a prospective study, where a nested case–control (1:5) design was adopted. For six patients who had abnormalities in liver function test after Polygonum multiflorum Thunb. (PM) ingestion (susceptible group), 30 patients with normal liver function were matched (tolerant group). Based on liquid chromatography–mass spectrometry, metabolomics analysis was done on serum samples prior to PM ingestion, to screen the differential metabolites and characterize metabolomic profiles of patient serum in the two groups. Multivariate analysis showed that there were remarkable separations between susceptible and tolerant groups. A total of 25 major differential metabolites were screened out, involving glycerophospholipid metabolism, sphingolipid metabolism, fatty acid metabolism, histidine metabolism and aromatic amino acid metabolism. Wherein, the area under the curve of the receiver operating characteristic curves of metabolites PE 22:6, crotonoyl-CoA, 2E-tetradecenoyl-CoA, phenyllactic acid, indole-5,6-quinone, phosphoribosyl-ATP were all greater than 0.9. The overall serum metabolic profile comprising of 25 metabolites could clearly distinguish susceptible and tolerant groups. This proof-of-concept study used metabolomics to characterize the metabolic profile of IDILI risk individuals before drug ingestion for the first time. The metabolome characteristics in patient serum before PM ingestion may predict the risk of liver injury after PM ingestion. [ABSTRACT FROM AUTHOR]

Summary: Salinity is an important environmental factor that adversely impacts crop growth and productivity. Malate dehydrogenases (MDHs) catalyse the reversible interconversion of malate and oxaloacetate using NAD(H)/NADP(H) as a cofactor and regulate plant development and abiotic stress tolerance. Vitamin B6 functions as an essential cofactor in enzymatic reactions involved in numerous cellular processes. However, the role of plastidial MDH in rice (Oryza sativa) in salt stress response by altering vitamin B6 content remains unknown. In this study, we identified a new loss‐of‐function osmdh1 mutant displaying salt stress‐tolerant phenotype. The OsMDH1 was expressed in different tissues of rice plants including leaf, leaf sheath, panicle, glume, bud, root and stem and was induced in the presence of NaCl. Transient expression of OsMDH1‐GFP in rice protoplasts showed that OsMDH1 localizes to chloroplast. Transgenic rice plants overexpressing OsMDH1 (OsMDH1OX) displayed a salt stress‐sensitive phenotype. Liquid chromatography–mass spectrometry (LC‐MS) metabolic profiling revealed that the amount of pyridoxine was significantly reduced in OsMDH1OX lines compared with the NIP plants. Moreover, the pyridoxine content was higher in the osmdh1 mutant and lower in OsMDH1OX plants than in the NIP plants under the salt stress, indicating that OsMDH1 negatively regulates salt stress‐induced pyridoxine accumulation. Furthermore, genome‐wide RNA‐sequencing (RNA‐seq) analysis indicated that ectopic expression of OsMDH1 altered the expression level of genes encoding key enzymes of the vitamin B6 biosynthesis pathway, possibly reducing the level of pyridoxine. Together, our results establish a novel, negative regulatory role of OsMDH1 in salt stress tolerance by affecting vitamin B6 content of rice tissues. [ABSTRACT FROM AUTHOR]