PubMed

Cell Rep Med. 2023 Jan 17;4(1):100897. doi: 10.1016/j.xcrm.2022.100897.ABSTRACTFeeding behavior must be continuously adjusted to match energy needs. Recent discoveries in murine models identified uridine as a regulator of energy balance. Here, we explore its contribution to the complex control of food intake in humans by administering a single dose of uridine monophosphate (UMP; 0.5 or 1 g) to healthy participants in two placebo-controlled studies designed to assess food behavior (registration: DRKS00014874). We establish that endogenous circulating uridine correlates with hunger and ensuing food consumption. It also dynamically decreases upon caloric ingestion, prompting its potential role in a negative feedback loop regulating energy intake. We further demonstrate that oral UMP administration temporarily increases circulating uridine and-when within the physiological range-enhances hunger and caloric intake proportionally to participants' basal energy needs. Overall, uridine appears as a potential target to tackle dysfunctions of feeding behavior in humans.PMID:36652907 | DOI:10.1016/j.xcrm.2022.100897

Plant Physiol Biochem. 2023 Jan 13;195:288-299. doi: 10.1016/j.plaphy.2023.01.020. Online ahead of print.ABSTRACTWild ginseng is thought to be superior in its medicinal quality to cultivated ginseng, potentially owing to the differences in active components. This study was designed accordingly to assess the differences in secondary metabolite components and their synthesis in wild and cultivated ginseng by using quantitative proteomics combined with secondary metabolomics approaches. A total of 72 secondary metabolites were found to be differentially abundant, of which dominant abundant in wild ginseng primarily included triterpenoid saponins (ginsenosides) and phytosterols. Ginsenoside diversity was increased in wild ginseng, particularly with respect to rare ginsenosides. Ginsenoside Rk1, F1, Rg5, Rh1, PPT, Rh2, and CK enriched in wild ginseng were validated by HPLC. In addition to ginsenosides, stigmasterol and β-sitosterol were accumulated in wild ginseng. 102 differentially expressed proteins between wild and cultivated ginseng were identified using iTRAQ labeling technique. Among them, 25 were related to secondary metabolism, mainly involved in sesquiterpene and triterpene biosynthesis, which was consistent with metabolomics results. Consistently, the activity levels of HMGR, FDPS, SS, SE, DS, CYP450, GT and CAS, which are key enzymes related to ginsenoside and phytosterol biosynthesis, were confirmed to be elevated in wild ginseng.The biosynthesis of ginsenosides and phytosterols in wild ginseng is higher than that in cultivated ginseng, which may be related to natural growth without artificial domestication. To some extent, this study explained the accumulation of pharmacodynamic components and overall quality of ginseng, which could provide reference for the germplasm improvement and planting of ginseng.PMID:36652850 | DOI:10.1016/j.plaphy.2023.01.020

Plant Physiol Biochem. 2023 Jan 13;195:275-287. doi: 10.1016/j.plaphy.2023.01.025. Online ahead of print.ABSTRACTThe pericarp of fruit can be differentiated into endocarp, mesocarp, and exocarp. To explore the differences in gene expression and metabolites in different tissues of the pericarp, the fruits of sumac (Toxicodendron vernicifluum) were separated into endocarp and mesocarp-exocarp. The metabolites and transcriptome of exocarp-mesocarp and endocarp of Toxicodendron vernicifluum were analyzed by HPLC-QTOF-MS/MS and RNA sequencing, respectively. A total of 52 phenolic compounds were identified, including 3 phenylpropane derivatives, 10 urushiol compounds and 39 flavonoids. The exocarp-mesocarp contained more urushiol compounds and flavonoid glycosides while the endocarp contained more biflavonoids, such as rhusflavone and dihydromorelloflavone. The characteristic component of endocarp was rhusflavone and the characteristic component of exocarp-mesocarp was urushiol (triene). Most of the genes involved in flavonoid synthesis pathway were upregulated in endocarp compared with exocarp-mesocarp and positively correlated with the content of flavonoids. The candidate genes related to the synthesis of components of flavonoid glycosides and biflavonoids were screened. Metabolomic and transcriptomic analyses provide new insights into the synthesis and distribution of flavonoid glycosides and biflavonoids in the fruits of Toxicodendron vernicifluum.PMID:36652849 | DOI:10.1016/j.plaphy.2023.01.025

J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Jan 11;1216:123603. doi: 10.1016/j.jchromb.2023.123603. Online ahead of print.ABSTRACTMyocardial ischemia/reperfusion (MI/R) injury is a life-threatening syndrome with high morbidity and mortality. Zhishi-Xiebai-Guizhi Decoction (ZSXBGZD) is a classic traditional Chinese medicine formula, used to treat cardiovascular diseases for centuries. However, its underlying medicinal mechanism has not been clearly elucidated, which hinders its widespread application. Here, the curative effects and therapeutic mechanism of ZSXBGZD against MI/R were addressed based on an integration of pharmaceutical evaluation and cellular metabolomics. First, a hypoxia/reoxygenation (H/R) model in H9c2 cells was employed to resemble MI/R and multiple pharmacological indicators were performed to assess the efficacy of ZSXBGZD. The results showed that ZSXBGZD possessed exceptional ability in attenuating cardiomyocyte injury, concerning oxidative stress, mitochondrial dysfunction, energy acquisition and cell apoptosis. Furthermore, a cell metabolomics approach based on HILIC and UPLC-Q-TOF-MS coupled with multivariate analysis was conducted to explore the metabolic regulation of ZSXBGZD. 38 differential polar metabolites related to H/R were uncovered, and 34 of them were reversed to normal state after the treatment of ZSXBGZD, revealing the perturbations of energy metabolism and amino acid metabolism. Moreover, formula decomposition justified the combination of single herbs to form ZSXBZGD and confirmed the pivotal status of Allii Macrostemonis Bulbus and Trichosanthis Fructus.PMID:36652817 | DOI:10.1016/j.jchromb.2023.123603

J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Jan 10;1216:123602. doi: 10.1016/j.jchromb.2023.123602. Online ahead of print.ABSTRACTKidney yang deficiency syndrome (KYDS) is a classic syndrome of traditional Chinese medicine (TCM). The salt-processed product of Semen Cuscuta (YP) is the monarch drug in Bushen Antai Mixture (BAM), can improve the reproductive dysfunction caused by KYDS, and the effect is better than that of raw products of Semen Cuscuta (SP). However, its mechanism is not completely clear yet. In this study, an integrated strategy combining untargeted metabolomics with microbiology was used to explore the mechanism of YP in the BAM improving KYDS. 16S rDNA gene sequencing showed that BAM containing YP (Y-BAM) had a significantly better regulatory effect on Desulfobacterota and Desulfovibrionaceae_unclassified than BAM containing SP (S-BAM). Untargeted metabolomics studies showed that Y-BAM significantly regulated 4 metabolites and 4 metabolic pathways. In addition, multi-index analysis showed that the effect of Y-BAM on arachidonic acid metabolism, tyrosine metabolism, purine metabolism, fructose and mannose metabolism and total metabolism was closer to that of the control group compared to S-BAM. The analysis of serum biochemical indexes showed that Y-BAM had more significant regulating effect on the levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T) and superoxide dismutase (SOD) in serum of KYDS rats compared to S-BAM. Spearman correlation analysis showed that there was a significant correlation between intestinal microorganisms and metabolites and serum biochemical indexes. For example, Desulfovibrionaceae_unclassified was positively correlated with arachidonic acid, and negatively correlated with SOD and LH. This study suggests that YP may enhance the regulation of intestinal flora and endogenous metabolism of KYDS, so that BAM shows a better therapeutic effect on KYDS, which also reasonably explains why BAM uses Semen Cuscuta stir-baked with salt solution.PMID:36652816 | DOI:10.1016/j.jchromb.2023.123602

Food Chem. 2023 Jan 9;410:135441. doi: 10.1016/j.foodchem.2023.135441. Online ahead of print.ABSTRACTThe effects of superfine yak bone powder (YBP) on human gut microbiota (HGM) were investigated by in vitro digestion and fermentation combined with microbiomics and metabolomics. Results showed that size reduction and protein structural degradation during digestion allowed superfine YBP to release more Ca2+ than CaCO3 powders with similar particle size. Moreover, the indigestible YBP further influenced HGM and was associated with increased occurrence of beneficial bacteria such as Megasphaera spp., Megamonas spp., Acidaminococcus spp., and Prevotella spp. The altered HGM was associated with greater production of short-chain fatty acids with 4-6 carbon atoms. Furthermore, the indigestible YBP was associated with up-regulation of many lipid-related metabolites, including taurine, secondary bile acids, saturated long-chain fatty acids, and ω-3/ω-6 polyunsaturated fatty acids, which modulated favorably lipid metabolic pathways. These findings implied the potential activity of superfine YBP as a food fortifier in favorably altering HGM community structure and regulating lipid metabolism.PMID:36652799 | DOI:10.1016/j.foodchem.2023.135441

Curr Opin Plant Biol. 2023 Jan 16;73:102332. doi: 10.1016/j.pbi.2022.102332. Online ahead of print.ABSTRACTFlowering plants have evolved extraordinarily diverse metabolites that underpin the floral visual and olfactory signals enabling plant-pollinator interactions. In some cases, these metabolites also provide unusual rewards that specific pollinators depend on. While some metabolites are shared by most flowering plants, many have evolved in restricted lineages in response to the specific selection pressures encountered within different niches. The latter are designated as specialized metabolites. Recent investigations continue to uncover a growing repertoire of unusual specialized metabolites. Increased accessibility to cutting-edge multi-omics technologies (e.g. genome, transcriptome, proteome, metabolome) is now opening new doors to simultaneously uncover the molecular basis of their synthesis and their evolution across diverse plant lineages. Drawing upon the recent literature, this perspective discusses these aspects and, where known, their ecological and evolutionary relevance. A primer on omics-guided approaches to discover the genetic and biochemical basis of functional specialized metabolites is also provided.PMID:36652780 | DOI:10.1016/j.pbi.2022.102332

Clin Cancer Res. 2023 Jan 18:CCR-22-2263. doi: 10.1158/1078-0432.CCR-22-2263. Online ahead of print.ABSTRACTPURPOSE: Inhibition of monocarboxylate transporter (MCT) 1-mediated lactate transport may have cytostatic/cytotoxic effects on tumour cells. We report results from the dose-escalation part of a first‑in‑human trial of AZD3965, a first-in-class MCT1 inhibitor, in advanced cancer.EXPERIMENTAL DESIGN: This multicentre, Phase 1, dose-escalation and dose-expansion trial enrolled patients with advanced solid tumours or lymphoma and no standard therapy options. Exclusion criteria included history of retinal/cardiac disease, due to MCT1 expression in the eye and heart. Patients received daily oral AZD3965 according to a 3+3 then rolling 6 design. Primary objectives were to assess safety and determine the maximum tolerated dose and/or recommended Phase 2 dose (RP2D). Secondary objectives for dose-escalation included measurement of pharmacokinetics and pharmacodynamic activity. Exploratory biomarkers included tumour expression of MCT1 and MCT4, functional imaging of biological impact and metabolomics.RESULTS: During dose-escalation, 40 patients received AZD3965 at 5-30 mg once daily or 10 or 15 mg twice daily (BD). Treatment‑emergent adverse events were primarily Grade 1/2, most commonly electroretinogram changes (retinopathy), fatigue, anorexia and constipation. Seven patients receiving ≥20 mg daily experienced dose-limiting toxicities (DLTs): Grade 3 cardiac troponin rise (n=1), asymptomatic ocular DLTs (n=5) and Grade 3 acidosis (n=1). Plasma pharmacokinetics demonstrated attainment of target concentrations; pharmacodynamic measurements indicated on‑target activity.CONCLUSIONS: AZD3965 is tolerated at doses that produce target engagement. DLTs were on-target and primarily dose-dependent, asymptomatic, reversible ocular changes. An RP2D of 10 mg BD was established for use in dose-expansion in cancers that generally express high MCT1/low MCT4 (not yet published).PMID:36652553 | DOI:10.1158/1078-0432.CCR-22-2263

PLoS One. 2023 Jan 18;18(1):e0280491. doi: 10.1371/journal.pone.0280491. eCollection 2023.ABSTRACTDiabetes mellitus is a multiorgan systemic disease impacting numerous ocular structures that results in significant ocular morbidity and often results in more frequent corneal and glaucoma surgeries for affected individuals. We hypothesize that the systemic metabolic and proteomic derangement observed in the progression of diabetes influences the composition of the aqueous humor (AH), which ultimately impacts the anterior segment health of the eye. To identify changes associated with diabetes progression, we mapped the metabolite profile and proteome of AH samples from patients with varying severities of type II diabetes (T2DM). Patients were classified as nondiabetic (ND or control), non-insulin-dependent diabetic without advanced features of disease (NAD-ni), insulin-dependent diabetic without advanced features (NAD-i), or diabetic with advanced features (AD). AH samples collected from the anterior chamber during elective ophthalmic surgery were evaluated for metabolite and protein expression changes associated with diabetic severity via gas chromatography/mass spectrometry and ultra-high performance liquid chromatography tandem mass spectrometry, respectively. Metabolic and proteomic pathway analyses were conducted utilizing MetaboAnalyst 4.0 and Ingenuity Pathway Analysis. A total of 14 control, 12 NAD-ni, 4 NAD-I, and 14 AD samples were included for analysis. Elevated levels of several branched amino acids (e.g., valine, leucine, isoleucine), and lipid metabolites (e.g., palmitate) were found only with increasing diabetic severity (i.e., the AD group). Similar proteomic trends were noted in amino acid and fatty acid metabolism and the unfolded protein/stress response. These results represent the first report of both metabolomic and proteomic evaluation of aqueous humor. Diabetes results in metabolic and proteomic perturbations detectable in the AH, and unique changes become manifest as T2DM severity worsens. Changes in AH composition may serve as an indicator of disease severity, risk assessment of anterior segment cells and structures, and potential future therapies.PMID:36652491 | DOI:10.1371/journal.pone.0280491

Curr Microbiol. 2023 Jan 18;80(2):77. doi: 10.1007/s00284-023-03187-2.ABSTRACTRhizobacteria that are helpful to plants can lessen the impacts of salt stress, and they may hold promise for the development of sustainable agriculture in the future. The present study was intended to explicate consortia of salt-tolerant plant-beneficial rhizobacteria for the amelioration of salinity stress in Arabidopsis plants. Inoculation with both the consortia positively influenced the growth of plants as indicated by total chlorophyll content, MDA content, and antioxidant enzyme activities under stressful conditions. Both the multi-trait consortia altered the expression profiles of stress-related genes including CSD1, CAT1, Wrky, Ein, Etr, and ACO. Furthermore, the metabolomic analysis indicated that inoculated plants modulated the metabolic profiles to stimulate physiological and biochemical responses in Arabidopsis plants to mitigate salt stress. Our study affirms that the consortia of salt-tolerant bacterial strains modulate the transcriptional as well as metabolic machinery of plants to protect them from salinity stress. Nevertheless, the findings of this study revealed that consortia are composed of salt-tolerant bacterial strains viz. Bacillus safensis NBRI 12M, B. subtilis NBRI 28B, and B. subtilis NBRI 33N demonstrated significant improvement in Arabidopsis plants under saline stress conditions.PMID:36652029 | DOI:10.1007/s00284-023-03187-2

Clin Res Cardiol. 2023 Jan 18. doi: 10.1007/s00392-023-02156-w. Online ahead of print.ABSTRACTBACKGROUND: Despite known sex-based differences in cardiovascular aging, differences in aging biology are poorly understood. We hypothesize that circulating metabolites studied cross-sectionally with cardiac aging may be associated with cardiovascular changes that distinguish cardiac aging in women.METHODS: A population-based cohort of community men and women without cardiovascular disease from Singapore underwent detailed clinical and echocardiography examinations. Cross-sectional associations between cardiac functional characteristics and metabolomics profiles were examined.RESULTS: Five hundred sixty-seven adults (48.9% women) participated. Women were younger (72 ± 4.4 years vs 73 ± 4.3 years, p = 0.022), had lower diastolic blood pressures (71 ± 11.0 mmHg vs 76 ± 11.2 mmHg, p < 0.0001, and less likely to have diabetes mellitus (18.0% vs 27.6%, p = 0.013) and smoking (3.8% vs 34.5%, p < 0.001). Body mass indices were similar (24 ± 3.8 kg/m2 vs 24 ± 3.4 kg/m2, p = 0.29), but women had smaller waist circumferences (81 ± 10.1 cm vs 85 ± 9.2 cm, p < 0.001). Women had a significantly higher E/e' ratios (10.9 ± 3.4 vs 9.9 ± 3.3, p = 0.007) and mitral A peak (0.86 ± 0.2 m/s vs 0.79 ± 0.2 m/s, p < 0.001) than men. Among women, lower E/e' ratio was associated with higher levels of C16 (OR 1.019, 95%CI 1.002-1.036, p = 0.029), C16:1 (OR 1.06, 95%CI 1.006-1.118, p = 0.028), serine (OR 1.019, 95%CI 1.002-1.036, p = 0.025), and histidine (OR 1.045, 95%CI 1.013-1.078, p = 0.006). Lower mitral A peak was associated with higher levels of histidine (OR 1.039, 95%CI 1.009-1.070, p = 0.011), isoleucine (OR 1.013, 95%CI 1.004-1.021, p = 0.004), and C20 (OR 1.341, 95%CI 1.067-1.684, p = 0.012).CONCLUSION: Impairments in diastolic functions were more frequent among older women compared to men, despite lower prevalence of vascular risk factors and preserved cardiac structure. Cardiac aging in women correlated with metabolites involved in fatty acid oxidation and tricyclic acid cycle fuelling.PMID:36651997 | DOI:10.1007/s00392-023-02156-w

ACS Nano. 2023 Jan 18. doi: 10.1021/acsnano.2c10623. Online ahead of print.ABSTRACTTwo-dimensional molybdenum disulfide (2D MoS2) nanomaterials are seeing increased use in several areas, and this will lead to their inevitable release into soils. Surface defects can occur on MoS2 nanosheets during synthesis or during environmental aging processes. The mechanisms of MoS2 nanosheet toxicity to soil invertebrates and the role of surface defects in that toxicity have not been fully elucidated. We integrated traditional toxicity end points, targeted energy metabolomics, and transcriptomics to compare the mechanistic differences in the toxicity of defect-free and defect-rich MoS2 nanosheets (DF-MoS2 and DR-MoS2) to Eisenia fetida using a coelomocyte-based in vivo assessment model. After organism-level exposure to DF-MoS2 for 96 h at 10 and 100 mg Mo/L, cellular reactive oxygen species (ROS) levels were elevated by 25.6-96.6% and the activity of mitochondrial respiratory electron transport chain (Mito-RETC) complex III was inhibited by 9.7-19.4%. The tricarboxylic acid cycling and glycolysis were also disrupted. DF-MoS2 preferentially up-regulated subcellular component motility processes related to microtubules and caused mitochondrial fission. Unlike DF-MoS2, DR-MoS2 triggered an increased degree of mitochondrial fusion, as well as more severe oxidative stress. The activities of Mito-RETC complexes (I, III, IV, V) associated with oxidative phosphorylation were significantly inhibited by 22.8-68.6%. Meanwhile, apoptotic pathways were activated upon DR-MoS2 exposure, which together with the depolarization of mitochondrial membrane potential, mediated significant apoptosis. In turn, genes related to cellular homeostasis and energy release were up-regulated to compensate for DR-MoS2-induced energy deprivation. Our study indicates that MoS2 nanosheets have nanospecific effects on E. fetida and also that the role of surface defects from synthesis or that accumulate from environmental impacts needs to be fully considered when evaluating the toxicity of these 2D materials.PMID:36651861 | DOI:10.1021/acsnano.2c10623

Microbiol Spectr. 2023 Jan 18:e0246422. doi: 10.1128/spectrum.02464-22. Online ahead of print.ABSTRACTScleractinian corals form symbiotic relationships with a variety of microorganisms, including endosymbiotic dinoflagellates of the family Symbiodiniaceae, and with bacteria, which are collectively termed coral holobionts. Interactions between hosts and their symbionts are critical to the physiological status of corals. Coral-microorganism interactions have been studied extensively, but dinoflagellate-bacterial interactions remain largely unexplored. Here, we developed a microbiome manipulation method employing KAS-antibiotic treatment (kanamycin, ampicillin, and streptomycin) to favor pigmented bacteria residing on cultured Cladocopium and Durusdinium, major endosymbionts of corals, and isolated several carotenoid-producing bacteria from cell surfaces of the microalgae. Following KAS-antibiotic treatment of Cladocopium sp. strain NIES-4077, pigmented bacteria increased 8-fold based on colony-forming assays from the parental strain, and 100% of bacterial sequences retrieved through 16S rRNA amplicon sequencing were affiliated with the genus Maribacter. Microbiome manipulation enabled host microalgae to maintain higher maximum quantum yield of photosystem II (variable fluorescence divided by maximum fluorescence [Fv/Fm]) under light-stress conditions, compared to the parental strain. Furthermore, by combining culture-dependent and -independent techniques, we demonstrated that species of the family Symbiodiniaceae and pigmented bacteria form strong interactions. Dinoflagellates protected bacteria from antibiotics, while pigmented bacteria protected microalgal cells from light stress via carotenoid production. Here, we describe for the first time a symbiotic relationship in which dinoflagellates and bacteria mutually reduce environmental stress. Investigations of microalgal-bacterial interactions further document bacterial contributions to coral holobionts and may facilitate development of novel techniques for microbiome-mediated coral reef conservation. IMPORTANCE Coral reefs cover less than 0.1% of the ocean floor, but about 25% of all marine species depend on coral reefs at some point in their life cycles. However, rising ocean temperatures associated with global climate change are a serious threat to coral reefs, causing dysfunction of the photosynthetic apparatus of endosymbiotic microalgae of corals, and overproducing reactive oxygen species harmful to corals. We manipulated the microbiome using an antibiotic treatment to favor pigmented bacteria, enabling their symbiotic microalgal partners to maintain higher photosynthetic function under insolation stress. Furthermore, we investigated mechanisms underlying microalgal-bacterial interactions, describing for the first time a symbiotic relationship in which the two symbionts mutually reduce environmental stress. Our findings extend current insights about microalgal-bacterial interactions, enabling better understanding of bacterial contributions to coral holobionts under stressful conditions and offering hope of reducing the adverse impacts of global warming on coral reefs.PMID:36651852 | DOI:10.1128/spectrum.02464-22

mSystems. 2023 Jan 18:e0080722. doi: 10.1128/msystems.00807-22. Online ahead of print.ABSTRACTThe sequence revolution revealed that bacteria-infecting viruses, known as phages, are Earth's most abundant biological entities. Phages have far-reaching impacts on the form and function of microbial communities and play a fundamental role in ecological processes. However, even well into the sequencing revolution, we have only just begun to explore the murky waters around the phage biology iceberg. Many viral reads cannot be assigned to a culturable isolate, and reference databases are biased toward more easily collectible samples, which likely distorts our conclusions. This minireview points out alternatives to mapping reads to reference databases and highlights innovative bioinformatic and experimental approaches that can help us overcome some of the challenges in phage research and better decipher the impact of phages on microbial communities. Moving beyond the identification of novel phages, we highlight phage metabolomics as an important influencer of bacterial host cell physiology and hope to inspire the reader to consider the effects of phages on host metabolism and ecosystems at large. We encourage researchers to report unassigned/unknown sequencing reads and contigs and to continue developing alternative methods to investigate phages within sequence data.PMID:36651762 | DOI:10.1128/msystems.00807-22

J Fish Dis. 2023 Jan 18. doi: 10.1111/jfd.13748. Online ahead of print.ABSTRACTCryptocaryon irritans is one of the most harmful marine parasites in mariculture. Copper sulphate is often used to kill parasites and the influence of copper sulphate on the tomont stage of C. irritans was explored in this study. The results showed that excystment rate was not significantly affected when tomonts were exposed to 5 mg/L (76.7%) and 10 mg/L (78.9%) of copper sulphate for 3 h. However, excystment rate was significantly inhibited when exposed to 15 mg/L (33.3%) for 3 h and 5 mg/L (28.9%), 10 mg/L (33.3%) and 15 mg/L (33.3%) for 6 h. After treatment with high concentrations of copper sulphate, the interior of the tomonts was fuzzy under the microscope, and the division process could not be observed. Metabolomic results combined with preliminary transcriptome analysis results showed that the tomonts were induced to produce linoleate, riboflavin, inositol and other substances under the stress of Cu2+ , which affected the antioxidant mechanism of the body. Using MDA content determination and antioxidant enzyme activity analysis, copper sulphate was found to cause oxidative damage to tomonts by affecting the generation of metabolites, leading to the death of tomonts.PMID:36651652 | DOI:10.1111/jfd.13748

Acta Pharm. 2022 Apr 13;72(3):437-448. doi: 10.2478/acph-2022-0023. Print 2022 Sep 1.ABSTRACTTo reveal the mechanism of anti-renal fibrosis effects of an n-butanol extract from Amygdalus mongolica, renal fibrosis was induced with unilateral ureteral obstruction (UUO) and then treated with an n-butanol extract (BUT) from Amygdalus mongolica (Rosaceae). Sixty male Sprague-Dawley rats were randomly divided into the sham-operated, renal fibrosis (RF) model, benazepril hydrochloride-treated model (1.5 mg kg-1) and BUT-treated (1.75, 1.5 and 1.25 g kg-1) groups and the respective drugs were administered intragastrically for 21 days. Related biochemical indices in rat serum were determined and histopathological morphology observed. Serum metabolomics was assessed with HPLC-Q-TOF-MS. The BUT reduced levels of blood urea nitrogen, serum creatinine and albumin and lowered the content of malondialdehyde and hydroxyproline in tissues. The activity of superoxide dismutase in tissues was increased and an improvement in the severity of RF was observed. Sixteen possible biomarkers were identified by metabolomic analysis and six key metabolic pathways, including the TCA cycle and tyrosine metabolism, were analyzed. After treatment with the extract, 8, 12 and 9 possible biomarkers could be detected in the high-, medium- and low-dose groups, respectively. Key biomarkers of RF, identified using metabolomics, were most affected by the medium dose. A. mongolica BUT extract displays a protective effect on RF in rats and should be investigated as a candidate drug for the treatment of the disease.PMID:36651545 | DOI:10.2478/acph-2022-0023

Nucleic Acids Res. 2023 Jan 18:gkac1237. doi: 10.1093/nar/gkac1237. Online ahead of print.ABSTRACTThe RNA-binding protein PURA has been implicated in the rare, monogenetic, neurodevelopmental disorder PURA Syndrome. PURA binds both DNA and RNA and has been associated with various cellular functions. Only little is known about its main cellular roles and the molecular pathways affected upon PURA depletion. Here, we show that PURA is predominantly located in the cytoplasm, where it binds to thousands of mRNAs. Many of these transcripts change abundance in response to PURA depletion. The encoded proteins suggest a role for PURA in immune responses, mitochondrial function, autophagy and processing (P)-body activity. Intriguingly, reduced PURA levels decrease the expression of the integral P-body components LSM14A and DDX6 and strongly affect P-body formation in human cells. Furthermore, PURA knockdown results in stabilization of P-body-enriched transcripts, whereas other mRNAs are not affected. Hence, reduced PURA levels, as reported in patients with PURA Syndrome, influence the formation and composition of this phase-separated RNA processing machinery. Our study proposes PURA Syndrome as a new model to study the tight connection between P-body-associated RNA regulation and neurodevelopmental disorders.PMID:36651277 | DOI:10.1093/nar/gkac1237

Nan Fang Yi Ke Da Xue Xue Bao. 2022 Dec 20;42(12):1765-1773. doi: 10.12122/j.issn.1673-4254.2022.12.03.ABSTRACTOBJECTIVE: To explore the role of the tumor suppressor gene NDRG2 in regulating lipid metabolism in hepatoma cells.METHODS: We analyzed the differential expression of NDRG2 gene between hepatocellular carcinoma tissues (n=809) and normal liver tissues (n=379) based on data from TNMplot database, and investigated the correlation between NDRG2 mRNA expression and the overall survival of the patients with hepatocellular carcinoma using THPA database, which was also used for analysis of NDRG2 expression levels in tumor cell lines for screening hepatoma cell lines. Human hepatoma cell line HepG2 was infected with a lentivirus containing NDRG2 cDNA, and the expression level of NDRG2 in the infected cells was detected using qPCR and Western blotting. Lipid metabolomics analysis was performed to analyze the regulatory effect of NDRG2 overexpression on lipid metabolism in HepG2 cells, and ELISA and Oil Red O staining were used to examine the changes in contents of phospholipids and triglyceride in NDRG2-overexpressing HepG2 cells.RESULTS: Analysis of the TNMplot database showed that NDRG2 expression level was significantly lower in hepatocellular carcinoma tissues than in normal liver tissues (P < 0.001). Analysis of THPA database showed that the patients with high NDRG2 mRNA levels had a longer survival time than those with low NDRG2 mRNA levels, and NDRG2 expression level was the highest in HepG2 cell line among the tumor cell lines. Metabolomics analysis showed that in HepG2 cells, NDRG2 overexpression led to changes in the contents of phospholipids, and among them lecithin PC, phosphatidyl glycerol PG, phosphatidyl ethanolamine PE, sphinophosphatidyl serine SM, and ceramide Cer exhibited significant changes. The results of ELISA and Oil Red O staining demonstrated that NDRG2 overexpression obviously reduced the contents of multiple phospholipids and significantly lowered the contents of triglyceride in HepG2 cells.CONCLUSION: NDRG2 regulates tumorigenesis of hepatocellular carcinoma by modulating the metabolism of phospholipids and triglyceride.PMID:36651243 | DOI:10.12122/j.issn.1673-4254.2022.12.03

Anal Chem. 2023 Jan 18. doi: 10.1021/acs.analchem.2c04165. Online ahead of print.ABSTRACTCell cycle is a significant factor toward cellular heterogeneity, so cell cycle discrimination is a precise measurement on the top of single-cell analysis. Single-cell analysis based on organic mass spectrometry has received great attention for its unique ability to profile single-cell metabolome, but the influence of cell cycle on cellular metabolome heterogeneity has been overlooked until now due to the lack of a compatible cell cycle discrimination method. Here, we report a robust protocol based on the combination of three small molecular indicators, consisting of two small molecular labels (Hoechst and docetaxel) and one cellular endogenous compound [phosphocholine (34:1)], to discriminate single cells at different cycle stages in real time by organic mass cytometry. More than 6000 HeLa cells were acquired by an improved organic mass cytometry system to build a cell cycle differentiation model. The model successfully discriminated single HeLa cells, SCC7, and Hep G2 cells, at G0/G1, S, and G2/M stages with larger than 85% sensitivity and larger than 89% specificity. Along with cell cycle discrimination, obvious heterogeneity of amino acids, nucleotides, energy metabolic intermediates, and phospholipids was observed among single cells at different cycle stages by this protocol, further demonstrating the necessity of cell cycle discrimination for cellular metabolome heterogeneity research and the potential of more endogenous small molecular compounds for cell cycle discrimination.PMID:36651064 | DOI:10.1021/acs.analchem.2c04165

Trials. 2023 Jan 17;24(1):35. doi: 10.1186/s13063-023-07085-7.ABSTRACTBACKGROUND: Using functional foods in the prevention and treatment of type 2 diabetes mellitus (T2DM) has increased across the world owing to their availability, cultural acceptability, and lower side effects. The present study will aim to examine the impact of bitter almond (Amygdalus communis L. var. Amara) gum as a functional food on metabolic profile, inflammatory markers, and mental health in women with T2DM.METHODS: We will conduct a randomized, triple-blind, placebo-controlled trial. A total of 44 women with T2DM will be randomly allocated into two groups: an intervention group (n = 20) and a placebo group (n = 20). Patients will receive either 5 g/d of bitter melon gum or a placebo for 8 weeks. Clinical and biochemical outcome parameters which include glycemic indices, lipid profile, inflammatory markers, oxidative stress indices, tryptophan (Trp), kynurenine (KYN), cortisol, glucagon-like peptide 1 (GLP-1), leptin, adiponectin, ghrelin, peroxisome proliferator-activated receptor (PPAR) gene expression, brain-derived neurotrophic factor (BDNF), endothelial cell adhesion molecules, plasminogen, cluster deference 4 (CD4), cluster deference 8 (CD8), anthropometric indices, blood pressure, dietary intake, and mental health will be measured at the baseline and end of the study. Statistical analysis will be conducted using the SPSS software (version 24), and P value less than 0.05 will be considered statistically significant.DISCUSSION: The present randomized controlled trial will aim to investigate any beneficial effects of bitter almond gum supplementation on the cardio-metabolic, immune-inflammatory, and oxidative stress biomarkers, as well as mental health in women with T2DM.ETHICS AND DISSEMINATION: The study protocol was approved by the Ethical Committee of the Tabriz University of Medical Sciences (IR.TBZMED.REC.1399.726).TRIAL REGISTRATION: Iranian Registry of Clinical Trials ( www.irct.ir/IRCT20150205020965N7 ).PMID:36650599 | PMC:PMC9847170 | DOI:10.1186/s13063-023-07085-7