PubMed

Int J Biol Macromol. 2023 Nov 16:128092. doi: 10.1016/j.ijbiomac.2023.128092. Online ahead of print.ABSTRACTThrombosis is a serious threat to human health and life. Fucoidan, a sulfated polysaccharide from brown algae, could prevent coagulation and thrombus after intravenous administration. However, more efforts are still needed to develop its oral agent. In the present study, the absorption and excretion of fucoidan (90.8 kDa) and its degradation products, Dfuc1 (19.2 kDa) and Dfuc2 (5.5 kDa), were determined by HPLC-MS/MS after acid degradation and 1-phenyl-3-methyl-5-pyrazolone derivatization, and their anticoagulation and antithrombotic activities were evaluated in vivo after oral administration. Results showed that the maximum concentrations of fucoidan, Dfuc1 and Dfuc2 in rat plasma all achieved at 2 h after oral administration (150 mg/kg), and they were 41.1 ± 10.6 μg/mL, 45.3 ± 18.5 μg/mL and 59.3 ± 13.7 μg/mL, respectively. In addition, fucoidan, Dfuc1 and Dfuc2 could all prolong the activated partial thromboplastin time in vivo from 23.7 ± 2.7 s (blank control) to 25.1 ± 2.6 s, 27.1 ± 1.7 s and 29.4 ± 3.6 s, respectively. Moreover, fucoidan and its degradation products showed similar antithrombotic effect in carrageenan-induced thrombosis mice, and untargeted metabolomics analysis revealed that they all markedly regulated the carrageenan-induced metabolite disorders, especially the arachidonic acid metabolism. Thus, the degradation products of fucoidan with lower molecular weights are more attractive for the development of oral antithrombotic agents.PMID:37979755 | DOI:10.1016/j.ijbiomac.2023.128092

J Nutr Biochem. 2023 Nov 16:109527. doi: 10.1016/j.jnutbio.2023.109527. Online ahead of print.ABSTRACTExcessive fructose corn syrup (FCS) intake brings a series of health problems. The aim of the present study was to explore the mechanism of FCS-induced metabolic disorders from the perspective of gut microbiota. Mice were fed for 16 weeks with normal or 30% FCS drinking water. Compared to the control group, FCS caused significantly higher fat deposition, hepatic steatosis, liver and intestinal inflammatory damages (p < 0.05). FCS increased the abundance of Muribaculaceae in vivo and in vitro, which was positively correlated with the indices of metabolic disorders (p < 0.05). In vivo and in vitro data indicated that FCS enhanced the microbial function involved in pentose phosphate pathway and arachidonic acid metabolism, metabolomics further demonstrated that FCS led to an increase in prostaglandins (the catabolites of arachidonic acid) (p < 0.05). Our study confirmed that FCS can directly promote gut microbiota to synthesize inflammatory factor prostaglandins, which provides new insights and directions for the treatment of FCS-induced metabolic disorders and inflammation.PMID:37979711 | DOI:10.1016/j.jnutbio.2023.109527

Ecotoxicol Environ Saf. 2023 Nov 16;268:115682. doi: 10.1016/j.ecoenv.2023.115682. Online ahead of print.ABSTRACTBees, essential for pollination in agriculture and global economic growth. However, the great wax moth (Galleria mellonella, GWM), a Lepidopteran insect, poses a substantial threat to bee colonies, contributing to a global decline in bee populations. Chlorantraniliprole (CH) is one of the primary insecticide used to control GWM due to its efficacy and low toxicity to bees. To improve beekeeping safety and reduce the risk of GWM developing resistance to prolonged use of CH, we investigated the potential of combining methionine (MET) which has been found to have insecticidal activity against certain Lepidoptera pests, with chlorantraniliprole for use in the apiculture industry. This study assessed the combined effects of MET and CH on GWM and honeybees by employing the maximum concentration of MET (1 %, w/w), previously reported as safe for honeybees, and the practical concentration of CH (1 mg/kg) for GWM control. The results revealed limited acute lethal toxicity of MET to GWM and honeybees, whereas the combined chronic exposure of MET and CH (MIX) led to significant synergistic lethal effects on GWM mortality. Nevertheless, the protective effect of MET on honeybees exposed to CH was significant under chronic exposure. Potential mechanisms underlying the synergistic actions of MET and CH may stem from MET-induced protection of the "Cysteine and methionine" and the "Glycine, serine, and threonine" metabolism pathways. Furthermore, immune stress mitigation was also observed in honeybee immune-related gene transcripts treated by the combination of MET and CH under both acute and chronic exposure. The effects of MET on CH activity in GWM and honeybees are likely due to metabolic regulation. This study suggests the potential of developing MET as a promising biopesticide or protective agent in the future.PMID:37979366 | DOI:10.1016/j.ecoenv.2023.115682

Food Chem. 2023 Nov 11;438:137967. doi: 10.1016/j.foodchem.2023.137967. Online ahead of print.ABSTRACTA comprehensive comparison of metabolomic, lipidomic, and proteomic profiles was conducted between the breast and leg muscles of Shitou goose (STE) and Wuzhong goose (WZE), which exhibit significant variations in body size and growth rate, to evaluate their impact on meat quality. WZE had higher intramuscular fat content in their breast muscles, which were also chewier and had higher drip and cooking losses than STE. Metabolomic analysis revealed differential regulation of amino acid and purine metabolism between WZE and STE. Lipidomic analysis indicated a higher abundance of PE and PC lipid molecules in WZE. Integration of proteomic and metabolomic data highlighted purine metabolism and amino acid biosynthesis as the major distinguishing pathways between STE and WZE. The primary differential pathways between breast and leg muscles were associated with energy metabolism and fatty acid metabolism. This comprehensive analysis provides valuable insights into the distinct meat quality of STE and WZE.PMID:37979274 | DOI:10.1016/j.foodchem.2023.137967

Pregnancy Hypertens. 2023 Nov 16;34:146-151. doi: 10.1016/j.preghy.2023.11.001. Online ahead of print.ABSTRACTOBJECTIVE: To determine whether mitochondrial haplogroups function as disease-modifiers or as susceptibility factors in preeclampsia using a traditional haplogroup association model.METHODS: This retrospective study haplotyped 235 control and 78 preeclamptic pregnancies from Denmark using either real-time PCR or Sanger sequencing depending on the rarity of the haplogroup.RESULTS: No significant association between haplogroups and the risk of preeclampsia was found, nor was any role for haplogroups in disease severity uncovered.CONCLUSION: Mitochondrial haplogroups are not associated with preeclampsia or the severity of preeclampsia in the Danish population. However, this study cannot exclude a role for less common mtDNA variation. Models that can examine these should be applied in preeclamptic patients.PMID:37979242 | DOI:10.1016/j.preghy.2023.11.001

Horm Behav. 2023 Nov 16;157:105453. doi: 10.1016/j.yhbeh.2023.105453. Online ahead of print.ABSTRACTUrban areas are characterised by the presence of sensory pollutants, such as anthropogenic noise and artificial light at night (ALAN). Animals can quickly adapt to novel environmental conditions by adjusting their behaviour, which is proximately regulated by endocrine systems. While endocrine responses to sensory pollution have been widely reported, this has not often been linked to changes in behaviour, hampering the understanding of adaptiveness of endocrine responses. Our aim was, therefore, to investigate the effects of urbanisation, specifically urban noise and light pollution, on hormone levels in male urban and forest túngara frogs (Engystomops pustulosus), a species with reported population divergence in behaviour in response to urbanisation. We quantified testosterone and corticosterone release rates in the field and in the lab before and after exposure to urban noise and/or light. We show that urban and forest frogs differ in their endocrine phenotypes under field as well as lab conditions. Moreover, in urban frogs exposure to urban noise and light led, respectively, to an increase in testosterone and decrease in corticosterone, whereas in forest frogs sensory pollutants did not elicit any endocrine response. Our results show that urbanisation, specifically noise and light pollution, can modulate hormone levels in urban and forest populations differentially. The observed endocrine responses are consistent with the observed behavioural changes in urban frogs, providing a proximate explanation for the presumably adaptive behavioural changes in response to urbanisation.PMID:37979210 | DOI:10.1016/j.yhbeh.2023.105453

J Clin Endocrinol Metab. 2023 Nov 18:dgad675. doi: 10.1210/clinem/dgad675. Online ahead of print.ABSTRACTCONTEXT: Pubertal girls with higher total body fat (TBF) demonstrate higher androgen levels. The cause of this association is unknown but is hypothesized to relate to insulin resistance.OBJECTIVE: To investigate the association between higher TBF and higher androgens in pubertal girls using untargeted metabolomics.METHODS: Serum androgens were determined using a quantitative mass spectrometry-based assay. Metabolomic samples were analyzed using liquid chromatography high-resolution mass spectrometry. Associations between TBF or BMI Z-score (exposure) and metabolomic features (outcome) and between metabolomic features (exposure) and serum hormones (outcome) were examined using gaussian generalized estimating equation models with the outcome lagged by one study visit. Benjamini-Hochberg false discovery rate (FDR) adjusted p-values were calculated to account for multiple testing. RaMP-DB (Relational database of Metabolomic Pathways) was used to conduct enriched pathway analyses among features nominally associated with body composition or hormones.RESULTS: Sixty-six pubertal, pre-menarchal girls (aged 10.9 ± 1.39 SD years; 60% White, 24% Black, 16% Other; 63% normal weight, 37% overweight/obese) contributed an average of 2.29 blood samples. BMI and TBF were negatively associated with most features including raffinose (a plant trisaccharide) and several bile acids. For BMI, RaMP-DB identified many enriched pathways related to bile acids. Androstenedione also showed strong negative associations with raffinose and bile acids.CONCLUSIONS: Metabolomic analyses of samples from pubertal girls did not identify an insulin resistance signature to explain the association between higher TBF and androgens. Instead, we identified potential novel signaling pathways that may involve raffinose or bile acid action at the adrenal gland.PMID:37978828 | DOI:10.1210/clinem/dgad675

Gut Pathog. 2023 Nov 17;15(1):56. doi: 10.1186/s13099-023-00584-7.ABSTRACTBACKGROUND: Gut infections of chickens caused by Ascaridia galli and Heterakis gallinarum are associated with impaired host performance, particularly in high-performing genotypes. Heterakis gallinarum is also a vector of Histomonas meleagridis that is often co-involved with ascarid infections. Here, we provide a first insight into the alteration of the chicken plasma and liver metabolome as a result of gastrointestinal nematode infections with concomitant histomonosis. 1H nuclear magnetic resonance (1H-NMR) based-metabolomics coupled with a bioinformatics analysis was applied to explore the variation in the metabolite profiles of the liver (N = 105) and plasma samples from chickens (N = 108) experimentally infected with A. galli and H. gallinarum (+H. meleagridis). This was compared with uninfected chickens at different weeks post-infection (wpi 2, 4, 6, 10, 14, 18) representing different developmental stages of the worms.RESULTS: A total of 31 and 54 metabolites were quantified in plasma and aqueous liver extracts, respectively. Statistical analysis showed no significant differences (P > 0.05) in any of the 54 identified liver metabolites between infected and uninfected hens. In contrast, 20 plasma metabolites including, amino acids, sugars, and organic acids showed significantly elevated concentrations in the infected hens (P < 0.05). Alterations of plasma metabolites occurred particularly in wpi 2, 6 and 10, covering the pre-patent period of worm infections. Plasma metabolites with the highest variation at these time points included glutamate, succinate, trimethylamine-N-oxide, myo-inositol, and acetate. Differential pathway analysis suggested that infection induced changes in (1) phenylalanine, tyrosine, and tryptophan metabolism, (2) alanine, aspartate and glutamate metabolism; and 3) arginine and proline metabolism (Pathway impact > 0.1 with FDR adjusted P-value < 0.05).CONCLUSION: In conclusion, 1H-NMR based-metabolomics revealed significant alterations in the plasma metabolome of high performing chickens infected with gut pathogens-A. galli and H. gallinarum. The alterations suggested upregulation of key metabolic pathways mainly during the patency of infections. This approach extends our understanding of host interactions with gastrointestinal nematodes at the metabolic level.PMID:37978563 | DOI:10.1186/s13099-023-00584-7

J Anim Sci Biotechnol. 2023 Nov 17;14(1):147. doi: 10.1186/s40104-023-00937-x.ABSTRACTBACKGROUND: Salpingitis is one of the common diseases in laying hen production, which greatly decreases the economic outcome of laying hen farming. Lactiplantibacillus plantarum was effective in preventing local or systemic inflammation, however rare studies were reported on its prevention against salpingitis. This study aimed to investigate the preventive molecular regulatory network of microencapsulated Lactiplantibacillus plantarum (MLP) against salpingitis through multi-omics analysis, including microbiome, transcriptome and metabolome analyses.RESULTS: The results revealed that supplementation of MLP in diet significantly alleviated the inflammation and atrophy of uterus caused by lipopolysaccharide (LPS) in hens (P < 0.05). The concentrations of plasma IL-2 and IL-10 in hens of MLP-LPS group were higher than those in hens of LPS-stimulation group (CN-LPS group) (P < 0.05). The expression levels of TLR2, MYD88, NF-κB, COX2, and TNF-α were significantly decreased in the hens fed diet supplemented with MLP and suffered with LPS stimulation (MLP-LPS group) compared with those in the hens of CN-LPS group (P < 0.05). Differentially expressed genes (DEGs) induced by MLP were involved in inflammation, reproduction, and calcium ion transport. At the genus level, the MLP supplementation significantly increased the abundance of Phascolarctobacterium, whereas decreased the abundance of Candidatus_Saccharimonas in LPS challenged hens (P < 0.05). The metabolites altered by dietary supplementation with MLP were mainly involved in galactose, uronic acid, histidine, pyruvate and primary bile acid metabolism. Dietary supplementation with MLP inversely regulates LPS-induced differential metabolites such as LysoPA (24:0/0:0) (P < 0.05).CONCLUSIONS: In summary, dietary supplementation with microencapsulated Lactiplantibacillus plantarum prevented salpingitis by modulating the abundances of Candidatus_Saccharimonas, Phascolarctobacterium, Ruminococcus_torques_group and Eubacterium_hallii_group while downregulating the levels of plasma metabolites, p-tolyl sulfate, o-cresol and N-acetylhistamine and upregulating S-lactoylglutathione, simultaneously increasing the expressions of CPNE4, CNTN3 and ACAN genes in the uterus, and ultimately inhibiting oviducal inflammation.PMID:37978561 | DOI:10.1186/s40104-023-00937-x

J Transl Med. 2023 Nov 17;21(1):824. doi: 10.1186/s12967-023-04604-7.ABSTRACTBACKGROUND: The morbidity of cancer keeps growing worldwide, and among that, the colorectal cancer (CRC) has jumped to third. Existing early screening tests for CRC are limited. The aim of this study was to develop a diagnostic strategy for CRC by plasma metabolomics.METHODS: A targeted amino acids metabolomics method was developed to quantify 32 plasma amino acids in 130 CRC patients and 216 healthy volunteers, to identify potential biomarkers for CRC, and an independent sample cohort comprising 116 CRC subjects, 33 precancerosiss patients and 195 healthy volunteers was further used to validate the diagnostic model. Amino acids-related genes were retrieved from Gene Expression Omnibus and Molecular Signatures Database and analyzed.RESULTS: Three were chosen out of the 32 plasma amino acids examined. The tryptophan / sarcosine / glutamic acid -based receiver operating characteristic (ROC) curve showed the area under the curve (AUC) of 0.955 (specificity 83.3% and sensitivity 96.8%) for all participants, and the logistic regression model were used to distinguish between early stage (I and II) of CRC and precancerosiss patients, which showed superiority to the commonly used carcinoembryonic antigen. The GO and KEGG enrichment analysis proved many alterations in amino acids metabolic pathways in tumorigenesis.CONCLUSION: This altered plasma amino acid profile could effectively distinguish CRC patients from precancerosiss patients and healthy volunteers with high accuracy. Prognostic tests based on the tryptophan/sarcosine/glutamic acid biomarkers in the large population could assess the clinical significance of CRC early detection and intervention.PMID:37978537 | DOI:10.1186/s12967-023-04604-7

BMC Psychiatry. 2023 Nov 17;23(1):856. doi: 10.1186/s12888-023-05329-z.ABSTRACTBACKGROUND: The brain-gut axis has gained increasing attention due to its contribution to the etiology of various central nervous system disorders. This study aims to elucidate the hypothesis that schizophrenia is associated with disturbances in intestinal microflora and imbalance in intestinal metabolites. By exploring the intricate relationship between the gut and the brain, with the goal of offering fresh perspectives and valuable insights into the potential contribution of intestinal microbial and metabolites dysbiosis to the etiology of schizophrenia.METHODS: In this study, we used a 16S ribosomal RNA (16S rRNA) gene sequence-based approach and an untargeted liquid chromatography-mass spectrometry-based metabolic profiling approach to measure the gut microbiome and microbial metabolites from 44 healthy controls, 41 acute patients, and 39 remission patients, to evaluate whether microbial dysbiosis and microbial metabolite biomarkers were linked with the severity of schizophrenic symptoms.RESULTS: Here, we identified 20 dominant disturbances in the gut microbial composition of patients compared with healthy controls, with 3 orders, 4 families, 9 genera, and 4 species. Several unique bacterial taxa associated with schizophrenia severity. Compared with healthy controls, 145 unusual microflora metabolites were detected in the acute and remission groups, which were mainly involved in environmental information processing, metabolism, organismal systems, and human diseases in the Kyoto encyclopedia of genes and genomes pathway. The Sankey diagram showed that 4 abnormal intestinal and 4 anomalous intestinal microbial metabolites were associated with psychiatric clinical symptoms.CONCLUSIONS: These findings suggest a possible interactive influence of the gut microbiota and their metabolites on the pathophysiology of schizophrenia.PMID:37978477 | DOI:10.1186/s12888-023-05329-z

BMC Psychiatry. 2023 Nov 17;23(1):852. doi: 10.1186/s12888-023-05351-1.ABSTRACTMethamphetamine (MA) abuse is recognized as a brain disorder, and physical activity has clear benefits for MA use disorders. The specific mechanisms by which physical activity alleviates MA use disorders are currently not fully understood. Based on this, the present study used untargeted metabolomics using liquid chromatography-mass spectrometry (LC-MS) to analyze the metabolic changes induced by MA in the brains of mice by exercise intervention. It was found that after 2 weeks of treadmill training, aerobic exercise modulated MA-induced brain metabolic disorders, in which 129 metabolites existed that were significantly differentiated in response to MA induction, and 32 metabolites were significantly affected by exercise. These differential metabolites were mainly enriched in glycerophospholipid metabolism, steroid hormone biosynthesis and degradation, and renin-angiotensin system pathways. To our knowledge, this study is the first to use LC-MS to investigate the effects of aerobic exercise on MA-induced brain metabolic profiling. The findings of this study provide new insights into exercise therapy using MA.PMID:37978352 | DOI:10.1186/s12888-023-05351-1

Sci Rep. 2023 Nov 17;13(1):20167. doi: 10.1038/s41598-023-46416-1.ABSTRACTVolatile organic compounds (VOCs) comprise a diverse range of metabolites with high vapour pressure and low boiling points. Although they have received attention, they are a largely unexplored part of the metabolome. Previous studies have shown that malaria infections produce characteristic, definitive, and detectable volatile signatures. Many transcriptional and metabolic differences are observed at different stages of the parasite Intraerythrocytic Developmental Cycle (IDC) as well as when artemisinin-resistant parasites are put under drug pressure. This prompted our research to characterize whether these responses are reflected at a volatile level in malaria during the IDC stages using gas chromatography-mass spectrometry. We investigated whether the resistant P. falciparum parasites would produce their own characteristic volatilome profile compared to near-isogenic wild-type parasite in vitro; firstly at three different stages of the IDC and secondly in the presence or absence of artemisinin drug treatment. Finally, we explored the VOC profiles from two media environments (Human serum and Albumax) of recently lab-adapted field parasite isolates, from Southeast Asia and West/East Africa, compared to long-term lab-adapted parasites. Recognizable differences were observed between IDC stages, with schizonts having the largest difference between wild type and resistant parasites, and with cyclohexanol and 2,5,5-trimethylheptane only present for resistant schizonts. Artemisinin treatment had little effect on the resistant parasite VOC profile, whilst for the wild type parasites compounds ethylbenzene and nonanal were greatly affected. Lastly, differing culturing conditions had an observable impact on parasite VOC profile and clustering patterns of parasites were specific to geographic origin. The results presented here provide the foundation for future studies on VOC based characterization of P. falciparum strains differing in abilities to tolerate artemisinin.PMID:37978324 | DOI:10.1038/s41598-023-46416-1

Nat Prod Res. 2023 Nov 17:1-11. doi: 10.1080/14786419.2023.2280171. Online ahead of print.ABSTRACTA rapid untargeted UHPLC-Q-TOF-ESI-MS/MS-Based metabolomic profiling of the medicinal plant Entada abyssinica was performed. A total of 18 metabolites were detected, of which 10 could not be identified. Based on this result, an extensive chemical investigation of the CH2Cl2-MeOH (1:1) extract of this plant was carried out, leading to the isolation of a new ceramide, named entadamide (1), together with nine known compounds: monomethyl kolavate (2), 24-hydroxytormentic acid (3) chondrillasterol (4), 3-O-β-D glucopyranosylstigmasterol (5), 3-O-β-D glucopyranosylsitosterol (6), quercetin 3'-methylether (7), 2,3-dihydroxypropyl icosanoate (8), 2,3-dihydroxy-propyl 23-hydroxytricosanoate (9) and 2,3-dihydroxy-propyl 24-hydroxytetracosanoate (10). Their structures were elucidated by the analyses of their spectroscopic and spectrometric data (1D and 2D NMR, and HRESI-MS) in comparison with those reported in the literature. Furthermore, the crude extract and some isolated compounds were tested against non-ciprofloxacin resistant strains viz, Pseudomonas aeruginosa (ATCC 27853), Escherichia coli (ATCC 25922), Samonella thyphi (ATCC 19430) and Samonella enterica (NR4294). The tested samples demonstrated significant activity against all the tested bacteria (MIC values: 3.12-12.5 μg/mL).PMID:37977828 | DOI:10.1080/14786419.2023.2280171

Anal Chim Acta. 2023 Dec 1;1283:341897. doi: 10.1016/j.aca.2023.341897. Epub 2023 Oct 15.ABSTRACTBACKGROUND: Breast fibroadenomas and phyllodes tumors are both fibroepithelial tumors with comparable histological characteristics. However, rapid and precise differential diagnosis is a tough point in clinical pathology. Given the tendency of phyllodes tumors to recur, the difficulty in differential diagnosis with fibroadenomas leads to the difficulty in optimal management for these patients.METHOD: In this study, we used Raman spectroscopy to differentiate phyllodes tumors from breast fibroadenomas based on the biochemical and metabolic composition and develop a classification model. The model was validated by 5-fold cross-validation in the training set and tested in an independent test set. The potential metabolic differences between the two types of tumors observed in Raman spectroscopy were confirmed by targeted metabolomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS).RESULTS: A total of 204 patients with formalin-fixed paraffin-embedded (FFPE) tissue samples, including 100 fibroadenomas and 104 phyllodes tumors were recruited from April 2014 to August 2021. All patients were randomly divided into the training cohort (n = 153) and the test cohort (n = 51). The Raman classification model could differentiate phyllodes tumor versus fibroadenoma with cross-validation accuracy, sensitivity, precision, and area under curve (AUC) of 85.58 % ± 1.77 %, 83.82 % ± 1.01 %, 87.65 % ± 4.22 %, and 93.18 % ± 1.98 %, respectively. When tested in the independent test set, it performed well with the test accuracy, sensitivity, specificity, and AUC of 83.50 %, 86.54 %, 80.39 %, and 90.71 %. Furthermore, the AUC was significantly higher for the Raman model than that for ultrasound (P = 0.0017) and frozen section diagnosis (P < 0.0001). When it came to much more difficult diagnosis between fibroadenoma and benign or small-size phyllodes tumor for pathological examination, the Raman model was capable of differentiating with AUC up to 97.45 % and 95.61 %, respectively. On the other hand, targeted metabolomic analysis, based on fresh-frozen tissue samples, confirmed the differential metabolites (including thymine, dihydrothymine, trans-4-hydroxy-l-proline, etc.) identified from Raman spectra between phyllodes tumor and fibroadenoma.SIGNIFICANCE AND NOVELTY: In this study, we obtained the molecular information map of breast phyllodes tumors provided by Raman spectroscopy for the first time. We identified a novel Raman fingerprint signature with the potential to precisely characterize and distinguish phyllodes tumors from fibroadenoma as a quick and accurate diagnostic tool. Raman spectroscopy is expected to further guide the precise diagnosis and optimal treatment of breast fibroepithelial tumors in the future.PMID:37977771 | DOI:10.1016/j.aca.2023.341897

J Biomed Res. 2023 Nov 15:418-430. doi: 10.7555/JBR.37.20230085. Online ahead of print.ABSTRACTHepatocellular carcinoma (HCC) is a highly heterogeneous malignancy and lacks effective treatment. Bulk-sequencing of different gene transcripts by comparing HCC tissues and adjacent normal tissues provides some clues for investigating the mechanisms or identifying potential targets for tumor progression. However, genes that are exclusively expressed in a subpopulation of HCC may not be enriched or detected through such a screening. In the current study, we performed a single cell-clone-based screening and identified galectin-14 as an essential molecule in the regulation of tumor growth. The aberrant expression of galectin-14 was significantly associated with a poor overall survival of liver cancer patients with database analysis. Knocking down galectin-14 inhibited the proliferation of tumor growth, whereas overexpressing galectin-14 promoted tumor growth in vivo. Non-targeted metabolomics analysis indicated that knocking down galectin-14 decreased glycometabolism; specifically that glycoside synthesis was significantly changed. Further study found that galectin-14 promoted the expression of cell surface heparan sulfate proteoglycans (HSPGs) that functioned as co-receptors, thereby increasing the responsiveness of HCC cells to growth factors, such as epidermal growth factor and transforming growth factor-alpha. In conclusion, the current study identifies a novel HCC-specific molecule galectin-14, which increases the expression of cell surface HSPGs and the uptake of growth factors to promote HCC cell proliferation.PMID:37977559 | DOI:10.7555/JBR.37.20230085

Sci Total Environ. 2023 Nov 15:168649. doi: 10.1016/j.scitotenv.2023.168649. Online ahead of print.ABSTRACTPerfluorooctane sulfonate (PFOS) alternatives are chemicals that are used to make a range of products. Researchers have found that PFOS alternatives are probably no less toxic than PFOS, which has aroused concern. It has also revealed that the pancreas may be harmed by exposure to PFOS alternatives. However, there is insufficient evidence to demonstrate the toxicity mechanisms of PFOS alternatives. This study demonstrates the adverse effects of three PFOS alternatives on the pancreatic health of mice. After subchronic exposure to PFOS alternatives at environmentally relevant concentrations (800 μg/L perfluorohexanesulfonate, 800 μg/L perfluorobutanesulfonate, and 3 μg/L sodium ρ-perfluorous nonenoxybenzene sulfonate) via drinking water for 6 weeks, toxicity mechanisms were elucidated by examining histopathology, immunity, endoplasmic reticulum stress, 16S rRNA, and short-chain fatty acid targeted metabolomics. Sodium ρ-perfluorous nonenoxybenzene sulfonate significantly increased levels of TNF-α, IL-6, p-PERK, and ATF-4 and decreased the abundance of Akkermansia muciniphila and Lactobacillus reuteri. In addition, the three PFOS alternatives changed the composition of the gut microbiota in mice. Short-chain fatty acids, which are metabolites of the gut microbiota, also significantly decreased. Correlation analysis demonstrates that the alteration of gut microbes is related to the adverse effects on the mice pancreas. Results suggest that the murine pancreas may be toxic endpoints of PFOS alternatives. This study alerts the threats to human health and accelerates the toxicology research of an increasing number of emerging PFOS alternatives.PMID:37977398 | DOI:10.1016/j.scitotenv.2023.168649

Comp Biochem Physiol C Toxicol Pharmacol. 2023 Nov 15:109786. doi: 10.1016/j.cbpc.2023.109786. Online ahead of print.ABSTRACTClimate change and other factors have contributed to an increased frequency and intensity of global wildfires in recent years. Ammonium-based fire retardants are widely used to suppress or delay the spread of fire and have generally been regarded as presenting a low risk of acute toxicity to fauna. However, studies have raised concerns about their potential to cause indirect or sub-lethal effects, and toxicity information regarding the potential for such impacts in aquatic species is limited. To address these knowledge gaps, we used an untargeted metabolomics approach to evaluate the sub-lethal physiological and metabolic responses of striped marsh frog (Limnodynastes peronii) tadpoles exposed to a concentration gradient of the ammonium polyphosphate (APP)-based fire retardant Phos-Chek LC95W (PC). Acute exposure (96 h) to PC significantly altered the relative abundance of 14 metabolites in whole tadpoles. The overall metabolic response pattern was consistent with effects reported for ammonia toxicity and also suggestive of energy dysregulation and osmotic stress associated with alterations to physicochemical water quality parameters in the PC treatments. Results suggest that run-off or accidental application of this formulation into waterways can have significant sub-lethal consequences on the biochemical profiles (i.e., the metabolome) of aquatic organisms and may be a concern for frog species that breed and develop in small, often ephemeral, waterbodies. Our study highlights the benefits of integrating untargeted metabolomics with other ecological and toxicological endpoints to provide a more holistic characterisation of the sub-lethal impacts associated with bushfire-fighting chemicals and with environmental contaminants more broadly.PMID:37977239 | DOI:10.1016/j.cbpc.2023.109786

Clin Chim Acta. 2023 Nov 15:117655. doi: 10.1016/j.cca.2023.117655. Online ahead of print.ABSTRACTMetabolomics has become a promising method for understanding pathological mechanisms. Plasma (PLS) is the most common sample type used for metabolomics studies, and dried blood spot (DBS) sampling has been regarded as a good strategy due to its unique characteristics. However, how results obtained from DBS can be correlated to results obtained from PLS remains unclear. To bridge the results and to investigate the feasibility of using DBS to study metabolomics, we performed a comparative study using 64 paired PLS and DBS samples. The number of features extracted from the two different sample types was investigated. The concentration correlations of the identified metabolites between the DBS and PLS were individually studied. Approximately 47% showed a strong correlation, 19% showed a moderate correlation, and 34% showed a low or even negligible correlation. Finally, we applied both PLS- and DBS-based metabolomics to explore the dysregulated metabolites in diabetes mellitus (DM) patients. Thirty-two non-DM subjects and 32 DM patients were enrolled, and 2 significant metabolites were found in both PLS and DBS samples. In summary, detailed correlation information between PLS and DBS metabolites was first explored in this study, and it is anticipated that these results could facilitate future applications in DBS-based metabolomics.PMID:37977234 | DOI:10.1016/j.cca.2023.117655

Semin Cell Dev Biol. 2023 Nov 15;156:11-21. doi: 10.1016/j.semcdb.2023.10.007. Online ahead of print.ABSTRACTThe successful treatment of oncological malignancies which results in long-term disease control or the complete eradication of cancerous cells necessitates the onset of adaptive immune responses targeting tumor-specific antigens. Such desirable anticancer immunity can be triggered via the induction of immunogenic cell death (ICD) of cancer cells, thus converting malignant cells into an in situ vaccine that elicits T cell mediated adaptive immune responses and establishes durable immunological memory. The exploration of ICD for cancer treatment has been subject to extensive research. However, functional heterogeneity among ICD activating therapies in many cases requires specific co-medications to achieve full-blown efficacy. Here, we described the hallmarks of ICD and classify ICD activators into three distinct functional categories namely, according to their mode of action: (i) ICD inducers, which increase the immunogenicity of malignant cells, (ii) ICD sensitizers, which prime cellular circuitries for ICD induction by conventional cytotoxic agents, and (iii) ICD enhancers, which improve the perception of ICD signals by antigen presenting dendritic cells. Altogether, ICD induction, sensitization and enhancement offer the possibility to convert well-established conventional anticancer therapies into immunotherapeutic approaches that activate T cell-mediated anticancer immunity.PMID:37977108 | DOI:10.1016/j.semcdb.2023.10.007