PubMed

Planta. 2023 Sep 30;258(5):91. doi: 10.1007/s00425-023-04242-9.ABSTRACTDue to harsh lifestyle changes, in the present era, nutritional security is needed along with food security so it is necessary to include underutilized cereal crops (UCCs) in our daily diet to counteract the rising danger of human metabolic illness. We can attain both the goal of zero hunger and nutritional security by developing improved UCCs using advanced pan-omics (genomics, transcriptomics, proteomics, metabolomics, nutrigenomics, phenomics and ionomics) practices. Plant sciences research progressed profoundly since the last few decades with the introduction of advanced technologies and approaches, addressing issues of food demand of the growing population, nutritional security challenges and climate change. However, throughout the expansion and popularization of commonly consumed major cereal crops such as wheat and rice, other cereal crops such as millet, rye, sorghum, and others were impeded, despite their potential medicinal and nutraceutical qualities. Undoubtedly neglected underutilized cereal crops (UCCs) also have the capability to withstand diverse climate change. To relieve the burden of major crops, it is necessary to introduce the new crops in our diet in the way of UCCs. Introgression of agronomically and nutritionally important traits by pan-omics approaches in UCCs could be a defining moment for the population's well-being on the globe. This review discusses the importance of underutilized cereal crops, as well as the application of contemporary omics techniques and advanced bioinformatics tools that could open up new avenues for future study and be valuable assets in the development and usage of UCCs in the perspective of green system biology. The increased and improved use of UCCs is dependent on number of factors that necessitate a concerted research effort in agricultural sciences. The emergence of functional genomics with molecular genetics might gear toward the reawakening of interest in underutilized cereals crops. The need of this era is to focus on potential UCCs in advanced agriculture and breeding programmes. Hence, targeting the UCCs, might provide a bright future for better health and scientific rationale for its use.PMID:37777666 | DOI:10.1007/s00425-023-04242-9

J Neurochem. 2023 Sep 30. doi: 10.1111/jnc.15960. Online ahead of print.ABSTRACTRett syndrome is an X-linked neurodevelopmental disorder caused by mutation of Mecp2 gene and primarily affects females. Glial cell dysfunction has been implicated in in Rett syndrome (RTT) both in patients and in mouse models of this disorder and can affect synaptogenesis, glial metabolism and inflammation. Here we assessed whether treatment of adult (5-6 months old) symptomatic Mecp2-heterozygous female mice with N-acetyl cysteine conjugated to dendrimer (D-NAC), which is known to target glia and modulate inflammation and oxidative injury, results in improved behavioral phenotype, sleep and glial inflammatory profile. We show that unbiased global metabolomic analysis of the hippocampus and striatum in adult Mecp2-heterozygous mice demonstrates significant differences in lipid metabolism associated with neuroinflammation, providing the rationale for targeting glial inflammation in this model. Our results demonstrate that treatment with D-NAC (10 mg/kg NAC) once weekly is more efficacious than equivalently dosed free NAC in improving the gross neurobehavioral phenotype in symptomatic Mecp2-heterozygous female mice. We also show that D-NAC therapy is significantly better than saline in ameliorating several aspects of the abnormal phenotype including paw clench, mobility, fear memory, REM sleep and epileptiform activity burden. Systemic D-NAC significantly improves microglial proinflammatory cytokine production and is associated with improvements in several aspects of the phenotype including paw clench, mobility, fear memory, and REM sleep, and epileptiform activity burden in comparison to saline-treated Mecp2-hetereozygous mice. Systemic glial-targeted delivery of D-NAC after symptom onset in an older clinically relevant Rett syndrome model shows promise in improving neurobehavioral impairments along with sleep pattern and epileptiform activity burden. These findings argue for the translational value of this approach for treatment of patients with Rett Syndrome.PMID:37777475 | DOI:10.1111/jnc.15960

Asian J Surg. 2023 Sep 28:S1015-9584(23)01455-0. doi: 10.1016/j.asjsur.2023.09.027. Online ahead of print.NO ABSTRACTPMID:37777406 | DOI:10.1016/j.asjsur.2023.09.027

Pharmacol Res. 2023 Sep 28:106943. doi: 10.1016/j.phrs.2023.106943. Online ahead of print.ABSTRACTBile acids (BAs), synthesized in the liver and modified by the gut microbiota, have been widely appreciated not only as simple lipid emulsifiers, but also as complex metabolic regulators and momentous signaling molecules, which play prominent roles in the complex interaction among several metabolic systems. Recent studies have drawn us eyes on the diverse physiological functions of BAs, to enlarge the knowledge about the "gut-bone" axis due to the participation about the gut microbiota-derived BAs to modulate bone homeostasis at physiological and pathological stations. In this review, we have summarized the metabolic processes of BAs and highlighted the crucial roles of BAs targeting bile acid-activated receptors (BARs), promoting the proliferation and differentiation of osteoblasts (OBs), inhibiting the activity of osteoclasts (OCs), as well as reducing articular cartilage degradation, thus facilitating bone repair. In addition, we have also focused on the bidirectional effects of BA signaling networks in coordinating the dynamic balance of bone matrix and demonstrated the promising effects of BAs on the development or treatment for pathological bone diseases. In a word, further clinical applications targeting BA metabolism or modulating gut metabolome and related derivatives may be developed as effective therapeutic strategies for bone destruction diseases.PMID:37777075 | DOI:10.1016/j.phrs.2023.106943

J Dairy Sci. 2023 Sep 28:S0022-0302(23)00707-5. doi: 10.3168/jds.2023-23841. Online ahead of print.ABSTRACTThe objective of this study was to characterize changes in the serum metabolome and various indicators of oxidative balance in dairy cows starting 2 wk before dry-off and continuing until wk 16 of lactation. Twelve Holstein dairy cows [body weight (BW) 745 ± 71 kg, body condition score 3.43 ± 0.66; mean ± SD] were housed in a tie-stall barn from 10 wk before to 16 wk after parturition. Cows were dried off 6 wk before the expected calving date (mean dry period length = 42 d). From 8 wk before calving to 16 wk after calving, blood samples were taken weekly to study redox metabolism by determining antioxidant capacity, measured as the ferric-reducing ability of plasma, reactive oxidative metabolites, oxidative stress index, oxidative damage of lipids, measured as thiobarbituric acid reactive substances, and glutathione peroxidase activity. According to these results, dairy cows had the lowest serum antioxidant capacity and greater levels of oxidative stress during the dry-off period and the early postpartum period. For metabolomics, a subset of serum samples including wk -7 (before dry-off), -5 (after dry-off), -1, 1, 5, 10, and 15 relative to calving were used. A targeted metabolomics approach was performed by liquid chromatography and flow injection with electrospray ionization triple quadrupole mass spectrometry using the MxP® Quant 500 kit. A total of 240 metabolites in serum were used in the final data analysis. Principal component analysis revealed a clear separation by days of sampling, indicating a remarkable shift in metabolic phenotype between the dry period and late and early lactation. Changes in many non-lipid metabolites associated with one-carbon metabolism, the tricarboxylic acid cycle, the urea cycle, and AA catabolism were observed in the study, with changes in AA serum concentrations likely related to factors such as energy and nitrogen balance, digestive efficiency, and changing diets. The study confirmed an extensive remodeling of the serum lipidome in peripartum dairy cows, highlighting the importance of changes in acylcarnitine (AcylCN), phosphatidylcholines (PC), and triacylglycerols (TG), as they play a crucial role in lipid metabolism. Results showed that short-chain AcylCN increased after dry-off and decreased thereafter, whereas lipid-derived AcylCN increased around parturition, suggesting that more fatty acids could enter mitochondria. Phospholipids and sphingolipids in serum showed changes during lactation. In particular, concentrations of sphingomyelins (SM), PC, and LysoPC decreased around calving but increased in mid- and late lactation. In contrast, concentrations of TG remained consistently low after parturition. The serum concentrations of bile acids fluctuated during the dry period and lactation, with glycocholic acid, cholic acid, glycodeoxycholic acid, and taurocholic acid showing the greatest concentrations. These changes are likely due to the interplay of diet, liver function, and the ability of the gut microbiota to convert primary to secondary bile acids. Overall, these descriptive results may aid in hypothesis generation, and the design and interpretation of future metabolite-based studies in dairy cows. Furthermore, they contribute to our understanding of the physiological ranges in serum metabolites relative to the lactation cycle of the dairy cow.PMID:37777004 | DOI:10.3168/jds.2023-23841

J Proteomics. 2023 Sep 28:105011. doi: 10.1016/j.jprot.2023.105011. Online ahead of print.ABSTRACTGallium has a long history as a chemotherapeutic agent. The mechanisms of action of Ga(III)-based anti-infectives are different from conventional antibiotics, which primarily result from the chemical similarities of Ga(III) with Fe(III) and substitution of gallium into iron-dependent biological pathways. However, more aspects of the molecular mechanisms of Ga(III) against human pathogens, especially its regulations on bacterial metabolic processes, remain to be understood. Herein, by using conventional quantitative proteomics approaches, we identified the protein changes of Pseudomonas aeruginosa (P. aeruginosa) in response to Ga(NO3)3 treatment. We show that Ga(III) exhibits bacteriostatic mode of action against P. aeruginosa through affecting the expressions of a number of key enzymes in the main metabolic pathways, including glycolysis, TCA cycle, amino acid metabolism, and protein and nucleic acid biosynthesis. In addition, decreased abundances of proteins associated with pathogenesis and virulence of P. aeruginosa were also identified. Moreover, the correlations between protein expressions and metabolome changes in P. aeruginosa upon Ga(III) treatment were identified and discussed. Our findings thus expand the understanding on the antimicrobial mechanisms of gallium that shed light on enhanced therapeutic strategies. BIOLOGICAL SIGNIFICANCE: Mounting evidence suggest that the efficacy and resistance of clinical antibiotics are closely related to the metabolic homeostasis in bacterial pathogens. Ga(III)-based compounds have been repurposed as antibacterial therapeutic candidates against antibiotics resistant pathogens, and represent a safe and promising treatment for clinical human infections, while more thorough understandings of how bacteria respond to Ga(III) treatment are needed. In the present study, we provide evidences at the proteome level to indicate Ga(III)-induced metabolic perturbations in P. aeruginosa. We identified and discussed the interference of Ga(III) on the expressions and activities of enzymes in the main metabolic pathways in P. aeruginosa. In view of our previous report that the antimicrobial efficacy of Ga(III) could be modulated according to Ga(III)-induced metabolome changes in P. aeruginosa, our current analyses may serve as theoretical basis for the development of efficient gallium-based therapies by exploiting bacterial metabolic mechanisms.PMID:37776994 | DOI:10.1016/j.jprot.2023.105011

Bioresour Technol. 2023 Sep 28:129812. doi: 10.1016/j.biortech.2023.129812. Online ahead of print.ABSTRACTIn practical engineering, nitrogen removal at low temperatures or low C/N ratios is difficult. Although strains can remove nitrogen well at low temperatures, there is no research on the performance and deep mechanism of strains under low C/N ratio stress. In this study, Pseudomonas sp. LW60 with superior nitrogen removal efficiency under low C/N ratio stress was isolated at 4 °C. With a C/N ratio of 2-10, the NH4+-N removal efficiency was 40.02 %-100 % at 4 °C. Furthermore, the resistance mechanism of Pseudomonas sp. LW60 to low C/N ratio stress was deeply investigated by multi-omics. The results of transcriptome, proteome, and metabolome revealed that the resistance of strain LW60 to low C/N ratio stress was attributed to enhanced central carbon metabolism, amino acid metabolism, and ABC transporters, rather than nitrogen removal pathways. This study isolated a strain with low C/N ratio tolerance and deeply explored its tolerance mechanism by multi-omics.PMID:37776911 | DOI:10.1016/j.biortech.2023.129812

Psychoneuroendocrinology. 2023 Sep 21;158:106395. doi: 10.1016/j.psyneuen.2023.106395. Online ahead of print.ABSTRACTBACKGROUND: During pregnancy, steroids enable physiological adaptations in response to many factors, including maternal stress or psychological functioning. While stress and psychological dysfunction can have endocrine-disrupting effects beyond cortisol disruption, associations between prenatal maternal stress or related psychological dysfunction and the broader steroid milieu remain understudied.AIM: To assess associations between independent and joint maternal stress and psychological functioning measures and steroid profiles in pregnancy (22-40 gestational weeks) in the Programming of Intergenerational Stress Mechanisms (PRISM) birth cohort (n = 334).METHODS: Serum metabolomics detected 42 steroids and their metabolites, which were grouped into five classes (pregnenolone, androgens, estrogens, progestin, and corticosteroids). The Perceived Stress Scale, Life Stressor Checklist-Revised, and Edinburgh Postnatal Depression Scale indexed lifetime traumatic/non-traumatic stressors, global prenatal stress appraisal, and depressive symptoms during pregnancy, respectively. Exposures were categorized as high-low using the corresponding 3rd quartiles. We assessed associations between both individual and joint stress exposures with steroid classes using linear mixed effect models and with individual steroids using linear regressions. We also examined fetal sex-specific effects.RESULTS: High prenatal perceived stress was independently associated with lower levels of androgens and estrogens in the overall sample [β (95%CI): androgens: -0.13 (-0.25;-0.01); estrogens: -0.16 (-0.31;-0.01)], particularly among women carrying males [androgens: -0.22 (-0.39;-0.05); estrogens: -0.28 (-0.50;-0.07)]. Results on estrogens were consistent when considering joint exposure to both greater lifetime stressors and higher prenatal perceived stress. We also found a single testosterone metabolite-5alpha-androstan-3alpha,17alpha-diol disulfate-negatively associated with both individual high perceived stress and joint exposure to high lifetime stressors and high perceived stress among women carrying males.CONCLUSIONS: Increased maternal perceived stress experienced in pregnancy was independently associated with lower maternal androgen and estrogen levels during pregnancy in the overall sample, particularly among women carrying males. Results on estrogens were consistent when we considered the joint exposure of increased lifetime stressors and higher prenatal perceived stress.PMID:37776732 | DOI:10.1016/j.psyneuen.2023.106395

J Neurol Sci. 2023 Sep 22;453:120812. doi: 10.1016/j.jns.2023.120812. Online ahead of print.ABSTRACTOBJECTIVE: Metabolic biomarkers can potentially inform disease progression in Alzheimer's disease (AD). The purpose of this study is to identify and describe a new set of diagnostic biomarkers for developing deep learning (DL) tools to predict AD using Ultra Performance Liquid Chromatography Mass Spectrometry (UPLC-MS/MS)-based metabolomics data.METHODS: A total of 177 individuals, including 78 with AD and 99 with cognitive normal (CN), were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort along with 150 metabolomic biomarkers. We performed feature selection using the Least Absolute Shrinkage and Selection Operator (LASSO). The H2O DL function was used to build multilayer feedforward neural networks to predict AD.RESULTS: The LASSO selected 21 metabolic biomarkers. To develop DL models, the 21 biomarkers identified by LASSO were imported into the H2O package. The data was split into 70% for training and 30% for validation. The best DL model with two layers and 18 neurons achieved an accuracy of 0.881, F1-score of 0.892, and AUC of 0.873. Several metabolomic biomarkers involved in glucose and lipid metabolism, in particular bile acid metabolites, were associated with APOE-ε4 allele and clinical biomarkers (Aβ42, tTau, pTau), cognitive assessments [the Alzheimer's Disease Assessment Scale-cognitive subscale 13 (ADAS13), the Mini-Mental State Examination (MMSE)], and hippocampus volume.CONCLUSIONS: This study identified a new set of diagnostic metabolomic biomarkers for developing DL tools to predict AD. These biomarkers may help with early diagnosis, prognostic risk stratification, and/or early treatment interventions for patients at risk for AD.PMID:37776718 | DOI:10.1016/j.jns.2023.120812

Food Chem. 2023 Sep 23;435:137581. doi: 10.1016/j.foodchem.2023.137581. Online ahead of print.ABSTRACTChestnut (Castanea sativa) shells (CS) are an undervalued antioxidant-rich by-product. This study explores the impact of in-vitro digestion on the bioaccessibility, bioactivity, and metabolic profile of CS extract prepared by Supercritical Fluid Extraction, aiming its valorization for nutraceutical applications. The results demonstrated significantly (p < 0.05) lower phenolic concentrations retained after digestion (38.57 µg gallic acid equivalents/mg dry weight (DW)), reaching 30% of bioaccessibility. The CS extract showed antioxidant/antiradical, hypoglycemic, and neuroprotective properties after in-vitro digestion, along with upmodulating effects on antioxidant enzymes activities and protection against lipid peroxidation. The metabolic profile screened by LC-ESI-LTQ-Orbitrap-MS proved the biotransformation of complex phenolic acids, flavonoids, and tannins present in the undigested extract (45.78 µg/mg DW of total phenolic concentration) into hydroxybenzoic, phenylpropanoic, and phenylacetic acids upon digestion (35.54 µg/mg DW). These findings sustain the valorization of CS extract as a promising nutraceutical ingredient, delivering polyphenols with proven bioactivity even after in-vitro digestion.PMID:37776654 | DOI:10.1016/j.foodchem.2023.137581

J Pharm Biomed Anal. 2023 Sep 26;236:115756. doi: 10.1016/j.jpba.2023.115756. Online ahead of print.ABSTRACTInsomnia is an accompanying symptom of many diseases and is closely associated with neurodegenerative diseases. Naoling Pian (NLP) is a patented Chinese medicine mainly used to treat insomnia. To evaluate the sedative and hypnotic effects of NLP and its modulatory effects on biological metabolites and metabolic pathways, rats with p-chlorophenylalanine (PCPA)-induced insomnia were given different doses of NLP by oral gavage for seven days. Diazepam (DZP) served as a positive control. Behavior was measured using the open field test, and neurotransmitter levels in the brain tissue related to sleep were measured using ELISA. The metabolic profiles and biomarkers of PCPA-induced insomnia in rats before and after NLP administration were analyzed using UPLC-Q/TOF-MS combined with multivariate data analysis. The results showed that the levels of 5-hydroxytryptamine, gamma-aminobutyric acid, norepinephrine, and dopamine in the brain tissue were significantly recovered in the NLP treatment groups, demonstrating similar or even superior therapeutic effects compared to the DZP group. The behavior of the PCPA-model rats partially recovered to normal levels after seven days of treatment. Metabolomics identified 30 metabolites in the urine as potential biomarkers of insomnia, and NLP significantly altered 25 of these, involving 21 metabolic pathways. NLP has a remarkable effect on insomnia, the therapeutic effects of which may be largely due to the rectification of metabolic disturbances. This is the first study of the sedative and hypnotic effects of NLP from a metabolomic perspective.PMID:37776625 | DOI:10.1016/j.jpba.2023.115756

Environ Int. 2023 Sep 16;180:108204. doi: 10.1016/j.envint.2023.108204. Online ahead of print.ABSTRACTFrequent outbreak of cyanobacteria is a serious problem for drinking water treatment. The microcystins released from Microcystis aeruginosa (M. aeruginosa) could cause irreversible damage to human health. Catalyst-free solar/periodate (PI) system has recently presented great potential for bacterial inactivation, whereas the application potential and underlying mechanisms of the effective M. aeruginosa control remain unclear. Our work delineated the key role of ROS that inactivating/harmless disposing M. aeruginosa in the simulated sunlight (SSL)/PI system. Singlet oxygen may specifically cause DNA damage but maintain membrane integrity, preventing the risk of microcystins leakage. The SSL/PI 300 μM system could also effectively inhibit M. aeruginosa recovery for >7 days and completely degrade microcystin-LR (50.0 μg/L) within 30 min. Non-targeted metabolomic analysis suggested that the SSL/PI system inactivated M. aeruginosa mainly by interrupting the Calvin-Benson cycle, which damaged the metabolic flux of glycolysis and its downstream pathways such as the oxidative PPP pathway and glutathione metabolism. Furthermore, the activated PI system exhibited an even better algal inhibition under natural sunlight irradiation, evidenced by the seriously damaged cell membrane of M. aeruginosa. Overall, this study reported the comprehensive mechanisms of algal control and application potentials of solar/PI systems. The findings facilitated the development of emerging algicidal technology and its application in controlling environmental harmful algae.PMID:37776621 | DOI:10.1016/j.envint.2023.108204

Animal. 2023 Sep 7;17(10):100981. doi: 10.1016/j.animal.2023.100981. Online ahead of print.ABSTRACTIt is well established that promoting the balance of nutrients and plant secondary metabolites (PSM) by feeding diverse forage physiologically improves ruminant production. However, the underlying mechanism remains unclear. To investigate the physiological mechanism related to the improvement of physiological stress tolerance, ruminants were fed diverse forage. Oxidative stress markers were quantified, and serum metabolomics was performed. Six crossbred Shiba wethers (32.8 ± 9.2 kg BW) were arranged in a replicated 3 × 3 Latin square design. The treatments were feeding only Sudan grass hay (100% SDN); feeding a mixture of Sudan grass and alfalfa hay (70:30, SDN-ALF); and feeding a mixture of Sudan grass, timothy grass, and alfalfa hay (35:35:30; SDN-TMT-ALF). Each diet group was fed its specific diet for 21 days with a 14-day adaptation period. Feed intake and digestibility, blood biochemistry, total antioxidant capacity (TAC), and superoxide dismutase (SOD) were analysed. In addition, blood serum metabolites were assessed by liquid chromatography-tandem mass spectrometry. The DM intake and DM, organic matter, and CP digestibility were higher (P < 0.05) in the SDN-TMT-ALF group than in the SDN group. The TAC was higher (P < 0.01) in the SDN-TMT-ALF and SDN-ALF groups (809.51 and 813.7 µM, respectively) than the SDN group (720.69 µM), while the SOD level was unchanged (P = 0.06) among the treatments. Total serum cholesterol and NH3 levels were higher (P < 0.05) in the SDN-TMT-ALF group (89.17 mg/dL and 242.42 µg/dL, respectively) than in the SDN group (71.00 mg/dL and 89.17 µg/dL). Additionally, the levels of nine metabolites in serum differed among the treatments (P < 0.05). Linoleic acid (LA) and cortisone, which are related to LA metabolism and the steroid biosynthesis pathway, were upregulated by the SDN-ALF and SDN-TMT-ALF diets compared to the SDN diet, suggesting the contribution of ALF to altering the metabolites. The levels of hippuric acid, which is a metabolite of phenolic compounds, were higher (P < 0.001) in the animals fed SDN, which contained higher phenolic and luteolin concentrations than the other diets. Pathway analysis suggested that the higher cortisone levels were derived from cholesterol due to upregulated glycolysis metabolism, which was positively related to increased ingestion, digestibility, and serum LA levels in animals given mixed forage. In conclusion, physiological stress tolerance in the animals was regulated by upregulation of LA and steroid hormone metabolism, which was associated with an increase in TAC rather than the ability of the animal to regulate its PSM intake.PMID:37776601 | DOI:10.1016/j.animal.2023.100981

Ecol Lett. 2023 Sep 30. doi: 10.1111/ele.14308. Online ahead of print.ABSTRACTMetabolomics provides an unprecedented window into diverse plant secondary metabolites that represent a potentially critical niche dimension in tropical forests underlying species coexistence. Here, we used untargeted metabolomics to evaluate chemical composition of 358 tree species and its relationship with phylogeny and variation in light environment, soil nutrients, and insect herbivore leaf damage in a tropical rainforest plot. We report no phylogenetic signal in most compound classes, indicating rapid diversification in tree metabolomes. We found that locally co-occurring species were more chemically dissimilar than random and that local chemical dispersion and metabolite diversity were associated with lower herbivory, especially that of specialist insect herbivores. Our results highlight the role of secondary metabolites in mediating plant-herbivore interactions and their potential to facilitate niche differentiation in a manner that contributes to species coexistence. Furthermore, our findings suggest that specialist herbivore pressure is an important mechanism promoting phytochemical diversity in tropical forests.PMID:37776563 | DOI:10.1111/ele.14308

Metabolomics. 2023 Sep 30;19(10):86. doi: 10.1007/s11306-023-02053-3.ABSTRACTINTRODUCTION: Femur head necrosis (FHN) is a challenging clinical disease with unclear underlying mechanism, which pathologically is associated with disordered metabolism. However, the disordered metabolism in cancellous bone of FHN was never analyzed by gas chromatography-mass spectrometry (GC-MS).OBJECTIVES: To elucidate altered metabolism pathways in FHN and identify putative biomarkers for the detection of FHN.METHODS: We recruited 26 patients with femur head necrosis and 22 patients with femur neck fracture in this study. Cancellous bone tissues from the femoral heads were collected after the surgery and were analyzed by GC-MS based untargeted metabolomics approach. The resulting data were analyzed via uni- and multivariate statistical approaches. The changed metabolites were used for the pathway analysis and potential biomarker identification.RESULTS: Thirty-seven metabolites distinctly changed in FHN group were identified. Among them, 32 metabolites were upregulated and 5 were downregulated in FHN. The pathway analysis showed that linoleic acid metabolism were the most relevant to FHN pathology. On the basis of metabolites network, L-lysine, L-glutamine and L-serine were deemed as the junctions of the whole metabolites. Finally, 9,12-octadecadienoic acid, inosine, L-proline and octadecanoic acid were considered as the potential biomarkers of FHN.CONCLUSION: This study provides a new insight into the pathogenesis of FHN and confirms linoleic acid metabolism as the core.PMID:37776501 | DOI:10.1007/s11306-023-02053-3

Microsc Res Tech. 2023 Sep 29. doi: 10.1002/jemt.24429. Online ahead of print.ABSTRACTDicleptera chinensis J. (Acanthaceae) has been employed in traditional medicinal systems for treating various ailments. It has been used as an anti-inflammatory, wound healing, diuretic, and detoxifying agent in different regions of the world. This study determines several pharmacognostic standards, which are useful to ensure safety, efficacy, and purity of D. chinensis. Different parts of the plant were examined through a scanning electron microscope and light microscope, and cross-section images revealed several useful botanical features of the plant. The color, size, odor, shape, and surface characteristics of plant parts were also examined macroscopically. Pharmacognostic standardization parameters including ash values, loss on drying, swelling index, hemolytic index, and foaming index were determined in accordance with WHO guidelines. Heavy metal analysis was executed through atomic absorption spectrophotometer which depicted the presence of heavy metals and trace elements within the acceptable range. Qualitative phytochemical tests for alkaloids, flavonoids, saponins, glycosides, tannins, carbohydrates, lipids, protein, and so forth of plant extract were also performed, which showed the valuable amount of these phytochemicals useful for medicinal purposes. Preliminary phytochemical tests provide an indication for major phytoconstituents classes present in the plant. These quantitative and qualitative microscopic features are helpful in establishing the pharmacopeia standards of plant. Assessment of various pharmacognostic features such as morphology of various plant parts explained along with physicochemical and phytochemical analysis could be very helpful for future research. RESEARCH HIGHLIGHTS: Pharmacognostic standardization is employed as reported evidence for correct identification of D. chinensis. Structures identified by scanning electron microscopy and light microscopy serve as diagnostic features of plant. Important secondary metabolites present in the plant suggest the need for further exploration through advanced metabolomics and other analytical techniques.PMID:37775982 | DOI:10.1002/jemt.24429

Pharmacotherapy. 2023 Sep 29. doi: 10.1002/phar.2882. Online ahead of print.ABSTRACTBACKGROUND: Levocarnitine (L-carnitine) has shown promise as a metabolic-therapeutic for septic shock, where mortality approaches 40%. However, high-dose (≥ 6 grams) intravenous supplementation results in a broad range of serum concentrations.OBJECTIVES: We sought to describe the population pharmacokinetics (PK) of high-dose L-carnitine, test various estimates of kidney function, and assess the correlation of PK parameters with pre-treatment metabolites in describing drug response for patients with septic shock.METHODS: We leveraged serum samples and metabolomics data from a phase II trial of L-carnitine in vasopressor-dependent septic shock. Patients were adaptively randomized to receive intravenous L-carnitine (6 grams, 12 grams, or 18 grams) or placebo. Serum was collected at baseline (T0); end-of-infusion (T12); and 24, 48, and 72 hours after treatment initiation. Population PK analysis was done with baseline normalized concentrations using nonlinear mixed effect models in the modeling platform Monolix. Various estimates of kidney function, patient demographics, dose received, and organ dysfunction were tested as population covariates.RESULTS: The final dataset included 542 serum samples from 130 patients randomized to L-carnitine. A two-compartment model with linear elimination and a fixed volume of distribution (17.1 liters) best described the data and served as a base structural model. Kidney function estimates as a covariate on the elimination rate constant (k) reliably improved model fit. Estimated glomerular filtration rate (eGFR), based on the 2021 Chronic Kidney Disease Epidemiology collaboration (CKD-EPI) equation with creatinine and cystatin C, outperformed creatinine clearance (Cockcroft-Gault) and older CKD-EPI equations that use an adjustment for self-identified race.CONCLUSIONS: High-dose L-carnitine supplementation is well-described by a two-compartment population PK model in patients with septic shock. Kidney function estimates that leverage cystatin C provided superior model fit. Future investigations into high-dose L-carnitine supplementation should consider baseline metabolic status and dose adjustments based on renal function over a fixed or weight-based dosing paradigm.PMID:37775945 | DOI:10.1002/phar.2882

Cardiovasc Diabetol. 2023 Sep 29;22(1):262. doi: 10.1186/s12933-023-01994-2.ABSTRACTBACKGROUND: Several large observational prospective studies have reported a protection by the traditional Mediterranean diet against type 2 diabetes, but none of them used yearly repeated measures of dietary intake. Repeated measurements of dietary intake are able to improve subject classification and to increase the quality of the assessed relationships in nutritional epidemiology. Beyond observational studies, randomized trials provide stronger causal evidence. In the context of a randomized trial of primary cardiovascular prevention, we assessed type 2 diabetes incidence according to yearly repeated measures of compliance with a nutritional intervention based on the traditional Mediterranean diet.METHODS: PREDIMED (''PREvención con DIeta MEDiterránea'') was a Spanish trial including 7447 men and women at high cardiovascular risk. We assessed 3541 participants initially free of diabetes and originally randomized to 1 of 3 diets: low-fat diet (n = 1147, control group), Mediterranean diet supplemented with extra virgin olive (n = 1154) or Mediterranean diet supplemented with mixed nuts (n = 1240). As exposure we used actual adherence to Mediterranean diet (cumulative average), yearly assessed with the Mediterranean Diet Adherence Screener (scoring 0 to 14 points), and repeated up to 8 times (baseline and 7 consecutive follow-up years). This score was categorized into four groups: < 8, 8-< 10, 10- < 12, and 12-14 points. The outcome was new-onset type 2 diabetes.RESULTS: Multivariable-adjusted hazard ratios from time-varying Cox models were 0.80 (95% confidence interval, 0.70-0.92) per + 2 points in Mediterranean Diet Adherence Screener (linear trend p = .001), and 0.46 (0.25-0.83) for the highest (12-14 points) versus the lowest (< 8) adherence. This inverse association was maintained after additionally adjusting for the randomized arm. Age- and sex-adjusted analysis of a validated plasma metabolomic signature of the Mediterranean Diet Adherence Screener (constituted of 67 metabolites) in a subset of 889 participants also supported these results.CONCLUSIONS: Dietary intervention trials should quantify actual dietary adherence throughout the trial period to enhance the benefits and to assist results interpretation. A rapid dietary assessment tool, yearly repeated as a screener, was able to capture a strong inverse linear relationship between Mediterranean diet and type 2 diabetes. Trial registration ISRCTN35739639.PMID:37775736 | DOI:10.1186/s12933-023-01994-2

ISME J. 2023 Sep 29. doi: 10.1038/s41396-023-01522-w. Online ahead of print.ABSTRACTNitrogen is a limiting nutrient for degraders function in hydrocarbon-contaminated environments. Biological nitrogen fixation by diazotrophs is a natural solution for supplying bioavailable nitrogen. Here, we determined whether the diazotroph Azotobacter chroococcum HN can provide nitrogen to the polycyclic aromatic hydrocarbon-degrading bacterium Paracoccus aminovorans HPD-2 and further explored the synergistic interactions that facilitate pyrene degradation in nitrogen-deprived environments. We found that A. chroococcum HN and P. aminovorans HPD-2 grew and degraded pyrene more quickly in co-culture than in monoculture. Surface-enhanced Raman spectroscopy combined with 15N stable isotope probing (SERS - 15N SIP) demonstrated that A. chroococcum HN provided nitrogen to P. aminovorans HPD-2. Metabolite analysis and feeding experiments confirmed that cross-feeding occurred between A. chroococcum HN and P. aminovorans HPD-2 during pyrene degradation. Transcriptomic and metabolomic analyses further revealed that co-culture significantly upregulated key pathways such as nitrogen fixation, aromatic compound degradation, protein export, and the TCA cycle in A. chroococcum HN and quorum sensing, aromatic compound degradation and ABC transporters in P. aminovorans HPD-2. Phenotypic and fluorescence in situ hybridization (FISH) assays demonstrated that A. chroococcum HN produced large amounts of biofilm and was located at the bottom of the biofilm in co-culture, whereas P. aminovorans HPD-2 attached to the surface layer and formed a bridge-like structure with A. chroococcum HN. This study demonstrates that distinct syntrophic interactions occur between A. chroococcum HN and P. aminovorans HPD-2 and provides support for their combined use in organic pollutant degradation in nitrogen-deprived environments.PMID:37775536 | DOI:10.1038/s41396-023-01522-w

Lancet Digit Health. 2023 Oct;5(10):e712-e736. doi: 10.1016/S2589-7500(23)00129-2.ABSTRACTData sharing is central to the rapid translation of research into advances in clinical medicine and public health practice. In the context of COVID-19, there has been a rush to share data marked by an explosion of population-specific and discipline-specific resources for collecting, curating, and disseminating participant-level data. We conducted a scoping review and cross-sectional survey to identify and describe COVID-19-related platforms and registries that harmonise and share participant-level clinical, omics (eg, genomic and metabolomic data), imaging data, and metadata. We assess how these initiatives map to the best practices for the ethical and equitable management of data and the findable, accessible, interoperable, and reusable (FAIR) principles for data resources. We review gaps and redundancies in COVID-19 data-sharing efforts and provide recommendations to build on existing synergies that align with frameworks for effective and equitable data reuse. We identified 44 COVID-19-related registries and 20 platforms from the scoping review. Data-sharing resources were concentrated in high-income countries and siloed by comorbidity, body system, and data type. Resources for harmonising and sharing clinical data were less likely to implement FAIR principles than those sharing omics or imaging data. Our findings are that more data sharing does not equate to better data sharing, and the semantic and technical interoperability of platforms and registries harmonising and sharing COVID-19-related participant-level data needs to improve to facilitate the global collaboration required to address the COVID-19 crisis.PMID:37775189 | DOI:10.1016/S2589-7500(23)00129-2