Search Results (139)

This study employs a machine learning approach to identify a small-molecule-based signature capable of predicting Alzheimer’s disease (AD). Utilizing metabolomics data from the plasma of a well-characterized cohort of 94 AD patients and 62 healthy controls; metabolite levels were assessed using the Biocrates MxP^® Quant 500 platform. Data preprocessing involved removing low-quality samples, selecting relevant biochemical groups, and normalizing metabolite data based on demographic variables such as age, sex, and fasting time. Linear regression models were used to identify concomitant parameters that consisted of the data for a given metabolite within each of the biochemical families that were considered. Detection of these “concomitant” metabolites facilitates normalization and allows sample comparison. Residual analysis revealed distinct metabolite profiles between AD patients and controls across groups, such as amino acid-related compounds, bile acids, biogenic amines, indoles, carboxylic acids, and fatty acids. Correlation heatmaps illustrated significant interdependencies, highlighting specific molecules like carnosine, 5-aminovaleric acid (5-AVA), cholic acid (CA), and indoxyl sulfate (Ind-SO₄) as promising indicators. Linear Discriminant Analysis (LDA), validated using Leave-One-Out Cross-Validation, demonstrated that combinations of four or five molecules could classify AD with accuracy exceeding 75%, sensitivity up to 80%, and specificity around 79%. Notably, optimal combinations integrated metabolites with both a tendency to increase and a tendency to decrease in AD. A multivariate strategy consistently identified included 5-AVA, carnosine, CA, and hypoxanthine as having predictive potential. Overall, this study supports the utility of combining data of plasma small molecules as predictors for AD, offering a novel diagnostic tool and paving the way for advancements in personalized medicine. Full article

Smith–Lemli–Opitz syndrome (SLOS) is a rare, autosomal recessive genetic disorder caused by mutations in the DHCR7 gene, which encodes the enzyme responsible for the final step in cholesterol biosynthesis. Impaired enzyme function leads to cholesterol deficiency, affecting the development and function of the entire organism. The accumulation of cholesterol precursors enhances the formation of oxysterols, which are involved in the pathomechanism of neurological, ophthalmological, and vascular changes in patients. This review analyzes 53 studies published between 2020 and 2025 on the molecular mechanisms underlying the clinical features of SLOS, including cholesterol deficiency, oxysterol accumulation, and the latest diagnostic methods, including LC-MS/MS chromatography and biomarkers such as GFAP for monitoring disease progression. MRI is discussed as a supportive tool for neuroimaging, along with advances in prenatal diagnostics, such as the detection of cholesterol precursors in neonatal hair. Therapeutic options are also reviewed, with particular emphasis on cholesterol supplementation, cholic acid, and experimental treatments such as vitamin E supplementation, statin therapy, gene therapy, and liver transplantation. Current research indicates that expanding knowledge in this area not only improves patient prognosis but also provides hope for the development of effective therapies in the future. Full article

This study analyzed the compression isotherms of 7β-alkyl cholic acid derivatives and compared them to those of cholic and deoxycholic acids to elucidate their orientation and molecular interactions (acidic aqueous substrate—pH 2; NaCl concentration—3 M; temperature—T = 298.15 K). It was found that the compression isotherm of the 7β-octyl derivative of cholic acid in the monomolecular layer is most similar to the compression isotherm of deoxycholic acid. In 7β-alkyl derivatives of cholic acid, the hydrophobic interaction energy in their aggregates from a monomolecular film increased with the length of the alkyl chain. However, this energy did not increase linearly with C atoms, suggesting the existence of a conformational equilibrium. In binary mixtures of the tested bile acids and lecithin, only the 7β-octyl derivatives of cholic acid and deoxycholic acid had orientations in which the steroid skeleton had a “vertical” position, i.e., only the C3 OH group was immersed in the aqueous substrate, which resulted in the maximum hydrophobic interaction with lecithin. In 7β-octyl derivatives, part of the octyl chain probably also participated in the interaction with lecithin. In 7β-propyl and 7β-butyl derivatives, C7 alkyl groups sterically shielded the C7 α-axial OH group. However, in the 7β-ethyl derivative the C7 OH group was not additionally sterically shielded, so this derivative, similarly to cholic acid, partially dissolved in the aqueous substrate after the collapse point. Full article

Background/Objectives: Abnormal bile acid (BA) pool may play an important role in inducing liver damage in sepsis. Farnesoid X receptor (FXR) is a main negative feedback regulator of BA metabolism. This study aims to explore the protective effect and mechanism of the FXR agonist obeticholic acid (OCA) on liver dysfunction when sepsis occurs. Methods: A rat model of sepsis was induced by cecal ligation and puncture (CLP) for 24 h. Systematic inflammation, tissue injury, hepatic FXR, and BA transporter expression were investigated in the CLP rats and sham-operated control rats with and without OCA pre-treatment (10 mg/kg, gavage) at 2 h before operation. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) assay was performed to access BA composition in the rats’ serum and livers. The injury and inflammatory effects of the elevated unconjugated BAs found in the CLP rats was further verified in a hepatic cell line BRL-3A in vitro. Results: Hepatic FXR was repressed in CLP rats, whereas OCA upregulated liver FXR and hepatic BA transporter expression, reduced total serum BA concentration, ameliorated the elevation of serum levels of IL-1β and IL-6, and improved liver and ileal tissue injuries. OCA administration reduced the elevated unconjugated BAs in both serum and liver, and effectively inhibited increases in cholic acid (CA), deoxycholic acid (DCA), and 7-ketoDCA concentrations in CLP rat livers. These BA fractions promoted the release of aspartate aminotransferase (AST) from BRL-3A cells and increased IL-6, CXCL2, and monocyte chemoattractant protein-1 (MCP-1) expression in the cells, along with enhanced transcription factor nuclear factor-κB activation. Conclusions: Liver inflammation and dysfunction during sepsis is attributable to significant changes in bile acid composition in the blood and liver. FXR activation reduces systemic inflammation and liver dysfunction by regulating bile acid homeostasis, especially inflammatory unconjugated bile acid components. Full article

Protein hydrolysates positively affect intestinal function in both humans and animals, but their impact on gut health and the gut microbial profile in cats has not been thoroughly investigated. In this study, a total of 30 adult cats were randomly assigned to one of three dietary treatments for a 60-day feeding trial. The three dietary treatments were as follows: (1) basal diet (CON), (2) diet containing 15% powdered chicken protein hydrolysate (HP15%), and (3) diet containing 15% liquid chicken protein hydrolysate (HL15%). Compared to the CON group, the HP15% group had a decreased calprotectin levels and fecal gases emissions (p < 0.05). A higher abundance of Bacteroidota, Veillonellaceae, and Bacteroidaceae, while a lower abundance of Firmicutes was showed in the HL15% group than that in the CON group (p < 0.05). At the genus level, compared with the CON group, an increased abundance of Bacteroides spp. and Bifidobacterium spp. was showed, whereas a reduced abundance of Alloprevotella spp. was presented in the HP15% and HL15% groups (p < 0.05). The metabolomic analysis revealed 1405 distinct metabolites between the HP15% and CON groups (p < 0.05, VIP-pred-OPLS-DA > 1), and the level of cholic acid decreased while the level of isodeoxycholic acid increased in the HP15% group (p < 0.05). The metabolomic analysis revealed 1910 distinct metabolites between the HL15% and CON groups (p < 0.05, VIP-pred-OPLS-DA > 1), and the levels of 4-coumaryl alcohol and enterolactone increased in the HL15% group (p < 0.05). In summary, this study suggested that partially replacing chicken meat with chicken protein hydrolysate in the diet of cats helps regulate the gut microbial community and metabolite profile and improves intestinal health. Full article

Bile acids (BAs) are important signaling molecules in the gastrointestinal (GI) tract and are associated with health and disease in humans and animals. Intestinal bacteria transform BA through deconjugation, dehydroxylation, and epimerization reactions, producing various isoforms, many of which have not been investigated in companion animal diseases. We aimed to develop and analytically validate a novel liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for the quantification of 30 BAs in dog feces, with a simple extraction procedure and on-line solid-phase extraction. Validation demonstrated good accuracy, precision, sensitivity, spiking recovery, dilution, and stability for 29 BAs. The method was applied to fecal samples from healthy dogs (H; n = 121) and dogs with chronic enteropathy (CE; n = 58). The immediate and downstream products of bacterial 7α-dehydroxylation reactions with cholic acid were lower in concentration in dogs with CE when compared to healthy dogs (deoxycholic acid, 3-oxo-deoxycholic acid, and 12-oxo-lithocholic acid; q < 0.001). Across all fecal samples, the products of hydroxysteroid dehydrogenase (including oxo- and iso-BA) made up an average of 30% of the total measured fecal BA pool (glycine-BA, 0.1%; taurine-BA, 2.2%; unconjugated BA, 53%). Full article

Feeding HC diets has been found to induce metabolic dysregulation in the colon. However, the mechanisms by which changes in colonic flora and metabolites damage the colonic epithelium are poorly studied. Therefore, the present experiment used a multi-omics technique to investigate the mechanism of colonic injury induced by high-concentrate diets in lambs. Twelve male Dumont lambs were randomly split into two groups: a low-concentrate diet (LC = concentrate/forage = 30:70) group and a high-concentrate diet (HC = concentrate/forage = 70:30) group. The results showed that the HC group presented significantly increased lipopolysaccharide (LPS) concentrations in the colonic epithelium and significantly decreased serum total cholesterol (TC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels (p < 0.05), which led to cavities and inflammatory cell infiltration in the colonic epithelium. The HC group had significantly lower pH and less VFAs in colon contents, as well as a significantly increased abundance of bacteria of the genera [Eubacterium]_coprostanoligenes_group, Rikenellaceae_RC9_gut_group, Treponema, Clostridia_UCG-014, Alistipes, Ruminococcus, Christensenellaceae_R-7_group, UCG-002, Bacteroidales_RF16_group and Lachnospiraceae_AC2044_group compared to the LC diet group. These microorganisms significantly increased the level of metabolites of cholic acid, chenodeoxycholic acid, LysoPA (P-16:0/0:0), methapyrilene, and fusaric acid. A transcriptome analysis showed that cytokine–cytokine receptor interaction, glutathione metabolism, and the peroxisome signaling pathway were downregulated in the colon epithelium of the lambs fed the HC diet. Therefore, the HC diet caused epithelial inflammation and oxidative damage by affecting the interaction between the microbial flora of the colon and metabolites and the host epithelium, which eventually disrupted colon homeostasis and had a negative impact on sheep health. Full article

This study aimed to examine the impact of varying concentrations of bile acids (BA) added to the feed on several aspects of Penaeus vannamei. The purity of BA was 25.29%, and its main components were 5.74% chenodeoxycholic acid, 6.27% allocholic acid, 3.20% cholic acid, 5.79% hyodeoxycholic acid, and 2.31% hyocholic acid. The experiment was designed with four groups: CT, BA1, BA2, and BA3, where BA were added to the shrimp basal diet at concentrations of 0.0 mg/kg, 0.1 mg/kg, 1.0 mg/kg, and 10.0 mg/kg, respectively. After 60 days of farming P. vannamei (initial body weight: 1.21 ± 0.05 g), the results showed that BA supplementation significantly improved growth performance, and BA2 group was the most significant, which increased the final weight (FBW) by 18.6%, weight gain rate (WGR) by 19.5%, and survival rate (SR) by 5.8% compared with the CT group (p < 0.05). Additionally, the activities of trypsin and lipase in gut tissue were significantly increased (p < 0.05). Furthermore, BA supplementation increased the activity of antioxidant-related enzymes in the hepatopancreas and enhanced the mRNA expression levels of gut-associated immune genes. In addition, the supplementation of 0.1 mg/kg BA significantly altered the gut microbial composition, reducing the proportion of harmful Proteobacteria while enhancing the relative abundance of beneficial microorganisms such as Firmicutes and Bacteroides. In conclusion, 1.0 mg/kg and 10.0 mg/kg BA supplementation significantly improved the growth performance, digestive capacity, and antioxidant capacity of shrimp, among which 1.0 mg/kg supplementation had the most significant effect and improved the intestinal microbial composition of shrimp. Full article

Our previous study demonstrated that γ-cyclodextrin (γ-CD)–perilla oil inclusion complexes increase plasma α-linolenic acid and eicosapentaenoic acid levels in healthy rats without adverse effects. The present study examined the effects of perilla oil, γ-CD, and their inclusion complexes on rats fed cholic acid (CA) to mimic the elevated gastrointestinal 12-hydroxylated (12OH) bile acid levels in high-fat diet-fed rats. Rats fed CA (CA group) tended to have higher AST, ALT, plasma total cholesterol (T-CHO), and triglyceride (TG) levels compared to controls fed a standard diet without CA. Rats fed CA and perilla oil (CA+LP group) showed a tendency for lower AST and plasma TG levels than those in the CA group. Rats fed CA and γ-CD (CA+CD group) had significantly higher AST, ALT, plasma T-CHO, and TG levels than the controls, indicating severe liver injury and dyslipidemia. Rats fed CA and the γ-CD–perilla oil inclusion complex (CA+IC group) had significantly lower AST and ALT levels than the CA+CD rats, with a trend towards lower plasma T-CHO and TG levels. Plasma α-linolenic acid and eicosapentaenoic acid levels were significantly higher in the CA+LP and CA+IC groups than in the controls and CA+CD groups. However, the CA+IC group tended to have lower α-linolenic acid levels and significantly lower eicosapentaenoic acid levels than the CA+LP group. This suggests an accelerated conversion of α-linolenic acid to eicosapentaenoic acid in the CA+IC group, which may contribute to the attenuation of liver injury and dyslipidemia. These findings suggest that γ-CD may exacerbate liver injury and dyslipidemia caused by elevated gastrointestinal 12OH bile acid levels, whereas γ-CD–perilla oil inclusion complexes may ameliorate these effects by altering fatty acid metabolism. Furthermore, we recommend evaluating γ-CD safety in both healthy and pathological models and carefully selecting compounds co-ingested with γ-CD. Full article

Background: Traumatic hemorrhage and infection are major causes of mortality in wounds caused by battlefield injuries, hospital procedures, and traffic accidents. Developing a multifunctional nano-drug capable of simultaneously controlling bleeding, preventing infection, and promoting wound healing is critical. This study aimed to design and evaluate a nanoparticle-based solution to address these challenges effectively. Methods: Using a one-pot assembly approach, we prepared a series of nanoparticles composed of poly-L-lysine and hyodeoxycholic acid (PLL-HDCA NPs). Theoretical simulations and experimental studies were combined to optimize their structure and functionality. In vitro platelet aggregation, antibacterial assays, cytotoxicity tests, and hemolysis evaluations were performed. In vivo efficacy was assessed in various hemorrhage models, a full-thickness skin defect model, and a skin irritation test. Results: PLL-HDCA NPs demonstrated effective induction of platelet aggregation and significantly reduced bleeding time and blood loss in mouse models, including tail vein, femoral vein, artery, and liver bleeding. Antibacterial assays revealed strong activity against E. coli and S. aureus. Wound healing studies showed that PLL-HDCA NPs promoted tissue repair in a full-thickness skin defect model. Cytotoxicity and hemolysis tests indicated minimal impact on human cells and significantly reduced hemolysis rates compared to PLL alone. Skin irritation tests confirmed the safety of PLL-HDCA NPs for external application. Conclusions: PLL-HDCA NPs represent a safe, efficient, and multifunctional nano-drug suitable for topical applications to control bleeding, combat infection, and facilitate wound healing, making them promising candidates for use in battlefield and hospital settings. Full article

Surfactants are very important compounds that are ubiquitous in biological systems and detergents. Among them, ferrocene surfactants are a very valuable class of stimuli-responsive materials since the presence of ferrocene moiety discloses the chance to control and even modify their amphiphilic properties via a redox-induced change in the surfactant charge. In this paper, we report a new ferrocene-based surfactant: a ferrocene C-3 derivative of cholic acid, a non-classical surfactant. The title compound of this work was meant to show the significant self-assembly behaviour typical of bile salts, improved by the presence of the aromatic ferrocene subunit. We intended to demonstrate that the presence of the redox mediator should provide the derivative with sensitivity to an oxidative stimulus and control over the aggregation properties. The title compound was prepared in two steps from easily accessible precursors, and its optical properties were investigated through UV-Vis absorption spectroscopy. The determination of its critical micellar concentration and redox potential confirmed this derivative’s amphiphilic nature and its tendency to be reversibly oxidized. Full article

The gut–liver axis and its interactions are essential for host physiology. Thus, we examined the jejunal microbiota, fermentation parameters, digestive enzymes, morphology, and liver metabolic profiles in different growth development lambs to investigate the liver–gut axis’s role in their development. One hundred male Hu lambs of similar birth weight and age were raised under the same conditions until they reached 180 days of age. Subsequently, the eight lambs with the highest (HADG) and lowest (LADG) average daily weight gains were slaughtered for index assessment. The study indicates that the body weight, carcass weight, propanoic acid, butyric acid, propanoic acid ratio, butyric acid ratio, and digestive enzymes (beta-glucosidase, microcrystalline cellulase, xylanase, and carboxymethyl cellulase) were significantly higher in HDAG lambs than in LADG lambs (p < 0.05). Additionally, there were no significant differences in the jejunal microbiota’s structure and function among lambs at different growth development stages (p > 0.05). Overall, our analysis revealed that HADG lambs compared to LADG lambs exhibited an up-regulation of metabolites (such as spermine, cholic acid, succinic acid, betaine, etc.) that were positively correlated with the butyric acid ratio, propanoic acid ratio, propanoic acid, xylanase, microcrystalline cellulase, beta-glucosidase, amylase, carboxymethyl cellulase, carcass weight, and body weight, while these metabolites were negatively correlated with the kidney, acetic acid, acetic acid/ propanoic acid, and acetic acid ratio. Furthermore, there was a significant correlation between liver metabolism and jejunal microbiota. This study revealed significant differences in hepatic metabolites and jejunal fermentation among lambs at different growth stages, which may inform targeted regulation strategies to enhance lamb productivity. Full article

Bile acid salts are steroid biosurfactants that build relatively small micelles compared to surfactants with an alkyl chain due to the rigid conformation of the steroid skeleton. In order to increase the capacity of micellar solubilization of the hydrophobic molecular guest, certain C7 alkyl derivatives were synthesized. Namely, introducing an alkyl group in the C7 position of the steroid skeleton results in a more effective increase in the micelle’s hydrophobic domain (core) than the introduction in the C3 position. In comparison, fewer synthetic steps are required than if alkyl groups are introduced into the C12 position of cholic acid in the Grignard reaction. Here, the thermodynamic parameters of micellization (demicellization) of C7 alkyl (number of C atoms in the alkyl group: 2, 3, 4, and 8) derivatives of cholic acid anion in an aqueous solution without additives are examined (which have not yet been determined) in the temperature interval T (10–40) °C. The critical micellar concentration and the change in the standard molar enthalpy of demicellization ($∆h_{\mathrm{d}\mathrm{e}\mathrm{m}\mathrm{i}\mathrm{c}}^0$) are determined by isothermal calorimetric titration (ICT). From the temperature dependence of $∆h_{\mathrm{d}\mathrm{e}\mathrm{m}\mathrm{i}\mathrm{c}}^0$, the change in the standard molar heat capacity of demicellization is obtained ($∆C_{\mathrm{d}\mathrm{e}\mathrm{m}\mathrm{i}\mathrm{c}}^0$), the value of which is proportional to the hydrophobic surface of the monomer, which in the micellar state is protected from hydrophobic hydration. The values of $∆C_{\mathrm{d}\mathrm{e}\mathrm{m}\mathrm{i}\mathrm{c}}^0$ indicate that in the case of C7-alkyl derivatives of cholic acid anion with butyl and octyl chains, parts of the steroid skeleton and alkyl chain remain shielded from hydration after disintegration of the micelle. Conformational analysis can show that starting from the C7 butyl chain in the alkyl chain, sequences with gauche conformation are also possible without the formation of steric repulsive strain between the alkyl chain and the steroid skeleton so that the C7 alkyl chain takes an orientation above the convex surface of the steroid skeleton instead of an elongated conformation toward the aqueous solution. This is a significant observation, namely, if the micelle is used as a carrier of a hydrophobic drug and after the breakdown of the micelle in the biological system, the released drug has a lower tendency to associate with the monomer if its hydrophobic surface is smaller, i.e., the alkyl chain is oriented towards the angular methyl groups of the steroid skeleton (the ideal monomer increases the hydrophobic domain of the micelle, but in aqueous solution, it adopts a conformation with the as small hydrophobic surface as possible oriented towards the aqueous solution)—which then does not disturb the passage of the drug through the cell membrane. Full article

Background/Objectives: Bacterial vaginosis (BV), an infection caused primarily by Gardnerella vaginalis, is the most prevalent vaginal infection. Although BV is often characterized by an asymptomatic course, it can lead to considerable health complications. Currently, BV therapy choices are limited, and available treatments are complicated by concerns about antibiotic resistance. Ceragenins, which together comprise an innovative class of low molecular-weight, cholic acid-based antibacterial agents, have emerged as potential alternatives to conventional treatments. Methods: This study investigates (i) the antibacterial activity of ceragenins against G. vaginalis in in vitro experimental settings at varied pH, and (ii) the effectiveness and anti-inflammatory properties of CSA-13 in a G. vaginalis-induced bacterial vaginosis animal model. Results and Conclusions: We demonstrate that ceragenins, particularly CSA-13, maintain their antibacterial efficacy throughout pH range of 4.5–7, with the highest activity observed at neutral pH (7.0). Additionally, in an animal model, beneficial effects of ceragenins are attributed to anti-inflammatory properties of these compounds, making these compounds promising agents as potential new treatment options against G. vaginalis-associated vaginal infections. Full article

The concentrations of fecal and serum bile acids (BAs) are known to be altered in human patients with chronic liver diseases (CLDs), especially those with biliary tract involvement (BTD). Scarce literature is available regarding fecal BA modifications during canine CLDs. This study aimed to evaluate fecal BAs in canine CLDs according to different clinical and clinicopathological variables. Forty-six dogs were enrolled. Canine feces were analyzed by HPLC. Cholic Acid (CA), Chenodeoxycholic Acid (CDCA), Ursodeoxycholic Acid (UDCA), Deoxycholic Acid (DCA), and Lithocholic Acid (LCA) were measured, and primary BAs (CA + CDCA), secondary BAs (UDCA + DCA + LCA), and the primary/secondary (P/S) ratio were calculated. Primary BAs (p < 0.0001), CA (p = 0.0003), CDCA (p = 0.003), the P/S ratio (p = 0.002), and total BAs (p = 0.005) were significatively higher in BTD dogs (n = 18) compared to in non-BTD dogs (n = 28). Fecal secondary BAs did not statistically differ between BTD and non-BTD dogs. Gastrointestinal clinical signs (p = 0.028) and diarrhea (p = 0.03) were significantly more prevalent in BTD dogs compared to in non-BTD dogs, supporting the hypothesis of some pathological mechanisms assimilable to bile acid diarrhea (BAD). Our results could reflect imbalances of the fecal BA metabolism in dogs with CLDs. Further studies involving gut microbiome and metabolomic assessment are needed to better understand the possible clinical implications of BA metabolism disruption and their potential role in canine CLDs. Full article