PubMed

Front Endocrinol (Lausanne). 2023 Dec 6;14:1267503. doi: 10.3389/fendo.2023.1267503. eCollection 2023.ABSTRACTOBJECTIVE: This prospective study aimed to evaluate the effect of beinaglutide combined with metformin versus aspart 30 with metformin on metabolic profiles and antidrug antibodies (ADAs) in patients with type 2 diabetes (T2D).METHODS: A total of 134 eligible participants were randomly assigned to the test group and the control group. Patients in the test group were treated with beinaglutide and metformin, whereas patients in the control group were randomly treated with aspart 30 and metformin, with a follow-up period of 6 months. The metabolic profiles and ADAs over 6 months were evaluated.RESULTS: After 6 months, 101 (75.37%) patients completed the study. Compared with the control group, the beinaglutide group had significant reductions in 2-h postprandial blood glucose (2hBG) and low blood glucose index (LBGI). Glycated hemoglobin (HbA1c) decreased in both groups relative to baseline. In the test group, one had treatment-emergent beinaglutide ADAs. Significant reductions in triglycerides (TG), non-fasting TG, weight, waist circumference (WC), and body mass index (BMI) were observed. The values of insulin sensitivity index (HOMA-IR) were decreased to a statistically higher degree with beinaglutide treatment.CONCLUSION: Beinaglutide reduces metabolic dysfunction, LBGI, and weight in patients of T2D with a low risk of ADAs. Beinaglutide may offer the potential for a disease-modifying intervention in cardiovascular disease (CVD).CLINICAL TRIAL REGISTRATION: www.chictr.org.cn, identifier ChiCTR2200061003.PMID:38125788 | PMC:PMC10731293 | DOI:10.3389/fendo.2023.1267503

Food Res Int. 2024 Jan;175:113746. doi: 10.1016/j.foodres.2023.113746. Epub 2023 Nov 26.ABSTRACTSojae semen germinatum (SSG) is derived from mature soybean seeds that have been germinated and dried, typically with sprouts measuring approximately 0.5 cm in length. SSG is traditionally known for its properties in clearing heat and moisture. Nevertheless, limited information was reported on the effects and mechanisms of SSG in alleviating urinary symptoms. This study employed urodynamic parameters to investigate the therapeutic effect of SSG water extract on overactive bladder (OAB) in the rat model with benign prostatic hyperplasia. Through a combination of transcriptomic and metabolomic analyses, the pathways and key proteins of the SSG treatment for OAB were identified and validated by ELISA and Western blotting. Furthermore, network pharmacology elucidated the roles of SSG's isoflavones acting on the target which was identified by above-mentioned multi-omics analysis. Our results indicate that SSG water extract significantly mitigated OAB by down-regulating the PGE2/EP1/PLCβ2/p-MLC signaling pathway. It was speculated that the active ingredient in the SSG on EP1 was genistein. This study provided valuable insights into the molecular mechanisms of SSG water extract, emphasizing the multi-target characteristics and critical pathways in improving OAB. Furthermore, this study contributes to the potential utilization of SSG as a functional food.PMID:38129051 | DOI:10.1016/j.foodres.2023.113746

Food Res Int. 2024 Jan;175:113734. doi: 10.1016/j.foodres.2023.113734. Epub 2023 Nov 24.ABSTRACTShrimp, renowned for its exceptional nutritional value, holds a pivotal position within the realm of aquatic products. The supplementation of extra oxygen to shrimp throughout the entire supply chain has found application within the commercial seafood market. In this study, a dual-platform metabolic analysis, coupled with multivariate data analysis, was employed to discern the impact of supplementary oxygen. Furthermore, this approach facilitated the construction of the post-mortem metabolic profile of shrimp during cold storage. A noticeable decrease of alcohols, ketones and carbohydrates which are related to the energy metabolism in shrimp has been found during cold storage, compared to the fresh shrimp. The degradation of nutritional amino acids was alleviated in shrimp after 4 h of extra oxygen supplement. Furthermore, a higher concentration of identified fatty acids, integral to lipid metabolism and functioning as flavor compounds was observed in shrimp subsequent to oxygen supplementation. Therefore, the additional oxygen supplementation exerted influence on multiple metabolic pathways, including nitrogen metabolism, amino acid and peptide metabolism, nucleotide metabolism, carbohydrate metabolism, and lipid metabolism. This study has constructed a comprehensive post-mortem metabolic profile of shrimp during cold storage, thereby establishing a theoretical foundation for the utilization of oxygen supplements in the preservation of seafood.PMID:38129045 | DOI:10.1016/j.foodres.2023.113734

Food Res Int. 2024 Jan;175:113711. doi: 10.1016/j.foodres.2023.113711. Epub 2023 Nov 28.ABSTRACTThe cashew apple remains an underutilized agricultural product despite its abundance as a by-product of cashew nut production. Anthocyanins are water-soluble pigments responsible for red, purple, and blue hues in plant tissues and have various health-promoting properties. To investigate the anthocyanin biosynthesis in cashew apples, fruits with varying peel colors from three cultivars were subjected to integrative analyses with metabolomics and transcriptomics. Through a UPLC-ESI-MS/MS-based targeted metabolomics analysis, a total of 26 distinct anthocyanin compounds were identified in the fruits of the three cashew cultivars. Subsequent quantification revealed that Pelargonidin-3-O-galactoside, Petunidin-3-O-arabinoside, and Cyanidin-3-O-galactoside were the primary contributors responsible for the red pigmentation in cashew apple peels. Following transcriptomic analysis showed that the expression levels of anthocyanin biosynthetic genes were predominantly higher in the red cashew apples as compared to the other two cultivars. Moreover, correlation analysis revealed that eight potential transcription factors implicated in the regulation of anthocyanin biosynthesis. Among these, four transcription factors exhibited positive correlations with both anthocyanin contents and anthocyanin biosynthetic gene expression, while the remaining four transcription factors displayed negative correlations. These findings provide a comprehensive understanding of the molecular basis of anthocyanin biosynthesis in cashew apple peels.PMID:38129034 | DOI:10.1016/j.foodres.2023.113711

Food Res Int. 2024 Jan;175:113654. doi: 10.1016/j.foodres.2023.113654. Epub 2023 Nov 2.ABSTRACT"Sulmona Red Garlic" is a well-known Italian traditional product. Bulbs, used for culinary purposes, have been largely investigated for their medicinal properties whereas aerial bulbils are usually removed as waste material. Here, for the first time, chemical composition and biological properties of the hydroalcoholic extract from aerial bulbils were investigated. Complementary information on metabolite composition were obtained using both NMR based untargeted and HPLC-DAD targeted methodologies. The NMR analysis revealed the presence of sugars, organic acids, amino acids, organosulphur compounds (methiin, alliin, allicin and cycloalliin), and other secondary metabolites. In particular, methiin and alliin were identified for the first time in the NMR spectra of aerial bulbil garlic extracts. Polyphenol content was determined by HPLC-DAD analysis: catechin, chlorogenic acid, and gallic acid turned out to be the most abundant phenolics. Hydroalcoholic extract blocked cell proliferation of colon cancer cell line HCT116 with an IC50 of 352.07 µg/mL, while it was non-toxic to myoblast cell line C2C12. In addition, it caused seedling germination reduction of two edible and herbaceous dicotyledon species, namely Cichorium intybus and C. endivia. Moreover, the same extract reduced the gene expression of TNF-α (tumor necrosis factor), HIF1-α (hypoxia-inducible factor), VEGFA (vascular endothelial growth factor), and transient receptor potential (TRP) M8 (TRPM8) indicating the ability to contrast cancer development through the angiogenic pathway. Final, in silico experiments were also carried out supporting the biological effects of organosulphur compounds, particularly alliin, which may directly interact with TRPM8. The results here reported suggest the potential use of garlic aerial bulbils often considered a waste product as a source in phytotherapeutic remedies.PMID:38129017 | DOI:10.1016/j.foodres.2023.113654

Food Res Int. 2024 Jan;175:113807. doi: 10.1016/j.foodres.2023.113807. Epub 2023 Dec 3.ABSTRACTThe health benefits of chestnut (Castanea sativa) shells (CSs) have been ascribed to phytochemicals, mainly phenolic compounds. Nevertheless, an exhaustive assessment of their intestinal absorption is vital considering a possible nutraceutical application. This study evaluated the bioactivity of CSs extract prepared by Supercritical Fluid Extraction and untargeted metabolomic profile upon in-vitro intestinal permeation across a Caco-2/HT29-MTX co-culture model. The results demonstrated the neuroprotective, hypoglycemic, and hypolipidemic properties of CSs extract by inhibition of acetylcholinesterase, α-amylase, and lipase activities. The untargeted metabolic profiling by LC-ESI-LTQ-Orbitrap-MS unveiled almost 60 % of lipids and 30 % of phenolic compounds, with 29 metabolic pathways indicated by enrichment analysis. Among phenolics, mostly phenolic acids, flavonoids, and coumarins permeated the intestinal barrier with most metabolites arising from phase I reactions (reduction, hydrolysis, and hydrogenation) and a minor fraction from phase II reactions (methylation). The permeation rates enhanced in the following order: ellagic acid < o-coumaric acid < p-coumaric acid < ferulaldehyde ≤ hydroxyferulic acid ≤ dihydroferulic acid < ferulic acid < trans-caffeic acid < trans-cinnamic acid < dihydrocaffeic acid, with better outcomes for 1000 µg/mL of extract concentration and after 4 h of permeation. Taken together, these findings sustained a considerable in-vitro intestinal absorption of phenolic compounds from CSs extract, enabling them to reach target sites and exert their biological effects.PMID:38129012 | DOI:10.1016/j.foodres.2023.113807

Food Res Int. 2024 Jan;175:113782. doi: 10.1016/j.foodres.2023.113782. Epub 2023 Dec 1.ABSTRACTAroma has an important influence on the aroma quality of chicken meat. This study aimed to identify the characteristic aroma substances in chicken meat and elucidate their metabolic mechanisms. Using gas chromatography-olfactometry and odor activity values, we identified nonanal, octanal, and dimethyl tetrasulfide as the basic characteristic aroma compounds in chicken meat, present in several breeds. Hexanal, 1-octen-3-ol, (E)-2-nonenal, heptanal, and (E,E)-2,4-decadienal were breed-specific aroma compounds found in native Chinese chickens but not in the meat of white-feathered broilers. Metabolomics analysis showed that L-glutamine was an important metabolic marker of nonanal, hexanal, heptanal, octanal, and 1-octen-3-ol. Exogenous supplementation experiments found that L-glutamine increased the content of D-glucosamine-6-P and induced the degradation of L-proline, L-arginine, and L-lysine to enhance the Maillard reaction and promote the formation of nonanal, hexanal, heptanal, octanal, and 1-octen-3-ol, thus improving the aroma profile of chicken meat.PMID:38129007 | DOI:10.1016/j.foodres.2023.113782

Food Res Int. 2024 Jan;175:113714. doi: 10.1016/j.foodres.2023.113714. Epub 2023 Nov 23.ABSTRACTSalmonella enterica is known to survive in desiccate environments and is often associated with low-moisture foods (LMFs). In this work, S. Typhimurium ATCC 14028 was found to survive better by achieving the least reductions (3.17 ± 0.20 Log CFU reduction) compared to S. Tennessee ATCC 10722 (3.82 ± 0.13 Log CFU reduction) and S. Newport ATCC 6962 (6.03 ± 0.36 Log CFU reduction) after 30 days on surfaces with a relative humidity of 49% at ambient temperature. A metabolomic analysis revealed that S. Typhimurium was still active in energy metabolism after 24 h in the desiccate environment and glycogen, an energy reserve, was drastically reduced. We followed up on the glycogen levels over 30 days and found indeed a sharp decline on the first day. However, the glycogens detected on day 7 were significantly higher (P < 0.05) and thereafter remained stable above the original levels until day 30. The expression levels of both glycogen anabolism- and catabolism-related genes (csrA, glgA, glgC, glgX) were significantly up-regulated at all tested points (P < 0.05). The glgA and glgC insertion mutants displayed weaker survivability on both dry surfaces and in representative LMFs (flour and milk powder) compared to the wild-type strain. This work highlights the role of glycogen during different periods of desiccation, which may bring novel insight into mitigating Salmonella by disrupting glycogen metabolism.PMID:38128983 | DOI:10.1016/j.foodres.2023.113714

Food Res Int. 2024 Jan;175:113713. doi: 10.1016/j.foodres.2023.113713. Epub 2023 Nov 24.ABSTRACTStrip/needle green teas (SGT/NGT) processed using innovative technologies are in high demand; however, mechanisms behind their color and flavor have not been comprehensively studied. We aimed to reveal the dynamics of major pigmented components (carotenoids, lipids, flavonoids, and Maillard products) and their contributions to the flavor of green teas. The total content of flavonoids in SGT and NGT were 255 ± 4.51 and 201 ± 3.91 mg·g-1, respectively; these values are slightly lower than that in fresh leaves (FLs), resulting in a fresh and sweet aftertaste. In average, carotene content in SGT/NGT (24.8 μg·g-1) was higher than in FL (17.4 μg·g-1), whilst xanthophyll content (603 μg·g-1) decreased to one-half of that in FL (310 μg·g-1). Among the 218 primary metabolites, glutamine, glutamic acid, and arginine were found to accumulate and were dominate contributors for the umami and sweet taste. Notably, more than 96 volatiles were screened and revealed their correlations with carotenoids, lipids, and amino acids. Overall, the synergism between pigments and their non-enzymatic derivates' contribution to GT characterized flavor was illustrated.PMID:38128982 | DOI:10.1016/j.foodres.2023.113713

Food Res Int. 2024 Jan;175:113622. doi: 10.1016/j.foodres.2023.113622. Epub 2023 Nov 3.ABSTRACTThe ripe Gannan navel oranges have an appealing aroma, but few studies have reported the changes of these aromatic substances during the growth of navel oranges. In this study, changes of aroma components in Gannan navel orange from 119 to 245 days after flowering were systematically studied using headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) coupled with multivariate analysis, including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). A total of 43 and 54 aroma components were identified in pulp and peel of navel orange, respectively. The odor active value (OAV) results indicated that 14 substances were the key aroma components during the growth of navel orange. Among them, the contribution of linalool, β-myrcene and limonene were the highest. The multivariate statistical analysis further confirmed that 14 and 18 compounds could be used as key markers to distinguish the pulp and peel at different growth stages, respectively. Results from this study contributed to a better understanding of the dynamic variation and retention of aroma compounds during navel orange growth, and have great potential for industrial application.PMID:38128975 | DOI:10.1016/j.foodres.2023.113622

Brain Res. 2023 Dec 19:148733. doi: 10.1016/j.brainres.2023.148733. Online ahead of print.ABSTRACTThere is an urgent need for new or repurposed therapeutics that protect against or significantly delay the clinical progression of neurodegenerative diseases such as Huntington's disease (HD), Parkinson's disease and Alzheimer's disease. In particular, preclinical studies are needed for well tolerated and brain-penetrating small molecules capable of mitigating the proteotoxic mitochondrial processes that are hallmarks of these diseases. We identified a unique suicide inhibitor of mitochondrial proline dehydrogenase (Prodh), N-propargylglycine (N-PPG), which has anticancer and brain-enhancing mitohormesis properties, and we hypothesize that induction of mitohormesis by N-PPG protects against neurodegenerative diseases. We carried out a series of mouse studies designed to: i) compare brain and metabolic responses while on oral N-PPG treatment (50 mg/kg, 9-14 days) of B6CBA wildtype (WT) and short-lived transgenic R6/2 (HD) mice; and ii) evaluate potential brain and systemwide stress rebound responses in WT mice 2 months after cessation of extended mitohormesis induction by well tolerated higher doses of N-PPG (100-200 mg/kg x 60 days). WT and HD mice showed comparable global evidence of N-PPG induced brain mitohormesis characterized by Prodh protein decay and increased mitochondrial expression of chaperone and Yme1l1 protease proteins. Interestingly, transcriptional analysis (RNAseq) showed partial normalization of HD whole brain transcriptomes toward those of WT mice. Comprehensive metabolomic profiles performed on control and N-PPG treated blood, brain, and kidney samples revealed expected N-PPG induced tissue increases in proline levels in both WT and HD mice, accompanied by surprising parallel increases in hydroxyproline and sarcosine. Two months after cessation of the higher dose N-PPG stress treatments, WT mouse brains showed robust rebound increases in Prodh protein levels and mitochondrial transcriptome responses, as well as altered profiles of blood amino acid-related metabolites. Our HD and WT mouse preclinical findings point to the brain penetrating and mitohormesis-inducing potential of the drug candidate, N-PPG, and provide new rationale and application insights supporting its further preclinical testing in various models of neurodegenerative diseases characterized by loss of mitochondrial proteostasis.PMID:38128812 | DOI:10.1016/j.brainres.2023.148733

J Adv Res. 2023 Dec 19:S2090-1232(23)00401-0. doi: 10.1016/j.jare.2023.12.016. Online ahead of print.ABSTRACTINTRODUCTION: Rumen epithelial parakeratosis, a common disease in ruminants caused by abnormalities in the ruminal stratified squamous epithelial keratinization process, negatively impacts ruminant health and performance. However, we still lack a comprehensive perception of the underlying mechanisms and the predisposing factors for this disorder.OBJECTIVES: Here, we investigated rumen epithelial cell heterogeneity, differentiation trajectories, and cornification to clarify the rumen epithelial keratinization process and discern the key ruminal metabolites contributing to rumen epithelial parakeratosis.METHODS: Twenty-four 14-day-old lambs were divided into three groups, including only milk feeding, milk plus alfalfa hay feeding, and milk plus corn-soybean concentrate starter feeding. At 42 days of age, the lambs were slaughtered, and rumen tissues were collected for single-cell RNA-sequencing (scRNA-seq), immunofluorescence, and quantitative real-time PCR (qRT-PCR) analyses. Ruminal fluid samples were collected for metabolomic analyses. Rumen epithelial organoid was used to verify the key ruminal metabolites contributing to parakeratosis.RESULTS: As expected, we observed that concentrate starter introduction resulted in rumen epithelial parakeratosis. Moreover, scRNA-seq analysis revealed a developmental impediment in the transition from differentiated keratinocytes to terminally differentiated keratinocytes (TDK) in lambs with concentrate starter introduction. Immunofluorescence and qRT-PCR analyses further verified the location and expression of marker genes of TDK. Metabolomic analysis showed a robust positive correlation between ruminal butyrate levels and rumen epithelial keratinization. More importantly, we successfully established a rumen organoid model capable of facilitating the study of the keratinization process in the rumen epithelia and further confirmed that high dose butyrate indeed contributed to rumen epithelial parakeratosis.CONCLUSION: Collectively, concentrate starter introduction induces ruminal epithelial parakeratosis by blocking keratinocyte differentiation with excessive ruminal butyrate accumulation in a neonatal lamb model. These findings enhance our understanding of rumen epithelial keratinization and provide valuable insights for addressing rumen epithelial parakeratosis using early nutritional intervention strategies.PMID:38128723 | DOI:10.1016/j.jare.2023.12.016

Fish Shellfish Immunol. 2023 Dec 19:109322. doi: 10.1016/j.fsi.2023.109322. Online ahead of print.ABSTRACTNocardia seriolae is a severe bacterial pathogen that has seriously affected the development of aquaculture industry. Largemouth bass (Micropterus salmoides) is a commercially significant freshwater fish that suffers a variety of environmental threats, including bacterial pathogens. However, the immune responses and metabolic alterations of largemouth bass to N. seriolae infection remain largely unclear. We discovered that N. seriolae caused pathological alterations in largemouth bass and shifted the transcript of immune-related and apoptotic genes in head kidney after infection. To answer the aforementioned question, a combined transcriptome and metabolome analysis was employed to explore the alterations in genes, metabolites, and metabolic pathways in largemouth bass following bacterial infection. A total of 3579 genes and 1929 metabolites are significant differentially changed in the head kidney post infection. In response to N. seriolae infection, host modifies the PI3K-Akt signaling pathway, TCA cycle, glycolysis, and amino acid metabolism. The integrated analysis of transcriptome and metabolome suggested that with the arginine metabolism pathway as the core, multiple biomarkers (arg gene, arginine) are involved in the antibacterial and immune functions of largemouth bass. Thus, we hypothesized that arginine plays a crucial role in the immune responses of largemouth bass against N. seriolae infection, and increasing arginine levels suitably is beneficial for the host against bacterial infection. Our results shed light on the regulatory mechanism of largemouth bass resistance to N. seriolae infection and contributed to the development of more effective N. seriolae resistance strategies.PMID:38128679 | DOI:10.1016/j.fsi.2023.109322

Fitoterapia. 2023 Dec 19:105782. doi: 10.1016/j.fitote.2023.105782. Online ahead of print.ABSTRACTStress, obesity, hormonal changes, and aging have been connected to cellulite aggravation resulting in skin dimpled appearance, a very common painless skin disorder with a female preponderance. Several Apiaceae plants have been traditionally used for cosmetic applications. However, their screening for anti-cellulite potential has not been deeply investigated. In this work, UPLC-HRMS/MS coupled with molecular networking was employed to glean a holistic overview of the chemodiversity of the metabolome of nine Apiaceae fruits. Additionally, the extracts were screened for in vitro antioxidant and anti-cellulite activities. Apium graveolens and Petroselinum crispum revealed excellent free radical scavenging activity, remarkably increased lipolysis, and decreased adipogenesis. Furthermore, apigenin and its glycosides were identified to be the major components in both extracts, which might be responsible for the antioxidant activity and anti-cellulite potential. Conclusively, these results signify the potent antioxidant and anti-cellulite properties of A. graveolens and P. crispum fruit extracts, holding potential for the development of plant derived products for cellulite management.PMID:38128622 | DOI:10.1016/j.fitote.2023.105782

Biochem Pharmacol. 2023 Dec 19:115992. doi: 10.1016/j.bcp.2023.115992. Online ahead of print.ABSTRACT4-octyl itaconate (4-OI) is a cell-permeable itaconate derivative with anti-inflammatory and antioxidant properties. However, its therapeutic potential for oxidative stress-induced liver injury remains unknown. This study investigated the hepatoprotective effects and mechanisms of 4-OI against oxidative damage in in vitro and in vivo models. 4-OI attenuated H2O2-induced cytotoxicity, oxidative stress, and mitochondrial dysfunction in L02 and HepG2 cells. Untargeted metabolomics profiling and pathway analysis identified the PI3K/AKT/mTOR and MAPK pathways as key regulators of 4-OI's protective effects. Specifically, 4-OI induced phosphorylation of AKT and ERK1/2, leading to activation of the Nrf2 signaling pathway. Nrf2 upregulated expression of the mitochondrial deacetylase Sirt3, which subsequently alleviated H2O2-induced cell injury. In mice, 4-OI reduced acetaminophen (APAP)-induced liver injury as evidenced by attenuated hepatocellular necrosis and decreased serum liver enzymes. It also elevated hepatic expression of Nrf2, Sirt3, p-AKT and p-ERK1/2. Inhibition of AKT, ERK1/2 or Nrf2 blocked the protective effects of 4-OI in vitro, suggesting its antioxidant activity is mediated by activating the Nrf2/Sirt3 pathway via AKT and ERK1/2 phosphorylation. In summary, 4-OI exerted antioxidant and hepatoprotective effects by activating the Nrf2/Sirt3 signaling pathway through AKT and ERK1/2 phosphorylation, which were elucidated using in vitro and in vivo oxidative stress models. This provides novel insights into the mechanisms of 4-OI against oxidative stress-related liver diseases.PMID:38128618 | DOI:10.1016/j.bcp.2023.115992

EBioMedicine. 2023 Dec 20;99:104907. doi: 10.1016/j.ebiom.2023.104907. Online ahead of print.ABSTRACTBACKGROUND: Diagnosing Cushing's syndrome (CS) is highly complex. As the diagnostic potential of urinary steroid metabolome analysis by gas chromatography-mass spectrometry (GC-MS) in combination with systems biology has not yet been fully exploited, we studied a large cohort of patients with CS.METHODS: We quantified daily urinary excretion rates of 36 steroid hormone metabolites. Applying cluster analysis, we investigated a control group and 168 patients: 44 with Cushing's disease (CD) (70% female), 18 with unilateral cortisol-producing adrenal adenoma (83% female), 13 with primary bilateral macronodular adrenal hyperplasia (PBMAH) (77% female), and 93 ruled-out CS (73% female).FINDINGS: Cluster-Analysis delineated five urinary steroid metabotypes in CS. Metabotypes 1, 2 and 3 revealing average levels of cortisol and adrenal androgen metabolites included patients with exclusion of CS or and healthy controls. Metabotype 4 reflecting moderately elevated cortisol metabolites but decreased DHEA metabolites characterized the patients with unilateral adrenal CS and PBMAH. Metabotype 5 showing strong increases both in cortisol and DHEA metabolites, as well as overloaded enzymes of cortisol inactivation, was characteristic of CD patients. 11-oxygenated androgens were elevated in all patients with CS. The biomarkers THS, F, THF/THE, and (An + Et)/(11β-OH-An + 11β-OH-Et) correctly classified 97% of patients with CS and 95% of those without CS. An inverse relationship between 11-deoxygenated and 11-oxygenated androgens was typical for the ACTH independent (adrenal) forms of CS with an accuracy of 95%.INTERPRETATION: GC-MS based urinary steroid metabotyping allows excellent identification of patients with endogenous CS and differentiation of its subtypes.FUNDING: The study was funded by the Else Kröner-Fresenius-Stiftung and the Eva-Luise-und-Horst-Köhler-Stiftung.PMID:38128413 | DOI:10.1016/j.ebiom.2023.104907

Biomed Pharmacother. 2023 Dec 20;170:116021. doi: 10.1016/j.biopha.2023.116021. Online ahead of print.ABSTRACTHepatocellular carcinoma (HCC) poses a heavy burden on human health with high morbidity and mortality rates. Systematic therapy is crucial for advanced and mid-term HCC, but faces a significant challenge from therapeutic resistance, weakening drug effectiveness. Metabolic reprogramming has gained attention as a key contributor to therapeutic resistance. Cells change their metabolism to meet energy demands, adapt to growth needs, or resist environmental pressures. Understanding key enzyme expression patterns and metabolic pathway interactions is vital to comprehend HCC occurrence, development, and treatment resistance. Exploring metabolic enzyme reprogramming and pathways is essential to identify breakthrough points for HCC treatment. Targeting metabolic enzymes with inhibitors is key to addressing these points. Inhibitors, combined with systemic therapeutic drugs, can alleviate resistance, prolong overall survival for advanced HCC, and offer mid-term HCC patients a chance for radical resection. Advances in metabolic research methods, from genomics to metabolomics and cells to organoids, help build the HCC metabolic reprogramming network. Recent progress in biomaterials and nanotechnology impacts drug targeting and effectiveness, providing new solutions for systemic therapeutic drug resistance. This review focuses on metabolic enzyme changes, pathway interactions, enzyme inhibitors, research methods, and drug delivery targeting metabolic reprogramming, offering valuable references for metabolic approaches to HCC treatment.PMID:38128187 | DOI:10.1016/j.biopha.2023.116021

Biomed Pharmacother. 2023 Dec 20;170:116030. doi: 10.1016/j.biopha.2023.116030. Online ahead of print.ABSTRACTGastric cancer (GC) is a malignant tumor of the gastrointestinal tract with a high mortality rate worldwide, a low early detection rate and a poor prognosis. The rise of metabolomics has facilitated the early detection and treatment of GC. Metabolism in the GC tumor microenvironment (TME) mainly includes glucose metabolism, lipid metabolism and amino acid metabolism, which provide energy and nutrients for GC cell proliferation and migration. Abnormal tumor metabolism can influence tumor progression by regulating the functions of immune cells and immune molecules in the TME, thereby contributing to tumor immune escape. Thus, in this review, we summarize the impact of metabolism on the TME during GC progression. We also propose novel strategies to modulate antitumor immune responses by targeting metabolism.PMID:38128177 | DOI:10.1016/j.biopha.2023.116030

Metabolomics. 2023 Dec 22;20(1):9. doi: 10.1007/s11306-023-02070-2.ABSTRACTINTRODUCTION: Biogenic volatile organic compounds (BVOCs) are emitted by all organisms as intermediate or end-products of metabolic processes. Individual BVOCs perform important physiological, ecological and climatic functions, and collectively constitute the volatilome-which can be reflective of organism taxonomy and health. Although BVOC emissions of tropical benthic reef taxa have recently been the focus of multiple studies, emissions derived from their temperate counterparts have never been characterised.OBJECTIVES: Characterise the volatilomes of key competitors for benthic space among Australian temperate reefs.METHODS: Six fragments/fronds of a temperate coral (Plesiastrea versipora) and a macroalga (Ecklonia radiata) from a Sydney reef site were placed within modified incubation chambers filled with seawater. Organism-produced BVOCs were captured on thermal desorption tubes using a purge-and-trap methodology, and were then analysed using GC × GC - TOFMS and multivariate tests.RESULTS: Analysis detected 55 and 63 BVOCs from P. versipora and E. radiata respectively, with 30 of these common between species. Each taxon was characterised by a similar relative composition of chemical classes within their volatilomes. However, 14 and 10 volatiles were distinctly emitted by either E. radiata or P. versipora respectively, including the halogenated compounds iodomethane, tribromomethane, carbon tetrachloride and trichloromonofluoromethane. While macroalgal cover was 3.7 times greater than coral cover at the sampling site, P. versipora produced on average 17 times more BVOCs per cm2 of live tissue, resulting in an estimated contribution to local BVOC emission that was 4.7 times higher than E. radiata.CONCLUSION: Shifts in benthic community composition could disproportionately impact local marine chemistry and affect how ecosystems contribute to broader BVOC emissions.PMID:38129550 | DOI:10.1007/s11306-023-02070-2

Sci Rep. 2023 Dec 21;13(1):22840. doi: 10.1038/s41598-023-50305-y.ABSTRACTParasitic roundworms cause significant sickness and mortality in animals and humans. In livestock, these nematodes have severe economic impact and result in losses in food production on a global scale. None of the currently available drugs ideally suit all treatment circumstances, and the development of drug-resistant nematode strains has become a challenge to control the infection. There is an urgent need to develop novel anthelmintic compounds. According to our previous report, N-methylbenzo[d]oxazol-2-amine (1) showed anthelmintic activity and lowest cytotoxicity. In this study, in vivo anthelmintic properties were evaluated using Trichinella spiralis infected mice. Toxicity was evaluated using the rats and mode of action using molecular docking and metabolomics approaches. The in vivo results demonstrate that a dose of 250 mg/kg reduced the T. spiralis abundance in the digestive tract by 49%. The 250 mg/kg Albendazole was served as control. The relatively low acute toxicity was categorized into chemical category 5, with an LD50 greater than 2000 mg/kg body. Molecular docking analysis showed the T. spiralis tubulin beta chain and glutamate-gated channels might not be the main targets of compound 1. Metabolomics analysis was used to explain the effects of compound 1 on the T. spiralis adult worm. The results demonstrated that compound 1 significantly up-regulated the metabolism of purine, pyrimidine and down-regulated sphingolipid metabolism. In conclusion, compound 1 could be a potential molecule for anthelmintic development. The bioavailability, pharmacokinetics, and absorption of this compound should be studied further to provide information for its future efficacy improvement.PMID:38129499 | DOI:10.1038/s41598-023-50305-y