Metabolic Profile Research Articles

Resting energy expenditure in women with polycystic ovary syndrome.

Is resting energy expenditure (REE) altered in women with polycystic ovary syndrome (PCOS)? Women with PCOS have a reduction in REE, when corrected for fat-free mass, independent of PCOS clinical phenotypes and BMI categories. Obesity is an important issue in women with PCOS, in terms of frequency and pathophysiological implications. It has been hypothesized that obesity may be favoured by alterations in REE, but the studies have been limited and conflicting. This case-control study was a comparison of 266 women with PCOS and 51 healthy controls, recruited in the Verona 3P study from 2010 to 2021. Women with PCOS diagnosed by the Rotterdam criteria, with normal thyroid function and no interfering medications, were referred to the outpatient clinic of a tertiary care centre of endocrinology and metabolism for a measurement of REE. Healthy controls were recruited in the same period and submitted to the same procedure. In all subjects, REE was measured by indirect calorimetry and serum androgens were measured by LC-MS/MS. In women with PCOS, insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp. REE was similar in women with PCOS and controls. However, REE corrected for fat-free mass (REE/FFM) was significantly lower in women with PCOS than in controls (31.8 ± 4.0 vs 35.4 ± 3.9kcal/kgFFM·day, P < 0.001). REE/FFM did not differ between normal-weight, overweight, or obese women with PCOS, and each of these subgroups showed lower REE/FFM values than controls. Reduced REE/FFM values were found in each phenotype of the syndrome. In multiple regression analysis, REE/FFM was independently associated with age and PCOS status, but not with fat mass. In PCOS women, REE/FFM was independently and directly associated with ovarian follicle number. Limitations of the study are the cross-sectional design, which limits the causal inference of the results, and the unavailability of precise information about lifestyle factors, which may be potential confounders. Further prospective studies are needed to establish the importance of this phenomenon in contributing to the weight excess of PCOS. A reduction of REE could potentially favour weight gain in women with PCOS and possibly contribute to the altered metabolic profile typical of this condition, even counteracting the therapeutic strategies aimed to reduce excess body fat in these women. Nevertheless, the presence of this abnormality in both obese/overweight and normal-weight patients suggests that other factors must play a role in this phenomenon. This work was supported by academic grants to PM from the University of Verona (FUR 2010-2022). All authors declare no conflict of interest. N/A.

Evaluation of Cytotoxicity and Metabolic Profiling of Synechocystis sp. Extract Encapsulated in Nano-Liposomes and Nano-Niosomes Using LC-MS, Complemented by Molecular Docking Studies

Liposomes and niosomes can be considered excellent drug delivery systems due to their ability to load all compounds, whether hydrophobic or hydrophilic. In addition, they can reduce the toxicity of the loaded drug without reducing its effectiveness. Synechocystis sp. is a unicellular, freshwater cyanobacteria strain that contains many bioactive compounds that qualify its use in industrial, pharmaceutical, and many other fields. This study investigated the potential of nano-liposomes (L) and nano-niosomes (N) for delivering Synechocystis sp. extract against cancer cell lines. Four different types of nanoparticles were prepared using a dry powder formulation and ethanol extract of Synechocystis sp. in both nanovesicles (N1 and N2, respectively) and liposomes (L1 and L2, respectively). Analysis of the formed vesicles using zeta analysis, SEM morphological analysis, and visual examination confirmed their stability and efficiency. L1 and L2 in this investigation had effective diameters of 419 and 847 nm, respectively, with PDI values of 0.24 and 0.27. Furthermore, the zeta potentials were found to range from −31.6 mV to −43.7 mV. Regarding N1 and N2, their effective diameters were 541 nm and 1051 nm, respectively, with PDI values of 0.31 and 0.35, and zeta potentials reported from −31.6 mV to −22.2 mV, respectively. Metabolic profiling tentatively identified 22 metabolites (1–22) from the ethanolic extract. Its effect against representative human cancers was studied in vitro, specifically against colon (Caco2), ovarian (OVCAR4), and breast (MCF7) cancer cell lines. The results showed the potential activities of the prepared N1, N2, L1, and L2 against the three cell lines, where L1 had cytotoxicity IC50 values of 19.56, 33.52, and 9.24 µg/mL compared to 26.27, 56.23, and 19.61 µg/mL for L2 against Caco2, OVCAR4, and MCF7, respectively. On the other hand, N1 exhibited IC50 values of 9.09, 11.42, and 2.38 µg/mL, while N2 showed values of 15.57, 18.17, and 35.31 µg/mL against Caco2, OVCAR4, and MCF7, respectively. Meanwhile, the formulations showed little effect on normal cell lines (FHC, OCE1, and MCF10a). All of the compounds were evaluated in silico against the epidermal growth factor receptor tyrosine kinase (EGFR). The molecular docking results showed that compound 21 (1-hexadecanoyl-2-(9Z-hexadecenoyl)-3-(6′-sulfo-alpha-D-quinovosyl)-sn-glycerol), followed by compounds 6 (Sulfoquinovosyl monoacylgycerol), 7 (3-Hydroxymyristic acid), 8 (Glycolipid PF2), 12 (Palmitoleic acid), and 19 (Glyceryl monostearate), showed the highest binding affinities. These compounds formed good hydrogen bond interactions with the key amino acid Lys721 as the co-crystallized ligand. These results suggest that nano-liposomes and nano-niosomes loaded with Synechocystis sp. extract hold promise for future cancer treatment development. Further research should focus on clinical trials, stability assessments, and pharmacological profiles to translate this approach into effective anticancer drugs.

Altered biliary microbial and metabolic profile reveals the crosstalk between NAFLD and cholelithiasis

BackgroundThe relationship between non-alcoholic fatty liver disease (NAFLD) and cholelithiasis is intricate, with alterations in the microenvironment potentially mediating this interplay. Thus, this study aimed to explore the biliary microbiota and metabolites of patients with cholelithiasis and detect changes induced by comorbid NAFLD. MethodsIn this study, 16S rRNA gene sequencing and metabolome analysis were performed on biliary samples collected from 35 subjects. Then, patients were stratified into two groups: the comorbidity group (n = 18), consisting of cholelithiasis patients with NAFLD, and the non-comorbidity group (n = 17), comprising cholelithiasis patients without NAFLD. ResultsComorbid NAFLD did not significantly increase α-diversity but affected β-diversity. A statistically significant difference was observed in the abundance of biliary metabolites between the two groups. Specifically, differences in the abundance of 4 phyla, 19 genera, and 28 metabolites were significant between the two groups. Correlation analysis demonstrated positive associations among 12α-hydroxylated bile acid levels, Pyramidobacter and Fusobacterium abundance, AST levels, and the fibrosis-4 index (p < 0.05, r > 0.3), all of which were increased in patients with cholelithiasis and comorbid NAFLD. ConclusionsThe relationship between cholelithiasis and NAFLD influences the biliary microbial and metabolic profile, creating a detrimental microenvironment that promotes the disease progression.

Metabolic profiling and combined therapeutic strategies unveil the cytotoxic potential of selenium-chrysin (SeChry) in NSCLC cells.

Lung cancer ranks as the predominant cause of cancer-related mortalities on a global scale. Despite progress in therapeutic interventions, encompassing surgical procedures, radiation, chemotherapy, targeted therapies and immunotherapy, the overall prognosis remains unfavorable. Imbalances in redox equilibrium and disrupted redox signaling, common traits in tumors, play crucial roles in malignant progression and treatment resistance. Cancer cells, often characterized by persistent high levels of reactive oxygen species (ROS) resulting from genetic, metabolic, and microenvironmental alterations, counterbalance this by enhancing their antioxidant capacity. Cysteine availability emerges as a critical factor in chemoresistance, shaping the survival dynamics of non-small cell lung cancer (NSCLC) cells. Selenium-chrysin (SeChry) was disclosed as a modulator of cysteine intracellular availability. This study comprehensively characterizes the metabolism of SeChry and investigates its cytotoxic effects in NSCLC. SeChry treatment induces notable metabolic shifts, particularly in selenocompound metabolism, impacting crucial pathways such as glycolysis, gluconeogenesis, the tricarboxylic acid (TCA) cycle, and amino acid metabolism. Additionally, SeChry affects the levels of key metabolites such as acetate, lactate, glucose, and amino acids, contributing to disruptions in redox homeostasis and cellular biosynthesis. The combination of SeChry with other treatments, such as glycolysis inhibition and chemotherapy, results in greater efficacy. Furthermore, by exploiting NSCLC's capacity to consume lactate, the use of lactic acid-conjugated dendrimer nanoparticles for SeChry delivery is investigated, showing specificity to cancer cells expressing monocarboxylate transporters.

Laboratory profiling of patients with long COVID in the Brazilian Amazon region: A cross-sectional study.

The condition commonly referred to as long coronavirus disease (COVID) is characterized by the continuation of symptoms, sometimes accompanied by new symptoms that persist after the resolution of acute coronavirus disease 2019 (COVID-19). This observational cross-sectional study investigated 332 patients with long COVID in the Brazilian Amazon region. The study aimed to elucidate the systemic interactions associated with long COVID by compiling the findings related to hematological, coagulation, immunological, metabolic, hepatic, renal, and muscular profiles. Participants with long COVID were identified using rigorous criteria and underwent thorough laboratory examinations. The obtained data were subsequently analyzed, allowing for comparisons, associations, and correlations between findings within distinct groups in the study. Significant associations were observed between hospitalization during the acute phase and persistent laboratory abnormalities, suggesting a potential link between acute severity and long-term effects. Notably, individuals with long COVID for over a year exhibited elevated levels of monocytes, prolonged prothrombin times, reduced prothrombin activity, high levels of lactate dehydrogenase, and an increased frequency of qualitative C-reactive protein detection. This study provides valuable insights into the laboratory risk profile of patients with long COVID, particularly in the unique context of the Amazon region, where patients exhibit persistent symptoms lasting up to 1261 days.

Radiotolerant endophytic bacteria and analysis of the effects of 137Cesium on the metabolome of Pantoea sp.

Some bacteria have developed mechanisms to withstand the stress caused by ionizing radiation. The ability of these radioresistant microorganisms to survive high levels of radiation is primarily attributed to their DNA repair mechanisms and the production of protective metabolites. To determine the effect of irradiation on bacterial growth, we propose to compare the metabolites produced by the irradiated isolates to those of the control (non-irradiated isolates) using mass spectrometry, molecular networking, and chemometric analysis. We identified the secondary metabolites produced by these bacteria and observed variations in growth following irradiation. Notably, after 48h of exposure to radiation, Pantoea sp. bacterial cells exhibited a significant 6-log increase compared to non-irradiated cells. Non-irradiated cells produce exclusively Pyridindolol, 1-hydroxy-4-methylcarbostyril, N-alkyl, and N-2-alkoxyethyl diethanolamine, while 5'-methylthioadenosine was detected only in irradiated cells. These findings suggest that the metabolic profile of Pantoea sp. remained relatively stable. The results obtained from this study have the potential to facilitate the development of innovative strategies for harnessing the capabilities of endophytic bacteria in radiological protection and bioremediation of radionuclides.

The effect of biofertilizers on nickel accumulation, nitrogen metabolism and amino acid profile of corn (Zea mays L.) exposed to nickel stress.

The issue of heavy metal pollution such as nickel poses a significant environmental concern, exerting detrimental effects on the growth and viability of plant life. Plants have various mechanisms to effectively manage heavy metal stress, including the ability to modify their amino acid type and content. This adaptive response allows plants to mitigate the detrimental effects caused by excessive heavy metal accumulation. The aim of this study was to investigate the effect of biofertilizers on nickel accumulation, nitrogen metabolism and amino acid profile of corn (Zea maysL.) cv. 'PL438' exposed to Ni stress. After disinfecting and soaking in water for 24 h, corn seeds were primed with bacterial biofertilizers (T2: NPK + FZ), fungal biofertilizers (T3: Arbuscular mycorrhizal fungi (AMF) + Trichoderma (T)), or a combination of them (T4: NPK + FZ + AMF + T) and were cultured by the hydroponic method in completely controlled conditions. Then, they were simultaneously exposed to nickel chloride at various rates (0, 75, or 150 µM) at the three-leaf stage. They were harvested two weeks later and were subjected to the measurement of Ni content, nitrate and nitrite content, nitrate reductase activity, and amino acid profile by high-performance liquid chromatography. The results showed that the application of Ni at higher rates increased Ni, nitrate, and nitrite contents and nitrate reductase activity. The study of Ni accumulation and TF revealed that Ni accumulated in the roots to a greater extent than in the shoots and TF was < 1 in all treatments. The shoot amino acid profile showed that the treatment of Ni+2 increased som amino acids such as aspartic acid, asparagine, serine, histidine, and glycine versus the control, whereas T4Ni+2 increased aspartic acid, glutamic acid, threonine and arginine. The change in amino acids in Ni-treated plants may play a key role in their adaptation to Ni stress. The findings indicate that biofertilizers played a crucial role in mitigating the negative impacts of Ni on corn plants through alterations in amino acid composition and decreased absorption and translocation of Ni.

Metabolic characteristic profiling of 1-amino-3,3-dimethyl-1-oxobutan-2-yl-derived indole and indazole synthetic cannabinoids in vitro

Characterizing the metabolic profiles of synthetic cannabinoids (SCs), a type of new psychoactive substances, is of particular importance for forensic detection and analysis. Although the metabolism of individual SCs derived from 1-amino-3,3-dimethyl-1-oxobutan-2-yl (ADB-SCs) has been reported, their metabolites also undergo a continuous change and combination of their tail and core regions. Therefore, elucidating the metabolic characteristics and effects of these structures is essential to enhance our understanding. In this study, the human liver microsome was used as the model for studying the in vitro phase I metabolism of 12 ADB-SCs, and the metabolites obtained were analyzed using ultra-high performance liquid chromatography–tandem four-level rod-electrostatic field orbital ion trap mass spectrometry to determine type, structure, and relative contents. The results indicated that hydroxylation and N-dealkylation were the major metabolic pathways in 12 ADB-SCs. The effects of the core and tail on the metabolism of these ADB-SCs were studied using theoretical calculations. For N-dealkylation metabolism, the strong electron-withdrawing conjugative effect of the –N= moiety in the pyrazole ring, steric hindrance of the tail, and electronic effect of substituents on the tail significantly affected metabolism. Further, it changed the relative contents of N-dealkylation metabolites. For hydroxylation, the reaction types were inconsistent at different parts. For instance, the phenyl group of the core is electrophilic, and its electron cloud density determines whether the phenyl group can be hydroxylated at the specific metabolic sites. Meanwhile, hydroxylation of the neopentyl moiety of the linked group involves the oxidation of aliphatic C–H bonds, whereas amide–hydroxylamine tautomerism affects hydroxylation metabolism. When the alkyl chain in the tail contains functional groups (such as –F and >CC<), oxidative defluorination or dihydrodiol metabolites are produced. Taken together, we systematically determined d the effect of functional groups in the core and tail of ADB-SCs on their metabolism, validating confirmed the feasibility of ADB-SC metabolism prediction based on their structural characteristics.

Effects of licorice extract in combination with a low-calorie diet on obesity indices, glycemic indices, and lipid profiles in overweight/obese women with polycystic ovary syndrome (PCOS): a randomized, double-blind, placebo-controlled trial

BackgroundPolycystic ovary syndrome (PCOS) is the most common ovarian dysfunction. Recent studies showed the effectiveness of licorice on metabolic profiles with inconsistent findings. So, we investigated the effect of licorice on obesity indices, glycemic indices, and lipid profiles in women with PCOS.MethodsThis randomized, double-blind, placebo-controlled trial was performed on 66 overweight/obese women with PCOS. The participants were randomly assigned to receive either 1.5 gr/day licorice extract plus a low-calorie diet (n = 33) or placebo plus a low-calorie diet (n = 33) for 8 weeks. Participants’ anthropometric indices and body composition were assessed using standard protocols. Fasting blood sugar (FBS), insulin levels, low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), and high-density lipoprotein-cholesterol (HDL-C) were measured using enzymatic kits. The homeostasis model assessment-insulin resistance (HOMA-IR) and HOMA of β-cell function (HOMA-B) were calculated using valid formulas.ResultsBetween-group comparisons demonstrated significant differences between the groups in terms of obesity indices (body weight, BMI, and body fat), lipid profiles (TG, TC, LDL-C, and HDL-C), FBS and insulin levels, HOMA-IR, and HOMA-B at the end of the study (P < 0.05). Supplementation with licorice plus a low-calorie diet was also more effective in improving all parameters than a low-calorie diet alone after adjusting for confounders (baseline values, age, weight changes, and physical activity changes) (P < 0.05).ConclusionThe findings showed that licorice consumption leads to improvements in obesity indices, glucose homeostasis, and lipid profiles compared to placebo. Due to possible limitations of the study, further research is needed to confirm these findings.

Probiotics may be useful for drug-induced liver dysfunction in patients with depression – A secondary analysis of a randomized clinical trial

Background & AimsThere is a need to identify new treatment options for depression with its comorbidities. Depression often coexists with liver steatosis and the two may share a pathophysiological overlap, including inflammation and microbiota changes. Probiotics might represent a safe option as an adjunctive therapy in patients with depression and possible liver steatosis. The paper presents the secondary analysis of a clinical trial of the effect of probiotic supplementation on the levels of non-invasive markers of liver steatosis and fibrosis in adult patients with depressive disorders. MethodsThe research had a two-arm, parallel-group, prospective, randomized, double-blind, controlled design on probiotics in depression. 116 participants received a probiotic preparation containing Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 over 60 days. Here, data from 92 subjects was analyzed. The following were assessed: alanine aminotransferase (ALT), alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio, Hepatic Steatosis Index, Framingham Steatosis Index, as well as non-invasive biomarkers of liver fibrosis (AST to Platelet Ratio Index, Fibosis-4 Index), or baseline socio-demographic, clinical, and laboratory parameters. ResultsThe probiotics did not influence liver steatosis and fibrosis parameters compared with placebo (p=.940 for HSI). However, the subgroup analysis revealed significant differences in liver-related parameters when stratified by the main diagnosis group (better improvement in steatosis indices after probiotics in depressive episode than mixed depression and anxiety disorder patients) or psychotropic medications use (better improvement in ALT-based indices after probiotics in antidepressant-treated subjects than those non-antidepressant-treated). The interplay between probiotics, medications, clinical and metabolic profiles of depression, and the changes in liver-related parameters has been discussed. ConclusionsMultiple factors may modulate the postulated hepatoprotective properties of probiotics efficacy in patients with depression. Further studies with larger sample sizes, different probiotic strains, and longer intervention period are necessary to assess the real significance of probiotics for liver health in this population. ClinicalTrials.gov identifierNCT04756544.

Light Stress Elicits Soilborne Disease Suppression Mediated by Root-secreted Flavonoids in Panax notoginseng

Abstract Developing disease-suppressive soils is an effective approach for managing soilborne diseases, which can be achieved through crop metabolism and root secretion modification that recruit beneficial soil microbiota. Many factors, such as light, can elicit and modify plant metabolomic activities, resulting in disease suppression. To investigate the impact of light, Panax notoginseng was planted in a greenhouse and forest, conditioned with three levels of light intensities, including the optimal (15% light transmittance of full light), suboptimal low (5% light transmittance of full light) and suboptimal high (30% light transmittance of full light) intensities. The rhizosphere microbiota of P. notoginseng and root rot disease caused by soilborne pathogen Ilyonectria destructans, and the mechanism was elucidated. Results showed that suboptimal light conditions alleviated root rot disease of P. notoginseng by enriching beneficial microbiota in the rhizosphere. Both low and high light stresses enhanced the secondary metabolism profile in favor of plant defense, particularly the flavonoid pathway. Notably, high light stress demonstrates a robust ability to promoted flavonoid metabolism and secretion, resulting in the enrichment of more beneficial microorganisms that suppressed the soilborne pathogen I. destructans. These findings highlight the potential for adjusting canopy light intensities to improve soil health and promote sustainable agriculture.

Metabolic profiling of different parts of Physalis alkekengi L. var. franchetii (Mast.) Makino based on UPLC-Q-Orbitrap-HRMS coupled with bioactivity assays

Physalis alkekengi L.var. franchetii (Mast.) Makino (PAF) is an important edible and medicinal plant resource in China. Historically, phytochemical studies have primarily examined the calyx and fruit due to their long-standing use in traditional Chinese medicine for their ability to clear heat and detoxify. Metabolites and bioactivities of other parts such as the leaves, stems and roots, are rarely studied. The study involved conducting metabolic profiling of five plant parts of PAF using UPLC-Q-Orbitrap-HRMS analysis, in conjunction with two bioactivity assays. A total of 95 compounds were identified, including physalins, flavonoids, sucrose esters, phenylpropanoids, nitrogenous compounds and fatty acids. Notably, 14 aliphatic sucrose esters, which are potentially novel compounds, were initially identified. Furthermore, one new aliphatic sucrose ester was purified and its structure was elucidated by 1D and 2D NMR analysis. The hierarchical clustering analysis and principal component analysis showed the close clustering of the root and stem, suggesting similarities in their chemical composition, whereas the leaf, calyx and fruit clustered more distantly. Orthogonal partial least-squares discriminant analysis results showed that 41 compounds potentially serve as marker compounds for distinguishing among plant parts. Variations in activity were observed among the plant parts during the comparative evaluation with biological assays. The calyx, leaf and fruit extracts showed stronger antibacterial and anti-inflammatory activities than the stem and root extracts, and 19 potential biomarkers were identified by S-plot analysis for the observed activities, including chlorogenic acid, luteolin, cynaroside, physalin A, physalin F, physalin J, apigetrin, quercetin-3β-D-glucoside and five ASEs, which likely explain the observed potent bioactivity.

Nephrectomy and high-salt diet inducing pulmonary hypertension and kidney damage by increasing Ang II concentration in rats

BackgroundChronic kidney disease (CKD) is a significant risk factor for pulmonary hypertension (PH), a complication that adversely affects patient prognosis. However, the mechanisms underlying this association remain poorly understood. A major obstacle to progress in this field is the lack of a reliable animal model replicating CKD-PH.MethodsThis study aimed to establish a stable rat model of CKD-PH. We employed a combined approach, inducing CKD through a 5/6 nephrectomy and concurrently exposing the rats to a high-salt diet. The model's hemodynamics were evaluated dynamically, alongside a comprehensive assessment of pathological changes in multiple organs. Lung tissues and serum samples were collected from the CKD-PH rats to analyze the expression of angiotensin-converting enzyme 2 (ACE2), evaluate the activity of key vascular components within the renin–angiotensin–aldosterone system (RAAS), and characterize alterations in the serum metabolic profile.ResultsAt 14 weeks post-surgery, the CKD-PH rats displayed significant changes in hemodynamic parameters indicative of pulmonary arterial hypertension. Additionally, right ventricular hypertrophy was observed. Notably, no evidence of pulmonary vascular remodeling was found. Further analysis revealed RAAS dysregulation and downregulated ACE2 expression within the pulmonary vascular endothelium of CKD-PH rats. Moreover, the serum metabolic profile of these animals differed markedly from the sham surgery group.ConclusionsOur findings suggest that the development of pulmonary arterial hypertension in CKD-PH rats is likely a consequence of a combined effect: RAAS dysregulation, decreased ACE2 expression in pulmonary vascular endothelial cells, and metabolic disturbances.Graphical

Unveiling Pathophysiological Insights: Serum Metabolic Dysregulation in Acute Respiratory Distress Syndrome Patients with Acute Kidney Injury.

Acute respiratory distress syndrome (ARDS) is associated with high mortality rates, which are further exacerbated when accompanied by acute kidney injury (AKI). Presently, there is a lack of comprehensive studies thoroughly elucidating the metabolic dysregulation in ARDS patients with AKI leading to poor outcomes. We hypothesized that metabolomics can be a potent tool to highlight the differences in the metabolic profile unraveling unidentified pathophysiological mechanisms of ARDS patients with and without AKI. 1H nuclear magnetic resonance spectroscopy was used to identify key metabolites in the serum samples of 75 patients. Distinct clusters of both groups were obtained as the study's primary outcome using multivariate analysis. Notable alternations in the levels of nine metabolites were identified. Pathway analysis revealed the dysregulation of five significant cycles, which resulted in various complications, such as hyperammonemia, higher energy requirements, and mitochondrial dysfunction causing oxidative stress. Identified metabolites also showed a significant correlation with clinical scores, indicating severity. This study shows the alterations in the metabolite concentration highlighting the difference in the pathophysiology of both patient groups and its association with outcome, pointing in the direction of a personalized medicine approach and holding significant promise for application in critical care settings to improve clinical outcomes.

Analysis of metabolic spectrum characteristics of naturally and cultivated Ophiocordyceps sinensis based on non-targeted metabolomics

The analysis of the differences in metabolic profiles between naturally Ophiocordyceps sinensis (NO) and cultivated Ophiocordyceps sinensis (CO) is an essential process for the medicinal value mining of Ophiocordyceps sinensis. Non-targeted metabolomics was used to compare the differences in metabolite composition and abundance between NO and CO. Total metabolite composition found that NO is rich in organic acids and derivatives, and CO is rich in lipids and lipid-like molecules. HCA found that organooxygen compounds, cinchona alkaloid, and fatty acyls had different abundances in NO and CO. The variable importance in projection value and quantitative analysis of metabolites found that NO was rich in l-iditol, malate, linoleic acid, and oleic acid; CO is rich in sucrose, perseitol, hydroquinidine, nonanoic acid, 1-hydroxy-2-naphthoic acid, hymol-β-d-glucoside, and gly-his-lys. these compounds have the potential to be biomarkers of NO and CO. KEGG enrichment analysis showed that ascorbate and aldarate metabolism, carbon metabolism, pyrimidine metabolism, and fatty acid biosynthesis were the most different metabolic pathways between NO and CO. Therefore, the analysis of the characteristics of NO and CO metabolites has reference value for finding their different medicinal functions.

Development of a Simple Cost Effective Oxygenation System for In Vivo Solution State NMR in 10 mm NMR Tubes.

In vivo NMR is evolving into an important tool to understand biological processes and environmental responses. Current approaches use flow systems to sustain the organisms with oxygenated water and food (e.g., algae) inside the NMR. However, such systems have the potential to leak and clog (potentially damaging costly hardware), require large volumes of media, and multiple expensive HPLC pumps. The proposed "oxygenation system", uses a simple "double slit" adapter and a single air/oxygen flow line into the NMR. The design is especially suited to larger diameter probes given that standard flow systems would require higher flow rates thus amplifying the potential and impact of leaks/clogs. Traditionally, in vivo NMR of small organisms (e.g., Daphnia) have required 2D NMR in combination with 13C enrichment to overcome susceptibility distortions and provide information rich metabolic profiles. Here Daphnia magna, Eisenia fetida and Artemia franciscana are used to demonstrate the potential of the oxygenation system. Survivability tests and 1H time-resolved monitoring were first performed on D. magna, while E. fetida contained enough biomass to permit 1H-13C HSQC, 13C-1H HETCOR and 31P NMR without isotopic enrichment. Finally, STOCSY of 1D 13C NMR was used to follow the growth of A. franciscana (without 13C enrichment) for 48 h after birth, which helps visualize trends across a series of 1D in vivo data. In summary, application of the oxygenation system toward larger diameter probes allows the collection of NMR data without enrichment, offering a promising solution to better understand processes in vivo.

Acquired hypoprolactinemia in men, possible phenotype.

The physiological role of prolactin (PRL) in men is still not well defined. The pathological increase is characterized by sexual function impairment along with possible negative consequences in body composition and metabolic profile. Conversely, the clinical significance of reduced PRL levels was only partially investigated or mainly neglected. The present paper aims to summarize and critically discuss possible phenotypes characterizing male subjects with reduced PRL levels. When possible, meta-analytic results were provided. Available data derived from patients seeking medical care for sexual dysfunction as well as from cross-sectional and longitudinal studies showed that low PRL in males is associated with a worse metabolic phenotype (including diabetes mellitus), mood disturbances (including anxiety and depression), and sexual dysfunctions (including psychogenic erectile and ejaculatory dysfunctions). Whether or not these features are direct consequences of reduced PRL levels or whether the latter reflect other pathway impairments such as serotoninergic failure cannot be clarified. The present data, however, emphasize that a deficiency of PRL should be taken into account and need further investigations.

Disrupted gut harmony in attention-deficit/hyperactivity disorder: Dysbiosis and decreased short-chain fatty acids

BackgroundAttention-Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder with complex genetic and environmental underpinnings. Emerging evidence suggests a significant role of gut microbiota in ADHD pathophysiology. This study investigates variations in gut microbiota composition and Short-Chain Fatty Acid (SCFA) profiles between children and adolescents with ADHD and healthy controls. MethodsThe study included 42 ADHD patients and 31 healthy controls, aged 6–18 years. Fecal samples were analyzed for microbial composition using 16S rRNA gene sequencing and for SCFA profiles through gas chromatography-mass spectrometry (GC-MS). The study assessed both α and β diversity of gut microbiota and quantified various SCFAs to compare between the groups. ResultsADHD subjects demonstrated significantly reduced gut microbiota diversity, as indicated by lower α-diversity indices (Shannon index, Observed species, Faith PD index) and a trend towards significance in β-diversity (Weighted UniFrac). Notably, the ADHD group exhibited significantly lower levels of key SCFAs, including acetic, propionic, isobutyric, isovaleric, and valeric acids, highlighting a distinct microbial and metabolic profile in these individuals. ConclusionThis study uncovers significant alterations in gut microbiota and SCFA profiles in children with ADHD, compared to healthy controls. The observed changes in SCFAs, known for their associations with other behavioral and neurologic pathologies, and for their role in neural signaling. These findings offer a metabolite fingerprint that could potentially lead to novel diagnostic and treatment approaches for ADHD, emphasizing the importance of gut microbiota in the disorder’s pathogenesis and management.

Metabolic profiling and biomarkers identification in cluster bean under drought stress using GC-MS technique.

The Cluster bean is an economically significant annual legume, widely known as guar. Plant productivity is frequently constrained by drought conditions. In this work, we have identified the untargeted drought stress-responsive metabolites in mature leaves of cluster beans under drought and control condition. To analyse the untargeted metabolites, gas chromatography-mass spectrometry (GC-MS) technique was used. Supervised partial least-squares discriminate analysis and heat map were used to identify the most significant metabolites for drought tolerance. The mature leaves of drought-treated C. tetragonoloba cv. 'HG-365' which is a drought-tolerant cultivar, showed various types of amino acids, fatty acids, sugar alcohols and sugars as the major classes of metabolites recognized by GC-MS metabolome analysis. Metabolite profiling of guar leaves showed 23 altered metabolites. Eight metabolites (proline, valine, D-pinitol, palmitic acid, dodecanoic acid, threonine, glucose, and glycerol monostearate) with VIP score greater than one were considered as biomarkers and three metabolite biomarkers (D-pinitol, valine, and glycerol monostearate) were found for the first time in guar under drought stress. In this work, four amino acids (alanine, valine, serine and aspartic acid) were also studied, which played a significant role in drought-tolerant pathway in guar. This study provides information on the first-ever GC-MS metabolic profiling of guar. This work gives in-depth details on guar's untargeted drought-responsive metabolites and biomarkers, which can plausibly be used for further identification of biochemical pathways, enzymes, and the location of various genes under drought stress.

Genome-scale community modelling elucidates the metabolic interaction in Indian type-2 diabetic gut microbiota

Type-2 diabetes (T2D) is a rapidly growing multifactorial metabolic disorder that induces the onset of various diseases in the human body. The compositional and metabolic shift of the gut microbiota is a crucial factor behind T2D. Hence, gaining insight into the metabolic profile of the gut microbiota is essential for revealing their role in regulating the metabolism of T2D patients. Here, we have focused on the genome-scale community metabolic model reconstruction of crucial T2D-associated gut microbes. The model-based analysis of biochemical flux in T2D and healthy gut conditions showed distinct biochemical signatures and diverse metabolic interactions in the microbial community. The metabolic interactions encompass cross-feeding of short-chain fatty acids, amino acids, and vitamins among individual microbes within the community. In T2D conditions, a reduction in the metabolic flux of acetate, butyrate, vitamin B5, and bicarbonate was observed in the microbial community model, which can impact carbohydrate metabolism. The decline in butyrate levels is correlated with both insulin resistance and diminished glucose metabolism in T2D patients. Compared to the healthy gut, an overall reduction in glucose consumption and SCFA production flux was estimated in the T2D gut environment. Moreover, the decreased consumption profiles of branch chain amino acids (BCAAs) and aromatic amino acids (AAAs) in the T2D gut microbiota can be a distinct biomarker for T2D. Hence, the flux-level analysis of the microbial community model can provide insights into the metabolic reprogramming in diabetic gut microbiomes, which may be helpful in personalized therapeutics and diet design against T2D.