PubMed

Int J Mol Sci. 2023 Mar 2;24(5):4816. doi: 10.3390/ijms24054816.ABSTRACTWucai (Brassica campestris L.) is a leafy vegetable that originated in China, its soluble sugars accumulate significantly to improve taste quality during maturation, and it is widely accepted by consumers. In this study, we investigated the soluble sugar content at different developmental stages. Two periods including 34 days after planting (DAP) and 46 DAP, which represent the period prior to and after sugar accumulation, respectively, were selected for metabolomic and transcriptomic profiling. Differentially accumulated metabolites (DAMs) were mainly enriched in the pentose phosphate pathway, galactose metabolism, glycolysis/gluconeogenesis, starch and sucrose metabolism, and fructose and mannose metabolism. By orthogonal projection to latent structures-discriminant s-plot (OPLS-DA S-plot) and MetaboAnalyst analyses, D-galactose and β-D-glucose were identified as the major components of sugar accumulation in wucai. Combined with the transcriptome, the pathway of sugar accumulation and the interact network between 26 DEGs and the two sugars were mapped. CWINV4, CEL1, BGLU16, and BraA03g023380.3C had positive correlations with the accumulation of sugar accumulation in wucai. The lower expression of BraA06g003260.3C, BraA08g002960.3C, BraA05g019040.3C, and BraA05g027230.3C promoted sugar accumulation during the ripening of wucai. These findings provide insights into the mechanisms underlying sugar accumulation during commodity maturity, providing a basis for the breeding of sugar-rich wucai cultivars.PMID:36902245 | DOI:10.3390/ijms24054816

Int J Mol Sci. 2023 Mar 1;24(5):4764. doi: 10.3390/ijms24054764.ABSTRACTThe small brown planthopper (SBPH, Laodelphax striatellus) is one of the most destructive insect pests in rice (Oryza sativa), which is the world's major grain crop. The dynamic changes in the rice transcriptome and metabolome in response to planthopper female adult feeding and oviposition have been reported. However, the effects of nymph feeding remain unclear. In this study, we found that pre-infestation with SBPH nymphs increased the susceptibility of rice plants to SBPH infestation. We used a combination of broadly targeted metabolomic and transcriptomic studies to investigate the rice metabolites altered by SBPH feeding. We observed that SBPH feeding induced significant changes in 92 metabolites, including 56 defense-related secondary metabolites (34 flavonoids, 17 alkaloids, and 5 phenolic acids). Notably, there were more downregulated metabolites than upregulated metabolites. Additionally, nymph feeding significantly increased the accumulation of seven phenolamines and three phenolic acids but decreased the levels of most flavonoids. In SBPH-infested groups, 29 differentially accumulated flavonoids were downregulated, and this effect was more pronounced with infestation time. The findings of this study indicate that SBPH nymph feeding suppresses flavonoid biosynthesis in rice, resulting in increased susceptibility to SBPH infestation.PMID:36902211 | DOI:10.3390/ijms24054764

Int J Mol Sci. 2023 Mar 1;24(5):4779. doi: 10.3390/ijms24054779.ABSTRACTRed LED light (R LED) is an efficient tool to improve seed germination and plant growth under controlled environments since it is more readily absorbed by photoreceptors' phytochromes compared to other wavelengths of the spectrum. In this work, the effect of R LED on the radicle emergence and growth (Phase III of germination) of pepper seeds was evaluated. Thus, the impact of R LED on water transport through different intrinsic membrane proteins, via aquaporin (AQP) isoforms, was determined. In addition, the remobilization of distinct metabolites such as amino acids, sugars, organic acids, and hormones was analysed. R LED induced a higher germination speed index, regulated by an increased water uptake. PIP2;3 and PIP2;5 aquaporin isoforms were highly expressed and could contribute to a faster and more effective hydration of embryo tissues, leading to a reduction of the germination time. By contrast, TIP1;7, TIP1;8, TIP3;1 and TIP3;2 gene expressions were reduced in R LED-treated seeds, pointing to a lower need for protein remobilization. NIP4;5 and XIP1;1 were also involved in radicle growth but their role needs to be elucidated. In addition, R LED induced changes in amino acids and organic acids as well as sugars. Therefore, an advanced metabolome oriented to a higher energetic metabolism was observed, conditioning better seed germination performance together with a rapid water flux.PMID:36902208 | DOI:10.3390/ijms24054779

Int J Mol Sci. 2023 Mar 1;24(5):4738. doi: 10.3390/ijms24054738.ABSTRACTNumerous studies have shown that oxidative stress resulting from an imbalance between the production of free radicals and their neutralization by antioxidant enzymes is one of the major pathological disorders underlying the development and progression of type 2 diabetes (T2D). The present review summarizes the current state of the art advances in understanding the role of abnormal redox homeostasis in the molecular mechanisms of T2D and provides comprehensive information on the characteristics and biological functions of antioxidant and oxidative enzymes, as well as discusses genetic studies conducted so far in order to investigate the contribution of polymorphisms in genes encoding redox state-regulating enzymes to the disease pathogenesis.PMID:36902173 | DOI:10.3390/ijms24054738

Int J Mol Sci. 2023 Mar 1;24(5):4724. doi: 10.3390/ijms24054724.ABSTRACTHypertrophic cardiomyopathy is one of the most common inherited cardiomyopathies and a leading cause of sudden cardiac death in young adults. Despite profound insights into the genetics, there is imperfect correlation between mutation and clinical prognosis, suggesting complex molecular cascades driving pathogenesis. To investigate this, we performed an integrated quantitative multi-omics (proteomic, phosphoproteomic, and metabolomic) analysis to illuminate the early and direct consequences of mutations in myosin heavy chain in engineered human induced pluripotent stem-cell-derived cardiomyocytes relative to late-stage disease using patient myectomies. We captured hundreds of differential features, which map to distinct molecular mechanisms modulating mitochondrial homeostasis at the earliest stages of pathobiology, as well as stage-specific metabolic and excitation-coupling maladaptation. Collectively, this study fills in gaps from previous studies by expanding knowledge of the initial responses to mutations that protect cells against the early stress prior to contractile dysfunction and overt disease.PMID:36902152 | DOI:10.3390/ijms24054724

Int J Mol Sci. 2023 Feb 28;24(5):4706. doi: 10.3390/ijms24054706.ABSTRACTNitrogen is one of the most important mineral elements for plant growth and development. Excessive nitrogen application not only pollutes the environment, but also reduces the quality of crops. However, are few studies on the mechanism of barley tolerance to low nitrogen at both the transcriptome and metabolomics levels. In this study, the nitrogen-efficient genotype (W26) and the nitrogen-sensitive genotype (W20) of barley were treated with low nitrogen (LN) for 3 days and 18 days, then treated with resupplied nitrogen (RN) from 18 to 21 days. Later, the biomass and the nitrogen content were measured, and RNA-seq and metabolites were analyzed. The nitrogen use efficiency (NUE) of W26 and W20 treated with LN for 21 days was estimated by nitrogen content and dry weight, and the values were 87.54% and 61.74%, respectively. It turned out to have a significant difference in the two genotypes under the LN condition. According to the transcriptome analysis, 7926 differentially expressed genes (DEGs) and 7537 DEGs were identified in the leaves of W26 and W20, respectively, and 6579 DEGs and 7128 DEGs were found in the roots of W26 and W20, respectively. After analysis of the metabolites, 458 differentially expressed metabolites (DAMs) and 425 DAMs were found in the leaves of W26 and W20, respectively, and 486 DAMs and 368 DAMs were found in the roots of W26 and W20, respectively. According to the KEGG joint analysis of DEGs and DAMs, it was discovered that glutathione (GSH) metabolism was the pathway of significant enrichment in the leaves of both W26 and W20. In this study, the metabolic pathways of nitrogen metabolism and GSH metabolism of barley under nitrogen were constructed based on the related DAMs and DEGs. In leaves, GSH, amino acids, and amides were the main identified DAMs, while in roots, GSH, amino acids, and phenylpropanes were mainly found DAMs. Finally, some nitrogen-efficient candidate genes and metabolites were selected based on the results of this study. The responses of W26 and W20 to low nitrogen stress were significantly different at the transcriptional and metabolic levels. The candidate genes that have been screened will be verified in future. These data not only provide new insights into how barley responds to LN, but also provide new directions for studying the molecular mechanisms of barley under abiotic stress.PMID:36902137 | DOI:10.3390/ijms24054706

Int J Mol Sci. 2023 Feb 28;24(5):4690. doi: 10.3390/ijms24054690.ABSTRACTVanilla planifolia is an orchid of cultural and economic value. However, its cultivation in many tropical countries is threatened by water stress. In contrast, V. pompona is a species that is tolerant of prolonged periods of drought. Due to the need for plants' resistant to water stress, the use of hybrids of these two species is considered. Therefore, the objective of this study was to evaluate the morphological and physio-chemical responses of in vitro vanilla seedlings of the parental genotype V. planifolia, and the hybrids V. planifolia × V. pompona and V. pompona × V. planifolia, which were then exposed over five weeks to polyethylene glycol-induced water stress (-0.49 mPa). Stem and root length, relative growth rate, number of leaves and roots, stomatal conductance, specific leaf area, and leaf water content were determined. Metabolites potentially associated with the response to water stress were identified in leaves, through untargeted and targeted metabolomics. Both hybrids exhibited a smaller decrease in the morphophysiological responses compared to V. planifolia and exhibited an enrichment of metabolites such as carbohydrates, amino acids, purines, phenols, and organic acids. Hybrids of these two species are considered as a potential alternative to the traditional cultivation of vanilla to face drought in a global warming scenario.PMID:36902119 | DOI:10.3390/ijms24054690

Int J Mol Sci. 2023 Feb 25;24(5):4541. doi: 10.3390/ijms24054541.ABSTRACTIntestinal transplantation (ITx) remains a lifesaving option for patients suffering from irreversible intestinal failure and complications from total parenteral nutrition. Since its inception, it became obvious that intestinal grafts are highly immunogenic, due to their high lymphoid load, the abundance in epithelial cells and constant exposure to external antigens and microbiota. This combination of factors and several redundant effector pathways makes ITx immunobiology unique. To this complex immunologic situation, which leads to the highest rate of rejection among solid organs (>40%), there is added the lack of reliable non-invasive biomarkers, which would allow for frequent, convenient and reliable rejection surveillance. Numerous assays, of which several were previously used in inflammatory bowel disease, have been tested after ITx, but none have shown sufficient sensibility and/or specificity to be used alone for diagnosing acute rejection. Herein, we review and integrate the mechanistic aspects of graft rejection with the current knowledge of ITx immunobiology and summarize the quest for a noninvasive biomarker of rejection.PMID:36901975 | DOI:10.3390/ijms24054541

Int J Mol Sci. 2023 Feb 24;24(5):4519. doi: 10.3390/ijms24054519.ABSTRACTHuman gut microbiota seems to drive the interaction with host metabolism through microbial metabolites, enzymes, and bioactive compounds. These components determine the host health-disease balance. Recent metabolomics and combined metabolome-microbiome studies have helped to elucidate how these substances could differentially affect the individual host pathophysiology according to several factors and cumulative exposures, such as obesogenic xenobiotics. The present work aims to investigate and interpret newly compiled data from metabolomics and microbiota composition studies, comparing controls with patients suffering from metabolic-related diseases (diabetes, obesity, metabolic syndrome, liver and cardiovascular diseases, etc.). The results showed, first, a differential composition of the most represented genera in healthy individuals compared to patients with metabolic diseases. Second, the analysis of the metabolite counts exhibited a differential composition of bacterial genera in disease compared to health status. Third, qualitative metabolite analysis revealed relevant information about the chemical nature of metabolites related to disease and/or health status. Key microbial genera were commonly considered overrepresented in healthy individuals together with specific metabolites, e.g., Faecalibacterium and phosphatidylethanolamine; and the opposite, Escherichia and Phosphatidic Acid, which is converted into the intermediate Cytidine Diphosphate Diacylglycerol-diacylglycerol (CDP-DAG), were overrepresented in metabolic-related disease patients. However, it was not possible to associate most specific microbiota taxa and metabolites according to their increased and decreased profiles analyzed with health or disease. Interestingly, positive association of essential amino acids with the genera Bacteroides were observed in a cluster related to health, and conversely, benzene derivatives and lipidic metabolites were related to the genera Clostridium, Roseburia, Blautia, and Oscillibacter in a disease cluster. More studies are needed to elucidate the microbiota species and their corresponding metabolites that are key in promoting health or disease status. Moreover, we propose that greater attention should be paid to biliary acids and to microbiota-liver cometabolites and its detoxification enzymes and pathways.PMID:36901949 | DOI:10.3390/ijms24054519

Int J Mol Sci. 2023 Feb 23;24(5):4418. doi: 10.3390/ijms24054418.ABSTRACTThe major oxidized product of cholesterol, 7-Ketocholesterol (7KCh), causes cellular oxidative damage. In the present study, we investigated the physiological responses of cardiomyocytes to 7KCh. A 7KCh treatment inhibited the growth of cardiac cells and their mitochondrial oxygen consumption. It was accompanied by a compensatory increase in mitochondrial mass and adaptive metabolic remodeling. The application of [U-13C] glucose labeling revealed an increased production of malonyl-CoA but a decreased formation of hydroxymethylglutaryl-coenzyme A (HMG-CoA) in the 7KCh-treated cells. The flux of the tricarboxylic acid (TCA) cycle decreased, while that of anaplerotic reaction increased, suggesting a net conversion of pyruvate to malonyl-CoA. The accumulation of malonyl-CoA inhibited the carnitine palmitoyltransferase-1 (CPT-1) activity, probably accounting for the 7-KCh-induced suppression of β-oxidation. We further examined the physiological roles of malonyl-CoA accumulation. Treatment with the inhibitor of malonyl-CoA decarboxylase, which increased the intracellular malonyl-CoA level, mitigated the growth inhibitory effect of 7KCh, whereas the treatment with the inhibitor of acetyl-CoA carboxylase, which reduced malonyl-CoA content, aggravated such a growth inhibitory effect. Knockout of malonyl-CoA decarboxylase gene (Mlycd-/-) alleviated the growth inhibitory effect of 7KCh. It was accompanied by improvement of the mitochondrial functions. These findings suggest that the formation of malonyl-CoA may represent a compensatory cytoprotective mechanism to sustain the growth of 7KCh-treated cells.PMID:36901848 | DOI:10.3390/ijms24054418

Int J Mol Sci. 2023 Feb 23;24(5):4406. doi: 10.3390/ijms24054406.ABSTRACTTriple negative breast cancer (TNBC) is a subtype of breast cancer with typically poorer outcomes due to its aggressive clinical behavior and lack of targeted treatment options. Currently, treatment is limited to the administration of high-dose chemotherapeutics, which results in significant toxicities and drug resistance. As such, there is a need to de-escalate chemotherapeutic doses in TNBC while also retaining/improving treatment efficacy. Dietary polyphenols and omega-3 polyunsaturated fatty acids (PUFAs) have been demonstrated to have unique properties in experimental models of TNBC, improving the efficacy of doxorubicin and reversing multi-drug resistance. However, the pleiotropic nature of these compounds has caused their mechanisms to remain elusive, preventing the development of more potent mimetics to take advantage of their properties. Using untargeted metabolomics, we identify a diverse set of metabolites/metabolic pathways that are targeted by these compounds following treatment in MDA-MB-231 cells. Furthermore, we demonstrate that these chemosensitizers do not all target the same metabolic processes, but rather organize into distinct clusters based on similarities among metabolic targets. Common themes in metabolic targets included amino acid metabolism (particularly one-carbon and glutamine metabolism) and alterations in fatty acid oxidation. Moreover, doxorubicin treatment alone generally targeted different metabolites/pathways than chemosensitizers. This information provides novel insights into chemosensitization mechanisms in TNBC.PMID:36901842 | DOI:10.3390/ijms24054406

Int J Mol Sci. 2023 Feb 23;24(5):4410. doi: 10.3390/ijms24054410.ABSTRACTIdiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by the aberrant accumulation of extracellular matrix in the lungs. nintedanib is one of the two FDA-approved drugs for IPF treatment; however, the exact pathophysiological mechanisms of fibrosis progression and response to therapy are still poorly understood. In this work, the molecular fingerprint of fibrosis progression and response to nintedanib treatment have been investigated by mass spectrometry-based bottom-up proteomics in paraffin-embedded lung tissues from bleomycin-induced (BLM) pulmonary fibrosis mice. Our proteomics results unveiled that (i) samples clustered depending on the tissue fibrotic grade (mild, moderate, and severe) and not on the time course after BLM treatment; (ii) the dysregulation of different pathways involved in fibrosis progression such as the complement coagulation cascades, advanced glycation end products (AGEs) and their receptors (RAGEs) signaling, the extracellular matrix-receptor interaction, the regulation of actin cytoskeleton, and ribosomes; (iii) Coronin 1A (Coro1a) as the protein with the highest correlation when evaluating the progression of fibrosis, with an increased expression from mild to severe fibrosis; and (iv) a total of 10 differentially expressed proteins (padj-value ≤ 0.05 and Fold change ≤-1.5 or ≥1.5), whose abundance varied in the base of the severity of fibrosis (mild and moderate), were modulated by the antifibrotic treatment with nintedanib, reverting their trend. Notably, nintedanib significantly restored lactate dehydrogenase B (Ldhb) expression but not lactate dehydrogenase A (Ldha). Notwithstanding the need for further investigations to validate the roles of both Coro1a and Ldhb, our findings provide an extensive proteomic characterization with a strong relationship with histomorphometric measurements. These results unveil some biological processes in pulmonary fibrosis and drug-mediated fibrosis therapy.PMID:36901840 | DOI:10.3390/ijms24054410

Int J Mol Sci. 2023 Feb 22;24(5):4379. doi: 10.3390/ijms24054379.ABSTRACTLipidomics and metabolomics are nowadays widely used to provide promising insights into the pathophysiology of cellular stress disorders. Our study expands, with the use of a hyphenated ion mobility mass spectrometric platform, the understanding of the cellular processes and stress due to microgravity. By lipid profiling of human erythrocytes, we annotated complex lipids such as oxidized phosphocholines, phosphocholines bearing arachidonic in their moiety, as well as sphingomyelins and hexosyl ceramides associated with microgravity conditions. Overall, our findings give an insight into the molecular alterations and identify erythrocyte lipidomics signatures associated with microgravity conditions. If the present results are confirmed in future studies, they may help to develop suitable treatments for astronauts after return to Earth.PMID:36901810 | DOI:10.3390/ijms24054379

Healthcare (Basel). 2023 Feb 23;11(5):658. doi: 10.3390/healthcare11050658.ABSTRACTHPV infection is one of the most studied risk factors in cervical cancer-the second most common cancer site and cause of death due to cancer in the Philippines. However, there is a lack of population-based epidemiological data on cervical HPV infection in the Philippines. Local reports on co-infections with other lower genital tract pathogens, commonly reported globally, are also lacking, which emphasizes the need to increase efforts in targeting HPV prevalence, genotype, and distribution. Hence, we aim to determine the molecular epidemiology and natural history of HPV infection among reproductive-age Filipino women using a community-based prospective cohort design. Women from rural and urban centers will be screened until the target sample size of 110 HPV-positive women (55 from rural sites and 55 from urban sites) is reached. Cervical and vaginal swabs will be collected from all screened participants. For HPV-positive patients, HPV genotypes will be determined. One hundred ten healthy controls will be selected from previously screened volunteers. The cases and controls will comprise the multi-omics subset of participants and will be followed up after 6 and 12 months for repeat HPV screening. Metagenomic and metabolomic analyses of the vaginal swabs will also be performed at baseline, after 6 months, and after 12 months. The results of this study will update the prevalence and genotypic distribution of cervical HPV infection among Filipino women, determine whether the current vaccines used for HPV vaccination programs capture the most prevalent high-risk HPV genotypes in the country, and identify vaginal community state types and bacterial taxa associated with the natural history of cervical HPV infection. The results of this study will be used as the basis for developing a biomarker that can help predict the risk of developing persistent cervical HPV infection in Filipino women.PMID:36900663 | DOI:10.3390/healthcare11050658

Foods. 2023 Feb 28;12(5):1025. doi: 10.3390/foods12051025.ABSTRACTThe flavor of chicken meat is influenced by muscle metabolites and regulatory genes and varies with age. In this study, the metabolomic and transcriptomic data of breast muscle at four developmental stages (days 1, 56, 98, and 120) of Beijing-You chickens (BJYs) were integrated and 310 significantly changed metabolites (SCMs) and 7,225 differentially expressed genes (DEGs) were identified. A Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that SCMs and DEGs were enriched in amino acid, lipid, and inosine monophosphate (IMP) metabolism pathways. Furthermore, genes highly associated with flavor amino acids, lipids, and IMP were identified by a weighted gene co-expression network analysis (WGCNA), including cystathionine β-synthase (CBS), glycine amidinotransferase (GATM), glutamate decarboxylase 2 (GAD2), patatin-like phospholipasedomain containing 6 (PNPLA6), low-specificity L-threonine aldolase (ItaE), and adenylate monophosphate deaminase 1 (AMPD1) genes. A regulatory network related to the accumulation of key flavor components was constructed. In conclusion, this study provides new perspectives regarding the regulatory mechanisms of flavor metabolites in chicken meat during development.PMID:36900542 | DOI:10.3390/foods12051025

Foods. 2023 Feb 27;12(5):998. doi: 10.3390/foods12050998.ABSTRACTA multi-omics approach was adopted to investigate the impact of lactic acid fermentation and seed germination on the composition and physicochemical properties of rye doughs. Doughs were prepared with either native or germinated rye flour and fermented with Saccharomyces cerevisiae, combined or not with a sourdough starter including Limosilactobacillus fermentum, Weissella confusa and Weissella cibaria. LAB fermentation significantly increased total titrable acidity and dough rise regardless of the flour used. Targeted metagenomics revealed a strong impact of germination on the bacterial community profile of sprouted rye flour. Doughs made with germinated rye displayed higher levels of Latilactobacillus curvatus, while native rye doughs were associated with higher proportions of Lactoplantibacillus plantarum. The oligosaccharide profile of rye doughs indicated a lower carbohydrate content in native doughs as compared to the sprouted counterparts. Mixed fermentation promoted a consistent decrease in both monosaccharides and low-polymerization degree (PD)-oligosaccharides, but not in high-PD carbohydrates. Untargeted metabolomic analysis showed that native and germinated rye doughs differed in the relative abundance of phenolic compounds, terpenoids, and phospholipids. Sourdough fermentation promoted the accumulation of terpenoids, phenolic compounds and proteinogenic and non-proteinogenic amino acids. Present findings offer an integrated perspective on rye dough as a multi-constituent system and on cereal-sourced bioactive compounds potentially affecting the functional properties of derived food products.PMID:36900515 | DOI:10.3390/foods12050998

Foods. 2023 Feb 24;12(5):972. doi: 10.3390/foods12050972.ABSTRACTVitamins are major cofactors to numerous key metabolic pathways in enological yeasts, and both thiamine and biotin, notably, are believed to be essential to yeast fermentation and growth, respectively. In order to further assess and clarify their role in winemaking, and in the resulting wine, alcoholic fermentations of a commercial Saccharomyces cerevisiae active dried yeast were conducted in synthetic media containing various concentrations of both vitamins. Growth and fermentation kinetics were monitored and proved the essential character of biotin in yeast growth, and of thiamine in fermentation. The synthetic wine volatile compounds were quantified, and notable influences of both vitamins appeared, through a striking positive effect of thiamine on the production of higher alcohols, and of biotin on fatty acids. Beyond the evidence of this influence on fermentations and on the production of volatiles, this work proves, for the first time, the impact held by vitamins on wine yeasts' exometabolome, investigated through an untargeted metabolomic analysis. This highlighted chemical differences in the composition of synthetic wines through a notably marked influence of thiamine on 46 named S. cerevisiae metabolic pathways, and especially in amino acid-associated metabolic pathways. This provides, overall, the first evidence of the impact held by both vitamins on the wine.PMID:36900489 | DOI:10.3390/foods12050972

Cancers (Basel). 2023 Mar 5;15(5):1607. doi: 10.3390/cancers15051607.ABSTRACTBACKGROUND: CPUL1, a phenazine analog, has demonstrated potent antitumor properties against hepatocellular carcinoma (HCC) and indicates a promising prospect in pharmaceutical development. However, the underlying mechanisms remain largely obscure.METHODS: Multiple HCC cell lines were used to investigate the in vitro effects of CPUL1. The antineoplastic properties of CPUL1 were assessed in vivo by establishing a xenograft nude mice model. After that, metabolomics, transcriptomics, and bioinformatics were integrated to elucidate the mechanisms underlying the therapeutic efficacy of CPUL1, highlighting an unanticipated involvement of autophagy dysregulation.RESULTS: CPUL1 suppressed HCC cell proliferation in vitro and in vivo, thereby endorsing the potential as a leading agent for HCC therapy. Integrative omics characterized a deteriorating scenario of metabolic debilitation with CPUL1, presenting an issue in the autophagy contribution of autophagy. Subsequent observations indicated that CPUL1 treatment could impede autophagic flow by suppressing autophagosome degradation rather than its formation, which supposedly exacerbated cellular damage triggered by metabolic impairment. Moreover, the observed late autophagosome degradation may be attributed to lysosome dysfunction, which is essential for the final stage of autophagy and cargo disposal.CONCLUSIONS: Our study comprehensively profiled the anti-hepatoma characteristics and molecular mechanisms of CPUL1, highlighting the implications of progressive metabolic failure. This could partially be ascribed to autophagy blockage, which supposedly conveyed nutritional deprivation and intensified cellular vulnerability to stress.PMID:36900398 | DOI:10.3390/cancers15051607

Diagnostics (Basel). 2023 Feb 23;13(5):861. doi: 10.3390/diagnostics13050861.ABSTRACTA wide range of histological as well as clinical properties are exhibited by B-cell non-Hodgkin's lymphomas. These properties could make the diagnostics process complicated. The diagnosis of lymphomas at an initial stage is essential because early remedial actions taken against destructive subtypes are commonly deliberated as successful and restorative. Therefore, better protective action is needed to improve the condition of those patients who are extensively affected by cancer when diagnosed for the first time. The development of new and efficient methods for early detection of cancer has become crucial nowadays. Biomarkers are urgently needed for diagnosing B-cell non-Hodgkin's lymphoma and assessing the severity of the disease and its prognosis. New possibilities are now open for diagnosing cancer with the help of metabolomics. The study of all the metabolites synthesised in the human body is called "metabolomics." A patient's phenotype is directly linked with metabolomics, which can help in providing some clinically beneficial biomarkers and is applied in the diagnostics of B-cell non-Hodgkin's lymphoma. In cancer research, it can analyse the cancerous metabolome to identify the metabolic biomarkers. This review provides an understanding of B-cell non-Hodgkin's lymphoma metabolism and its applications in medical diagnostics. A description of the workflow based on metabolomics is also provided, along with the benefits and drawbacks of various techniques. The use of predictive metabolic biomarkers for the diagnosis and prognosis of B-cell non-Hodgkin's lymphoma is also explored. Thus, we can say that abnormalities related to metabolic processes can occur in a vast range of B-cell non-Hodgkin's lymphomas. The metabolic biomarkers could only be discovered and identified as innovative therapeutic objects if we explored and researched them. In the near future, the innovations involving metabolomics could prove fruitful for predicting outcomes and bringing out novel remedial approaches.PMID:36900005 | DOI:10.3390/diagnostics13050861

Cells. 2023 Mar 4;12(5):806. doi: 10.3390/cells12050806.ABSTRACTThe identification of Parkinson's disease (PD) biomarkers has become a main goal for the diagnosis of this neurodegenerative disorder. PD has not only been intrinsically related to neurological problems, but also to a series of alterations in peripheral metabolism. The purpose of this study was to identify metabolic changes in the liver in mouse models of PD with the scope of finding new peripheral biomarkers for PD diagnosis. To achieve this goal, we used mass spectrometry technology to determine the complete metabolomic profile of liver and striatal tissue samples from WT mice, 6-hydroxydopamine-treated mice (idiopathic model) and mice affected by the G2019S-LRRK2 mutation in LRRK2/PARK8 gene (genetic model). This analysis revealed that the metabolism of carbohydrates, nucleotides and nucleosides was similarly altered in the liver from the two PD mouse models. However, long-chain fatty acids, phosphatidylcholine and other related lipid metabolites were only altered in hepatocytes from G2019S-LRRK2 mice. In summary, these results reveal specific differences, mainly in lipid metabolism, between idiopathic and genetic PD models in peripheral tissues and open up new possibilities to better understand the etiology of this neurological disorder.PMID:36899942 | DOI:10.3390/cells12050806