PubMed

Metabolites. 2024 Jun 30;14(7):372. doi: 10.3390/metabo14070372.ABSTRACTDiabetes mellitus is considered to be the most common health issue affecting almost 1 in 11 adults globally. Oral health complications including xerostomia, periodontal disease, dental caries, and soft tissue lesions are prevalent among individuals with diabetes, and therefore an understanding of the potential association between salivary metabolites and dental caries progression would enable the early detection and prevention of this non-communicable disease. Therefore, the aim of this study was to compare salivary biomarkers between individuals with type 2 diabetes (T2DM) with those without this disorder (ND) using 1H NMR-based metabolomics strategies. The objectives were to identify T2DM-associated biomarker signatures and their potential impact on dental caries. In addition, HbA1c and vitamin D levels were also analysed for this purpose.METHODS: Stimulated whole-mouth saliva (SWS) samples were collected from T2DM and ND (n = 30 in each case) participants randomly selected from a group of 128 participants recruited for this case-control study. All participants were advised to refrain from eating, drinking, and smoking for at least 1-2 h prior to sample collection. Following preparation, SWS supernatants underwent 1H NMR analysis at an operating frequency of 800 MHz, and the dataset acquired was analysed using a range of multivariate metabolomics techniques.RESULTS: Metabolomics analysis of data acquired demonstrated that, together with up- and downregulated blood HbA1c and vitamin D levels, key salivary discriminators between these two classifications included lactate, taurine, creatinine, α-glucose, and formate to a lesser extent. The bacterial catabolites lactate and formate were both significantly upregulated in the T2DM group, and these have previously been implicated in the pathogenesis of dental caries. Significance analysis of metabolites (SAM)-facilitated AUROC analysis yielded an 83% accuracy for this distinction.CONCLUSION: In conclusion, this study highlights the significant differences in salivary metabolites between individuals with T2DM and healthy controls. Such differences appear to be related to the development and progression of dental caries in T2DM patients.PMID:39057695 | DOI:10.3390/metabo14070372

Metabolites. 2024 Jun 28;14(7):367. doi: 10.3390/metabo14070367.ABSTRACTConventional diagnostic tools for prostate cancer (PCa), such as prostate-specific antigen (PSA), transrectal ultrasound (TRUS), digital rectal examination (DRE), and tissue biopsy face, limitations in individual risk stratification due to invasiveness or reliability issues. Liquid biopsy is a less invasive and more accurate alternative. Metabolomic analysis of extracellular vesicles (EVs) holds a promise for detecting non-genetic alterations and biomarkers in PCa diagnosis and risk assessment. The current research gap in PCa lies in the lack of accurate biomarkers for early diagnosis and real-time monitoring of cancer progression or metastasis. Establishing a suitable approach for observing dynamic EV metabolic alterations that often occur earlier than being detectable by other omics technologies makes metabolomics valuable for early diagnosis and monitoring of PCa. Using four distinct metabolite extraction approaches, the metabolite cargo of PC3-derived large extracellular vesicles (lEVs) was evaluated using a combination of methanol, cell shearing using microbeads, and size exclusion filtration, as well as two fractionation chemistries (pHILIC and C18 chromatography) that are also examined. The unfiltered methanol-microbeads approach (MB-UF), followed by pHILIC LC-MS/MS for EV metabolite extraction and analysis, is effective. Identified metabolites such as L-glutamic acid, pyruvic acid, lactic acid, and methylmalonic acid have important links to PCa and are discussed. Our study, for the first time, has comprehensively evaluated the extraction and separation methods with a view to downstream sample integrity across omics platforms, and it presents an optimised protocol for EV metabolomics in PCa biomarker discovery.PMID:39057690 | DOI:10.3390/metabo14070367

Metabolites. 2024 Jun 26;14(7):360. doi: 10.3390/metabo14070360.ABSTRACTLC-MS/MS analyses have been reported as challenging for the reliable separation and quantification of cyanogenic glycosides (CNGs), especially (R)-prunasin and sambunigrin isomers found in American elderberry (Sambucus nigra L. subsp. canadensis (L.) Bolli). Hence, a novel multiple reaction monitoring (MRM)-based ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated in the present study for simultaneous separation and quantification of five CNGs, including amygdalin, dhurrin, linamarin, (R)-prunasin, and (S)-prunasin (commonly referred to as sambunigrin). Initially, the role of ammonium formate was investigated as an aqueous mobile-phase additive in developing MRM-based UHPLC-MS/MS. Later, chromatographic conditions for the resolved separation of (R)-prunasin and sambunigrin were identified. Validation studies confirmed that the developed method has good linearity and acceptable precision and accuracy. A noticeable matrix effect (mainly signal enhancement) was observed in leaf samples only. This method was used to detect and quantify CNGs, including (R)-prunasin and sambunigrin, in leaf and fruit samples of American elderberry. Among the studied CNGs, only (R)-prunasin was detected in the leaf samples. Interestingly, (S)-prunasin (sambunigrin) was not detected in the samples analyzed, even though it has been previously reported in elderberry species.PMID:39057683 | DOI:10.3390/metabo14070360

Metabolites. 2024 Jun 26;14(7):359. doi: 10.3390/metabo14070359.ABSTRACTWheat bran (WB) is a low-value by-product of the wheat milling industry. Solid-state fermentation with Rhizopus oligosporus is performed to improve WB's nutritional quality (RH). Twenty-five mice (11-week-old C57BL/6N male mice) were divided into three groups. The first group was fed a control diet (n = 8), the second group a 10% WB-supplemented diet (n = 8), and the last group had a 10% RH-supplemented diet (n = 9). The diet treatment was administered for 4 days before dextran sodium sulfate (DSS, 3% in drinking water) was administered for 9 days. RH supplementation prevented bodyweight loss and reduced the disease activity index in mice. An increase in the level of SCFAs in mouse intestines was detected post-RH supplementation, suggesting that SCFAs might have contributed to its anti-colitis effect. Metabolome analysis was conducted to explore other bioactive compounds in RH. R. oligosporus fermentation significantly increased the amounts of ergothioneine, arginine, branched-chain amino acids, and adenosine in wheat bran. All of these compounds are known to have antioxidant and anti-inflammatory capacities. These bioactive compounds might also have contributed to the RH's ability to ameliorate DSS-induced colitis.PMID:39057682 | DOI:10.3390/metabo14070359

Metabolites. 2024 Jun 23;14(7):356. doi: 10.3390/metabo14070356.ABSTRACTAmyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease type of motor neuron disorder characterized by degeneration of the upper and lower motor neurons resulting in dysfunction of the somatic muscles of the body. The ALS condition is manifested in progressive skeletal muscle atrophy and spasticity. It leads to death, mostly due to respiratory failure. Within the pathophysiology of the disease, muscle energy metabolism seems to be an important part. In our study, we used blood plasma from 25 patients with ALS diagnosed by definitive El Escorial criteria according to ALSFR-R (Revised Amyotrophic Lateral Sclerosis Functional Rating Scale) criteria and 25 age and sex-matched subjects. Aside from standard clinical biochemical parameters, we used the NMR (nuclear magnetic resonance) metabolomics approach to determine relative plasma levels of metabolites. We observed a decrease in total protein level in blood; however, despite accelerated skeletal muscle catabolism characteristic for ALS patients, we did not detect changes in plasma levels of essential amino acids. When focused on alterations in energy metabolism within muscle, compromised creatine uptake was accompanied by decreased plasma creatinine. We did not observe changes in plasma levels of BCAAs (branched chain amino acids; leucine, isoleucine, valine); however, the observed decrease in plasma levels of all three BCKAs (branched chain alpha-keto acids derived from BCAAs) suggests enhanced utilization of BCKAs as energy substrate. Glutamine, found to be increased in blood plasma in ALS patients, besides serving for ammonia detoxification, could also be considered a potential TCA (tricarboxylic acid) cycle contributor in times of decreased pyruvate utilization. When analyzing the data by using a cross-validated Random Forest algorithm, it finished with an AUC of 0.92, oob error of 8%, and an MCC (Matthew's correlation coefficient) of 0.84 when relative plasma levels of metabolites were used as input variables. Although the discriminatory power of the system used was promising, additional features are needed to create a robust discriminatory model.PMID:39057679 | DOI:10.3390/metabo14070356

Metabolites. 2024 Jun 23;14(7):354. doi: 10.3390/metabo14070354.ABSTRACTTo investigate the dynamic changes in hippocampal metabolism after microwave radiation using liquid chromatography in tandem with mass spectrometry/mass spectrometry (LC-MS/MS) and to identify potential biomarkers. Wistar rats were randomly assigned to a sham group and a microwave radiation group. The rats in the microwave radiation group were exposed to 2.856 GHz for 15 min for three times, with 5 min intervals. The rats in the sham group were not exposed. Transmission electron microscope revealed blurring of the synaptic cleft and postsynaptic dense thickening in hippocampal neurons after microwave radiation. Metabolomic analysis revealed 38, 24, and 39 differentially abundant metabolites at 3, 7, and 14 days after radiation, respectively, and the abundance of 9 metabolites, such as argininosuccinic acid, was continuously decreased. After microwave radiation, the abundance of metabolites such as argininosuccinic acid was successively decreased, indicating that these metabolites could be potential biomarkers for hippocampal tissue injury.PMID:39057677 | DOI:10.3390/metabo14070354

Metabolites. 2024 Jun 22;14(7):351. doi: 10.3390/metabo14070351.ABSTRACTIn the conducted research, a murine model for ulcerative colitis (UC) was established utilizing dextran sodium sulfate (DSS) to investigate the therapeutic potential of dandelion root polysaccharide extracts on this disease. This study employed an analysis of gut microbiota composition and serum metabolomics to understand the biochemical effects of these polysaccharides. Sequencing of the 16S ribosomal DNA component indicated an increased presence of Bacteroides in the DSS-treated model group, contrasting with a significant enhancement in Faecalibaculum populations in mice treated with dandelion root polysaccharides (DPs). This shift suggests a pivotal role of DPs in elevating fecal N-butyric acid levels-a crucial factor in the maintenance of gut microbiota equilibrium. Through metabolomic profiling of serum, this research identified distinct metabolic changes across the control, DSS model, and DP treatment groups, highlighting four major differential metabolites: (2S)-2-amino-3-[[(2R)-2-butanoyloxy-3-propanoyloxypropoxy]-hydroxyphosphoryl]oxypropanoic acid; (1R,8S,9S)-3,4-dihydroxy-8-methoxy-11,11-dimethyl-5-propan-2-yl-16-oxatetracyclo [7.5.2.01,10.02,7]hexadeca-2,4,6-trien-15-one; Aspartylasparagine; and Nap-Phe-OH. These metabolites are implicated in mitigating oxidative stress, suggesting that DPs facilitate a protective mechanism for the intestinal lining through various biochemical pathways. Additionally, a notable correlation was established between the altered gut microbiota and the serum metabolomic profiles, underscoring the intricate interplay between these two biological systems in the context of UC. This study's outcomes illustrate that UC induces significant alterations in both gut microbiota and metabolic signatures, whereas dandelion root polysaccharides exhibit a profound ameliorative effect on these disruptions. This investigation underscores the therapeutic promise of dandelion root polysaccharides in the management of UC by modulating gut microbiota and metabolic pathways.PMID:39057673 | DOI:10.3390/metabo14070351

Metabolites. 2024 Jun 21;14(7):349. doi: 10.3390/metabo14070349.ABSTRACTSulfur mustard (SM) is a highly potent alkylating vesicant agent and remains a relevant threat to both civilians and military personnel. The eyes are the most sensitive organ after airborne SM exposure, causing ocular injuries with no antidote or specific therapeutics available. In order to identify relevant biomarkers and to obtain a deeper understanding of the underlying biochemical events, we performed an untargeted metabolomics analysis using liquid chromatography coupled to high-resolution mass spectrometry of plasma samples from New Zealand white rabbits ocularly exposed to vapors of SM. Metabolic profiles (332 unique metabolites) from SM-exposed (n = 16) and unexposed rabbits (n = 8) were compared at different time intervals from 1 to 28 days. The observed time-dependent changes in metabolic profiles highlighted the profound dysregulation of the sulfur amino acids, the phenylalanine, the tyrosine and tryptophan pathway, and the polyamine and purine biosynthesis, which could reflect antioxidant and anti-inflammatory activities. Taurine and 3,4-dihydroxy-phenylalanine (Dopa) seem to be specifically related to SM exposure and correspond well with the different phases of ocular damage, while the dysregulation of adenosine, polyamines, and acylcarnitines might be related to ocular neovascularization. Additionally, neither cysteine, N-acetylcysteine, or guanine SM adducts were detected in the plasma of exposed rabbits at any time point. Overall, our study provides an unprecedented view of the plasma metabolic changes post-SM ocular exposure, which may open up the development of potential new treatment strategies.PMID:39057672 | DOI:10.3390/metabo14070349

Mar Drugs. 2024 Jul 18;22(7):320. doi: 10.3390/md22070320.ABSTRACTEpiphytic diatoms growing in Mediterranean seagrass meadows, particularly those of the genus Cocconeis, are abundant and ecologically significant, even in naturally acidified environments. One intriguing aspect of some benthic diatoms is their production of an unidentified cell-death-promoting compound, which induces destruction of the androgenic gland in Hippolyte inermis Leach, 1816, a shrimp exhibiting protandric hermaphroditism, principally under normal environmental pH levels. The consumption of Cocconeis spp. by this shrimp is vital for maintaining the stability of its natural populations. Although many attempts have been made to reveal the identity of the apoptotic compound, it is still unknown. In this study, we strategically integrated a bioactivity-based fractionation, a metabolomic approach, and two different experimental avenues to identify potential apoptotic metabolites from Cocconeis scutellum var. parva responsible for the sex reversal in H. inermis. Our integrated analysis uncovered two potential candidate metabolites, one putatively identified as a lysophosphatidylglycerol (LPG) (16:1) and the other classified as a fatty acid ester. This is the first time LPG (16:1) has been reported in C. scutellum var. parva and associated with cell-death processes. These candidate metabolites mark substantial progress in elucidating the factors responsible for triggering the removal of the androgenic gland in the early post-larval phases of H. inermis.PMID:39057429 | DOI:10.3390/md22070320

Mar Drugs. 2024 Jun 28;22(7):302. doi: 10.3390/md22070302.ABSTRACTThe marine Streptomyces harbor numerous biosynthetic gene clusters (BGCs) with exploitable potential. However, many secondary metabolites cannot be produced under laboratory conditions. Co-culture strategies of marine microorganisms have yielded novel natural products with diverse biological activities. In this study, we explored the metabolic profiles of co-cultures involving Streptomyces sp. 2-85 and Cladosporium sp. 3-22-derived from marine sponges. Combining Global Natural Products Social (GNPS) Molecular Networking analysis with natural product database mining, 35 potential antimicrobial metabolites annotated were detected, 19 of which were exclusive to the co-culture, with a significant increase in production. Notably, the Streptomyces-Fungus interaction led to the increased production of borrelidin and the discovery of several analogs via molecular networking. In this study, borrelidin was first applied to combat Saprolegnia parasitica, which caused saprolegniosis in aquaculture. We noted its superior inhibitory effects on mycelial growth with an EC50 of 0.004 mg/mL and on spore germination with an EC50 of 0.005 mg/mL compared to the commercial fungicide, preliminarily identifying threonyl-tRNA synthetase as its target. Further analysis of the associated gene clusters revealed an incomplete synthesis pathway with missing malonyl-CoA units for condensation within this strain, hinting at the presence of potential compensatory pathways. In conclusion, our findings shed light on the metabolic changes of marine Streptomyces and fungi in co-culture, propose the potential of borrelidin in the control of aquatic diseases, and present new prospects for antifungal applications.PMID:39057412 | DOI:10.3390/md22070302

J Fungi (Basel). 2024 Jul 19;10(7):500. doi: 10.3390/jof10070500.ABSTRACTMonascus pigments (MPs) and monacolin K (MK) are important secondary metabolites produced by Monascus spp. This study aimed to investigate the effect of soybean protein isolate (SPI) on the biosynthesis of MPs and MK based on the analysis of physiological indicators, transcriptomes, and metabolomes. The results indicated that the growth, yellow MPs, and MK production of Monascus pilosus MS-1 were significantly enhanced by SPI, which were 8.20, 8.01, and 1.91 times higher than that of the control, respectively. The utilization of a nitrogen source, protease activity, the production and utilization of soluble protein, polypeptides, and free amino acids were also promoted by SPI. The transcriptomic analysis revealed that the genes mokA, mokB, mokC, mokD, mokE, mokI, and mokH which are involved in MK biosynthesis were significantly up-regulated by SPI. Moreover, the glycolysis/gluconeogenesis, pyruvate metabolism, fatty acid degradation, tricarboxylic acid (TCA) cycle, and amino acid metabolism were effectively up-regulated by SPI. The metabolomic analysis indicated that metabolisms of amino acid, lipid, pyruvate, TCA cycle, glycolysis/gluconeogenesis, starch and sucrose, and pentose phosphate pathway were significantly disturbed by SPI. Thus, MPs and MK production promoted by SPI were mainly attributed to the increased biomass, up-regulated gene expression level, and more precursors and energies.PMID:39057385 | DOI:10.3390/jof10070500

J Fungi (Basel). 2024 Jul 9;10(7):471. doi: 10.3390/jof10070471.ABSTRACTBlack rot (Guignardia bidwellii) and downy mildew (Plasmopara viticola) are two major grapevine diseases against which the development of efficient biocontrol solutions is required in a context of sustainable viticulture. This study aimed at evaluating and comparing the efficacy and modes of action of bacterial culture supernatants from Bacillus velezensis Buz14 and B. ginsengihumi S38. Both biocontrol agents (BCA) were previously demonstrated as highly effective against Botrytis cinerea in grapevines. In semi-controlled conditions, both supernatants provided significant protection against black rot and downy mildew. They exhibited antibiosis against the pathogens by significantly decreasing G. bidwellii mycelial growth, but also the release and motility of P. viticola zoospores. They also significantly induced grapevine defences, as stilbene production. The LB medium, used for the bacterial cultures, also showed partial effects against both pathogens and induced plant defences. This is discussed in terms of choice of experimental controls when studying the biological activity of BCA supernatants. Thus, we identified two bacterial culture supernatants as new potential biocontrol products exhibiting multi-spectrum antagonist activity against different grapevine key pathogens and having a dual mode of action.PMID:39057356 | DOI:10.3390/jof10070471

Insects. 2024 Jul 6;15(7):507. doi: 10.3390/insects15070507.ABSTRACTThis study examines the phenotypic differences between wild-derived F2 Central Valley mosquitoes and the insecticide-susceptible Rockefeller (Rock) lab strain of Ae. aegypti. Given the rarity of wild pyrethroid-susceptible populations, the focus of this work is to develop an understanding of the resistance physiology in this invasive mosquito population and explore the potential of metabolites as diagnostic biomarkers for metabolic resistance. This study utilizes metabolomic, gene expression, and lifespan data for a comparison between strains. The findings indicate that wild-derived mosquitoes with greater metabolic resistance have a lifespan sensitivity to restricted larval nutrition. In terms of metabolism and gene expression, Central Valley mosquitoes show increased activity in oxidoreductase, glutathione metabolism, and the pentose phosphate pathway. Conversely, Rock mosquitoes display signs of metabolic inefficiency and mitochondrial dysregulation, likely tolerated due to the consistency and nutritional abundance of a controlled lab environment. The study also examines Ae. aegypti P450 and GSTE profiles in relation to other insecticide-resistant groups. While metabolomic data can differentiate our study groups, the challenges in biomarker development arise from few detected markers meeting high fold change thresholds.PMID:39057240 | DOI:10.3390/insects15070507

Curr Issues Mol Biol. 2024 Jul 4;46(7):6960. doi: 10.3390/cimb46070415.ABSTRACTAfiq Adham Abd Rasib and Roohaida Othman were not included as authors in the original publication [...].PMID:39057102 | DOI:10.3390/cimb46070415

Curr Issues Mol Biol. 2024 Jul 13;46(7):7430-7446. doi: 10.3390/cimb46070441.ABSTRACTObesity is marked by excessive fat accumulation in the adipose tissue, which disrupts metabolic processes and causes chronic systemic inflammation. Commonly, body mass index (BMI) is used to assess obesity-related risks, predicting potential metabolic disorders. However, for a better clustering of obese patients, we must consider molecular and epigenetic changes which may be responsible for inflammation and metabolic changes. Our study involved two groups of patients, obese and healthy donors, on which routine analysis were performed, focused on BMI, leukocytes count, and C-reactive protein (CRP) and completed with global DNA methylation and gene expression analysis for genes involved in inflammation and adipogenesis. Our results indicate that obese patients exhibited elevated leukocytes levels, along with increased BMI and CRP. The obese group revealed a global hypomethylation and upregulation of proinflammatory genes, with adipogenesis genes following the same trend of being overexpressed. The study confirms that obesity is linked to systematic inflammation and metabolic dysfunction through epigenetic and molecular alterations. The CRP was correlated with the hypomethylation status in obese patients, and this fact may contribute to a better understanding of the roles of specific genes in adipogenesis and inflammation, leading to a better personalized therapy.PMID:39057082 | DOI:10.3390/cimb46070441

Curr Issues Mol Biol. 2024 Jun 26;46(7):6390-6406. doi: 10.3390/cimb46070382.ABSTRACTAmidst the burgeoning interest in rotating magnetic fields (RMF) within biological research, there remains a notable gap in the scientific evidence concerning the long-term safety of RMF. Thus, this study aimed to investigate the safety of protracted exposure to a 0.2 T, 4 Hz RMF over 10 months in mice. Two-month-old female C57BL/6 mice were randomly allocated to either the RMF group (exposed to 0.2 T, 4 Hz real RMF) or the SHAM group (exposed to 0 T, 4 Hz sham RMF). Throughout the experiment, the murine weekly body weights were recorded, and their behavioral traits were assessed via open field tests. In the final month, a comprehensive evaluation of the murine overall health was conducted, encompassing analyses of blood parameters, histomorphological examination of major organs, and skeletal assessments using X-ray and micro-CT imaging. The murine immune system and lipid metabolism were evaluated through immunochip analysis and metabolomics. Notably, no discernible adverse effects with RMF exposure were observed. Murine body weight, locomotor behavior, organ histomorphology, and skeletal health remained unaffected by RMF. Blood analysis revealed subtle changes in hormone and lipid levels between the SHAM and RMF groups, yet these differences did not reach statistical significance. Moreover, RMF led to elevated serum interleukin-28 (IL-28) levels, albeit within the normal range, and modest alterations in serum lipid metabolites. Conclusively, mice exposed to the 0.2 T, 4 Hz RMF for 10 months displayed no significant signs of chronic toxicity, indicating its potential clinical application as a physical therapy.PMID:39057024 | DOI:10.3390/cimb46070382

Environ Toxicol Chem. 2024 Jul 26. doi: 10.1002/etc.5960. Online ahead of print.ABSTRACTTraditional approaches for monitoring aquatic pollution primarily rely on chemical analysis and the detection of pollutants in the aqueous environments. However, these methods lack realism and mechanistic insight and, thus, are increasingly supported by effect-based methods, which offer sensitive endpoints. In this context, daphnids, a freshwater species used extensively in molecular ecotoxicology, offer fast and noninvasive approaches to assess the impact of pollutants. Among the phenotypic endpoints used, feeding rate is a highly sensitive approach because it provides evidence of physiological alterations even in sublethal concentrations. However, there has been no standardized method for measuring feeding rate in daphnids, and several approaches follow different protocols. There is a diversity among tests employing large volumes, extensive incubation times, and high animal densities, which in turn utilize measurements of algae via fluorescence, radiolabeling, or counting ingested cells. These tests are challenging and laborious and sometimes require cumbersome instrumentation. In the present study, we optimized the conditions of a miniaturized fast, sensitive, and high-throughput assay to assess the feeding rate based on the ingestion of fluorescent microparticles. The protocol was optimized in neonates in relation to the concentration of microplastic and the number of animals to increase reproducibility. Daphnids, following exposures to nonlethal concentrations, were incubated with microplastics; and, as filter feeders, they ingest microparticles. The new approach revealed differences in the physiology of daphnids in concentrations below the toxicity limits for a range of pollutants of different modes of action, thus proving feeding to be a more sensitive and noninvasive endpoint in pollution assessment. Environ Toxicol Chem 2024;00:1-11. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.PMID:39056977 | DOI:10.1002/etc.5960

Cells. 2024 Jul 19;13(14):1220. doi: 10.3390/cells13141220.ABSTRACTThe MAPK signaling pathway with BRAF mutations has been shown to drive the pathogenesis of 40-60% of melanomas. Inhibitors of this pathway's BRAF and MEK components are currently used to treat these malignancies. However, responses to these treatments are not always successful. Therefore, identifying noninvasive biomarkers to predict treatment responses is essential for personalized medicine in melanoma. Using noninvasive 1H magnetic resonance spectroscopy (1H MRS), we previously showed that BRAF inhibition reduces lactate and alanine tumor levels in the early stages of effective therapy and could be considered as metabolic imaging biomarkers for drug response. The present work demonstrates that these metabolic changes observed by 1H MRS and those assessed by 31P MRS are also found in preclinical human melanoma models treated with MEK inhibitors. Apart from 1H and 31P MRS, additional supporting in vitro biochemical analyses are described. Our results indicate significant early metabolic correlations with response levels to MEK inhibition in the melanoma models and are consistent with our previous study of BRAF inhibition. Given these results, our study supports the potential clinical utility of noninvasive MRS to objectively image metabolic biomarkers for the early prediction of melanoma's response to MEK inhibition.PMID:39056801 | DOI:10.3390/cells13141220

Biology (Basel). 2024 Jul 9;13(7):511. doi: 10.3390/biology13070511.ABSTRACTThe aim of this study was to investigate the metabolic changes associated with the anti-obesity effects of fermented blackberry extracts in the liver tissues of high-fat-diet-fed mice using mass spectrometry-based metabolomics analysis. C57BL/6J mice were divided into eight groups: normal-diet-fed mice, high-fat-diet-fed mice, high-fat diet treated with blackberry extract, high-fat-diet mice treated with blackberry fermented by L. plantarum, and high-fat diet with blackberry fermented by L. brevis. After 12 weeks, the high-fat-diet group exhibited a greater increase in liver weight compared to the control group, and among the groups, the group administered with blackberry fermented with L. plantarum showed the most pronounced reduction in liver weight. As the primary organ responsible for amino acid metabolism, the liver is crucial for maintaining amino acid homeostasis. In our study, we observed that the levels of several essential amino acids, including isoleucine and valine, were decreased by the high-fat diet, and were recovered by administration of blackberry extract fermented with L. plantarum. Our results demonstrated the potential of blackberry extract fermented with L. plantarum as a functional material for metabolic disorders by restoring some of the amino acid metabolism disturbances induced by a high-fat diet.PMID:39056704 | DOI:10.3390/biology13070511

Biology (Basel). 2024 Jun 30;13(7):488. doi: 10.3390/biology13070488.ABSTRACTThe rapid development of the mariculture industry has been hindered by limited coastal aquaculture space. To utilize the abundant inland saline-alkaline water, we studied the physiological effects of high carbonate alkalinity stress and high pH stress on Fenneropenaeus chinensis. The study employed quantitative proteomics by tandem mass tag (TMT) and non-targeted metabolomics analysis using a liquid chromatograph mass spectrometer (LC-MS) to understand the physiological and biochemical adaptive mechanisms of the hepatopancreas of F. chinensis in response to saline-alkaline stress at the molecular level. We designed two stress groups as follows: a high carbonate alkalinity (CA) group and a combined high carbonate alkalinity and high pH (CP) group. The study found that the protein and metabolic profiles of the two stress groups were changed, and the CP group, which was exposed to dual stresses, incurred more severe damage to the hepatopancreas compared to that of the CA group. After exposure to CA and CP, the hepatopancreas of F. chinensis showed significant alterations in 455 proteins and 50 metabolites, and 1988 proteins and 272 metabolites, respectively. In addition, F. chinensis upregulated the level of energy metabolism in the hepatopancreas to defend against osmotic imbalance caused by CA or CP stress, which was demonstrated by the significant upregulation of important proteins and metabolites in glycolysis, pyruvate metabolism, TCA cycle, and fatty acid oxidation. Additionally, pattern recognition receptors, the phenol oxidase system, and various immune-related metabolic enzymes and metabolites were also affected. The immune homeostasis of F. chinensis was affected by the alteration of the antioxidant system following exposure to CA or CP. These findings provide valuable information for F. chinensis saline-alkaline water cultivation practices.PMID:39056683 | DOI:10.3390/biology13070488