PubMed

Foods. 2024 Dec 24;14(1):7. doi: 10.3390/foods14010007.ABSTRACTIn the present study, we analyzed the bioactive curcuminoids content in eight capsules (DS-1-DS-7 and DS-9), one tablet (DS-8), three ground turmeric samples (DS-10-DS-12), and three ground turmeric rhizomes (TR-1, TR-2, and TR-3). Initial screening with infrared and ultraviolet-visible spectroscopy coupled with a principal component analysis (PCA) revealed distinct differences between the samples analyzed. Hence, targeted and untargeted analyses were performed using ultra-high-performance liquid chromatography and gas chromatography coupled with mass spectrometry detections. The results show that the total curcuminoids content ranged from 1.3 to 69.8 mg/100 mg and the volatile component ranged from 0.7 to 9.1 mg/100 mg. The percentage ratio of the three prominent curcuminoids, bisdesmethoxycurcumin (BMC), desmethoxycurcumin (DMC), and curcumin (CUR), also varied remarkably compared to the expected ratio (BMC:DMC:CUR ratio of 1:2:6) described in the literature. The three prominent volatile compounds identified in most samples were ar-turmerone, turmerone, and curlone. The results demonstrated significant differences in the volatile compound levels among the DS and dried rhizome samples. The non-targeted analysis resulted in the identification of over 40 compounds, including bioactives such as piperine, phenolic acids, and amino acids. A disintegration study was performed on limited DS according to the United States Pharmacopeia protocol. The results reveal that all the selected DS samples passed the disintegration test. An analysis of curcuminoids from DS samples in neutral and acidic solutions demonstrated that all curcuminoids (BMC, DMC, and CUR) existed in the keto and enol forms and their concentrations changed with pH. This study will be of significant interest to manufacturers, consumers, and pharmacologists to accurately understand the bioactivities of three curcuminoids in different isomeric forms.PMID:39796297 | DOI:10.3390/foods14010007

Int J Mol Sci. 2025 Jan 6;26(1):427. doi: 10.3390/ijms26010427.ABSTRACTGlutaminase controls the first step in glutaminolysis, impacting bioenergetics, biosynthesis and oxidative stress. Two isoenzymes exist in humans, GLS and GLS2. GLS is considered prooncogenic and overexpressed in many tumours, while GLS2 may act as prooncogenic or as a tumour suppressor. Glioblastoma cells usually lack GLS2 while they express high GLS. We investigated how GLS2 expression modifies the metabolism of glioblastoma cells, looking for changes that may explain GLS2's potential tumour suppressive role. We developed LN-229 glioblastoma cells stably expressing GLS2 and performed isotope tracing using U-13C-glutamine and metabolomic quantification to analyze metabolic changes. Treatment with GLS inhibitor CB-839 was also included to concomitantly inhibit endogenous GLS. GLS2 overexpression resulted in extensive metabolic changes, altering the TCA cycle by upregulating part of the cycle but blocking the synthesis of the 6-carbon intermediates from acetyl-CoA. Expression of GLS2 caused downregulation of PDH activity through phosphorylation of S293 of PDHA1. GLS2 also altered nucleotide levels and induced the accumulation of methylated metabolites and S-adenosyl methionine. These changes suggest that GLS2 may be a key regulator linking glutamine and glucose metabolism, also impacting nucleotides and epigenetics. Future research should ascertain the mechanisms involved and the generalizability of these findings in cancer or physiological conditions.PMID:39796278 | DOI:10.3390/ijms26010427

Int J Mol Sci. 2025 Jan 3;26(1):367. doi: 10.3390/ijms26010367.ABSTRACTRapeseed (Brassica napus L.) is an important crop for healthy edible oil and stockfeed worldwide. However, its growth and yield are severely hampered by black rot, a destructive disease caused by Xanthomonas campestris pv. campestris (Xcc). Despite the identification of several quantitative trait loci (QTLs) associated with resistance to black rot in Brassica crops, the underlying molecular mechanisms remain largely unexplored. In this study, we investigated Xcc-induced transcriptomic and metabolic changes in the leaves of two rapeseed varieties: Westar (susceptible) and ZS5 (resistant). Our findings indicated that Xcc infection elicited more pronounced overall transcriptomic and metabolic changes in Westar compared to ZS5. Transcriptomic analyses revealed that the phenylpropanoid biosynthesis, cutin, suberine and wax biosynthesis, tryptophan metabolism, and phenylalanine metabolism were enriched in both varieties. Notably, photosynthesis was down-regulated in Westar after infection, whereas this down-regulation occurred at a later stage in ZS5. Integrated analyses of transcriptome and metabolome revealed that the tryptophan metabolism pathway was enriched in both varieties. Indolic glucosinolates and indole-3-acetic acid (IAA) are two metabolites derived from tryptophan. The expression of genes involved in the indolic glucosinolate pathway and the levels of indolic glucosinolates were significantly elevated in both varieties post-infection. Additionally, exogenous application of IAA promoted the development of black rot, whereas the use of an IAA synthesis inhibitor attenuated black rot development in both resistant and susceptible rapeseed varieties. These findings provide valuable molecular insights into the interactions between rapeseed and Xcc, facilitating the advancement of black rot resistance breeding in Brassica crops.PMID:39796224 | DOI:10.3390/ijms26010367

Int J Mol Sci. 2025 Jan 3;26(1):351. doi: 10.3390/ijms26010351.ABSTRACTPlant growth and development require water, but excessive water hinders growth. Sesame (Sesamum indicum L.) is an important oil crop; it is drought-tolerant but sensitive to waterlogging, and its drought tolerance has been extensively studied. However, the waterlogging tolerance of sesame still has relatively few studies. In this study, two kinds of sesame, R (waterlogging-tolerant) and S (waterlogging-intolerant), were used as materials, and they were treated with waterlogging stress for 0, 24, 72, and 120 h. Physiological analysis showed that after waterlogging, sesame plants responded to stress by increasing the contents of ascorbate peroxidase (APX), glutathione (GSH), and some other antioxidants. The results of the multi-omics analysis of sesame under waterlogging stress revealed 15,652 (R) and 12,156 (S) differentially expressed genes (DEGs), 41 (R) and 47 (S) differentially expressed miRNAs (DEMis), and 896 (R) and 1036 (S) differentially accumulated metabolites (DAMs). The combined DEMi-DEG analysis that 24 DEMis regulated 114 DEGs in response to waterlogging stress. In addition, 13 hub genes and three key pathways of plant hormone signal transduction, glutathione metabolism, and glyoxylate and dicarboxylate metabolism were identified by multi-omics analysis under waterlogging stress. The results showed that sesame regulated the content of hormones and antioxidants and promoted energy conversion in the plant through the above pathways to adapt to waterlogging stress. In summary, this study further analyzed the response mechanism of sesame to waterlogging stress and provides helpful information for the breeding of plants for waterlogging tolerance and genetic improvement.PMID:39796205 | DOI:10.3390/ijms26010351

Int J Mol Sci. 2025 Jan 1;26(1):317. doi: 10.3390/ijms26010317.ABSTRACTStroke is the leading cause of death and disability worldwide, with ischemic stroke accounting for the majority of these. HBA is the active ingredient in Gastrodia elata and has potential therapeutic effects on central nervous system diseases. In this study, the cell model of cerebral ischemia was replicated by the culture method of oxygen-glucose deprivation/reoxygenation, and the rat model of vascular dementia was established by the two-vessel occlusion method. Metabolomics technology was employed to analyze the metabolic changes in ischemic neurons induced by HBA, and potential therapeutic targets were verified. The protective effects of HBA on ischemic neurons and their mitochondria were examined through multiple indicators, and the related mechanisms were verified. HBA can improve post-ischemic cognitive impairment in rats, and its mechanism is related to the regulation of the choline-activated phospholipase D2/Sirtuin 1/peroxisome proliferator-activated receptor-γ coactivator 1α pathway to improve mitochondrial function and reduce autophagic activity to maintain mitochondrial homeostasis. It is concluded that HBA has a protective effect on neuronal damage and cognitive impairment caused by cerebral ischemia by regulating key metabolites and signaling pathways, and that it provides a new molecular target for the treatment of cerebral ischemia.PMID:39796170 | DOI:10.3390/ijms26010317

Int J Mol Sci. 2024 Dec 31;26(1):291. doi: 10.3390/ijms26010291.ABSTRACTRegeneration after ischemia requires to be promoted by (re)perfusion of the affected tissue, and, to date, there is no therapy that covers all needs. In treatment with mesenchymal stem cells (MSC), the secretome acts via paracrine mechanisms and has a positive influence on vascular regeneration via proangiogenic factors. A lack of standardization and the high complexity of vascular structures make it difficult to compare angiogenic readouts from different studies. This emphasizes the need for improved approaches and the introduction of an index in the preclinical setting. A characterization of human MSC secretomes obtained from one of the three formats-single cells, small, and large spheroids-was performed using the chicken aortic ring assay in combination with a modified angiogenic activity index (AAI) and an angiogenic profile. While the secretome of the small spheroid group showed an inhibitory effect on angiogenesis, the large spheroid group impressed with a fully pro-angiogenic response, and a higher AAI compared to the single cell group, underlying the suitability of these three-stem cell-derived secretomes with their distinct angiogenic properties to validate the AAI and the novel angiogenic profile established here.PMID:39796147 | DOI:10.3390/ijms26010291

Int J Mol Sci. 2024 Dec 31;26(1):294. doi: 10.3390/ijms26010294.ABSTRACTSoybean has outstanding nutritional and medicinal value because of its abundant protein, oil, and flavonoid contents. This crop has rich seed coat colors, such as yellow, green, black, brown, and red, as well as bicolor variants. However, there are limited reports on the synthesis of flavonoids in the soybean seed coats of different colors. Thus, the seed coat metabolomes and transcriptomes of five soybean germplasms with yellow (S141), red (S26), brown (S62), green (S100), and black (S124) seed coats were measured. In this study, 1645 metabolites were detected in the soybean seed coat, including 426 flavonoid compounds. The flavonoids differed among the different-colored seed coats of soybean germplasms, and flavonoids were distributed in all varieties. Procyanidins A1, B1, B6, C1, and B2, cyanidin 3-O-(6″-malonyl-arabinoside), petunidin 3-(6″-p-coumaryl-glucoside) 5-glucoside, and malvidin 3-laminaribioside were significantly upregulated in S26_vs._S141, S62_vs._S141, S100_vs._S141, and S124_vs._S141 groups, with a variation of 1.43-2.97 × 1013 in terms of fold. The differences in the contents of cyanidin 3-O-(6″-malonyl-arabinoside) and proanthocyanidin A1 relate to the seed coat color differences of red soybean. Malvidin 3-laminaribioside, petunidin 3-(6″-p-coumaryl-glucoside) 5-glucoside, cyanidin 3-O-(6″-malonyl-arabinoside), and proanthocyanidin A1 affect the color of black soybean. The difference in the contents of procyanidin B1 and malvidin 3-glucoside-4-vinylphenol might be related to the seed coat color differences of brown soybeans. Cyanidin 3-gentiobioside affects the color of green soybean. The metabolomic-transcriptomic combined analysis showed that flavonoid biosynthesis is the key synthesis pathway for soybean seed color formation. Transcriptome analysis revealed that the upregulation of most flavonoid biosynthesis genes was observed in all groups, except for S62_vs._S141, and promoted flavonoid accumulation. Furthermore, CHS, CHI, DFR, FG3, ANR, FLS, LAR, and UGT88F4 exhibited differential expression in all groups. This study broadens our understanding of the metabolic and transcriptomic changes in soybean seed coats of different colors and provides new insights into developing bioactive substances from soybean seed coats.PMID:39796145 | DOI:10.3390/ijms26010294

Int J Mol Sci. 2024 Dec 31;26(1):281. doi: 10.3390/ijms26010281.ABSTRACTOlfactory ensheathing cell (OEC) transplantation demonstrates promising therapeutic results in neurological disorders, such as spinal cord injury. The emerging cell-free secretome therapy compensates for the limitations of cell transplantation, such as low cell survival rates. However, the therapeutic benefits of the human OEC secretome remain unclear. We harvested the secretome from human mucosal OECs and characterized its protein content, identifying 709 proteins in the human OEC secretome from three donors in two passages. Thirty-nine proteins, including neurological-related proteins, such as profilin-1, and antioxidants, such as peroxiredoxin-1 and glutathione S-transferase, were shared between the six samples. The secretome consistently demonstrated potential effects such as antioxidant activity, neuronal differentiation, and quiescence exit of neural stem cells (NSCs). The total secretome produced by OECs protects NSCs from H2O2-induced reactive oxygen species accumulation. During induction of neuronal differentiation, secretomes promoted neurite outgrowth, axon elongation, and expression of neuronal markers. The secretome ameliorated bone morphogenetic protein 4- and fibroblast growth factor 2-induced quiescence of NSCs. The human OEC secretome triggers NSCs to exit prime quiescence, which is related to increased phosphoribosomal protein S6 expression and RNA synthesis. The human OEC secretome has beneficial effects on NSCs and may be applied in neurological disease studies.PMID:39796134 | DOI:10.3390/ijms26010281

Int J Mol Sci. 2024 Dec 31;26(1):264. doi: 10.3390/ijms26010264.ABSTRACTIn our previous research, we found that CYP6CY3 not only participates in the detoxification metabolism of neonicotinoid insecticides in cotton aphid but also affects their growth and development. However, how does transgenic cotton expressing dsAgCYP6CY3 affect the growth and development of cotton aphid? In this study, we combined transcriptome and metabolome to analyze how to inhibit the growth and development of cotton aphid treated with transgenic cotton expressing dsAgCYP6CY3-P1 (TG cotton). The results suggested that a total of 509 differentially expressed genes (DEGs) were identified based on the DESeq method, and a total of 431 differential metabolites (DAMs) were discovered using UPLC-MS in the metabolic analysis. Additionally, multiple DEGs and DAMs of glycolytic and The tricarboxylic acid (TCA) cycle pathways were significantly down-regulated. Pyruvate carboxylase (PC), citrate synthase (CS), malate dehydrogenase (MDH) enzyme activities and pyruvate content were reduced in cotton aphid treated with TG cotton. In addition, TG cotton could significantly decrease the total sugar content from the body and honeydew in cotton aphid. The above results indicated that TG cotton inhibited glycolysis and the TCA cycle, and this inhibition is consistent with previous studies showing that cotton aphid fed on TG cotton showed significantly reduced body length and weight as well as delayed molting. These findings provide a new strategy for reducing the transmission of viruses by cotton aphid honeydew, preventing fungal growth, mitigating impacts on normal photosynthesis and improving cotton quality.PMID:39796120 | DOI:10.3390/ijms26010264

Int J Mol Sci. 2024 Dec 30;26(1):240. doi: 10.3390/ijms26010240.ABSTRACTWeightlifting demands explosive power and neuromuscular coordination in brief, repeated intervals. These physiological demands underscore the critical role of nutrition, not only in optimizing performance during competitions but also in supporting athletes' rigorous training adaptations and ensuring effective recovery between sessions. As weightlifters strive to enhance their performance, well-structured nutritional strategies are indispensable. In this comprehensive review, we explored how weightlifters can optimize their performance through targeted nutritional strategies, including carbohydrate intake for glycogen replenishment and proteins for muscle growth and recovery. Additionally, the roles of key supplements, such as creatine, beta-alanine, and branch-chained amino acids in enhancing strength, delaying fatigue, and supporting muscle repair were discussed. A comprehensive literature review was conducted using PubMed, Google Scholar, and Web of Science to gather studies on nutritional strategies for weightlifting performance and training adaptation. The review focused on English-language articles relevant to weightlifters, including studies on powerlifting, while excluding those involving non-human subjects. Weightlifting requires explosive power, and proper nutrition is vital for performance and recovery, emphasizing the role of carbohydrate, protein, and fat intake. Nutrient timing and personalized strategies, informed by genetic and metabolomic analyses, enhance recovery and performance, while supplements like creatine, caffeine, and beta-alanine can significantly improve results when used correctly. Sustainable nutritional strategies are essential for enhancing weightlifter performance, emphasizing a balanced approach over extreme diets or excessive supplements. Further research is needed to refine these strategies based on individual athlete characteristics, ensuring consistent top-level performance throughout competitive seasons.PMID:39796095 | DOI:10.3390/ijms26010240

Int J Mol Sci. 2024 Dec 28;26(1):174. doi: 10.3390/ijms26010174.ABSTRACTOne of the most important characteristics of ornamental plants is leaf color, which enhances the color of plant landscapes and attracts pollinators for reproduction. The leaves of Impatiens hawkeri 'Sakimp005' are initially green, then the middle part appears yellow, then gradually become white, while the edge remains green. In the study, leaves of I. hawkeri 'Sakimp005', in four developmental stages (S1-G, S2-C, S3-C, and S4-C), were selected for the determination of pigment content, chromaticity values, integrative metabolomics, and transcriptomics analyses. The carotenoid content of leaves varied significantly and regularly at four stages, and the colorimetric values corroborated the phenotypic observations. The results of integrative metabolomics and transcriptomics analysis show that the accumulation of two carotenoids (lutein and zeaxanthin), to different degrees in the leaves of I. hawkeri 'Sakimp005' at four stages, led to the vary yellowing phenomenon. We speculated that the carotenoid biosynthesis (containing two branches: α-branch and β-branch) in leaves by IhLUT1 and IhLUT5 in the α-branch and IhBCH2 genes in the β-branch differed. These findings provide a molecular basis for Impatiens plants' leaf color breeding and improve the knowledge of the leaf color mechanism.PMID:39796032 | DOI:10.3390/ijms26010174

Int J Mol Sci. 2024 Dec 28;26(1):165. doi: 10.3390/ijms26010165.ABSTRACTAsthma is a chronic inflammatory respiratory disease that affects millions globally and poses a serious public health challenge. Current therapeutic strategies, including corticosteroids, are constrained by variable patient responses and adverse effects. In this study, a polyphenolic extract derived from the Tibetan medicinal plant Spenceria ramalana Trimen (SRT) was employed and shown to improve experimentally (ovalbumin + cigarette smoke, OVA + CS) induced asthma in rats. Initially, the potential therapeutic mechanism of the polyphenolic components in SRT on OVA + CS-induced asthma was predicated by network pharmacology analysis. Subsequently, in vivo experiments identified that SRT polyphenols exhibit significant anti-asthmatic activities, primarily mediated by lowering inflammatory cell counts such as the WBC (white blood cell), eosinophils, and neutrophils, decreasing the expression of inflammatory cytokines (IL-4, IL-5, IL-13, and TNF-α), alleviating lung histological damage (reduced inflammation, collagen deposition, and mucus secretion), and enhancing the epithelial barrier integrity (upregulation of ZO-1, occludin, and claudin-1). Additionally, SRT polyphenols downregulated the PI3K/Akt (Phosphoinositide 3-kinase/protein kinase B) signaling pathway, improved gut microbiota disruption, and regulated fecal metabolites (glucose-6-glutamate, PS (16:0/0:0), 8-aminocaprylic acid, galactonic acid, Ascr#10, 2,3,4,5,6,7-hexahydroxyheptanoic acid, phosphodimethylethanolamine, muramic acid, 9-oxohexadeca-10e-enoic acid, and sedoheptulose) in asthmatic rats. In conclusion, SRT polyphenols exerted multifaceted protective effects against OVA + CS-induced asthma in rats, highlighting their potential value in preventing asthma via the PI3K/Akt signaling pathway.PMID:39796021 | DOI:10.3390/ijms26010165

Int J Mol Sci. 2024 Dec 27;26(1):154. doi: 10.3390/ijms26010154.ABSTRACTOxidative phosphorylation and glycolysis are the main ATP-generating pathways in cell metabolism. The balance between these two pathways is frequently altered to carry out cell-specific activities in response to stimuli involving activation, proliferation, or differentiation. Despite being a useful tool for researching metabolic profiles in real time in relatively small numbers of cancer cells, the main Agilent Seahorse XF Pro Analyzer (Agilent Technologies, Santa Clara, CA, USA) guideline is currently not fully detailed in the distinction between suspensions vs. adherent cancer cells. This article provides step-by-step protocols for profiling metabolic fluxes in suspension vs. adherent cancer cells via Seahorse technology, including adjustments for normalisation of data on the basis of the number of viable cells or the total protein content. Owing to the adaptations of plates, reagents, cell count, and protein quantification, it is possible to (i) analyse both adherent and suspension cells with a single instrument; (ii) conduct all experiments in 96-well plates, thus using fewer cells, media, and reagents; (iii) determine the effect of a drug or compound directly on cell metabolism; (iv) normalise data on the basis of the number of viable cells or the total protein content via a spectrophotometer; and (v) achieve notable savings in cost and time.PMID:39796012 | DOI:10.3390/ijms26010154

Int J Mol Sci. 2024 Dec 26;26(1):90. doi: 10.3390/ijms26010090.ABSTRACTObesity and its related diseases, such as type 2 diabetes (T2DM), cardiovascular disease (CVD), and metabolic fatty liver disease (MAFLD), require new diagnostic markers for earlier detection and intervention. The aim of this study is to demonstrate the potential of metabolomics as a tool for identifying biomarkers associated with obesity and its comorbidities in every age group. The presented systematic review makes an important contribution to the understanding of the potential of metabolomics in identifying biomarkers of obesity and its complications, especially considering the influence of branched-chain amino acids (BCAAs), amino acids (AAs) and adipokines on the development of T2DM, MAFLD, and CVD. The unique element of this study is the combination of research results from the last decade in different age groups and a wide demographic range. The review was based on the PubMed and Science Direct databases, and the inclusion criterion was English-language original studies conducted in humans between 2014 and 2024 and focusing on the influence of BCAAs, AAs or adipokines on the above-mentioned obesity complications. Based on the PRISMA protocol, a total of 21 papers were qualified for the review and then assigned to a specific disease entity. The collected data reveal that elevated levels of BCAAs and some AAs strongly correlate with insulin resistance, leading to T2DM, MAFLD, and CVD and often preceding conventional clinical markers. Valine and tyrosine emerge as potential markers of MAFLD progression, while BCAAs are primarily associated with insulin resistance in various demographic groups. Adipokines, although less studied, offer hope for elucidating the metabolic consequences of obesity. The review showed that in the case of CVDs, there is still a lack of studies in children and adolescents, who are increasingly affected by these diseases. Moreover, despite the knowledge that adipokines play an important role in the pathogenesis of obesity, there are no precise findings regarding the correlation between individual adipokines and T2DM, MAFLD, or CVD. In order to be able to introduce metabolites into the basic diagnostics of obesity-related diseases, it is necessary to develop panels of biochemical tests that will combine them with classical markers of selected diseases.PMID:39795949 | DOI:10.3390/ijms26010090

Int J Mol Sci. 2024 Dec 25;26(1):67. doi: 10.3390/ijms26010067.ABSTRACTThe black garden ant (Lasius niger) is a widely distributed species across Europe, North America, and North Africa, playing a pivotal role in ecological processes within its diverse habitats. However, the microbiome associated with L. niger remains poorly investigated. In the present study, we isolated a novel species, Paenarthrobacter lasiusi, from the soil of the L. niger anthill. The genome of P. lasiusi S21 was sequenced, annotated, and searched for groups of genes of physiological, medical, and biotechnological importance. Subsequently, a series of microbiological, physiological, and biochemical experiments were conducted to characterize P. lasiusi S21 with respect to its sugar metabolism, antibiotic resistance profile, lipidome, and capacity for atmospheric nitrogen fixation, among others. A notable feature of the P. lasiusi S21 genome is the presence of two prophages, which may have horizontally transferred host genes involved in stress responses. P. lasiusi S21 synthesizes a number of lipids, including mono- and digalactosyldiacylglycerol, as well as steroid compounds that are typically found in eukaryotic organisms rather than prokaryotes. P. lasiusi S21 exhibits resistance to penicillins, lincosamides, fusidins, and oxazolidinones, despite the absence of specific genes conferring resistance to these antibiotics. Genomic data and physiological tests indicate that P. lasiusi S21 is nonpathogenic to humans. The genome of P. lasiusi S21 contains multiple operons involved in heavy metal metabolism and organic compound inactivation. Consequently, P. lasiusi represents a novel species with an intriguing evolutionary history, manifesting in distinctive genomic, metabolomic, and physiological characteristics. This species may have potential applications in the bioaugmentation of contaminated soils.PMID:39795926 | DOI:10.3390/ijms26010067

Int J Mol Sci. 2024 Dec 24;26(1):45. doi: 10.3390/ijms26010045.ABSTRACTGenetic studies of haematological cancers have pointed out the heterogeneity of leukaemia in its different subpopulations, with distinct mutations and characteristics, impacting the treatment response. Next-generation sequencing (NGS) and genome-wide analyses, as well as single-cell technologies, have offered unprecedented insights into the clonal heterogeneity within the same tumour. A key component of this heterogeneity that remains unexplored is the intracellular metabolome, a dynamic network that determines cell functions, signalling, epigenome regulation, immunity and inflammation. Understanding the metabolic diversities among cancer cells and their surrounding environments is therefore essential in unravelling the complexities of leukaemia and improving therapeutic strategies. Here, we describe the currently available methodologies and approaches to addressing the dynamic heterogeneity of leukaemia progression. In the second section, we focus on metabolic leukaemic vulnerabilities in acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL). Lastly, we provide a comprehensive overview of the most interesting clinical trials designed to target these metabolic dependencies, highlighting their potential to advance therapeutic strategies in leukaemia treatment. The integration of multi-omics data for cancer identification with the metabolic states of tumour cells will enable a comprehensive "micro-to-macro" approach for the refinement of clinical practices and delivery of personalised therapies.PMID:39795903 | DOI:10.3390/ijms26010045

Int J Mol Sci. 2024 Dec 24;26(1):42. doi: 10.3390/ijms26010042.ABSTRACTExtracellular vesicles (EVs) are lipid bilayer-bound particles released from cells that cannot replicate on their own, play a crucial role in intercellular communication, and are implicated in various physiological and pathological processes. Within the domain of embryo culture media research, extensive studies have been conducted to evaluate embryo viability by analyzing spent culture medium. Advanced methodologies such as metabolomic profiling, proteomic and genomic analyses, transcriptomic profiling, non-coding RNA assessments, and oxidative status measurements have been employed to further understand the molecular characteristics of embryos and improve selection criteria for successful implantation. In the field of EVs, only a limited number of studies have been conducted on embryo-conditioned medium, indicating a significant gap in knowledge regarding the potential role of EVs in embryo development and implantation. Therefore, this review aims to evaluate current research findings on EVs enriched from animal and human embryo spent medium. By unraveling the potential link between embryo-derived EVs and embryo selection in clinical settings, such research might enhance embryo-selection methods in assisted reproductive technologies, eventually increasing the success rates of fertility treatments and advancing our understanding of mechanisms underlying successful embryo development and implantation in humans.PMID:39795901 | DOI:10.3390/ijms26010042

Int J Mol Sci. 2024 Dec 24;26(1):28. doi: 10.3390/ijms26010028.ABSTRACTVerticillium wilt (VW) caused by Verticillium dahliae (Vd) is a devastating fungal cotton disease characterized by high pathogenicity, widespread distribution, and frequent variation. It leads to significant losses in both the yield and quality of cotton. Identifying key non-synonymous single nucleotide polymorphism (SNP) markers and crucial genes associated with VW resistance in Gossypium hirsutum and Gossypium barbadense, and subsequently breeding new disease-resistant varieties, are essential for VW management. Here, we sequenced the transcriptome and metabolome of roots of TM-1 (G. hirsutum) and Hai7124 (G. barbadense) after 0, 1, and 2 days of V991 inoculation. Transcriptome analysis identified a total of 72,752 genes, with 5814 differentially expressed genes (DEGs) determined through multiple group comparisons. KEGG enrichment analysis revealed that the key pathways enriched by DEGs obtained from both longitudinal and transverse comparisons contained the glutathione metabolism pathway. Metabolome analysis identified 995 metabolites, and 22 differentially accumulated metabolites (DAMs), which were correlated to pathways including glutathione metabolism, degradation of valine, leucine, and isoleucine, and biosynthesis of terpenoids, alkaloids, pyridine, and piperidine. The conjoint analysis of transcriptomic and metabolomic sequencing revealed DAMs and DEGs associated with the glutathione metabolism pathway, and the key candidate gene GH_D11G2329 (glutathione S-transferase, GSTF8) potentially associated with cotton response to VW infection was selected. These findings establish a basis for investigating the mechanisms underlying the cotton plant's resistance to VW.PMID:39795888 | DOI:10.3390/ijms26010028

Plants (Basel). 2025 Jan 4;14(1):133. doi: 10.3390/plants14010133.ABSTRACTThe depletion of the ozone layer has resulted in elevated ultraviolet-B (UV-B) radiation levels, posing a significant risk to terrestrial plant growth. Rhododendron chrysanthum Pall. (R. chrysanthum), adapted to high-altitude and high-irradiation environments, has developed unique adaptive mechanisms. This study exposed R. chrysanthum to UV-B radiation for two days, with an 8 h daily treatment, utilizing metabolomic and transcriptomic analyses to explore the role of WRKY transcription factors in the plant's UV-B stress response and their regulation of flavonoid synthesis. UV-B stress resulted in a significant decrease in rETR and Ik and a significant increase in 1-qP. These chlorophyll fluorescence parameters indicate that UV-B stress impaired photosynthesis in R. chrysanthum. Faced with the detrimental impact of UV-B radiation, R. chrysanthum is capable of mitigating its effects by modulating its flavonoid biosynthetic pathways to adapt positively to the stress. This study revealed changes in the expression of 113 flavonoid-related metabolites and 42 associated genes, with WRKY transcription factors showing significant correlation with these alterations. WRKY transcription factors can influence the expression of key enzyme genes in the flavonoid metabolic pathway, thereby affecting metabolite production. A theoretical reference for investigating plant stress physiology is provided in this work, which also offers insights into the stress responses of alpine plants under adverse conditions.PMID:39795393 | DOI:10.3390/plants14010133

Plants (Basel). 2025 Jan 3;14(1):123. doi: 10.3390/plants14010123.ABSTRACTEuphorbia jolkinii dominates the subalpine meadows in Shangri-La (Southwest China) owing to its potent allelopathic effects. However, the effects underlying its allelopathy require further characterization at the physiological and molecular levels. In this study, the physiological, biochemical, and metabolic mechanisms underlying E. jolkinii allelopathy were investigated using Arundinella hookeri as a receptor plant. The treatment of A. hookeri seedlings with E. jolkinii aqueous extract (EJAE) disrupted their growth by inhibiting photosynthesis, disrupting oxidation systems, and increasing soluble sugar accumulation and chlorophyll synthesis. Collectively, this causes severe impairment accompanied by abnormal photosynthesis and reduced biomass accumulation. Moreover, EJAE treatment suppressed gibberellin, indoleacetic acid, zeatin, salicylic acid, and jasmonic acid levels while promoting abscisic acid accumulation. Further metabolomic analyses identified numerous differentially abundant metabolites primarily enriched in the α-linolenic, phenylpropanoid, and flavonoid biosynthesis pathways in EJAE-treated A. hookeri seedlings. This study demonstrated that E. jolkinii exhibits potent and comprehensive allelopathic effects on receptor plants, including a significant disruption of endogenous hormone synthesis, the inhibition of photosynthesis, an impairment of membrane and oxidation systems, and changes in crucial metabolic processes associated with α-linolenic, phenylpropanoid, and flavonoid biosynthesis. Thus, our study provides a solid theoretical foundation for understanding the regulatory mechanisms underlying E. jolkinii allelopathy.PMID:39795383 | DOI:10.3390/plants14010123