Search Results (34)

The transition period, spanning approximately three weeks before and after parturition, represents one of the most critical physiological windows in dairy production. Profound metabolic, endocrine, and immune adaptations occur as the cow shifts from gestation to lactation, predisposing high-yielding cows to oxidative stress, inflammation, and metabolic imbalance. Negative energy and metabolisable protein balances stimulate extensive lipolysis and the accumulation of non-esterified fatty acids (NEFAs) and β-hydroxybutyrate (BHBA), which can impair hepatic function and postpartum performance. This review integrates recent advances in the understanding of metabolic and immunometabolic regulation during transition, emphasising the interplay among energy metabolism, oxidative stress, and immune dysregulation. It critically re-evaluates current nutritional interventions including controlled-energy and negative DCAD diets, rumen-protected polyunsaturated fatty acids, and methyl donor amino acids while highlighting the emerging potential of injectable trace minerals as adjunct strategies to improve metabolic resilience. The review concludes by outlining remaining knowledge gaps and proposing a framework linking physiological mechanisms with targeted nutritional management. Full article

This study aimed to elucidate the intrinsic regulatory mechanisms by comparing milk quality, blood metabolomics, and physiological indices between high-yielding (BH, n = 15, high milk yield, daily milk yield with 4.08 ± 0.17 kg) and low-yielding (BL, n = 15, low milk yield, daily milk yield with 2.54 ± 0.26 kg) Guanzhong dairy goats during early lactation. The results showed that the lactose content in the BH group was significantly lower than that in the BL group (p < 0.05), but the total daily lactose yield was 60 g higher. No significant differences were observed in milk fat or milk protein (p > 0.05). Among blood biochemical indices, total protein (TP), glucose (GLU), and alkaline phosphatase (ALP) were significantly lower in the BH group (p < 0.05), while β-hydroxybutyrate (BHBA) was significantly higher (p < 0.05). Milk yield exhibited a highly significant negative correlation with TP and creatinine (CRE). Regarding immune and antioxidant indices, catalase (CAT), glutathione peroxidase (GSH-Px), IgM, and IL-2 were significantly elevated in the BH group (p < 0.05), while IL-6 was significantly reduced (p < 0.05). CAT and IL-2 showed positive correlations with milk yield. Using a subset of animals for in-depth profiling (n = 6 per group)Serum metabolomics identified 184 differential metabolites (114 upregulated, 70 downregulated). In the BH group, betaine, acylcarnitines, and L-valine exhibited significant negative correlations with milk yield, implicating pathways related to fatty acid -oxidation, methyl donor regulation, and amino acid metabolism. These findings indicate that high-yielding dairy goats achieve efficient lactation through enhanced fatty acid β-oxidation, optimized methyl donor regulation for milk fat synthesis, and prioritized allocation of amino acids towards the mammary gland. Full article

Background: Amyotrophic lateral sclerosis (ALS) evolution is influenced by many dietary factors, biochemical and hormonal inter-relations and gut microbiota. This study focuses on dynamics by conducting a plasmatic quantitative analysis of six of the main short-chain fatty acids (SCFAs) for ALS patients and the shifts in circulating SCFA profiles during ALS progression as well as their potential responsiveness or change due to dietary modulation. Methods: A 12-month prospective study in parallel with control group determinations was conducted. The patients diagnosed with ALS were evaluated at the start of the study (T0) followed by a six-month observation time frame (T1) and after another six months of a Mediterranean diet intervention (T2). Plasma SCFAs were determined using liquid chromatography coupled to mass spectrometry to showcase the plasmatic profiles. Correlation between plasma levels of SCFAs and patients’ clinical characteristics next to correlations between plasma SCFA levels at T1 and T2 were performed. Results: A significant increase between control group and patients at T0 was observed for acetic, propionic, butyric and hydroxy-butyric acid. Hexanoic acid levels stagnated and 4-methyl-valeric acid concentrations decreased. Evolutions from T1 and T2 impacted acetate, propionate and 4-methyl-valerate. Conclusions: The study offers a better understanding regarding the differences in SCFA levels in ALS patients. The Mediterranean diet may impact the levels of acetic and propionic acid, indicating the modulation of SCFA production by gut microbiota. Full article

Acetoacetyl-CoA thiolase deficiency, also known as Beta-ketothiolase deficiency (BKTD), is an autosomal recessive organic aciduria included in the Italian newborn screening (NBS) panel. It is caused by mutations in the ACAT1 gene, which encodes the mitochondrial acetyl-CoA acetyltransferase. Its deficiency impairs the degradation of isoleucine and acetoacetyl-CoA, leading to the accumulation of toxic metabolites. We describe three cases of BKTD. The first newborn showed increase in C5:1, C4DC/C5OH, C3DC/C4OH in the NBS. Urinary organic acids (uOAs) revealed marked excretion of 2-methyl-3-hydroxybutyrate. Tiglylglycine was absent. Genetic testing identified the compound heterozygosity for two pathogenic ACAT1 variants. The second patient showed increased levels of C5:1, C4DC/C5OH, C3DC/C4OH in the NBS. uOAs revealed 2-methyl-3-hydroxybutyrate and tiglylglycine. A homozygous VUS in ACAT1 was identified. The third case showed elevation of C4DC/C5OH, C3DC/C4OH in the NBS, with a slight increase in C5:1. uOAs showed 2-methyl-3-hydroxybutyrate and tiglylglycine. A homozygous missense VUS was identified in the ACAT1 gene. BKTD exhibited variable NBS biochemical phenotypes across the three cases. While C5OH and C5:1, the primary markers, were not consistently elevated in all our cases, C4OH strongly increased in all three. Our findings support the use of C4OH in a combined marker strategy to improve BKTD NBS. Full article

Background: Charcot–Marie–Tooth (CMT) is a group of inherited diseases impairing the peripheral nervous system. CMT originates from genetic variants that affect proteins fundamental for the myelination of peripheral nerves and survival. Moreover, environmental and humoral factors can impact disease development and evolution. Currently, no therapy is available. Metabolomics is an emerging field of biomedical research that enables the development of novel biomarkers for neurodegenerative diseases by targeting metabolic pathways or metabolites. This study aimed to evaluate the metabolomics profile of CMT disease by comparing patients with healthy individuals. Methods: A total of 22 CMT patients (CMT) were included in this study and were demographically matched with 26 healthy individuals (C). Serum samples were analyzed through Nuclear Magnetic Resonance spectroscopy, and multivariate and univariate statistical analyses were subsequently applied. Results: A supervised model showed a clear separation (R²X = 0.3; R²Y = 0.7; Q² = 0.4; p-value = 0.0004) between the two classes of subjects, and nine metabolites were found to be significantly different (2-hydroxybutyrate, 3-hydroxybutyrate, 3-methyl-2-oxovalerate, choline, citrate, glutamate, isoleucine, lysine, and methyl succinate). The combined ROC curve showed an AUC of 0.94 (CI: 0.9–1). Additional altered metabolic pathways were also identified within the disease context. Conclusion: This study represents a promising starting point, demonstrating the efficacy of metabolomics in evaluating CMT patients and identifying novel potential disease biomarkers. Full article

Cocoa pod husk (CPH), a significant agricultural byproduct of cocoa production, presents an opportunity for sustainable valorization through biotechnological methods. This study aimed to enhance the nutritional, antioxidant, and therapeutic properties of CPH using solid-state fermentation (SSF) with Rhizopus stolonifer. Physicochemical characterization confirmed CPH’s suitability for SSF, providing a nutrient-rich and favorable environment for fungal growth. The fermentation process significantly improved protein recovery (11.327 ± 0.859 mg g⁻¹) and antioxidant activity, with ORAC (51.68 ± 0.35 mmol TE g⁻¹) and DPPH (7.09 ± 0.05 µmol TE g⁻¹) assays demonstrating marked increases in redox potential, particularly at 144 h and 96 h of fermentation, respectively. GC-MS analysis revealed the generation of bioactive compounds in fermented CPH (CPHF), including methyl 3-hydroxybutyrate, 10,12-Tricosadiynoic acid, and palmitic acid, which are known for their antioxidant, anti-inflammatory, and therapeutic properties. Additionally, phenolic compounds are biotransformed into more bioavailable forms, further enhancing the functional value of the material. This work demonstrates that SSF can effectively transform CPH from an agricultural waste product into a high-value biomaterial with potential applications in functional food, nutraceutical, and pharmaceutical industries. By addressing waste management challenges and promoting the development of innovative bio-based products, this study highlights the promising role of SSF in advancing sustainable and circular biotechnological solutions. Full article

Background: Malnutrition and muscle weakness are highly prevalent in critically admitted patients. To overcome sarcopenia and muscle weakness, physical activity and neuromuscular electric stimulation have been introduced with limited efficacy. Thus, several anabolic remedies have been introduced. An adequate increase in protein support according to indirect calorimetry and body composition and methyl hydroxybutyrate (HMB) is emerging. Therefore, we wanted to investigate the impact of HMB-enriched whey formula on the nutritional status, muscle weakness, and clinical course of critically ill patients undergoing nutritional status multimodal assessment and physical rehabilitation. Methods: We consecutively enrolled critically ill adult patients admitted to the intensive care unit (ICU) of “Santa Maria Hospital”, Terni, Italy. All patients underwent preliminary anthropometric, laboratory tests, nutritional (bioimpedance vector analysis and indirect calorimetry), and ultrasound muscle assessment at admission (T0). Laboratory tests monitoring continued throughout the ICU stay. Nutritional and muscle strength assessment was taken weekly throughout the patient’s ICU stay. All patients were enterally administered with a whey protein-enriched formula. Ten days after admission (during the physical rehabilitation period), patients were randomly administered a mixture of essential amino acids and methyl hydroxybutyrate (HMB). Results: We consecutively enrolled 54 ICU patients. At the baseline, survivors (n = 46) were significantly younger than non-survivors. The latter had a worse SAPS II score, nutritional status, and risk, with no significant difference in basal metabolism. Prealbumin values significantly correlated with improved nutritional status and metabolism. Starting from 10 days upon ICU admission, the pennation angle (used as a measure of muscle strength) significantly correlated with the improvement in nutritional status. Whey proteins were well tolerated. Its administration showed a tendency to improve the pennation angle. No specific effect of the mixture containing essential amino acids and methyl hydroxybutyrate was observed. Nutritional status improvement and the rise of basal metabolism were significantly correlated with the extubation time. On the other hand, the reduction in muscle weakness was not significantly correlated with the timing of extubation. Conclusions: Whey protein formula administration can significantly improve nutritional status and basal metabolism in ICU patients. This is reflected in improved muscle strength. Whey protein administration shows a tendency toward a rise in pennation angle. A similar and non-specific trend was observed upon HMB mixture add-one. Further prospective large-scale controlled studies are needed to confirm these promising results. Full article

Four previously undescribed pentacyclic triterpenoid saponins, pannosides F–I (1–4), were isolated from the halophyte Aster tripolium L. (Tripolium pannonicum), and their chemical structures were elucidated using 1D and 2D NMR spectroscopy and mass spectrometry. Comprehensive structural analysis revealed the presence of distinct aglycone and glycosidic moieties, along with complex acylation patterns. The acyl chains of pannosides, 3-hydroxybutyrate (3-HB) residues, were derivatized with (S)- and (R)- phenylglycine methyl ester to resolve the absolute configurations of the chiral centers in 3-HB. Then, the acyl chain-containing saponins, pannosides were evaluated for their antiviral activities against enterovirus A71 (EV71), coxsackievirus B3 (CVB3), and rhinovirus 1B (HRV1B). Pannosides exhibited antiviral activities against HRV1B, EV71, and CVB3. These findings suggest that saponins from A. tripolium exhibit potential antiviral activities and could be further explored for their therapeutic applications. Full article

We aimed to investigate the characteristics of serum metabolomics in aneurysmal subarachnoid hemorrhage patients (aSAH) with different 3-month outcomes (good = modified Rankin score: 0–3 vs. poor = mRS 4–6). We collected serum samples from 46 aSAH patients at 24 (D1) and 168 (D7) hours after injury for analysis by liquid chromatography-mass spectrometry. Ninety-six different metabolites were identified. Groups were compared using multivariate (orthogonal partial least squares discriminant analysis), univariate, and receiving operator characteristic (ROC) methods. We observed a marked decrease in serum homocysteine levels at the late phase (D7) compared to the early phase (D1). At both D1 and D7, mannose and sorbose levels were notably higher, alongside elevated levels of kynurenine (D1) and increased 2-hydroxybutyrate, methyl-galactoside, creatine, xanthosine, p-hydroxyphenylacetate, N-acetylalanine, and N-acetylmethionine (all D7) in the poor outcome group. Conversely, levels of guanidinoacetate (D7) and several amino acids (both D1 and D7) were significantly lower in patients with poor outcomes. Our results indicate significant changes in energy metabolism, shifting towards ketosis and alternative energy sources, both in the early and late phases, even with adequate enteral nutrition, particularly in patients with poor outcomes. The early activation of the kynurenine pathway may also play a role in this process. Full article

The properties, features of thermal behavior and crystallization of copolymers containing various types of valerate monomers were studied depending on the set and ratio of monomers. We synthesized and studied the properties of three-component copolymers containing unusual monomers 4-hydroxyvalerate (4HV) and 3-hydroxy-4-methylvalerate (3H4MV), in addition to the usual 3-hydroxybutyrate (3HB) and 3-hydroxyvalerate (3HV) monomers. The results showed that P(3HB-co-3HV-co-4HV) and P(3HB-co-3HV-co-3H4MV) terpolymers tended to increase thermal stability, especially for methylated samples, including an increase in the gap between melting point (T_melt) and thermal degradation temperature (T_degr), an increase in the melting point and glass transition temperature, as well as a lower degree of crystallinity (40–46%) compared with P(3HB-co-3HV) (58–66%). The copolymer crystallization kinetics depended on the set and ratio of monomers. For terpolymers during exothermic crystallization, higher rates of spherulite formation (G_max) were registered, reaching, depending on the ratio of monomers, 1.6–2.0 µm/min, which was several times higher than the G_max index (0.52 µm/min) for the P(3HB-co-3HV) copolymer. The revealed differences in the thermal properties and crystallization kinetics of terpolymers indicate that they are promising polymers for processing into high quality products from melts. Full article

Bio-based cross-linkers can fulfill the role of enhancing additives in bio-sourced curable materials that do not compare with artificial resin precursors. Isosorbide dimethacrylate (ISDMMA) synthesized from isosorbide (ISD) can serve as a cross-linker from renewable sources. Isosorbide is a bicyclic carbon molecule produced by the reaction modification of sorbitol and the optimal conditions of this reaction were studied in this work. The reaction temperature of 130 °C and 1% w/w amount of para-toluenesulfonic acid (p-TSA) were determined as optimal and resulted in a yield of 81.9%. Isosorbide dimethacrylate was synthesized via nucleophilic substitution with methacrylic anhydride (MAA) with the conversion of 94.1% of anhydride. Formed ISD and ISDMMA were characterized via multiple verification methods (FT-IR, MS, ¹H NMR, and XRD). Differential scanning calorimetry (DSC) proved the curability of ISDMMA (activation energy E_a of 146.2 kJ/mol) and the heat-resistant index of ISDMMA (T_s reaching value of 168.9) was determined using thermogravimetric analysis (TGA). Characterized ISDMMA was added to the precursor mixture containing methacrylated alkyl 3-hydroxybutyrates (methyl ester M3HBMMA and ethyl ester E3HBMMA), and the mixtures were cured via photo-initiation. The amount of ISDMMA cross-linker increased all measured parameters obtained via dynamic mechanical analysis (DMA), such as storage modulus (E’) and glass transition temperature (T_g), and the calculated cross-linking densities (ν_e). Therefore, the enhancement influence of bio-based ISDMMA on resins from renewable sources was confirmed. Full article

Osteoarthritis (OA) is a common cause of lameness in sport horses with a significant economic impact. The prevention of OA is crucial since no effective treatment is available. This study aimed to apply untargeted metabolomic analysis to investigate the differences in synovial fluid (SF) composition between healthy and OA-affected joints in horses. SF collected from healthy (n.8) and OA (n.11) horses was analyzed using H-NMR analysis. Metabolomic analysis allowed 55 different metabolites to be identified and quantified in SF samples. Nineteen metabolites were found to be differently concentrated in OA compared to control horses. Synovial fluids from the OC group were found to be higher in 1,3-dihydroxyacetone but lower in tryptophan, phenylalanine, tyrosine, uridine, creatinine, creatine, glycine, choline, asparagine, glutamine, arginine, 3-hydroxybutyrate, valine, 2-hydroxyisovalerate, α-ketoisovaleric acid, 3-methyl-2-oxovalerate, 3-hydroxyisobutyrate, isoleucine, and methionine compared to the controls. A variety of SF metabolites significantly changed following joint disease, demonstrating the complex mechanism underlying osteoarthritis in horses and highlighting the value of applying the metabolomic approach in clinical research. Full article

Polyhydroxyalkanoates (PHAs) are aliphatic polyesters synthesized intracellularly by microorganisms as a carbon-storage substance. Among the various PHAs, 3-hydroxybutyrate (3HB)-based copolymers are crystalline polymers widely used as biodegradable plastics. Recently, PHAs containing α-carbon-methylated monomers, such as 3-hydroxy-2-methylbutyrate (3H2MB) and 3-hydroxy-2-methylvalerate (3H2MV), have been synthesized and characterized. However, a binary copolymer of 3HB and 3H2MV, P(3HB-co-3H2MV), had not yet been synthesized, and its material properties had not been investigated. In this study, P(3HB-co-11 mol% 3H2MV) (PHBMV11) was synthesized with recombinant Escherichia coli LSBJ, using trans-2-methyl-2-pentenoic acid as the 3H2MV precursor. The thermal properties of PHBMV11 were characterized using differential scanning calorimetry (DSC), and the results were compared with those of P(3HB-co-12 mol% 3-hydroxyvalerate) (PHBV12) to explore the effect of α-carbon methylation in the comonomer unit. PHBMV11 exhibited a higher enthalpy of fusion during the DSC heating process and higher crystallization temperature during the DSC cooling process than those of PHBV12. The half-crystallization time of PHBMV11 was slightly longer than that of the P(3HB) homopolymer and much shorter than that of PHBV12 previously reported. The α-carbon methylation of the 3H2MV unit also has a positive effect on the crystallization of 3HB-based copolymers, as the 3H2MB unit demonstrated previously. Full article

Molecular hybrids obtained by connecting two or more bioactive molecules through a metabolizable linker are used as multi-target drugs for the therapy of multifactorial diseases. Ascorbic acid, as well as the ketone bodies acetoacetate and (R)-3-hydroxybutyrate, are bioactive molecules that have common fields of application in the treatment and prevention of neurodegenerative diseases and cardiac injuries as well. In spite of this, the preparation of ascorbic acid ketone body hybrids is uncovered by the literature. Herein, we report the lipase-catalyzed condensation of methyl acetoacetate with ascorbic acid, which affords the 6-O-acetoacetyl ascorbic acid in quantitative yield. The same approach, employing the methyl (R)-3-hydroxybutyrate in place of the methyl acetoacetate, allows the preparation of the 6-O-(R)-3-hydroxybutyryl ascorbic acid in 57% yield. A better result (90% overall yield) is achieved through the lipase-catalyzed coupling of ascorbic acid with methyl (R)-3-O-methoxymethyl-3-hydroxybutyrate followed by the cleavage of the MOM protecting group. The two novel products are fully characterized and additional information on the antioxidant activity of the new products is also given. Full article

In this study, a marine brown alga Sargassum cristaefolium-derived fungal strain, Penicillium sumatraense SC29, was isolated and identified. Column chromatography of the extracts from liquid fermented products of the fungal strain was carried out and led to the isolation of six compounds. Their structures were elucidated by spectroscopic analysis and supported by single-crystal X-ray diffraction as four previously undescribed (R)-3-hydroxybutyric acid and glycolic acid derivatives, namely penisterines A (1) and C–E (3–5) and penisterine A methyl ether (2), isolated for the first time from natural resources, along with (R)-3-hydroxybutyric acid (6). Of these compounds identified, penisterine E (5) was a unique 6/6/6-tricyclic ether with an acetal and two hemiketal functionalities. All the isolates were subjected to in vitro anti-angiogenic assays using a human endothelial progenitor cell (EPCs) platform. Among these, penisterine D (4) inhibited EPC growth, migration, and tube formation without any cytotoxic effect. Further, in in vivo bioassays, the percentages of angiogenesis of compound 3 on Tg (fli1:EGFP) transgenic zebrafish were 54% and 37% as the treated concentration increased from 10.2 to 20.4 µg/mL, respectively, and the percentages of angiogenesis of compound 4 were 52% and 41% as the treated concentration increased from 8.6 to 17.2 µg/mL, respectively. The anti-angiogenic activity of penisterine D (4) makes it an attractive candidate for further preclinical investigation. Full article