BAR502/fibrate conjugates: synthesis, biological evaluation and metabolic profile.

BAR502, a bile acid analogue, is active as dual FXR/GPBAR1 agonist and represents a promising lead for the treatment of cholestasis and NASH. In this paper we report the synthesis and the biological evaluation of a library of hybrid compounds prepared by combining, through high-yield condensation reaction, some fibrates with BAR502.The activity of the new conjugates was evaluated towards FXR, GPBAR1 and PPARα receptors, employing transactivation or cofactor recruitment assays. Compound 1 resulted as the most promising of the series and was subjected to further pharmacological investigation, together with stability evaluation and cell permeation assessment. We have proved by LCMS analysis that compound 1 is hydrolyzed in mice releasing clofibric acid and BAR505, the oxidized metabolite of BAR502, endowed with retained dual FXR/GPBAR1 activity.

Altered biliary microbial and metabolic profile reveals the crosstalk between NAFLD and cholelithiasis.

BACKGROUND: The relationship between non-alcoholic fatty liver disease (NAFLD) and cholelithiasis is intricate, with alterations in the microenvironment potentially mediating this interplay. Thus, this study aimed to explore the biliary microbiota and metabolites of patients with cholelithiasis and detect changes induced by comorbid NAFLD. METHODS: In this study, 16S rRNA gene sequencing and metabolome analysis were performed on biliary samples collected from 35 subjects. Then, patients were stratified into two groups: the comorbidity group (n=18), consisting of cholelithiasis patients with NAFLD, and the non-comorbidity group (n=17), comprising cholelithiasis patients without NAFLD. RESULTS: Comorbid NAFLD did not significantly increase α-diversity but affected ß-diversity. A statistically significant difference was observed in the abundance of biliary metabolites between the two groups. Specifically, differences in the abundance of 4 phyla, 19 genera, and 28 metabolites were significant between the two groups. Correlation analysis demonstrated positive associations among 12α-hydroxylated bile acid levels, Pyramidobacter and Fusobacterium abundance, AST levels, and the fibrosis-4 index (p < 0.05, r > 0.3), all of which were increased in patients with cholelithiasis and comorbid NAFLD. CONCLUSIONS: The relationship between cholelithiasis and NAFLD influences the biliary microbial and metabolic profile, creating a detrimental microenvironment that promotes the disease progression.

Study on Cytochrome P450 Metabolic Profile of Paclitaxel on Rats using QTOF-MS.

BACKGROUND: Paclitaxel (PTX) is a key drug used for chemotherapy for various cancers. The hy-droxylation metabolites of paclitaxel are different between humans and rats. Currently, there is little infor-mation available on the metabolic profiles of CYP450 enzymes in rats. OBJECTIVE: This study evaluated the dynamic metabolic profiles of PTX and its metabolites in rats and in vitro. METHODS: Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrome-try (UHPLC-Q-TOF-MS) and LC-MS/MS were applied to qualitative and quantitative analysis of PTX and its metabolites in rats' liver microsomes and recombinant enzyme CYP3A1/3A2. Ten specific inhibitors [NF (CYP1A1), FFL (CYP1A2), MOP (CYP2A6), OND (CYP2B6), QCT (CYP2C8), SFP (CYP2C9), NKT (CYP2C19), QND (CYP2D6), MPZ (CYP2E1) and KTZ (CYP3A4)] were used to identify the metabolic pathway in vitro. RESULTS: Four main hydroxylated metabolites of PTX were identified. Among them, 3'-p-OH PTX and 2-OH PTX were monohydroxylated metabolites identified in rats and liver microsome samples, and 6α-2-di-OH PTX and 6α-5"-di-OH PTX were dihydroxylated metabolites identified in rats. CYP3A recombinant enzyme studies showed that the CYP3A1/3A2 in rat liver microsomes was mainly responsible for metabolizing PTX into 3'-p-OH-PTX and 2-OH-PTX. However, 6α-OH PTX was not detected in rat plasma and liver microsome samples. CONCLUSION: The results indicated that the CYP3A1/3A2 enzyme, metabolizing PTX into 3'-p-OH-PTX and 2-OH-PTX, is responsible for the metabolic of PTX in rats. The CYP2C8 metabolite 6α-OH PTX in humans was not detected in rat plasma in this study, which might account for the interspecies metabolic differences between rats and humans. This study will provide evidence for drug-drug interaction research in rats.

Metabolomics-based search for lung cancer markers among patients with different smoking status.

Tobacco smoking is the main etiological factor of lung cancer (LC), which can also cause metabolome disruption. This study aimed to investigate whether the observed metabolic shift in LC patients was also associated with their smoking status. Untargeted metabolomics profiling was applied for the initial screening of changes in serum metabolic profile between LC and chronic obstructive pulmonary disease (COPD) patients, selected as a non-cancer group. Differences in metabolite profiles between current and former smokers were also tested. Then, targeted metabolomics methods were applied to verify and validate the proposed LC biomarkers. For untargeted metabolomics, a single extraction-dual separation workflow was applied. The samples were analyzed using a liquid chromatograph-high resolution quadrupole time-of-flight mass spectrometer. Next, the selected metabolites were quantified using liquid chromatography-triple-quadrupole mass spectrometry. The acquired data confirmed that patients' stratification based on smoking status impacted the discriminating ability of the identified LC marker candidates. Analyzing a validation set of samples enabled us to determine if the putative LC markers were truly robust. It demonstrated significant differences in the case of four metabolites: allantoin, glutamic acid, succinic acid, and sphingosine-1-phosphate. Our research showed that studying the influence of strong environmental factors, such as tobacco smoking, should be considered in cancer marker research since it reduces the risk of false positives and improves understanding of the metabolite shifts in cancer patients.

Exploring the diversity and functional profile of microbial communities of Brazilian soils with high salinity and oil contamination.

Environmental pollution associated with the petroleum industry is a major problem worldwide. Microbial degradation is extremely important whether in the extractive process or in bioremediation of contaminants. Assessing the local microbiota and its potential for degradation is crucial for implementing effective bioremediation strategies. Herein, contaminated soil samples of onshore oil fields from a semiarid region in the Northeast of Brazil were investigated using metagenomics and metataxonomics. These soils exhibited hydrocarbon contamination and high salinity indices, while a control sample was collected from an uncontaminated area. The shotgun analysis revealed the predominance of Actinomycetota and Pseudomonadota, while 16S rRNA gene amplicon analysis of the samples showed Actinomycetota, Bacillota, and Pseudomonadota as the most abundant. The Archaea domain phylotypes were assigned to Thermoproteota and Methanobacteriota. Functional analysis and metabolic profile of the soil microbiomes exhibited a broader metabolic repertoire in the uncontaminated soil, while degradation pathways and surfactant biosynthesis presented higher values in the contaminated soils, where degradation pathways of xenobiotic and aromatic compounds were also present. Biosurfactant synthetic pathways were abundant, with predominance of lipopeptides. The present work uncovers several microbial drivers of oil degradation and mechanisms of adaptation to high salinity, which are pivotal traits for sustainable soil recovery strategies.

Potential relationships between apelin and metabolic-associated indices in transition dairy cows.

Metabolic disorders pose significant challenges in transition dairy cows. Numerous parameters have been investigated in this context, and apelin has recently emerged as a potential metabolic indicator. Accordingly, this study aimed to assess the associations between this hormone and other metabolic parameters. Twenty-two adult Holstein-Friesian dairy cows, 21 days before their expected calving date, were selected for blood sampling and serum separation at four time points: 21 and 10 days before calving and 10 and 21 days after parturition. Serum concentrations of apelin, leptin, insulin, cortisol, T3, T4, non-esterified fatty acids, glucose, total protein, albumin, globulin, aspartate aminotransferase, alanine transaminase, triglycerides, cholesterol, high, low and very low-density lipoproteins, total, direct and indirect bilirubin were measured in these samples. Surrogate indices for insulin resistance, body condition score, and milk production were also evaluated. Throughout the transition period, a significant increase in apelin levels was observed. Various models were employed to identify associations between apelin and the studied metabolic parameters. Notably, significant correlations between apelin and Leptin, Insulin, Cortisol, T3, T4, NEFA, Cholesterol, LDL, VLDL, Total Protein, Albumin, Globulin, Total Bilirubin, Direct Bilirubin and Indirect Bilirubin were observed, with some being immediate while others developed over time. These findings indicate a mutual influence between apelin and specific metabolic indices. Changes in any component of the metabolic profile at one stage can lead to alterations in apelin levels in subsequent stages. The correlations uncovered between apelin and other components of the metabolic profile in transitioning dairy cows offer valuable insights, contributing to a better understanding of the potential effects of apelin on the studied indicators and vice versa.

Metabolic activity of gut microbial enrichment cultures from different marine species and their transformation abilities to plastic additives.

The role of the gut microbiota in host physiology has been previously elucidated for some marine organisms, but little information is available on their metabolic activity involved in transformation of environmental pollutants. This study assessed the metabolic profiles of the gut microbial cultures from grouper (Epinephelus coioides), green mussel (Perna viridis) and giant tiger prawn (Penaeus monodon) and investigated their transformation mechanisms to typical plastic additives. Community-level physiological profiling analysis confirmed the utilization profiles of the microbial cultures including carbon sources of carbohydrates, amines, carboxylic acids, phenolic compounds, polymers and amino acids, and the plastic additives of organophosphate flame retardants, tetrabromobisphenol A derivates and bisphenols. Using in vitro incubation, triphenyl phosphate (TPHP) was found to be rapidly metabolized into diphenyl phosphate by the gut microbiota as a representative ester-containing plastic additive, whereas the transformation of BPA (a representative phenol) was relatively slower. Interestingly, all three kinds of microbial cultures efficiently transformed the hepatic metabolite of BPA (BPA-G) back to BPA, thereby increasing its bioavailability in the body. The specific enzyme analysis confirmed the ability of the gut microbiota to perform the metabolic reactions. The results of 16S rRNA sequencing and network analysis revealed that the genera Escherichia-Shigella, Citrobacter, and Anaerospora were functional microbes, and their collaboration with fermentative microbes played pivotal roles in the transformation of the plastic additives. The structure-specific transformations by the gut microbiota and their distinct bioavailability deserve more attention in the future.

Inter-facility characterization of bacteria in seafood processing plants: Exploring potential reservoirs of spoilage organisms and the resistome.

A study was conducted in fish processing facilities to investigate the microbial composition, microbial metabolic potential, and distribution of antibiotic resistance genes. Whole metagenomic sequencing was used to analyze microbial communities from different processing rooms, operators and fish products. Taxonomic analyses identified the genera Pseudomonas and Psychrobacter as the most prevalent bacteria. A Principal Component Analysis revealed a distinct separation between fish product and environmental samples, as well as differences between fish product samples from companies processing either Gadidae or Salmonidae fish. Some particular bacterial genera and species were associated with specific processing rooms and operators. Metabolic analysis of metagenome assembled genomes demonstrated variations in microbiota metabolic profiles of microbiota across rooms and fish products. The study also examined the presence of antibiotic-resistance genes in fish processing environments, contributing to the understanding of microbial dynamics, metabolic potential, and implications for fish spoilage.

Phenolic and Metabolic Profiles, Antioxidant Activities, Glycemic Control, and Anti-Inflammatory Activity of Three Thai Papaya Cultivar Leaves.

This study thoroughly examined the proximate composition, bioactive composition, and in vitro biological activities of three different cultivars of papaya leaf extracts (PLEs) as potential functional ingredients and nutraceuticals. The dark green leaves of three papaya cultivars, Khaek Dam (KD), Holland (H), and Thai Local (L), were used in this study. The protein content of the leaves ranged from 25.96 to 32.18%, the fat content ranged from 7.34 to 11.66%, the carbohydrate content ranged from 5.80 to 17.91%, the moisture content ranged from 6.02 to 6.49%, the ash content ranged from 11.23 to 12.40%, and the fiber content ranged from 23.24 to 38.48%. The L cultivar possessed significantly higher protein and carbohydrate contents, whereas the H cultivar had the highest ash content (p < 0.05). The total phenolic content (TPC) ranged from 113.94 to 173.69 mg GAE/g extract, with the KD cultivar having the highest TPC (p < 0.05). Several metabolic compounds such as phenolic compounds (particularly kaempferol, isorhamnetin, quercetin, ferulic acid, isoferulic acid, salicylic acid, sinapic acid, syringic acid, and vanillin), terpenoids (such as eucalyptol), glycosides, and indole were identified. The PLE from the KD cultivar had the highest levels of DPPH• inhibition, metal chelation, reducing power, and antidiabetic activity (p < 0.05), suggesting superior biological activity. All three PLEs reduced the proliferation of RAW 264.7 cells in a dose-dependent manner with low nitric oxide formation. These results indicate that the papaya leaf, particularly from the KD cultivar, could be a promising source of functional food ingredients.

Peripartal changes of metabolic and hormonal parameters in Romanian spotted cows and their relation with retained fetal membranes.

This clinical study investigates various metabolic and physiological parameters in dairy cows during puerperium. Retained fetal membranes (RFM) is a significant postpartum complication that can affect the overall health, fertility and productivity of dairy cattle. The research focuses on changes in total proteins, albumin, glucose, triglycerides, total cholesterol, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), cortisol, insulin, and insulin-like growth factor 1 (IGF-1) levels among cows experiencing normal post-partum period (NP) and those with RFM. A significant increase in protein levels was noted during the post-partum period in the RFM group, indicating physiological impacts of RFM at this stage. Albumin levels showed significant differences, highlighting a significant biological effect of RFM in the post-partum period. Glucose levels varied significantly in the weeks leading to parturition, suggesting altered metabolic states in cows that suffered RFM. Triglyceride and cholesterol levels were significantly higher during the antepartum period in the group that experienced reproductive failure, indicating substantial alterations in lipid metabolism which could herald the apparition of RFM. AST and ALT levels provided insights into cellular stress and liver function, with significant increases noted around parturition which could be attributed to the substantial physiological strain of parturition itself. Cortisol levels were higher in RFM cows 2 weeks before parturition, which could indicate an increasing stress response or a physiological preparation for the upcoming labor, and may be more pronounced in cows predisposed to RFM. Insulin levels decreased significantly before and at parturition in RFM cows, indicating a strong energy deficit. IGF-1 levels decreased significantly in RFM cows after parturition. Significant changes in metabolic parameters, such as glucose, triglycerides, and cholesterol levels, delineate the pronounced metabolic challenges faced by cows with RFM. The study elucidates that while some variations are noted as parturition approaches, the most substantial impacts attributable to RFM on metabolic and physiological parameters occur after parturition. These changes may have implications for the health, recovery, and productivity of cows postpartum, suggesting the need for targeted management strategies to mitigate the effects of RFM.

Clinico-Metabolic Profile and Follow-Up of Familial Cases Compared to Sporadic Cases in a Lyon Series of Type 1 Diabetic Children.

OBJECTIVE: This study aimed to describe the clinical, biochemical, therapeutic, and progressive characteristics of children with familial type 1 diabetes (T1D) compared to those with non-familial T1D. Compare within the first group, the phenotype of type 1 diabetics inherited from the father with those inherited from the mother. PATIENTS AND METHODS: We conducted a retrospective study lasting 10 years at the L'hôpital Femme Mère Enfant (Woman-Mother-Child Hospital) in Lyon, France. Cases were any child diagnosed with T1D for at least 12 months who had a parent with T1D. Each case was matched with a T1D control without a family history of T1D, of the same age, same sex and same year of discovery. Cases group was divided into two subgroups according to the sex of the parent with T1D. RESULTS: A total of 43 children had a TD1 parent (family group) of whom 27 cases were the father. Forty four T1D children without any T1D parent were matched (sporadic group). The family group had consulted earlier (p < 0.001), were less in initial diabetic ketoacidosis (p = 0.016), and had a lower HbA1C level lower (p < 0.001) and lower initial insulin requirements (p < 0.001). During follow-up, it was noted that the evolution of Hb1AC, insulin requirements, and chronic complications were similar in familial and non-familial cases (p = 0.943, p = 0.450, p = 0.664, respectively). The patients in the T1D mother group seemed better balanced than those of the T1D father with an average HbA1C at 10 years of follow-up of 7.82% in the maternal group compared to 9.10% in the paternal group (p = 0.021). CONCLUSION: This study shows that familial T1D is a protective factor against the initial severity of T1D in offspring. Paternal T1D presents a more severe initial and progressive clinico-biological character than T1D inherited from the mother. However, during follow-up, other psycho-environmental factors could modify this observation.

Comparison of the efficacy of 0.9% normal saline with balanced crystalloid (Plasmalyte) in maintaining the metabolic profile in head injury patients undergoing evacuation of acute subdural haematoma - A randomised controlled trial.

Background and Aims: The choice of intravenous fluids is important in patients with traumatic brain injury (TBI), where large volumes may be required for resuscitation. Our study aimed to compare 0.9% normal saline (NS) with balanced crystalloid (Plasmalyte) in TBI patients in terms of metabolic and coagulation profile, brain relaxation score (BRS) and renal functions using serum urea, creatinine and urinary tissue inhibitor of metalloproteinases-2* insulin-like growth factor binding protein-7, [TIMP-2]*[IGFBP7], value to assess the risk of acute kidney injury. Methods: This randomised controlled trial on 90 TBI patients undergoing emergency craniotomy and subdural haematoma evacuation was conducted in a tertiary care institute. The patients were randomised to receive either NS (Group NS) or Plasmalyte (Group P) as the intraoperative maintenance fluid. The primary outcome measures included the potential of hydrogen (pH), base excess (BE) and chloride values from an arterial blood gas. The secondary outcomes were the coagulation profile, BRS and urinary [TIMP-2]*[IGFBP7]. The two groups' metabolic profile differences were analysed using two-way repeated analysis of variance. BRS was analysed using the Mann-Whitney U test. A P value < 0.05 was considered to be statistically significant. Results: The pH and chloride values were significantly higher, and the BE values were significantly lower in Group P compared to Group NS (P < 0.001). Brain relaxation and coagulation profiles were comparable between the two groups. Serum creatinine (P = 0.002) and urinary [TIMP-2]*[IGFBP7] (P = 0.042) were significantly higher in the NS group. Conclusion: Plasmalyte maintains a more favourable metabolic profile than NS in TBI patients without affecting brain relaxation adversely.

Metabolic Profile of Offspring of Mothers with Gestational Diabetes Mellitus.

Introduction: Gestational diabetes mellitus (GDM) is defined as diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes before gestation. Unrecognized and untreated GDM confers significantly greater maternal and fetal risk, which is largely related to the degree of hyperglycemia. The specific risks of diabetes in pregnancy include but are not limited to, spontaneous abortion, pre-eclampsia, fetal anomalies, macrosomia, neonatal hypoglycemia, hyperbilirubinemia, and respiratory distress syndrome. Additionally, GDM is also implicated in long-term metabolic derangements in the offspring in the form of obesity/overweight, hypertension, dysglycemia, insulin resistance, and dyslipidemias later in life. To determine the prevalence of anthropometric and metabolic derangements in children between 1 and 5 years of age, born to women with GDM. Methods: This hospital-based cross-sectional study was conducted between November 2019 and November 2021 at our Pediatric Endocrine Clinic. Women were diagnosed as having GDM based on the American Diabetes Association Criteria (2019). History regarding the treatment of the GDM (diet only/diet and medical treatment) and detailed physical examination, including anthropometry and blood pressure, were recorded. Blood samples were collected from children for the estimation of their metabolic profile. Results: Overweight, obesity, and severe obesity were present in 18 (11.3%), 2 (1.3%), and 2 (1.3%) children, respectively. Hypertension was found in 21 (19.4%) children. Elevated LDL, triglyceride, and total cholesterol were seen in 3 (1.9%), 84 (52.5%), and 1 (0.6%) children, respectively. Impaired fasting glucose (IFG) was found in 6 (3.8%) children, while 27 (16.9%) subjects were found to be having impaired glucose tolerance after OGTT. Insulin resistance was found in 30 (18.8%) children. GDM mothers with a higher BMI tended to have children with a higher BMI (correlation coefficient, r = .414, P < .001). Higher serum triglyceride levels (r = -0.034, P = 0.672) were recorded in children, irrespective of the BMI of their mothers. There was no significant correlation of maternal BMI with blood pressure (r = -0.134, P = 0.091) or with HOMA-IR (r = 0.00, P = 0.996) in children. However, mothers with a higher BMI had children with statistically higher fasting blood glucose (r = +0.339, P = <0.001) as well as blood glucose 2 hours after OGTT (r = +0.297, P = <0.001). This positive correlation of maternal BMI with the glucose metabolism of their offspring was observed for both male and female genders. Conclusion: Children of women with GDM had a higher BMI, and the mode of treatment for GDM did not lead to differences in childhood BMI. The higher BMI of a GDM mother is associated with altered glucose metabolism in their offspring. Deranged levels of triglyceride across the gender were not found to be statistically significant. This has implications for future metabolic and cardiovascular risks in targeting this group for intervention studies to prevent obesity and disorders of glucose metabolism as one potential strategy to prevent adverse metabolic health outcomes.

Salvia miltiorrhiza stem-leaf of total phenolic acid conversion products alleviate myocardial ischemia by regulating metabolic profiles, intestinal microbiota and metabolites.

Myocardial ischemia (MI) is a significant contributor to ischemic heart diseases like angina pectoris and myocardial infarction. Reactive oxygen species produced during MI can trigger lipid peroxidation, damaging cell structure and function. Salvia miltiorrhiza (SM) has been widely used clinically in the treatment of cardiovascular diseases. However, in the process of rooting, the aboveground parts of this plant are usually discarded by tons. To make better use of these plant resources, the phenolic acids extracted and purified from the aerial part of SM were studied and chemically transformed, and the potential protective effect and possible mechanism of salvianolic acids containing a higher content of salvianolic acid A on MI were obtained. The transformed products of SM stem-leaves total phenolic acids with 8.16 % salvianolic acid A showed a better protective effect on the isoproterenol (ISO)-induced acute MI injury rat model. It can improve ST segment changes and has good antioxidant, anti-inflammatory and anticoagulant effects. In addition, the dysbiosis of gut microbiota and the related metabolic levels of short chain fatty acids (SCFAs), phenylalanine and glycerophospholipids were improved. This was achieved by reducing the abundance of Bacteroides, Faecalibaculum, and L-phenylalanine levels. In addition, the abundance of probiotics in Butyricoccus, Roseburia, and norank_f_Eubacterium_coprostanoligenes_group, as well as the contents of propionic acid and isobutyric acid, LPCs and PCs were increased. In conclusion, total phenolic acids of SM stem-leaves showed protective effects against ISO-induced rats, especially the strongest effect after conversion, which is a new option for the prevention and treatment of MI.

Assessment of Vitamin Concentrations in Patients with Hashimoto's Thyroiditis and Their Relationships with Thyroid Function, Biochemical Status, and Anthropometric Parameters-A Preliminary Study.

Hashimoto's thyroiditis (HT) is the leading cause of hypothyroidism, affecting mainly the female population. Many patients with HT have metabolic disorders and nutritional deficiencies. The aim of this study was to evaluate vitamin D, A, E, B2, and B6 concentrations, thyroid function, metabolic profile, and anthropometric parameters of patients with Hashimoto's thyroiditis. In 81 female patients with HT (study group), vitamin A and B2 concentrations were significantly lower than in 34 healthy women (control group). No differences were noted in vitamin D, E, and B6 concentrations between groups. Moreover, HT patients had similar anthropometric parameters, lipid profiles, and glucose and insulin concentrations compared to controls. This study showed some relationships between vitamin concentrations and anthropometric or biochemical profiles in HT patients. Among others, in the HT group, the concentration of vitamin D was positively correlated with the level of HDL and negatively correlated with BMI, total fat mass, and insulin level, which influence cardiovascular risk. The results indicate that patients with HT should be routinely tested for vitamin concentrations to prevent nutritional deficiencies. Further studies are also needed on the role of vitamins in the development and progression of HT and the presence of metabolic complications in this population.

Analytical and Clinical Interference of Sample Hemolysis in Evaluating Blood Biochemical and Endocrine Parameters in Cows.

Hemolysis is a common cause of errors in laboratory tests as it affects blood parameters and leads to a positive or negative bias. This study aims to examine the relationship between the level of hemolysis (expressed as cell-free hemoglobin concentration, g/L) and the variability of metabolic and endocrine parameters and to determine the threshold level of hemolysis that causes an analytically and clinically significant bias for the twenty most frequently examined blood parameters in cows. Paired blood samples of 10 mL each were obtained from 30 cows. One was subjected to mechanical trauma and plasma was extracted directly from the other. Hemolyzed and non-hemolyzed samples from the same animal were mixed to obtain final samples with cell-free hemoglobin concentrations of 0, 1, 2, 4, 6, 8, and 10 g/L. Metabolic and endocrine parameters were measured in the samples and their deviation and the linear equation between the level of hemolysis and the deviation were determined. The following threshold values of hemolysis were determined, which correspond to the acceptable analytical (lower value) and clinical (upper value) levels of parameter variability: BHB 0.96 and 4.81; NEFA 0.39 and 3.31; GLU 0.38 and 3.90; ALB 1.12 and 6.11; TPROT 1.40 and 6.80; UREA 6.62 and 20.1; TBIL 0.75 and 5.65; AST 0.11 and 2.18; GGT 1.71 and 8.90, LDH 0.01 and 0.11, ALP 0.97 and 2.95; TGC 1.56 and 15.5; CHOL 1.29 and 8.56; Ca 5.68 and 25.7; P 0.57 and 8.43; Mg 1.10 and 8.47; INS 1.15 and 3.89; T3 8.19 and 15.6; T4 8.97 and 18.5; and CORT 2.78 and 11.22 g/L cell-free hemoglobin. Three decision levels are available for each metabolic and endocrine parameter: if hemolysis is below the lower (analytical) threshold value, results can be reported without restriction; if hemolysis is between the lower and upper thresholds, the results can be issued with guidance in the form of corrective linear equations; and if hemolysis is above the upper (clinical) threshold, the results and sample must be discarded. This method contributes to an optimal approach to hemolysis interference with metabolic profile parameters in blood samples from cows.

Variations of blood metabolites in single- and multiple-bearing Ossimi ewes during the transition period.

Evaluation of the metabolic profile indices allows early detection and treatment of various metabolic disorders during the transition period in ewes. This study aimed to determine the variations in the blood metabolites around lambing in Ossimi ewes. The blood metabolites were investigated in ewes with single (n = 27) and multiple (n = 9) lambs at 3- and 1-week pre-lambing and 3-week post-lambing. The plasma concentrations of glucose were higher in single-bearing ewes than those in multiple-bearing ewes (p < .05), moreover, its lowest value was measured at 1-week prepartum in both groups. Throughout the study period, the serum concentrations of non-esterified fatty acids (NEFA) were significantly increased in ewes with multiple lambs compared to ewes with single lambs (p < .05), and the highest value was found at 1-week before parturition in both groups. In addition, the serum level of beta-hydroxybutyric acid (BHBA) was higher at 3-week postpartum, and it was significantly increased in multiple-bearing ewes than that in single-bearing ones (p < .05) at 3-week pre-lambing. In both groups, the lowest values of total proteins were determined 1-week before lambing, and its concentrations, at 3- and 1-week prepartum, were higher in ewes with single lambs than those with multiple lambs (p < .05). In contrast, the serum concentrations of albumin were significantly lowered 1-week postpartum (p < .05), and without significant differences between both groups (p > .05). The serum activities of aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) were significantly increased at 1-week after parturition in both groups (p < .05). Furthermore, the serum activities of AST were higher in multiple-bearing ewes than those in single-bearing ones at 3-week pre-lambing and 3-week post-lambing (p < .05). Variable positive and negative correlations were determined among the blood metabolites. In conclusion, physiological adaptations are associated with the fluctuation of the blood metabolites around lambing. The higher the number of foetuses the higher the metabolic variations in Ossimi ewes. Therefore, regular metabolic profiling for health monitoring may be necessary to avoid disease development during the transition period.

Metabolic effects and cardiovascular disease risks of antiviral treatments in patients with chronic hepatitis B.

Different antiviral treatments for chronic hepatitis B (CHB) have been known to have different metabolic effects. This study aimed to reveal whether tenofovir alafenamide (TAF)-induced dyslipidemia and its associated outcomes are significant. This study utilized 15-year historical cohort including patients with CHB in Korea and consisted of two parts: the single-antiviral and switch-antiviral cohorts. In the single-antiviral cohort, patients were divided into four groups (entecavir [ETV]-only, tenofovir disoproxil fumarate [TDF]-only, TAF-only, and non-antiviral). Propensity score matching (PSM) and linear regression model were sequentially applied to compare metabolic profiles and estimated atherosclerotic cardiovascular disease (ASCVD) risks longitudinally. In the switch-antiviral cohort, pairwise analyses were conducted in patients who switched NAs to TAF or from TAF. In the single-antiviral cohort, body weight and statin use showed significant differences between groups before PSM, but well-balanced after PSM. Changes in total cholesterol were significantly different between groups (-2.57 mg/dL/year in the TDF-only group and +2.88 mg/dL/year in the TAF-only group; p = 0.002 and p = 0.02, respectively). In the TDF-only group, HDL cholesterol decreased as well (-0.55 mg/dL/year; p < 0.001). The TAF-only group had the greatest increase in ASCVD risk, followed by the TDF-only group and the non-antiviral group. In the switch-antiviral cohort, patients who switched from TDF to TAF had a higher total cholesterol after switching (+9.4 mg/dL/year) than before switching (-1.0 mg/dL/year; p = 0.047). Sensitivity analysis on data with an observation period set to a maximum of 3 years for NA treatment showed consistent results on total cholesterol (-2.96 mg/dL/year in the TDF-only group and +3.09 mg/dL/year in the TAF-only group; p = 0.001 and p = 0.005, respectively). Another sensitivity analysis conducted on statin-treated patients revealed no significant change in cholesterol and ASCVD risk. TAF was associated with increased total cholesterol, whereas TDF was associated with decreased total and HDL cholesterol. Both TAF and TDF were associated with increased ASCVD risks, and statin use might mitigate these risks.

Targeted and untargeted serum NMR metabolomics to reveal initial kidney disease in diabetes mellitus.

Serum 1H NMR metabolomics has been used as a diagnostic tool for screening type 2 diabetes (T2D) with chronic kidney disease (CKD) as comorbidity. This work aimed to evaluate 1H NMR data to detect the initial kidney damage and CKD in T2D subjects, through multivariate statistical analysis. Clinical data and biochemical parameters were obtained for classifying five experimental groups using KDIGO guidelines: Control (healthy subjects), T2D, T2D-CKD-mild, T2D-CKD-moderate, and T2D-CKD-severe. Serum 1H NMR spectra were recorded to follow two strategies: one based on metabolite-to-creatinine (Met/Cr) ratios as targeted metabolomics, and the second one based on untargeted metabolomics from the 1H NMR profile. A prospective biomarkers panel of the early stage of T2D-CKD based in metabolite-to-creatinine ratio (ornithine/Cr, serine/Cr, mannose/Cr, acetate/Cr, acetoacetate/Cr, formate/Cr, and glutamate/Cr) was proposed. Later, a statistical model based on non-targeted metabolomics was used to predict initial CKD, and its metabolic pathway analysis allowed identifying the most affected pathways: phenylalanine, tyrosine, and tryptophan biosynthesis; valine, leucine, and isoleucine degradation; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and histidine metabolism. Nonetheless, further studies with a larger cohort are advised to precise ranges in metabolite-to-creatinine ratios and evaluate the prediction pertinency to detect initial CKD in T2D patients in both statistical models proposed.

Cardiometabolic and Metabolic Profiles of Lean/Normal, Overweight and Obese Patients with Nonalcoholic Fatty Liver Disease.

Purpose: Disagreements about the risk of non-obese, non-alcoholic fatty liver disease for cardiometabolic outcomes occurred widely. This study aims to characterize the cardiometabolic and metabolic profile of lean/normal, overweight and obese patients with nonalcoholic fatty liver disease on a big sample. Patients and methods: Appeared healthy adults who participated in health examinations during the year of 2019-2022 were screened for fatty liver diagnosis. BMI classified fatty livers as lean, overweight and obese. Eleven cardiometabolic metrics (SBP: systolic blood pressure; DBP: diastolic blood pressure; TC: total cholesterol; TG: triglycerides; HDL: high-density lipoprotein cholesterol; LDL: low-density lipoprotein cholesterol) and metabolic metrics (GLU: blood glucose; GHB: glycated haemoglobin; UA: uric acid; AST: aspartate aminotransferase; ALT: alanine aminotransferase) were included, described and compared among BMI categories. Results: There were 56,496 fatty livers diagnosed by ultrasound in this study. In total, the lean fatty liver had lowest mean SBP, DBP, GLU, TG, UA, AST, and ALT but highest TC and HDL among BMI categories (all p < 0.001). The number of abnormal metrics in total was 2.5, 2.9 and 3.4 in lean, overweight, and obesity, respectively (p < 0.001, p_trend < 0.001). Visualized data showed that lean fatty liver was similar but milder in all metabolic metrics than overweight and obesity at the young ages. However, lean fatty liver had higher coefficients of age and risk of metabolic abnormality regression (p <0.001 for SBP, DBP, GLU, GHB, TC). Conclusion: The lean type of fatty livers at a younger age has a relatively favourable cardiometabolic and metabolic profile compared to overweight and obese fatty livers. Due to the possible catch-up effect of metabolic dysfunctions in young lean fatty liver, lean fatty liver may have the same health outcomes as overweight/obesity fatty liver in long term. The evaluation and intervention may be critical for young lean fatty liver management to slowdown the rapid progress of metabolic dysfunction.