Galactose 2.49g / Palmitic acid 2.5mg powder and solvent for suspension for injection 2.5g vials

Multidrug-resistant (MDR) tumors and cancer cell lines demonstrate a wide variety of biochemical changes. In this study we used drug-sensitive wild-type (wt) cancer cell lines and respective MDR subclones, and we demonstrate the accumulation of distinct lipids in MDR cells. These lipids were either absent or present at very low levels in drug-sensitive cells. The compounds, termed lipid-1 and lipid-2, migrated on thin-layer chromatography as a doublet. They could be radiolabeled by incubating MCF-7-AdrR (Adriamycin-resistant) breast cancer cells with [3H]serine, [3H]palmitic acid, or [3H]galactose. Utilization of these precursors by MCF-7-wt cells for synthesis of lipid-1 and -2 was minimal. Two inhibitors of sphingolipid biosynthesis, L-cycloserine and fumonisin B1, prevented the observed accumulation of the lipid compounds. An inhibitor of glucosylceramide synthesis, 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol, completely abolished the formation of lipid-1 and -2 in MCF-7-AdrR cells and, to a lesser extent, inhibited the formation of lactosylceramides and gangliosides. Utilizing mass spectrometry, the multidrug resistance-associated lipids were further characterized as monoglycosylceramides of two major species that contained either 16-carbon (palmitic) or 24-carbon (lignoceric and nervonic) fatty acids. The carbohydrate head group of glycosylceramides was identified as glucose, not galactose, thus designating the accumulated lipids as glucosylceramides. Incorporation of [3H]palmitic acid into glucosylceramide was strikingly higher (8-10 times) in MCF-7-AdrR cells compared with MCF-7-wt cells. Since the rate of glucosylceramide degradation in MCF-7-AdrR cells was not attenuated, accelerated glycosphingolipid synthesis in MDR cells is suggested. Glucosylceramide also accumulated in KB-V-1, a vinblastine-resistant epidermoid carcinoma but not in KB-3-1, drug-sensitive wt cells. MDR ovarian adenocarcinoma cells (NIH:OVCAR-3) also contained elevated levels of glucosylceramide. Our results demonstrate a correlation between cellular drug resistance and alterations in glucosylceramide metabolism.

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Cognitive impairment, the leading cause of traumatic brain injury (TBI)-related disability, adversely affects the quality of life of TBI patients, and exacts a personal and economic cost that is difficult to quantify. The underlying pathophysiological mechanism is currently unknown, and an effective treatment of the disease has not yet been identified. This study aimed to advance our understanding of the mechanism of disease pathogenesis; thus, metabolomics based on gas chromatography/mass spectrometry (GC-MS), coupled with multivariate and univariate statistical methods were used to identify potential biomarkers and the associated metabolic pathways of post-TBI cognitive impairment. A biomarker panel consisting of nine serum metabolites (serine, pyroglutamic acid, phenylalanine, galactose, palmitic acid, arachidonic acid, linoleic acid, citric acid, and 2,3,4-trihydroxybutyrate) was identified to be able to discriminate between TBI patients with cognitive impairment, TBI patients without cognitive impairment and healthy controls. Furthermore, associations between these metabolite markers and the metabolism of amino acids, lipids and carbohydrates were identified. In conclusion, our study is the first to identify several serum metabolite markers and investigate the altered metabolic pathway that is associated with post-TBI cognitive impairment. These markers appear to be suitable for further investigation of the disease mechanisms of post-TBI cognitive impairment.

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The subcritical water extraction of Undaria pinnatifida (blade, sporophyll, and root) was evaluated to determine its chemical properties and biological activities. The extraction was conducted at 180 °C and 3 MPa. Root extracts exhibited the highest phenolic content (43.32 ± 0.19 mg phloroglucinol/g) and flavonoid content (31.54 ± 1.63 mg quercetin/g). Sporophyll extracts had the highest total sugar, reducing sugar, and protein content, with 97.35 ± 4.23 mg glucose/g, 56.44 ± 3.10 mg glucose/g, and 84.93 ± 2.82 mg bovine serum albumin (BSA)/g, respectively. The sporophyll contained the highest fucose (41.99%) and mannose (10.37%), whereas the blade had the highest galactose (48.57%) and glucose (17.27%) content. Sporophyll had the highest sulfate content (7.76%). Key compounds included sorbitol, glycerol, L-fucose, and palmitic acid. Root extracts contained the highest antioxidant activity, with IC50 values of 1.51 mg/mL (DPPH), 3.31 mg/mL (ABTS+), and 2.23 mg/mL (FRAP). The root extract exhibited significant α-glucosidase inhibitory activity with an IC50 of 5.07 mg/mL, indicating strong antidiabetic potential. The blade extract showed notable antihypertensive activity with an IC50 of 0.62 mg/mL. Hence, subcritical water extraction to obtain bioactive compounds from U. pinnatifida, supporting their use in functional foods, cosmetics, and pharmaceuticals is highlighted. This study uniquely demonstrates the variation in bioactive compound composition and bioactivities across different parts of U. pinnatifida, providing deeper insights. Significant correlations between chemical properties and biological activities emphasize the use of U. pinnatifida extracts for chronic conditions.

Abstract licence: CC BY

Understanding the metabolic profile within the follicular microenvironment is crucial for optimizing reproductive efficiency in camels. In this study, we examined the metabolomic profile of camel follicular fluid (FF) during the breeding (n = 10) and non-breeding seasons (n = 10). Gas chromatography-mass spectrometry (GC-MS) was utilized to describe the metabolites present in follicular fluid samples. The results found considerable differences in the metabolomics profiles between the breeding and non-breeding seasons. Hexadecenoic acid, galactose and glucose levels were significantly (P < 0.05) higher in camel FF during the breeding season, while 9-octadecenamide, oleonitrile, glycine, octadecanamide, cholesterol, and propanoic acid were higher (P < 0.05) in FF during the non-breeding season. Multivariante analyses pointed to those 9 metabolites, and univariate analysis showed hexadecenoic acid, galactose, glucose, and oleanitril were the most significant ones in camel follicular fluid collected during both breeding and non-breeding seasons. The univariate and multivariate analyses showed an increase in the levels of hexadecanoic acid, galactose, glucose, and a depletion in the level of oleanitrile in the breeding season compared to the non-breeding season. The ROC curve and statistical analysis showed that hexadecanoic acid, galactose, and oleanitril with AUC = 1 were promising to be seasonal biomarkers of fertility in female camels. In conclusion, the metabolomic analysis of camel FF reveals distinct changes in metabolite levels between breeding and non-breeding seasons, reflecting adaptive metabolic responses to support reproductive processes. These results offer valuable insights into the reproductive physiology of camels and offer practical implications for potential biomarkers and assessing the reproductive status in camels, which can be utilized in reproductive management and conservation efforts in these valuable animal species.

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Aging and insulin resistance are intertwined factors in the development of metabolic diseases such as type 2 diabetes and cardiovascular disorders. Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has shown promising cardioprotective effects in preclinical and clinical studies of metabolic diseases. Yet, its action on insulin-resistant aged subjects is not clearly defined. This study aimed to investigate the effects of liraglutide on intracellular zinc levels, including its modulation of oxidative stress, mitochondrial function, and Endoplasmic Reticulum (ER) stress in a novel insulin-resistant senescent model. Insulin resistance and senescence were confirmed by reduced glucose uptake and increased β-Galactosidase Staining and increased p-H2A.X (Ser139) levels after 24 h of co-incubation with bovine serum albumin (BSA) conjugated palmitic acid (PA; 50 µM) and 278 mM D-galactose (D-Gal) in human AC16 cells. Our findings showed upregulated expression of ER and mitochondrial proteostasis markers in the early minutes of liraglutide treatment. In addition, chronic but not acute liraglutide treatment significantly increased intracellular zinc levels, accompanied by improved mitochondrial membrane potential and reduced reactive oxygen species in the insulin-resistant senescent model. Casein kinase 2 inhibition completely abolished liraglutide-induced zinc elevation and mitochondrial improvements in the chronic context, highlighting the role of casein kinase 2 in the subcellular signaling of liraglutide. These findings indicate that liraglutide alters intracellular zinc and modulates endoplasmic reticulum-mitochondria communication, giving insight into its therapeutic potential in metabolic cardiomyopathies linked to insulin resistance and aging.

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BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD), the most common chronic liver disease worldwide, is closely linked to obesity and metabolic syndrome. The reason some patients with MASLD develop metabolic dysfunction-associated steatohepatitis (MASH) and which metabolic changes in the liver are linked to its progression are unclear. METHODS: ) selected for laparoscopic gastric bypass surgery. Liver metabolomics and liver RNA sequencing data were used to study metabolic differences between those with steatosis and those with MASH. Validation was performed in a French cohort of 227 patients with obesity and MASLD. RESULTS: Overall, 45 metabolites differed between patients with steatosis and those with MASH. Novel MASH-associated metabolites included n-acetylneuraminate (β = 0.276), pentose acid (β = -0.290), UDP-galactose (β = -0.413), gamma/beta-tocopherol (β = -0.317), and guanidinosuccinate (β = -0.289) (all p < 0.05). In the validation cohort, 8 of 20 metabolites, including n-acetylneuraminate and plasmalogens 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE(P-16:0/20:4) and 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE(P-18:0/20:4), were linked to MASH (p < 0.05). The 45 significantly altered metabolites formed two clusters with different associations with metabolic parameters, depending on their correlation with liver histological features. Kyoto Encyclopedia of Genes and Genomes analysis revealed that elevated metabolites in MASH were associated with inflammatory pathways; those decreased in MASH were linked to fatty acid degradation and amino acid and pyruvate metabolism. CONCLUSION: Transitioning from simple steatosis to MASH is associated with distinct alterations in liver metabolites and systemic metabolic traits, highlighting disease progression-associated pathways.

Abstract licence: CC BY-NC-ND

In this study, a lipid disorder Alzheimer's disease (AD) model was developed with high-fat diet and D-galactose injected intraperitoneally (HFD & D-gal) to evaluate the activities of Buyang Huanwu Decoction (BYHWD) compared with donepezil hydrochloride. The learning and memory abilities of BYHWD were evaluated by Morris water maze test (MWM). The lipid levels in serum, histopathology, and immunohistochemistry of hyperphosphorylated tau protein in hippocampal neurons were conducted to prove the therapy effects of BYHWD. After the identification of constituents absorbed into the brain using LC-MS, UPLC-TQ-MS was employed to analyze endogenous lipid metabolites in the hippocampi of mice. Based on the validated differential markers identified through lipidomics analysis, we further substantiated potential therapeutic pathway of BYHWD through the application of molecular docking technology. The mechanism underlying BYHWD was subsequently confirmed by palmitic acid-injured HT22 cells. The results showed that BYHWD significantly improved the cognitive deficits and regulated the lipid levels of HFD & D-gal mice. BYHWD also protected the neuronal cell condition of hippocampal neurons, increased the density of dendritic spines, and reduced the expression of P-tau. Lipidomics revealed that 41 differential lipid metabolites were retuned after BYHWD administration, and this change may be related to the PPARγ pathway. Calycosin-7-glucoside showed good interaction with PPARγ in vivo composition analysis. Calycosin-7-glucoside increased the mRNA expression levels of lipid metabolism-related enzymes and PPARγ, as well as the expression of PPARγ protein in vitro study. BYHWD activated the PPARγ pathway to induce peroxisome proliferation and regulated lipid metabolism disorders in the AD mice brain.

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Mychonastes homosphaera MHSC24 is a green microalga newly isolated from a brackish coastal site in Korea. This study represents the first indigenous record of this species in the country. It provides a comprehensive characterization of its morphological, molecular, physiological, and biochemical characteristics. This microalga was identified through morphological observations and multilocus phylogenetic analyses. Strain MHSC24 exhibited robust growth under mesophilic temperatures (15–27 °C), moderate light intensities (88–300 μmol photons m−2 s−1), and low salinity levels (0–10 PSU). Optimal growth was observed at 27 °C, 193 μmol photons m−2 s−1, and 0 PSU. Under standard cultivation, the strain exhibited high protein levels (~54% of dry weight, DW) and accumulated substantial amounts of canthaxanthin (5.59 mg g−1 DW), the predominant carotenoid in its pigment profile. Thus, MHSC24 is a promising candidate for sustainable protein- and carotenoid-based applications. Palmitic acid (11.95 mg g−1 DW) and galactose (2.07 mg g−1 DW) were the predominant fatty acid and monosaccharide, respectively. The physiological resilience, high protein yield, and substantial canthaxanthin accumulation of MHSC24 support its potential utilization in the functional food, feed, and nutraceutical sectors. Therefore, this study provides a basis for optimized cultivation strategies and industrial exploitation of indigenous Korean microalgae.

Abstract licence: CC BY

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the hepatic expression of systemic metabolic derangement; however, we have limited understanding of its progression or improvement, and there's a lack of adequate tools to monitor these changes. Metabolomics can provide dynamic biomarkers that reflect pathophysiological change. OBJECTIVE: To describe the effects of weight-loss oriented Mediterranean diet on clinical, laboratory and metabolomic profiles in a cohort of genetically characterized obese and overweight MASLD patients. METHODS: In a prospective cohort, 148 adults with ultrasound-confirmed MASLD started a personalized, nutritionist-guided, hypocaloric Mediterranean diet, supported by regular counselling. Weight loss was classified as <5%, 5-10%, or >10% of baseline. Single-nucleotide polymorphisms in PNPLA3, TM6SF2, MBOAT7 and GCKR were genotyped and combined into a weighted polygenic risk score. Untargeted gas chromatography-mass spectrometry profiled fasting serum samples at baseline and study end. Data were processed by partial least squares discriminant analysis, variable importance in projection scoring, and pathway enrichment. RESULTS: Mean weight decreased by about 8% and controlled attenuation parameter declined by nearly 17%, with greatest steatosis reduction in PNPLA3 G-allele carriers. Metabolomic modelling achieved 92% classification accuracy and revealed fourteen key metabolites. Caproic acid, glycerol and hydroxypropanedioic acid increased consistently, whereas palmitic acid and d-galactose decreased. Enriched pathways included galactose, butanoate and glycerolipid metabolism. Metabolic shifts scaled with weight loss intensity and differed by genotype. CONCLUSIONS: Mediterranean diet-induced weight loss triggers rapid, weight-dependent and genotype-modulated metabolomic reprogramming that parallels hepatic fat clearance. Caproic acid, glycerol and hydroxypropanedioic acid constitute biomarkers and combined with genetic risk assessment, may support precision nutrition strategies for MASLD.

Abstract licence: CC BY