PubMed

Diabetes. 2024 Apr 9:db240033. doi: 10.2337/db24-0033. Online ahead of print.NO ABSTRACTPMID:38593250 | DOI:10.2337/db24-0033

Nanomedicine (Lond). 2024 Apr 9. doi: 10.2217/nnm-2023-0357. Online ahead of print.ABSTRACTAim: To investigate the influence of fluorine in reducing the adsorption of immune-reactive proteins onto PEGylated gold nanoparticles. Methods: Reversible addition fragmentation chain transfer polymerization, the Turkevich method and ligand exchange were used to prepare polymer-coated gold nanoparticles. Subsequent in vitro physicochemical and biological characterizations and proteomic analysis were performed. Results: Fluorine-modified polymers reduced the adsorption of complement and other immune-reactive proteins while potentially improving circulatory times and modulating liver toxicity by reducing apolipoprotein E adsorption. Fluorine actively discouraged phagocytosis while encouraging the adsorption of therapeutic targets, CD209 and signaling molecule calreticulin. Conclusion: This study suggests that the addition of fluorine in the surface coating of nanoparticles could lead to improved performance in nanomedicine designed for the intravenous delivery of cargos.PMID:38593053 | DOI:10.2217/nnm-2023-0357

Plants (Basel). 2024 Mar 16;13(6):859. doi: 10.3390/plants13060859.ABSTRACTOcotea, the largest genus in the Lauraceae family, encompasses numerous species of scientific interest. However, most Ocotea species have only been described morphologically. This study used an untargeted metabolomics workflow with UHPLC-HRMS and GNPS-FBMN to provide the first chemical evaluation of the polar specialized metabolites of O. delicata leaves. Leaves from three O. delicata specimens were extracted using ultrasound-assisted extraction with 70% ethanol. Among the examined samples, 44 metabolites, including alkaloids and flavonoids, were identified. In contrast to other Ocotea species, O. delicata has a wider diversity of kaempferol derivatives than quercetin. The biomass of the specimens showed a significant correlation with the chemical profile. The similarity among specimens was mostly determined by the concentrations of quinic acid, kaempferol glycosides, and boldine. The evaluated specimens exhibited chemical features similar to those of species classified as New World Ocotea, with the coexistence of aporphine and benzylisoquinoline alkaloids.PMID:38592892 | DOI:10.3390/plants13060859

Plants (Basel). 2024 Mar 15;13(6):857. doi: 10.3390/plants13060857.ABSTRACTUnder stress or in optimum conditions, plants foster a specific guild of symbiotic microbes to strengthen pivotal functions including metabolic regulation. Despite that the role of the plant genotype in microbial selection is well documented, the potential of this genotype-specific microbial assembly in maintaining the host homeostasis remains insufficiently investigated. In this study, we aimed to assess the specificity of the foliar metabolic response of contrasting olive genotypes to microbial inoculation with wet-adapted consortia of plant-growth-promoting rhizobacteria (PGPR), to see if previously inoculated plants with indigenous or exogenous microbes would display any change in their leaf metabolome once being subjected to drought stress. Two Tunisian elite varieties, Chetoui (drought-sensitive) and Chemleli (drought-tolerant), were tested under controlled and stressed conditions. Leaf samples were analyzed by gas chromatography-mass spectrometry (GC-TOFMS) to identify untargeted metabolites. Root and soil samples were used to extract microbial genomic DNA destined for bacterial community profiling using 16S rRNA amplicon sequencing. Respectively, the score plot analysis, cluster analysis, heat map, Venn diagrams, and Krona charts were applied to metabolic and microbial data. Results demonstrated dynamic changes in the leaf metabolome of the Chetoui variety in both stress and inoculation conditions. Under the optimum state, the PGPR consortia induced noteworthy alterations in metabolic patterns of the sensitive variety, aligning with the phytochemistry observed in drought-tolerant cultivars. These variations involved fatty acids, tocopherols, phenols, methoxyphenols, stilbenoids, triterpenes, and sugars. On the other hand, the Chemleli variety displaying comparable metabolic profiles appeared unaffected by stress and inoculation probably owing to its tolerance capacity. The distribution of microbial species among treatments was distinctly uneven. The tested seedlings followed variety-specific strategies in selecting beneficial soil bacteria to alleviate stress. A highly abundant species of the wet-adapted inoculum was detected only under optimum conditions for both cultivars, which makes the moisture history of the plant genotype a selective driver shaping microbial community and thereby a useful tool to predict microbial activity in large ecosystems.PMID:38592857 | DOI:10.3390/plants13060857

Plants (Basel). 2024 Mar 12;13(6):816. doi: 10.3390/plants13060816.ABSTRACTThe grapevine (Vitis vinifera L.) is widely cultivated worldwide owing to the substantial commercial value of the grapes and other products derived from their processing, wines in particular. The grapevine is characterized by a remarkable phenotypic plasticity within the same variety, which shapes the final berry quality attributes hence reflecting the complex interactions between the plant and the environment leading to the expression of wine typicity. In this study, we explored the metabolomic and transcriptomic basis of the plasticity of Glera, a white berry grapevine variety particularly renowned for the production of wine Prosecco. The two selected vineyards varied for site altitude and pedoclimatic conditions. We highlighted that these environments determined different berry ripening dynamics at the level of both technological parameters and the total abundance and intrafamily distribution of phenolic compounds. Moreover, a clear impact on the grape aroma profile was observed. The genome-wide gene expression analysis of the berries revealed remarkable differences in the ripening transcriptomic program, reflecting the differences in water status, light exposure, and temperature experienced by the plants while growing at the two sites. Overall, this survey portrayed how the quality attributes of the cv 'Glera' grape berries may be affected by different environmental conditions within the typical area of Prosecco wine production.PMID:38592837 | DOI:10.3390/plants13060816

Plants (Basel). 2024 Mar 12;13(6):804. doi: 10.3390/plants13060804.ABSTRACTBACKGROUND: Thesium chinense known as the "plant antibiotic" is a facultative root hemi-parasitic herb while Prunella vulgaris can serve as its host. However, the molecular mechanisms underlying the communication between T. chinense and its host remained largely unexplored. The aim of this study was to provide a comprehensive view of transferred metabolites and mobile mRNAs exchanged between T. chinense and P. vulgaris.RESULTS: The wide-target metabolomic and transcriptomic analysis identified 5 transferred metabolites (ethylsalicylate, eriodictyol-7-O-glucoside, aromadendrin-7-O-glucoside, pruvuloside B, 2-ethylpyrazine) and 50 mobile genes between T. chinense and P. vulgaris, as well as haustoria formation related 56 metabolites and 44 genes. There were 4 metabolites (ethylsalicylate, eriodictyol-7-O-glucoside, aromadendrin-7-O-glucoside and pruvuloside B) that are transferred from P. vulgaris to T. chinense, whereas 2-ethylpyrazine was transferred in the opposite direction. Furthermore, we inferred a regulatory network potentially involved in haustoria formation, where three metabolites (N,N'-Dimethylarginine/SDMA, NG,NG-Dimethyl-L-arginine, 2-Acetoxymethyl-anthraquinone) showed significant positive correlations with the majority of haustoria formation-related genes.CONCLUSIONS: These results suggested that there was an extensive exchange of information with P. vulgaris including transferred metabolites and mobile mRNAs, which might facilitate the haustoria formation and parasition of T. chinense.PMID:38592814 | DOI:10.3390/plants13060804

Plants (Basel). 2024 Mar 13;13(6):828. doi: 10.3390/plants13060828.ABSTRACTUnderstanding the impact of drought stress on Arabica coffee physiology and metabolism is essential in the pursuit of developing drought-resistant varieties. In this study, we explored the physiological and metabolite changes in coffee genotypes exhibiting varying degrees of tolerance to drought-namely, the relatively tolerant Ca74110 and Ca74112, and the sensitive Ca754 and CaJ-19 genotypes-under well-watered conditions and during terminal drought stress periods at two time points (0 and 60 days following the onset of stress). The metabolite profiling uncovered significant associations between the growth and the physiological characteristics of coffee genotypes with distinct drought tolerance behaviors. Initially, no marked differences were observed among the genotypes or treatments. However, at the 60-day post-drought onset time point, notably higher shoot growth, biomass, CO2 assimilation, pigments, and various physiological parameters were evident, particularly in the relatively tolerant genotypes. The metabolite profiling revealed elevations in glucose, maltose, amino acids, and organic acids, and decreases in other metabolites. These alterations were more pronounced in the drought-tolerant genotypes, indicating a correlation between enhanced compatible solutes and energy-associated metabolites crucial for drought tolerance mechanisms. This research introduces GC-MS-based metabolome profiling to the study of Ethiopian coffee, shedding light on its intricate responses to drought stress and paving the way for the potential development of drought-resistant coffee seedlings in intensified agro-ecological zones.PMID:38592785 | DOI:10.3390/plants13060828

Appl Microbiol Biotechnol. 2024 Apr 9;108(1):292. doi: 10.1007/s00253-024-13099-1.ABSTRACTPulchinenoside B4, a natural saponin monomer from the Pulsatilla plant, plays an important role as an immunomodulator in the treatment of acute inflammation. Oral ulcer (OU) is a common ulcerative injury disease that occurs in the oral mucosa, including mucosal ulceration and abnormalities of lips and tongue. A close correlation exists between gut microbiota and circulating metabolites in patients with OU. However, the correlation between gut microbiota and serum metabolomics is not clear. Therefore, this study aimed to explore the changes in gut microbiota and metabolites in OU. The 16S ribosomal RNA (16S rRNA) gene sequencing was used to detect the changes in the composition of gut microbiota in OU rat model. Moreover, the endogenous small metabolites were explored by collecting the non-targeted serum metabolomics data. A total of 34 OU-related biomarkers were identified, mainly related to fatty acid metabolism and inflammatory pathways. The administration of B4 effectively reduced the occurrence of OU and restored the levels of multiple endogenous biomarkers and key gut microbial species to the normal level. This study demonstrated that the gut microbiota and metabolites were altered in the OU rat model, which were significantly restored to the normal level by B4, thereby showing good application prospects in the treatment of OU. KEY POINTS: • The first investigating the correlation between OU and gut microbiota. • A close correlation between metabolites and gut microbiota in OU disease was successfully identified. • Pulchinenoside B4 ameliorates oral ulcers in rats by modulating gut microbiota and metabolites.PMID:38592514 | DOI:10.1007/s00253-024-13099-1

J Clin Med. 2024 Feb 21;13(5):1222. doi: 10.3390/jcm13051222.ABSTRACTBackground: Major depressive disorder (MDD) is a leading cause of disability worldwide. At present, however, there are no established biomarkers that have been validated for diagnosing and treating MDD. This study sought to assess the diagnostic and predictive potential of the differences in serum amino acid concentration levels between MDD patients and healthy controls (HCs), integrating them into interpretable machine learning models. Methods: In total, 70 MDD patients and 70 HCs matched in age, gender, and ethnicity were recruited for the study. Serum amino acid profiling was conducted by means of chromatography-mass spectrometry. A total of 21 metabolites were analysed, with 17 from a preset amino acid panel and the remaining 4 from a preset kynurenine panel. Logistic regression was applied to differentiate MDD patients from HCs. Results: The best-performing model utilised both feature selection and hyperparameter optimisation and yielded a moderate area under the receiver operating curve (AUC) classification value of 0.76 on the testing data. The top five metabolites identified as potential biomarkers for MDD were 3-hydroxy-kynurenine, valine, kynurenine, glutamic acid, and xanthurenic acid. Conclusions: Our study highlights the potential of using an interpretable machine learning analysis model based on amino acids to aid and increase the diagnostic accuracy of MDD in clinical practice.PMID:38592058 | DOI:10.3390/jcm13051222

J Cell Mol Med. 2024 Apr;28(8):e18202. doi: 10.1111/jcmm.18202.ABSTRACTSecondary hyperparathyroidism has a significant impact on the overall well-being of the body. Capsiates, known for their antioxidant and metabolic properties, have emerged as a promising alternative treatment for secondary hyperparathyroidism. This study aims to evaluate the effects and mechanisms of capsiates in the treatment of secondary hyperparathyroidism. To achieve our research objectives, we conducted a study on patients' serum and examined changes in metabolic markers using serum metabolomics. We induced secondary hyperparathyroidism in rat through dietary intervention and divided them into four groups. The first group, referred to as the Parathyroid Hormone (PTH) group, received a low-calcium and high-phosphate diet (0.2% calcium, 1.2% phosphorus). The second group served as the control group, receiving a standard phosphate and calcium diet (0.6% calcium, 0.6% phosphorus). The third group, called the capsiates group, consisted of rat from the control group treated with capsiates (intraperitoneal injection of 2 mg/kg capsiates for 2 weeks after 2 weeks of dietary intervention). The fourth group was the capsiates-treated PTH group. Subsequently, we conducted ribose nucleic acid (RNA) sequencing on parathyroid gland cells and evaluated serum thyroxine levels, oxidative stress, expression of proteins associated with vascular neogenesis, measurement of SOD, GSH and 3-nitrotyrosine, micro-CT and histological staining. The serum metabolomic data revealed a significant decrease in capsiate levels in the secondary hyperparathyroidism group. Administration of capsiates to PTH rat resulted in increased calcium levels compared to the PTH group. Additionally, the PTH + Capsiates group showed significantly lower levels of PTH and phosphate compared to the PTH group. The PTH group exhibited a notable increase in the quantity and size of mitochondria compared to the control group. Following capsiates administration to the PTH group, there was a significant reduction in the number of mitochondria and length of microvilli, but an increase in the size of mitochondria compared to the PTH group. Sequencing analysis revealed that vascular endothelial growth factor (VEGF) and Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) play crucial roles in this process. Vascular-related variables and downstream signalling were significantly elevated in hyperthyroidism and were alleviated with capsaicin treatment. Finally, combining capsiates with the PTH group improved bone mineral density, Tb.N, BV.TV, Cs.Th, Tt.Ar, OPG, Ob.TV and Oc.TV, as well as the mineral apposition rate, but significantly decreased Tb.Sp and Receptor Activator for Nuclear Factor-κ B Ligand (RANKL) compared to the PTH group. The findings suggest that capsiates can improve secondary hyperparathyroidism and ameliorated osteoporosis outcomes by inhibiting angiogenesis and reducing oxidative stress.PMID:38591872 | DOI:10.1111/jcmm.18202

J Cell Biochem. 2024 Apr 9. doi: 10.1002/jcb.30566. Online ahead of print.ABSTRACTWe investigated the effects of obesity on metabolic, inflammatory, and oxidative stress parameters in the adipose tissue of patients with fatal COVID-19. Postmortem biopsies of subcutaneous adipose tissue were obtained from 25 unvaccinated inpatients who passed from COVID-19, stratified as nonobese (N-OB; body mass index [BMI], 26.5 ± 2.3 kg m-2) or obese (OB BMI 34.2 ± 5.1 kg m-2). Univariate and multivariate analyses revealed that body composition was responsible for most of the variations detected in the metabolome, with greater dispersion observed in the OB group. Fifteen metabolites were major segregation factors. Results from the OB group showed higher levels of creatinine, myo-inositol, O-acetylcholine, and succinate, and lower levels of sarcosine. The N-OB group showed lower levels of glutathione peroxidase activity, as well as higher content of IL-6 and adiponectin. We revealed significant changes in the metabolomic profile of the adipose tissue in fatal COVID-19 cases, with high adiposity playing a key role in these observed variations. These findings highlight the potential involvement of metabolic and inflammatory pathways, possibly dependent on hypoxia, shedding light on the impact of obesity on disease pathogenesis and suggesting avenues for further research and possible therapeutic targets.PMID:38591648 | DOI:10.1002/jcb.30566

World J Diabetes. 2024 Mar 15;15(3):502-518. doi: 10.4239/wjd.v15.i3.502.ABSTRACTBACKGROUND: Jianpi Gushen Huayu Decoction (JPGS) has been used to clinically treat diabetic nephropathy (DN) for many years. However, the protective mechanism of JPGS in treating DN remains unclear.AIM: To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS: We first evaluated the therapeutic potential of JPGS on a DN mouse model. We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics. Furthermore, we examined the effects of JPGS on c-Jun N-terminal kinase (JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3).RESULTS: The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress. Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice. A total of 51 differential metabolites were screened. Pathway analysis results indicated that nine pathways significantly changed between the control and model groups, while six pathways significantly altered between the model and JPGS groups. Pathways related to cysteine and methionine metabolism; alanine, tryptophan metabolism; aspartate and glutamate metabolism; and riboflavin metabolism were identified as the key pathways through which JPGS affects DN. Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION: JPGS could markedly treat mice with streptozotocin (STZ)-induced DN, which is possibly related to the regulation of several metabolic pathways found in kidneys. Furthermore, JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathway-mediated apoptosis in DN mice.PMID:38591083 | PMC:PMC10999033 | DOI:10.4239/wjd.v15.i3.502

Oncoimmunology. 2024 Apr 4;13(1):2338951. doi: 10.1080/2162402X.2024.2338951. eCollection 2024.ABSTRACTRecently, we showed that an autologous DC-based vaccine induces an increase in immunosuppressive PD-L1+ tumor-associated macrophages (TAM) both in the tumor and the tumor draining lymph nodes, thereby blunting the efficacy of therapeutic immunization. Only the combination of the DC vaccine with anti-PD-L1 immune checkpoint inhibition, but not the use of antibodies targeting PD-1 alone, was able to set off CD8+ cytotoxic T lymphocyte (CTL)-mediated tumor suppression in mice. In sum, we delineated a PD-L1 checkpoint blockade-based strategy to avoid TAM-induced T cell exhaustion during DC vaccine therapy.PMID:38590800 | PMC:PMC11000604 | DOI:10.1080/2162402X.2024.2338951

World Allergy Organ J. 2024 Mar 31;17(4):100894. doi: 10.1016/j.waojou.2024.100894. eCollection 2024 Apr.ABSTRACTBACKGROUND: Allergic conjunctivitis (AC) afflicts a significant portion of the global populace. Yet, its metabolic foundations remain largely unexplored.METHODS: We applied Mendelian Randomization (MR) and Linkage Disequilibrium Score Regression (LDSC) to scrutinize a cohort comprising 20 958 AC cases and 356 319 controls. Data were amalgamated from the metabolomics GWAS server and the FinnGen project, under strict quality control protocols.RESULTS: Using two-sample MR analysis, 486 blood metabolites were investigated in relation to AC. The IVW approach highlighted 18 metabolites as closely tied to AC risk; of these, 16 retained significance post sensitivity assessments for heterogeneity and horizontal pleiotropy. LDSC analysis, adopted to bolster our findings and negate confounders from shared genetic markers, revealed 8 metabolites with marked heritability, including: palmitate (OR = 0.614), 3-methoxytyrosine (OR = 0.657), carnitine (OR = 1.368), threonate (OR = 0.828), N-[3-(2-Oxopyrrolidin-1-yl)propyl]acetamide (OR = 1.257), metoprolol acid metabolite (OR = 0.982), oleoylcarnitine (OR = 0.635), and 2-palmitoylglycerophosphocholine (OR = 1.351).CONCLUSION: AC is precipitated by ocular responses to environmental allergens. Our study unveils a causal link between 8 blood metabolites and AC. This insight accentuates the role of metabolites in AC onset, suggesting novel avenues for its early prediction, targeted prevention, and tailored therapeutic interventions.PMID:38590722 | PMC:PMC10999487 | DOI:10.1016/j.waojou.2024.100894

Food Funct. 2024 Apr 9. doi: 10.1039/d3fo05535c. Online ahead of print.ABSTRACTLactiplantibacillus plantarum NCUH001046 (LP)-fermented tomatoes exhibited the potential to alleviate obesity in our previous study. This subsequent study further delves deeper into the effects of LP fermentation on the physicochemical properties, bioactivities, and hepatic lipid metabolism modulation of tomatoes, as well as the analysis of potential bioactive compounds exerting obesity-alleviating effects. Results showed that after LP fermentation, viable bacterial counts peaked at 9.11 log CFU mL-1 and sugar decreased, while organic acids, umami amino acids, total phenols, and total flavonoids increased. LP fermentation also improved the inhibition capacities of three digestive enzyme activities and Enterobacter cloacae growth, as well as antioxidant activities. Western blot results indicated that fermented tomatoes, especially live probiotic-fermented tomatoes (LFT), showed improved effects compared to unfermented tomatoes in reducing hepatic lipid accumulation by activating the AMPK signal pathway. UHPLC-Q-TOF/MS-based untargeted metabolomics analysis showed that chlorogenic acid, capsiate, tiliroside, irisflorentin, and homoeriodictyol levels increased after fermentation. Subsequent cell culture assays demonstrated that irisflorentin and homoeriodictyol reduced lipid accumulation via enhancing AMPK expression in oleic acid-induced hyperlipidemic HepG2 cells. Furthermore, Spearman's correlation analysis indicated that the five phenols were positively associated with hepatic AMPK pathway activation. Consequently, it could be inferred that the five phenols may be potential bioactive compounds in LFT to alleviate obesity and lipid metabolism disorders. In summary, these findings underscored the transformative potential of LP fermentation in enhancing the bioactive profile of tomatoes and augmenting its capacity to alleviate obesity and lipid metabolism disorders. This study furnished theoretical underpinnings for the functional investigation of probiotic-fermented plant-based foods.PMID:38590277 | DOI:10.1039/d3fo05535c

J Med Chem. 2024 Apr 8. doi: 10.1021/acs.jmedchem.4c00435. Online ahead of print.ABSTRACTCisplatin (cDDP) resistance is a matter of concern in triple-negative breast cancer therapeutics. We measured the metabolic response of cDDP-sensitive (S) and -resistant (R) MDA-MB-231 cells to Pd2Spermine(Spm) (a possible alternative to cDDP) compared to cDDP to investigate (i) intrinsic response/resistance mechanisms and (ii) the potential cytotoxic role of Pd2Spm. Cell extracts were analyzed by untargeted nuclear magnetic resonance metabolomics, and cell media were analyzed for particular metabolites. CDDP-exposed S cells experienced enhanced antioxidant protection and small deviations in the tricarboxylic acid cycle (TCA), pyrimidine metabolism, and lipid oxidation (proposed cytotoxicity signature). R cells responded more strongly to cDDP, suggesting a resistance signature of activated TCA cycle, altered AMP/ADP/ATP and adenine/uracil fingerprints, and phospholipid biosynthesis (without significant antioxidant protection). Pd2Spm impacted more markedly on R/S cell metabolisms, inducing similarities to cDDP/S cells (probably reflecting high cytotoxicity) and strong additional effects indicative of amino acid depletion, membrane degradation, energy/nucleotide adaptations, and a possible beneficial intracellular γ-aminobutyrate/glutathione-mediated antioxidant mechanism.PMID:38590144 | DOI:10.1021/acs.jmedchem.4c00435

J Ethnopharmacol. 2024 Apr 6:118163. doi: 10.1016/j.jep.2024.118163. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Plants in the genus Hypericum (Hypericaceae), include more than 500 species worldwide, and many are valued for their medicinal properties, and are used as traditional herbal medicines. However, only H. perforatum is officially recognized as herbal drug in several pharmacopoeias, and used as an antidepressant clinically. Hypericum perforatum had been used as an herbal medicine since the Han Dynasty (206 B.C. -220 A.D.) in China. It taxonomically belongs to the section Hypericum in the genus Hypericum. There are about 42 species in the section Hypericum, with six species occurring in China. All six are recorded as traditional herbal medicines for treating aliments, including hepatitis, malaria, traumatic hemorrhage, irregular menstruation, wounds, and bruises.AIM OF THE STUDY: The study aimed to characterize the chemical profiles of five phylogenetically related Hypericum species, and compare their metabolites with three H. perforatum products. Informed by ethnobotanical use, the extracts prepared from the five species were further investigated into anticancer, anti-inflammatory and antiplasmodial activity. This study tested the hypothesis that systematic metabolomic and bioactivity characterization of species in section Hypericum will help to validate their phytotherapeutic use and reveal potential drug lead compounds.MATERIALS AND METHODS: Targeted and non-targeted metabolic analyses coupled with chemometrics were conducted on H. perforatum and four medicinal species, H. attenuatum, H. enshiense, H. erectum, and H. faberi, native to China from section Hypericum. UPLC-QTOF-MS/MS and UPLC-TQD-MS/MS were used for non-targeted and targeted metabolic analyses, respectively. Cytotoxicity bioassays on four cancer cell lines, anti-inflammation tests and anti-plasmodial activity on Plasmodium falciparum 3D7, selected based on traditional medicinal use, were evaluated on extracts from Hypericum species. Progenesis QI and EZinfo were used for chemometrics analysis to link the chemical profile and bioassay activity to aid in the identification of bioactive compounds.RESULTS: In total, 58 compounds were identified from the five species, including compounds with well-characterized bioactivity. Hypericum attenuatum, H. erectum, and H. perforatum, displayed the highest cytotoxicity, and contain the cytotoxic compounds petiolin A, prolificin A, and hypercohin G, respectively. Hypericum faberi and H. perforatum showed the highest anti-inflammatory activity, with pseudohypericin, quercetin and chlorogenic acid being observed at higher concentrations. Hypericum perforatum and H. erectum showed anti-plasmodial activity, with higher hyperforin and xanthones in these species that may account for the anti-plasmodial activity.CONCLUSIONS: This study characterized the chemical differences among five Hypericum species using metabolomics. These ethnomedically important species were tested for their biological activities in three distinct in vitro assays. The ethnobotanical data were useful for identifying bioactive Hypericum species. Hypericum attenuatum, H. erectum and H. faberi are promising phytotherapeutic species, although they are much less studied than H. perforatum, St. John's wort. Combining ethnobotanical surveys with chemometric analyses and bioactivity screening can greatly enhance the discovery of promising active constituents.PMID:38588986 | DOI:10.1016/j.jep.2024.118163

Chemosphere. 2024 Apr 6:141921. doi: 10.1016/j.chemosphere.2024.141921. Online ahead of print.ABSTRACT2,3',4,4',5-pentachlorodiphenyl (PCB 118), a highly representative PCB congener, has been frequently detected in various environments, garnering much attention across the scientific community. The degradation of highly chlorinated PCBs by aerobic microorganisms is challenging due to their hydrophobicity and persistence. Herein, the biodegradation and adaptation mechanisms of Methylorubrum sp. ZY-1 to PCB 118 were comprehensively investigated using an integrative approach that combined degradation performance, product identification, metabolomic and transcriptomic analyses. The results indicated that the highest degradation efficiency of 0.5 mg L-1 PCB 118 reached 75.66% after seven days of inoculation when the bacteria dosage was 1.0 g L-1 at pH 7.0. A total of eleven products were identified during the degradation process, including low chlorinated PCBs, hydroxylated PCBs, and ring-opening products, suggesting that strain ZY-1 degraded PCB 118 through dechlorination, hydroxylation, and ring-opening pathways. Metabolomic analysis demonstrated that the energy supply and redox metabolism of strain ZY-1 was disturbed with exposure to PCB 118. To counteract this environmental stress, strain ZY-1 adjusted both the fatty acid synthesis and purine metabolism. The analysis of transcriptomics disclosed that multiple intracellular and extracellular oxidoreductases (e.g., monooxygenase, alpha/beta hydrolase and cytochrome P450) participated in the degradation of PCB 118. Besides, active efflux of PCB 118 and its degradation intermediates mediated by multiple transporters (e.g., MFS transporter and ABC transporter ATP-binding protein) might enhance bacterial resistance against these substances. These discoveries provided the inaugural insights into the biotransformation of strain ZY-1 to PCB 118 stress, illustrating its potential in the remediation of contaminated environments.PMID:38588902 | DOI:10.1016/j.chemosphere.2024.141921

BMC Genomics. 2024 Apr 8;25(1):351. doi: 10.1186/s12864-024-10223-3.NO ABSTRACTPMID:38589781 | DOI:10.1186/s12864-024-10223-3

NMR Biomed. 2024 Apr 8:e5157. doi: 10.1002/nbm.5157. Online ahead of print.ABSTRACTCellular senescence is characterized by stable cell cycle arrest. Senescent cells exhibit a senescence-associated secretory phenotype that can promote tumor progression. The aim of our study was to identify specific nuclear magnetic resonance (NMR) spectroscopy-based markers of cancer cell senescence. For metabolic studies, we employed murine liver carcinoma Harvey Rat Sarcoma Virus (H-Ras) cells, in which reactivation of p53 expression induces senescence. Senescent and nonsenescent cell extracts were subjected to high-resolution proton (1H)-NMR spectroscopy-based metabolomics, and dynamic metabolic changes during senescence were analyzed using a magnetic resonance spectroscopy (MRS)-compatible cell perfusion system. Additionally, the ability of intact senescent cells to degrade the extracellular matrix (ECM) was quantified in the cell perfusion system. Analysis of senescent H-Ras cell extracts revealed elevated sn-glycero-3-phosphocholine, myoinositol, taurine, and creatine levels, with decreases in glycine, o-phosphocholine, threonine, and valine. These metabolic findings were accompanied by a greater degradation index of the ECM in senescent H-Ras cells than in control H-Ras cells. MRS studies with the cell perfusion system revealed elevated creatine levels in senescent cells on Day 4, confirming the 1H-NMR results. These senescence-associated changes in metabolism and ECM degradation strongly impact growth and redox metabolism and reveal potential MRS signals for detecting senescent cancer cells in vivo.PMID:38589764 | DOI:10.1002/nbm.5157