PubMed

Heliyon. 2024 Sep 27;10(21):e38650. doi: 10.1016/j.heliyon.2024.e38650. eCollection 2024 Nov 15.ABSTRACTThe assessment of medication toxicity and safety is pivotal during pregnancy. Curdione, a sesquiterpene compound extracted from Curcumae Radix, displays beneficial properties in terms of anti-inflammatory, tumor growth suppression, and anti-coagulative effects. However, its reproductive toxicity and precise mechanism remain unclear. This study aims to explore the mechanism of curdione-induced toxicity damage in HTR-8/SVneo cells through the epigenetics, proteomics, and metabolomics, and experimental verification. The results showed that curdione elicited alterations in m6A modification, gene expression, protein levels, and cellular metabolism of HTR-8/SVneo cells. Additionally, curdione induces oxidative stress, mitochondrial and DNA damage, while also downregulating the expression of Wnt6, β-catenin, ZO-1, and CLDN1 proteins. Curdione has the potential to modulate oxidative stress, mitochondrial dysfunction, and disruption of tight junctions via the Wnt/β-catenin signaling pathway, which contributes to cellular damage in HTR-8/SVneo cells.PMID:39524727 | PMC:PMC11550733 | DOI:10.1016/j.heliyon.2024.e38650

Eco Environ Health. 2024 May 9;3(4):407-411. doi: 10.1016/j.eehl.2024.05.001. eCollection 2024 Dec.ABSTRACTImage 1.PMID:39524475 | PMC:PMC11541422 | DOI:10.1016/j.eehl.2024.05.001

Transl Pediatr. 2024 Oct 1;13(10):1777-1788. doi: 10.21037/tp-24-288. Epub 2024 Oct 28.ABSTRACTBACKGROUND: Pectus excavatum (PE) is the most common chest wall deformity, characterized by an insidious onset, gradual progression, and challenges in early diagnosis. It is often accompanied by emaciation and distinctive metabolic traits, which may provide valuable insights into its internal physiological and biochemical mechanisms. Our study attempted to screen out biomarkers by identifying the metabolic characteristics of PE, and the results provide a scientific basis for the early diagnosis of PE.METHODS: Untargeted metabolomic and lipidomic analyses using liquid chromatography-mass spectrometry was conducted on serum samples obtained from 20 patients diagnosed with PE and 30 healthy case-controls. Principal component analysis and partial least squares discriminant analysis were employed to assess the quality of the metabolic profiling and delineate the metabolic differences between the PE and healthy cohorts. Receiver operating characteristic analysis was conducted to evaluate the predictive accuracy of the selected biomarkers. Pathway analysis of the dysregulated metabolites was utilized to elucidate the underlying pathological pathways.RESULTS: Fourteen metabolites and seven lipids were found to be differentially expressed between patients with PE and healthy controls. Indole-3-acetaldehyde showed potential as a biomarker for PE, with an area under the curve value of 0.94, making it effective in distinguishing patients with PE. Pathway analysis revealed enrichment of several pathological pathways, such as valine, leucine, and isoleucine biosynthesis; sphingolipid metabolism; glycine, serine, and threonine metabolism; and glycerophospholipid metabolism.CONCLUSIONS: In our study, we employed a multiomics approach to comprehensively examine dysregulated serological molecules in PE patients, and the analyses revealed potential biomarkers for early diagnosis and provided information for pathological studies.PMID:39524383 | PMC:PMC11543133 | DOI:10.21037/tp-24-288

iScience. 2024 Oct 16;27(11):111184. doi: 10.1016/j.isci.2024.111184. eCollection 2024 Nov 15.ABSTRACTIntracranial aneurysms (IAs) are benign cerebrovascular maladies characterized by wall dilatation in the intracranial arteries. Nevertheless, spontaneous aneurysmal rupture can cause a life-threatening spontaneous subarachnoid hemorrhage (SAH). Emerging evidence indicates potential associations between gut dysbiosis and IAs pathogenesis, though the relationship with IA rupture remains unclear. This research analyzed 124 fecal samples for microbiomics and 160 for metabolomics, with the discovery and validation sets established for cross-validation. We identified differential gut microbiota and metabolites associated with ruptured intracranial aneurysms (RIAs) and developed a superior risk assessment model. Subsequent integrative analyses and validation revealed a significant link between disrupted unsaturated fatty acid and essential amino acid metabolic pathways and IA rupture, driven by alterations in gut microbiota. This study underscores the potential association between the gut-brain axis and IA rupture, while also highlighting gut microbiota dysbiosis as a potential risk factor for IA rupture and providing biomarkers for assessment.PMID:39524364 | PMC:PMC11550638 | DOI:10.1016/j.isci.2024.111184

iScience. 2024 Oct 12;27(11):111159. doi: 10.1016/j.isci.2024.111159. eCollection 2024 Nov 15.ABSTRACTLow birthweight (LBW) increases the risk of adult-onset diseases, including kidney diseases, with intergenerational consequences; however, the underlying mechanisms and effective interventions are unclear. To examine the cross-generational effects of LBW, we established an LBW mouse model through reduced uterine perfusion pressure (RUPP) and investigated the therapeutic potential of tadalafil, a phosphodiesterase 5 inhibitor, on LBW-associated consequences. RUPP-pups (R1) had lower fetal and birth weights, delayed renal development, and fewer glomeruli than Sham-pups. In adulthood, R1 mice exhibited persistently fewer glomeruli and elevated blood pressure, while Tadalafil-R1 mice showed reduced hypertension in both sexes and improved renal pathological changes in males. Additionally, pregnant R1 mice displayed inadequate gestational liver hypertrophy, impaired hepatic purine metabolism, and diminished placental angiogenesis, resulting in fetal growth restriction in the subsequent generation. These findings underscore the lasting impact of LBW on adult health and future generations and suggest tadalafil's potential to mitigate LBW-associated risks.PMID:39524353 | PMC:PMC11546680 | DOI:10.1016/j.isci.2024.111159

Cancers (Basel). 2024 Oct 30;16(21):3671. doi: 10.3390/cancers16213671.ABSTRACTThe gut microbiome has emerged as a crucial player in modulating cancer therapies, including radiotherapy. In the case of breast cancer, the interplay between the microbiome and radiotherapy-derived metabolites may enhance therapeutic outcomes and minimize adverse effects. In this review, we explore the bidirectional relationship between the gut microbiome and breast cancer. We explain how gut microbiome composition influences cancer progression and treatment response, and how breast cancer and its treatments influence microbiome composition. A dual role for radiotherapy-derived metabolites is explored in this article, highlighting both their therapeutic benefits and potential hazards. By integrating genomics, metabolomics, and bioinformatics tools, we present a comprehensive overview of these interactions. The study provides real-world insight through case studies and clinical trials, while therapeutic innovations such as probiotics, and dietary interventions are examined for their potential to modulate the microbiome and enhance treatment effectiveness. Moreover, ethical considerations and patient perspectives are discussed, ensuring a comprehensive understanding of the subject. Towards revolutionizing treatment strategies and improving patient outcomes, the review concludes with future research directions. It also envisions integrating microbiome and metabolite research into personalized breast cancer therapy.PMID:39518108 | DOI:10.3390/cancers16213671

BMC Musculoskelet Disord. 2024 Nov 6;25(1):883. doi: 10.1186/s12891-024-08010-y.ABSTRACTBACKGROUND: Adult growth hormone deficiency (AGHD) is associated with an increased risk of fractures and impaired bone microstructure. Understanding the metabolic changes accompanying bone deterioration in AGHD might provide insights into mechanisms behind molecular changes and develop new biomarkers or nutritional strategies for bone destruction. Our study aimed to investigate the association between altered metabolite patterns and impaired bone microstructure in adult rats with growth hormone deficiency.METHODS: Thirty seven-week-aged adult Lewis dwarf homozygous (dw/dw) rats (five females and five males), and adult Lewis dwarf heterozygous (dw/ +) rats (five females and five males) rats were compared. Micro-computed tomography (Micro-CT) was used to examine the bone's microstructure. Hematoxylin and eosin (H&E) staining were used to quantify the histological characteristics. Liquid chromatography-mass spectrometry untargeted serum metabolomic analysis was applied in the study. ELISA was used to measure serum bone turnover markers and IGF-1 levels.RESULTS: Adult dw/dw rats exhibited great reductions in trabecular volume bone density (Tb.vBMD), bone volume/total volume (BV/TV), and cortical thickness (Ct. Th) compared with adult dw/ + rats (all p values < 0.05), indicating significant impairment in bone microstructure. The serum metabolite profiles revealed substantial differences between the dw/dw rats and dw/ + rats. A total of 134 differential metabolites in positive ion mode and 49 differential metabolites in negative mode were identified. Five metabolites, including Lysophosphatidylcholine(LPC) 20:3, LPC22:6, LPC22:4, cortisol and histamine levels were upregulated in dw/dw rats. The steroid hormone biosynthesis and bile secretion pathways were the main perturbed metabolic pathways. There were significant associations between differential metabolites and the impaired bone microstructure parameters, indicating that the selected metabolites might serve as potential biomarkers for deteriorated bone microstructure in AGHD.CONCLUSION: Adult dw/dw rats exhibit impaired bone microstructure and distinct serum metabolic profiles, and the altered metabolites were significantly associated with bone microstructure destruction. This provides a new insight into understanding the mechanism of bone deterioration in AGHD patients from a metabolic perspective.PMID:39508246 | DOI:10.1186/s12891-024-08010-y

Elife. 2024 Nov 7;13:e100068. doi: 10.7554/eLife.100068.ABSTRACTThe gut microbiota is implicated in the pathogenesis of hyperuricemia (HUA) and gout. However, it remains unclear whether probiotics residing in the host gut, such as Lactobacillus, can prevent HUA development. Herein, we isolated Lactobacillus plantarum SQ001 from the cecum of HUA geese and conducted in vitro assays on uric acid (UA) and nucleoside co-culture. Metabolomics and genome-wide analyses, revealed that this strain may promote nucleoside uptake and hydrolysis through its nucleoside hydrolase gene. The functional role of iunH gene was confirmed via heterologous expression and gene knockout studies. Oral administration of L. plantarum SQ001 resulted in increased abundance of Lactobacillus species and reduced serum UA levels. Furthermore, it downregulated hepatic xanthine oxidase, a key enzyme involved in UA synthesis, as well as renal reabsorption protein GLUT9, while enhancing the expression of renal excretion protein ABCG2. Our findings suggest that L. plantarum has potential to ameliorate gut microbial dysbiosis with HUA, thereby offering insights into its potential application as a probiotic therapy for individuals with HUA or gout.PMID:39508089 | DOI:10.7554/eLife.100068

Sichuan Da Xue Xue Bao Yi Xue Ban. 2024 Sep 20;55(5):1195-1201. doi: 10.12182/20240960403.ABSTRACTOBJECTIVE: Radioactive intestinal injury is a common complication during radiotherapy of tumors. The aim of this study is to observe the effect of ionizing radiation on short-term changes in intestinal bile acids and to investigate the radioprotective effect of bile acids on intestinal cells.METHODS: A rat model of small intestinal injury was constructed by exposing the abdomen of the rats to daily irradiation at 2 Gy for 4 d in succession. The bile acids were quantified using metabolomics analysis. IEC-6 cells, a small intestinal epithelial cell line, were divided into a dimethyl sulfoxide (DMSO) control group receiving DMSO and 0 Gy irradiation, a glycoursodeoxycholic acid (GUDCA) experimental group receiving GUDCA and 0 Gy irradiation, a DMSO irradiation group receiving DMSO and 10 Gy irradiation, and a GUDCA irradiation group receiving GUDCA and 10 Gy irradiation. Cell viability and cytotoxicity was assessed by CCK-8 assay test. The apoptosis rate of cells was determined by flow cytometry. The colony formation rate and the radiosensitivity of the cells were determined by colony formation assay on solid media. The expression levels of proteins associated with cell death were determined using Western blot.RESULTS: After exposure to irradiation, the small intestine tissues of the rats showed typical radioactive intestinal injury. In addition, various bile acids showed fluctuation before and after irradiation. Among the bile acids, GUDCA increased significantly at 3 d after irradiation, but returned to the pre-irradiation level at 7 d after irradiation. Compared with the control group, after GUDCA treatment at 20 μmol/L for 24 h, the cell viability rate after irradiation was significantly higher than that of the DMSO group (P<0.05); the expression levels of the proteins, including PARP, caspase-3, RIP, and GSDMD, were significantly lower than those in the control group (P<0.05). After GUDCA treatment at 20 μmol/L for 24 h and 48 h, the cell apoptosis rate of the cells after irradiation was lower than that of the DMSO group (P<0.05). Compared with the DMSO control group, the colony formation ability of the GUDCA experimental group was stronger than that of the DMSO group after irradiation at 0, 2, 4, and 6 Gy (P<0.05). D0, or the mean lethal dose, of the GUDCA group was 6.374, while that of the DMSO group was 4.572. Compared with the DMSO control group, the D0 value of the GUDCA treatment group increased, and the sensitization enhancement ratio (SER) was 0.717.CONCLUSION: After exposing the abdomen of rats to irradiation, the intestinal bile acid metabolism of the rats will change significantly, and GUDCA can produce radioprotective effects on intestinal cells to a certain extent.PMID:39507959 | PMC:PMC11536250 | DOI:10.12182/20240960403

Food Chem X. 2024 Oct 16;24:101899. doi: 10.1016/j.fochx.2024.101899. eCollection 2024 Dec 30.ABSTRACTBlack tea's quality and flavor are largely influenced by its processing stages, which affect its volatile and non-volatile phytochemicals. This study aimed to optimized black tea manufacturing by investigating withering time, fermentation time, and temperature's impact on sensory quality. Using a U*15 (157) uniform design, optimal conditions were determined: 14 h of withering, 5.6 h of fermentation, and a 34 °C temperature. A verification experiment analyzed the volatile and non-volatile profiles. HPLC, GC-MS, and LC-MS revealed dynamic changes in phytochemicals. Among 157 VOCs and 2642 metabolites, 19 VOCs (VIP > 1.5) were crucial for aroma, while 50 (VIP > 1.5, p < 0.01) characteristic metabolites were identified. During processing, fragrant volatile compounds like linalool oxides, geraniol, benzeneacetaldehyde, benzaldehyde, methyl salicylate, and linalyl acetate increased, contributing to rose and honey like aromas. These changes were crucial in developing the characteristic flavor and color of black tea. Twenty-four new compounds formed, while 80 grassy odor volatiles decreased. Non-volatile metabolites changed notably, with decreased catechins and increased gallic acid. Theaflavin compounds rose initially but declined later. This study outlines metabolite changes in Yunkang 10 black tea, crucial for flavor enhancement and quality control.PMID:39507928 | PMC:PMC11539724 | DOI:10.1016/j.fochx.2024.101899

Front Toxicol. 2024 Oct 23;6:1465728. doi: 10.3389/ftox.2024.1465728. eCollection 2024.ABSTRACTCannabinoid hyperemesis syndrome presents as a complex of symptoms and signs encompassing nausea, vomiting, abdominal pain, and hot water bathing behavior, most typically in a heavy cannabis user. Its presentation is frequently associated with hypothalamic-pituitary-adrenal axis activation with stress and weight loss. Recent investigation has identified five statistically significant mutations in patients distinct from those of frequent cannabis users who lack the symptoms, affecting the TRPV1 receptor, two dopamine genes, the cytochrome P450 2C9 enzyme that metabolizes tetrahydrocannabinol, and the adenosine triphosphate-binding cassette transporter. The syndrome is associated with escalating intake of high potency cannabis, or alternatively, other agonists of the cannabinoid-1 receptor including synthetic cannabinoids. Some patients develop environmental triggers in scents or foods that suggest classical conditioned responses. Various alternative "causes" are addressed and refuted in the text, including exposure to pesticides, neem oil or azadirachtin. Nosological confusion of cannabinoid hyperemesis syndrome has arisen with cyclic vomiting syndrome, whose presentation and pathophysiology are clearly distinct. The possible utilization of non-intoxicating antiemetic cannabis components in cannabis for treatment of cannabinoid hyperemesis syndrome is addressed, along with future research suggestions in relation to its genetic foundation and possible metabolomic signatures.PMID:39507417 | PMC:PMC11537899 | DOI:10.3389/ftox.2024.1465728

J Inflamm Res. 2024 Nov 2;17:8027-8045. doi: 10.2147/JIR.S480307. eCollection 2024.ABSTRACTOBJECTIVE: This study aimed to establish a model for identifying chronic gastritis with the traditional Chinese medicine damp phlegm pattern by examining metabolite changes in the tongue coating of patients. It also explored the role of metabolic pathways in the pathogenesis of this condition.METHODS: This cross-sectional study involved 300 patients diagnosed with chronic gastritis. Of these, 200 patients exhibited the damp phlegm pattern, while 100 did not. Metabolomic methods employing GC-TOF-MS and UHPLC-QE-MS were utilized to identify various metabolites in the tongue coating of patients. An identification model for chronic gastritis with the damp phlegm pattern was created based on ROC curves derived from differential biomarkers. Additionally, 50 samples not included in model construction were collected for external validation.RESULTS: Comparison of the damp phlegm pattern group with the non-damp phlegm pattern group revealed a total of 116 differential metabolites. Among these, lipids and lipid-like compounds were most abundant, comprising 27 types, which included four lipid metabolites related to sphingomyelin metabolism. The ROC model, which included phenol, 2.6-diaminoheptanedioic acid, and N-hexadecanoyl pyrrolidine, demonstrated the highest accuracy, with accuracy, sensitivity, and specificity metrics of 94.0%, 91.0%, and 87.0%, respectively. Furthermore, external validation using tongue coating metabolites from 50 patients revealed accuracy, sensitivity, and specificity in the validation set of 93.9%, 90.6%, and 83.3%, respectively.CONCLUSION: Differential metabolites between patients with the damp phlegm pattern and those without are primarily lipids and lipid-like compounds. N-hexadecanoyl pyrrolidine, phenol, and 2.6-diaminoheptanedioic acid may serve as potential biomarkers for chronic gastritis characterized by the damp phlegm pattern.PMID:39507266 | PMC:PMC11539634 | DOI:10.2147/JIR.S480307

Front Vet Sci. 2024 Oct 23;11:1477575. doi: 10.3389/fvets.2024.1477575. eCollection 2024.ABSTRACTThe aim of this study was to explore whether and how Bacillus subtilis KC1 can enhance the growth performance of Mycoplasma gallisepticum (MG)-infected broilers. Broilers were randomly divided into 4 groups: the control group (basal diet), the MG group (basal diet + MG challenge), the KC group (basal diet + B. subtilis KC1 supplementation), the KC + MG group (basal diet + B. subtilis KC1 supplementation + MG challenge). The results showed that, compared to the control group, MG group exhibited significantly reduced body weight and average daily gain, and increased feed conversion ratio of broilers. However, compared to the MG group, the B. subtilis KC1 + MG group exhibited significantly improved above indicators of growth performance. In addition, compared to the MG group, B. subtilis KC1 + MG group exhibited increased superoxide dismutase levels and reduced levels of malondialdehyde, interleukin-1β, and tumor necrosis factor-α of broilers. Furthermore, metabolomics and transcriptomics analyses indicated that MG infection disrupted amino acid metabolism in broilers, whereas B. subtilis KC1 supplementation alleviated the abnormal amino acid metabolism caused by MG. These results suggested that B. subtilis KC1 may alleviate the poor growth performance caused by MG infection in broilers by improving amino acid metabolism.PMID:39507220 | PMC:PMC11538993 | DOI:10.3389/fvets.2024.1477575

Heliyon. 2024 Oct 10;10(20):e38814. doi: 10.1016/j.heliyon.2024.e38814. eCollection 2024 Oct 30.ABSTRACTBACKGROUND: Renzhu Jianwei Granula (RJG) is a traditional Chinese medicine compound initially formulated to address precancerous lesions for gastric cancer. The aim of this study was to assess RJG's efficacy in treating precancerous lesions of gastric cancer through a comprehensive meta-analysis of randomized clinical trials.METHODS: Two authors separately conducted an exhaustive search across three databases (PubMed, CNKI and Wanfang) without imposing any restrictions on publication year or language. Eligible studies, spanning from the inception of databases to July 18th, 2024, were included. Valid data were summarized and those with a group size of 3 or more were preserved. R software and Cochrane collaboration tools were employed for sensitivity analysis and assessing the quality of the included studies. The data from selected studies were transformed into risk ratios (RRs) and subjected to meta-analysis. This study was prospectively registered in PROSPERO.RESULTS: Data from 9 studies encompassing 912 participants revealed that the RJG group exhibited superior clinical efficacy compared to the control group, with an RR of 0.36 (95 % confidence interval (CI): 0.25 to 0.52). RJG demonstrated enhanced efficacy over the control group in both comprehensive efficacy (RR: 0.42, 95 % CI: 0.31 to 0.55) and gastroscopy efficacy (RR: 0.56, 95 % CI: 0.46 to 0.69). Moreover, significant improvements in pathological features such as atrophy (RR: 0.58, 95 % CI: 0.45 to 0.73), dysplasia (RR: 0.41, 95 % CI: 0.27 to 0.61), and intestinal metaplasia (RR: 0.54, 95 % CI: 0.43 to 0.69) in precancerous lesions of gastric cancer were observed following RJG administration.CONCLUSION: This study's synthesized data provide compelling evidence of RJG's substantial therapeutic impact in ameliorating symptoms associated with precancerous lesions of gastric cancer.TRIAL REGISTRATION NUMBER: The study protocol was registered at PROSPERO (CRD42024572606).PMID:39506958 | PMC:PMC11538645 | DOI:10.1016/j.heliyon.2024.e38814

BMC Vet Res. 2024 Nov 6;20(1):505. doi: 10.1186/s12917-024-04339-7.ABSTRACTBACKGROUND: Studying the effect of dietary Spirulina and lysozyme supplementation on the metabolome and proteome of liver tissue contributes to understanding potential hepatic adaptations of piglets to these novel diets. This study aimed to understand the influence of including 10% Spirulina on the metabolome and proteome of piglet liver tissue. Three groups of 10 post-weaned piglets, housed in pairs, were fed for 28 days with one of three experimental diets: a cereal and soybean meal-based diet (Control), a base diet with 10% Spirulina (SP), and an SP diet supplemented with 0.01% lysozyme (SP + L). At the end of the trial, animals were sacrificed and liver tissue was collected. Metabolomics analysis (n = 10) was performed using NMR data analysed with PCA and PLS-DA. Proteomics analysis (n = 5) was conducted using a filter aided sample preparation (FASP) protocol and Tandem Mass Tag (TMT)-based quantitative approach with an Orbitrap mass spectrometer.RESULTS: Growth performance showed an average daily gain reduction of 9.5% and a feed conversion ratio increase of 10.6% in groups fed Spirulina compared to the control group. Metabolomic analysis revealed no significant differences among the groups and identified 60 metabolites in the liver tissue. Proteomics analysis identified 2,560 proteins, with 132, 11, and 52 differentially expressed in the Control vs. SP, Control vs. SP + L and SP vs. SP + L comparisons, respectively. This study demonstrated that Spirulina enhances liver energy conversion efficiency, detoxification and cellular secretion. It improves hepatic metabolic efficiency through alterations in fatty acid oxidation (e.g., upregulation of enzymes like fatty acid synthase and increased acetyl-CoA levels), carbohydrate catabolism (e.g., increased glucose and glucose-6-phosphate), pyruvate metabolism (e.g., higher levels of pyruvate and phosphoenolpyruvate carboxykinase), and cellular defence mechanisms (e.g., upregulation of glutathione and metallothionein). Lysozyme supplementation mitigates some adverse effects of Spirulina, bringing physiological responses closer to control levels. This includes fewer differentially expressed proteins and improved dry matter, organic matter and energy digestibility. Lysozyme also enhances coenzyme availability, skeletal myofibril assembly, actin-mediated cell contraction, tissue regeneration and development through mesenchymal migration and nucleic acid synthesis pathways.CONCLUSIONS: While Spirulina inclusion had some adverse effects on growth performance, it also enhanced hepatic metabolic efficiency by improving fatty acid oxidation, carbohydrate catabolism and cellular defence mechanisms. The addition of lysozyme further improved these benefits by reducing some of the negative impacts on growth and enhancing nutrient digestibility, tissue regeneration, and overall metabolic balance. Together, Spirulina and lysozyme demonstrate potential as functional dietary components, but further optimization is needed to fully realize their benefits without compromising growth performance.PMID:39506864 | DOI:10.1186/s12917-024-04339-7

Br J Dermatol. 2024 Nov 7:ljae432. doi: 10.1093/bjd/ljae432. Online ahead of print.NO ABSTRACTPMID:39506538 | DOI:10.1093/bjd/ljae432

Bioessays. 2024 Nov 6:e2400154. doi: 10.1002/bies.202400154. Online ahead of print.ABSTRACTHematopoiesis unfolds within the bone marrow niche where hematopoietic stem cells (HSCs) play a central role in continually replenishing blood cells. The hypoxic bone marrow environment imparts peculiar metabolic characteristics to hematopoietic processes. Here, we discuss the internal metabolism of HSCs and describe external influences exerted on HSC metabolism by the bone marrow niche environment. Importantly, we suggest that the metabolic environment and metabolic cues are intertwined with HSC cell fate, and are crucial for hematopoietic processes. Metabolic dysregulation within the bone marrow niche during acute stress, inflammation, and chronic inflammatory conditions can lead to reduced HSC vitality. Additionally, we raise questions regarding metabolic stresses imposed on HSCs during implementation of stem cell protocols such as allo-SCT and gene therapy, and the potential ramifications. Enhancing our comprehension of metabolic influences on HSCs will expand our understanding of pathophysiology in the bone marrow and improve the application of stem cell therapies.PMID:39506498 | DOI:10.1002/bies.202400154

Physiol Plant. 2024 Nov-Dec;176(6):e14592. doi: 10.1111/ppl.14592.ABSTRACTSoil salinization, which severely limits crop yield and quality, has become a global environmental and resource issue. Melatonin plays an important role in plant responses to salt stress. Smooth bromegrass is an important forage with excellent feed value and is widely grown in northern and north-west China for pasture and sand binding. However, the physiological and molecular mechanisms underlying exogenous melatonin regulation of salt stress in smooth bromegrass are not clear. This study compared the phenotype, physiological, transcriptome, and metabolome profiles of two varieties with contrasting salt tolerance attributes under salt and melatonin treatment. After melatonin treatment, the catalase (CAT) and ascorbate peroxidase (APX) activity, proline content, actual photochemical efficiency (Y(II)), relative water content, and fresh weight above ground were significantly higher than under salt treatment, while relative conductivity, H2O2 content, and Na+/K+ ratio were significantly lower than salt treatment. The transcriptome and metabolite profiling analysis of smooth bromegrass seedlings treated without melatonin under salt stress identified the presence of 22522 differentially expressed genes (DEGs) and 862 differentially expressed metabolites (DEMs) in SS, 17809 DEGs and 812 DEMs in ST, while treated with melatonin under salt stress identified the presence of 7033 DEGs and 177 DEMs in SS, 2951 DEGs and 545 DEMs in ST. Furthermore, in response to salt stress, melatonin may be involved in regulating the correlation between DEGs and DEMs in flavonoid biosynthesis, proline biosynthesis, and melatonin biosynthesis. Moreover, melatonin participated in mediating melatonin biosynthesis pathways and affected the expression of ASMT in response to salt stress.PMID:39506145 | DOI:10.1111/ppl.14592

Commun Biol. 2024 Nov 6;7(1):1450. doi: 10.1038/s42003-024-07137-x.ABSTRACTThe aim of this study was to explore the intricate relationship between serum metabolomics and lifestyle factors, shedding light on their impact on health in the context of breast cancer risk. Detailed metabolic profiles of 2283 female participants in the Trøndelag Health Study (HUNT study) were obtained through nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS).We show that lifestyle-related variables can explain up to 30% of the variance in individual metabolites. Age and obesity were the primary factors affecting the serum metabolic profile, both associated with increased levels of triglyceride-rich very low-density lipoproteins (VLDL) and intermediate-density lipoproteins (IDL), amino acids and glycolysis-related metabolites, and decreased levels of high-density lipoproteins (HDL). Moreover, factors like hormonal changes associated with menstruation and contraceptive use or education level influence the metabolite levels.Participants were clustered into three distinct clusters based on lifestyle-related factors, revealing metabolic similarities between obese and older individuals, despite diverse lifestyle factors, suggesting accelerated metabolic aging with obesity. Our results show that metabolic associations to cancer risk may partly be explained by modifiable lifestyle factors.PMID:39506131 | DOI:10.1038/s42003-024-07137-x

Acta Pharmacol Sin. 2024 Nov 6. doi: 10.1038/s41401-024-01409-2. Online ahead of print.ABSTRACTRAS is the most frequently mutated oncoprotein for cancer driving. Understanding of RAS biology and discovery of druggable lynchpins in RAS pathway is a prerequisite for targeted therapy of RAS-mutant cancers. The recent identification of KRASG12C inhibitor breaks the "undruggable" curse on RAS and has changed the therapy paradigm of KRAS-mutant cancers. However, KRAS mutations, let alone KRASG12C mutation, account for only part of RAS-mutated cancers. Targeted therapies for cancers harboring other RAS mutations remain the urgent need. In this study we explored the pivotal regulatory molecules that allow for broad inhibition of RAS mutants. By comparing the expression levels of nucleotide pyrophosphatase (NPPS) in a panel of cell lines and the functional consequence of increased NPPS expression in RAS-mutant cells, we demonstrated that cancer cells with various kinds of RAS mutations depended on NPPS for growth and survival, and that this dependence conferred a vulnerability of RAS-mutant cancer to treatment of NPPS inhibition. RAS-mutant cells, compared with RAS-wildtype cells, bored and required an upregulation of NPPS. Transcriptomics and metabolomics analyses revealed a NPPS-dependent hyperglycolysis in RAS-mutant cells. We demonstrated that NPPS promoted glucose-derived glycolytic intermediates in RAS-mutant cells by enhancing its interaction with hexokinase 1 (HK1), the enzyme catalyzing the first committed step of glycolysis. Pharmacological inhibition of NPPS-HK1 axis using NPPS inhibitor Enpp-1-IN-1 or HK1 inhibitor 2-deoxyglucose (2-DG), or genetic interfere with NPPS suppressed RAS-mutant cancers in vitro and in vivo. In conclusion, this study reveals an unrecognized mechanism and druggable lynchpin for modulation of pan-mutant-RAS pathway, proposing a new potential therapeutic approach for treating RAS-mutant cancers.PMID:39506063 | DOI:10.1038/s41401-024-01409-2