Possible Missing Sources of Atmospheric Glyoxal Part II: Oxidation of Toluene Derived from the Primary Production of Marine Microorganisms
Glyoxal has been implicated as a significant contributor to the formation of secondary organic aerosols, which play a key role in our ability to estimate the impact of aerosols on climate. Elevated concentrations of glyoxal over open ocean waters suggest that there exists an additional source, different from urban and forest environments, which has yet to be identified.
Antioxidant Therapy in Neonatal Hypoxic Ischemic Encephalopathy: Adjuvant or Future Alternative to Therapeutic Hypothermia?
Oxidative stress-related diseases in newborns arise from pro-oxidant/antioxidant imbalance in both term and preterm neonates. Pro-oxidant/antioxidant imbalance has shown to be present in different pathological conditions such as hypoxic ischemic encephalopathy (HIE), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and patent ductus arteriosus (PDA).
Modulation of Urea Transport Attenuates TLR2-Mediated Microglial Activation and Upregulates Microglial Metabolism In Vitro
Alzheimer's disease (AD) is a neurodegenerative disorder traditionally characterised by the presence of amyloid beta (Aβ) plaques and neurofibrillary tau tangles in the brain. However, emerging research has highlighted additional metabolic hallmarks of AD pathology. These include the metabolic reprogramming of microglia in favour of glycolysis over oxidative phosphorylation. This shift is attributed to an 'M1'-like pro-inflammatory phenotype, which exacerbates neuroinflammation and contributes to neuronal damage. The urea cycle also presents as an altered metabolic pathway in AD, due to elevated urea levels and altered expression of urea cycle enzymes, metabolites, and transporters in the brain. However, to date, these changes remain largely unexplored. This study focuses on understanding the effects of extracellular urea and urea transporter-B (UT-B) inhibition on inflammatory changes in lipoteichoic acid (LTA)-stimulated BV2 microglia and on the viability of SH-SY5Y neuronal cells under oxidative stress and neurotoxic conditions. In BV2 microglia, UT-B inhibition demonstrated a notable anti-inflammatory effect by reducing the formation of nitric oxide (NO) and the expression of tumour necrosis factor α (TNFα) and CCL2 in response to stimulation with the toll-like receptor (TLR)2 agonist, lipoteichoic acid (LTA). This was accompanied by a reduction in extracellular urea and upregulation of UT-B expression. The application of exogenous urea was also shown to mediate the inflammatory profile of BV2 cells in a similar manner but had only a modest impact on UT-B expression. While exposure to LTA alone did not alter the microglial metabolic profile, inhibition of UT-B upregulated the expression of genes associated with both glycolysis and fatty acid oxidation. Conversely, neither increased extracellular urea nor UT-B inhibition had a significant impact on cell viability or cytotoxicity in SH-SY5Y neurones exposed to oxidative stressors tert-butyl hydroperoxide (t-BHP) and 6-hydroxydopamine (6-OHDA). This study further highlights the involvement of urea transport in regulating the neuroinflammation associated with AD. Moreover, we reveal a novel role for UT-B in maintaining microglial metabolic homeostasis. Taken together, these findings contribute supporting evidence to the regulation of UT-B as a therapeutic target for intervention into neuroinflammatory and neurodegenerative disease.
Detection of Sugar Syrups in Honey Using Untargeted Liquid Chromatography-Mass Spectrometry and Chemometrics
: Honey is one of the most adulterated foods worldwide, and several analytical methods have been developed over the last decade to detect syrup additions to honey. These include approaches based on stable isotopes and the specific detection of individual marker compounds or foreign enzymes. Proton nuclear magnetic resonance (H-NMR) spectroscopy is applied as a rapid and comprehensive screening method, which also enables the detection of quality parameters and the analysis of the geographical and botanical origin. However, especially for the detection of foreign sugars, H-NMR has insufficient sensitivity. : Since untargeted liquid chromatography-mass spectrometry (LC-MS) is more sensitive, we used this approach for the detection of positive and negative ions in combination with a recently developed data processing workflow for routine laboratories based on bucketing and random forest for the detection of rice, beet and high-fructose corn syrup in honey. : We show that the distinction between pure and adulterated honey is possible for all three syrups, with classification accuracies ranging from 98 to 100%, while the accuracy of the syrup content estimation depends on the respective syrup. For rice and beet syrup, the deviations from the true proportion were in the single-digit percentage range, while for high-fructose corn syrup they were much higher, in some cases exceeding 20%. : The approach presented here is very promising for the robust and sensitive detection of syrup in honey applied in routine laboratories.
Understanding the Role of Alcohol in Metabolic Dysfunction and Male Infertility
Over the past 40-50 years, demographic shifts and the obesity epidemic have coincided with significant changes in lifestyle habits, including a rise in excessive alcohol consumption. This increase in alcohol intake is a major public health concern due to its far-reaching effects on human health, particularly on metabolic processes and male reproductive function. This narrative review focuses on the role of alcohol consumption in altering metabolism and impairing testicular function, emphasizing the potential damage associated with both acute and chronic alcohol intake. Chronic alcohol consumption has been shown to disrupt liver function, impair lipid metabolism, and dysregulate blood glucose levels, contributing to the development of obesity, metabolic syndrome, and related systemic diseases. In terms of male reproductive health, alcohol can significantly affect testicular function by lowering testosterone levels, reducing sperm quality, and impairing overall fertility. The extent of these effects varies, depending on the frequency, duration, and intensity of alcohol use, with chronic and abusive consumption posing greater risks. The complexity of alcohol's impact is further compounded by individual variability and the interaction with other lifestyle factors such as diet, stress, and physical activity. Despite growing concern, research on alcohol's effects remains inconclusive, with significant discrepancies across studies regarding the definition and reporting of alcohol consumption. These inconsistencies highlight the need for more rigorous, methodologically sound research to better understand how alcohol consumption influences metabolic and reproductive health. Ultimately, a clearer understanding is essential for developing targeted public health interventions, particularly in light of rising alcohol use, demographic changes, and the ongoing obesity crisis.
Leflunomide-Induced Weight Loss: Involvement of DAHPS Activity and Synthesis of Aromatic Amino Acids
Leflunomide, an isoxazole immunosuppressant, is widely used in the treatment of diseases such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA) as well as lupus nephritis (LN). In recent years, clinical data have shown that some patients have obvious weight loss, liver injury, and other serious adverse reactions after taking leflunomide. However, the causes and mechanisms by which leflunomide reduces weight are unclear. Therefore, we used a mouse animal model to administer leflunomide, and we observed that the weight of mice in the leflunomide experimental group was significantly reduced ( < 0.01). In this animal experiment, a metabolomic method was used to analyze the livers of the mice in the experimental group and found that the main difference in terms of metabolic pathways was in the metabolism of aromatic amino acids, and it was confirmed that leflunomide can inhibit the limitations of phenylalanine, tyrosine, and tryptophan biosynthesis. Our study revealed that leflunomide inhibited the activity of DAHPS in the gut microbiota, disrupting the metabolism of phenylalanine, tyrosine, and tryptophan, as well as the metabolism of carbohydrates and lipids. Leflunomide also increased endoplasmic reticulum stress by activating the PERK pathway, thereby promoting CHOP expression and increasing apoptosis-induced liver damage. These effects may be related to the observed weight loss induced by leflunomide.
Analysis of the Urine Volatilome of COVID-19 Patients and the Possible Metabolic Alterations Produced by the Disease
Alterations in metabolism caused by SARS-CoV-2 infection have been highlighted in various investigations and have been used to search for biomarkers in different biological matrices. However, the selected biomarkers vary greatly across studies. Our objective is to provide a robust selection of biomarkers, including results from different sample treatments in the analysis of volatile organic compounds (VOCs) present in urine samples from patients with COVID-19. Between September 2021 and May 2022, urine samples were collected from 35 hospitalized COVID-19 patients and 32 healthy controls. The samples were analyzed by headspace (HS) solid phase microextraction (SPME) coupled to gas chromatography-mass spectrometry (GC-MS). Analyses were conducted on untreated urine samples and on samples that underwent specific pretreatments: lyophilization and treatment with sulfuric acid. Partial Least Squares Linear Discriminant Analysis (PLS-LDA) and Subwindow Permutation Analysis (SPA) models were established to distinguish patterns between COVID-19 patients and healthy controls. The results identify compounds that are present in different proportions in urine samples from COVID-19 patients compared to those from healthy individuals. Analysis of urine samples using HS-SPME-GC-MS reveals differences between COVID-19 patients and healthy individuals. These differences are more pronounced when methods that enhance VOC formation are used. However, these pretreatments can cause reactions between sample components, creating additional products or removing compounds, so biomarker selection could be altered. Therefore, using a combination of methods may be more informative when evaluating metabolic alterations caused by viral infections and would allow for a better selection of biomarkers.
Comparison of Free Flavonoids and the Polyphenol Content in the Bran of a Newly Developed Sorghum Variety and Two Commercially Available Sorghum Varieties
: is a source of many bioactive components, such as polyphenols. Those components are present mainly in its bran, often removed in industrial processes through decortication. In that sense, this work aimed to analyze the polyphenol content, especially free flavonoids, from the bran of a newly developed variety compared to other commercially available varieties. The samples were white sorghum TDN Sorgho, red sorghum Mini Sorgho, and the newly developed red sorghum RILN-156. First, decortication was conducted to obtain the bran samples, which were triturated and then sieved. The use of colorimetric methods allowed the general quantification of the polyphenolic components. First, the polyphenol content was extracted using 70% methanol. Then, the samples' total phenolic content, total flavonoid content, total tannin content, total anthocyanin content, and antioxidant potential were determined. To analyze the different components and identify the free flavonoids, an untargeted metabolomics analysis (with liquid chromatography coupled with mass spectrometer (LC/MS) and capillary electrophoresis coupled with a mass spectrometer (CE/MS)) was performed. The results have shown that apart from anthocyanin and tannin, the newly developed variety, RILN-156, presented the highest concentration of polyphenolic content, including a higher antioxidant capacity. The exploratory analysis identified 19 flavonoids within the samples, with galangin and daidzein being the most abundant ones. These results show a promising finding for using this newly developed sorghum variety (RILN-156) industrially and further investigating its health benefits. They also elucidate the differences between colored sorghum within themselves and with white sorghum varieties.
Liver Transcriptome Analysis Reveals the Mechanisms of Metabolic Adaptation of Xizang Sheep to Seasonal Changes
: The Xizang sheep is a unique breed of sheep in the highland regions of China that has gradually developed physiological characteristics adapted to the plate environment through long-term natural selection and artificial breeding. However, little is known about the molecular basis of metabolic adaptation to seasons in Xizang sheep. : In this study, liver tissues from Xizang sheep in summer (SL) and autumn (AL) were selected for transcriptome sequencing to explore the metabolic adaptability of Xizang sheep to seasons. : The results showed that a total of 12,046 differentially expressed genes (DEGs) were identified, with 1123 genes significantly upregulated and 951 genes significantly downregulated in autumn. The top five pathways enriched for DEGs were Metabolic pathways, Phagosome, Valine, leucine and isoleucine degradation, Propanoate metabolism, and Fatty acid metabolism, which are involved in immune regulation, fat oxidation, and synthesis. The reduction in lipid synthesis, fatty acid oxidation, and fat breakdown metabolism promotes gluconeogenesis by inhibiting the Peroxisome proliferator-activated receptors (PPAR) and Phosphoinositide 3-kinase- Protein kinase B (PI3K-Akt) signaling pathways. : This process helps to maintain the whole-body energy homeostasis of Xizang sheep, facilitating their adaptation to the seasonal changes in the extreme high-altitude environment. These findings provide foundational data for studying the molecular mechanisms of metabolic adaptation to seasons in ruminants.
Possible Missing Sources of Atmospheric Glyoxal Part I: Phospholipid Oxidation from Marine Algae
Glyoxal has been implicated as a significant contributor to the formation of secondary organic aerosols, which play a key role in our ability to estimate the impact of aerosols on climate. Elevated concentrations of glyoxal over remote ocean waters suggests that there is an additional source, distinct from urban and forest environments, which has yet to be identified. Herein, we demonstrate that the ocean can serve as an appreciable source of glyoxal in the atmosphere due to microbiological activity.
Identification of Spatial Specific Lipid Metabolic Signatures in Long-Standing Diabetic Kidney Disease
Diabetic kidney disease (DKD) is a major complication of diabetes leading to kidney failure. This study investigates lipid metabolism profiles of long-standing DKD (LDKD, diabetes duration > 10 years) by integrative analysis of available single-cell RNA sequencing and spatial multi-omics data (focusing on spatial continuity samples) from the Kidney Precision Medicine Project. Two injured cell types, an injured thick ascending limb (iTAL) and an injured proximal tubule (iPT), were identified and significantly elevated in LDKD samples. Both iTAL and iPT exhibit increased lipid metabolic and biosynthetic activities and decreased lipid and fatty acid oxidative processes compared to TAL/PT cells. Notably, compared to PT, iPT shows significant upregulation of specific injury and fibrosis-related genes, including and . Meanwhile, comparing iTAL to TAL, inflammatory-related genes such as and are significantly upregulated. Furthermore, spatial metabolomics analysis reveals regionally distributed clusters in the kidney and notably differentially expressed lipid metabolites, such as triglycerides, glycerophospholipids, and sphingolipids, particularly pronounced in the inner medullary regions. These findings provide an integrative description of the lipid metabolism landscape in LDKD, highlighting injury-associated cellular processes and potential molecular mechanisms.
Influence of Uric Acid on Vascular and Cognitive Functions: Evidence for an Ambivalent Relationship
The growing recognition of the public health impact of cognitive impairment and dementia has sparked a global initiative to identify risk factors and develop strategies to prevent or slow the progression of these cognitive disorders. Uric acid, the end product of the metabolism of purine nucleotides, has been reported as a key factor of many conditions potentially involved in cognitive dysfunction/dementia. In addition, some studies support the hypothesis that elevated uric acid levels could reduce the risk of Alzheimer's disease, slow down the decline of cognition, and delay the progression of Alzheimer's disease, while other evidence achieves opposite positions. These discrepancies might reflect a biological ambivalence for uric acid depending on a very complex interplay of factors that include its concentrations achieved in biological fluids, the nature, and concentration of free radicals, the presence and concentration of other antioxidant molecules, potentially responsible for bi-directional effects of uric acid on brain health/functioning. In this narrative review, we attempt to elucidate the influential role of uric acid metabolism in cognitive functioning by discussing pathophysiological mechanisms putatively involved, being well aware that none of them can be considered one-sided due to the complexity of the human organism.
Rapid Determination of Methamphetamine, Methylenedioxymethamphetamine, Methadone, Ketamine, Cocaine, and New Psychoactive Substances in Urine Samples Using Comprehensive Two-Dimensional Gas Chromatography
This study evaluates the applicability of a comprehensive two-dimensional gas chromatography-flame ionisation detection (GC×GC-FID) approach for the simultaneous determination of 12 underivatised psychoactive drugs, including new psychoactive substances, that comprised of amphetamine, methamphetamine, mephedrone, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, α-pyrrolidinovalerophenone, -ethylpentylone (ephylone), norketamine, ketamine, 3,4-methylenedioxypyrovalerone, methadone, and cocaine. Separation was effected using a non-polar first dimension (D) and a polar second dimension (D) column, demonstrating an improved separation of drug compounds compared to a polar/non-polar column configuration. Interference-free baseline separation of all psychoactive compounds in a urine matrix was achieved within 8 min. The GC×GC-FID method was validated according to the guidelines defined by Standard Practices for Method Validation in Forensic Toxicology. The calibration curves for the 12 psychoactive drugs were well correlated (r > 0.99) within the concentration ranges of 50-1500 ng mL. Detection limits of 10-20 ng mL were obtained, and good repeatability and reproducibility (CV < 11.4%) were attained for retention times and peak areas. Method recoveries for the small-scale solvent extraction procedure ranged from 96.9 to 114.5%, and bias was between -3.1% and 14.5%. The validated approach was successfully applied for the determination of these illicit compounds in spiked urine samples of different concentrations, highlighting its potential for rapid forensic drug screening.
Introduction to the Proteomic Analysis of Placentas with Fetal Growth Restriction and Impaired Lipid Metabolism
Fetal growth restriction (FGR) is a disorder defined as the failure of a fetus to achieve its full biological development potential due to decreased placental function, which can be attributed to a range of reasons. FGR is linked to negative health outcomes during the perinatal period, including increased morbidity and mortality. Long-term health problems, such as impaired neurological and cognitive development, as well as cardiovascular and endocrine diseases, have also been found in adulthood. Aspirin administered prophylactically to high-risk women can effectively prevent FGR. FGR pregnancy care comprises several steps, including the weekly assessment of several blood vessels using Doppler measurements, amniotic fluid index (AFI), estimated fetal weight (EFW), cardiotocography (CTG), as well as delivery by 37 weeks. Pregnancy is a complex condition characterized by metabolic adjustments that guarantee a consistent provision of vital metabolites allowing the fetus to grow and develop. The lipoprotein lipid physiology during pregnancy has significant consequences for both the fetus and baby, and for the mother. In the course of a typical pregnancy, cholesterol levels increase by roughly 50%, LDL-C (low-density lipoprotein cholesterol) levels by 30-40%, HDL-C by 25% (high-density lipoprotein cholesterol). Typically, there is also a 2- to 3-fold increase in triglycerides. Low maternal blood cholesterol levels during pregnancy are linked to a decrease in birth weight and an increased occurrence of microcephaly. FGR impacts the placenta during pregnancy, resulting in alterations in lipid metabolism. Research has been undertaken to distinguish variations in protein expression between normal placentas and those impacted by FGR. This can aid in comprehending the fundamental pathogenic mechanisms of FGR and perhaps pave the way for the creation of novel diagnostic and treatment methods. Commonly employed approaches for detecting and analyzing variations in placental proteomes include mass spectrometry, bioinformatic analysis, and various proteomic techniques.
Non-Targeted Metabolomics of White Rhinoceros Colostrum and Its Changes During Early Lactation by H Nuclear Magnetic Resonance Spectroscopy
Dynamic changes in components from colostrum to mature milk occur in any mammal. However, the time it takes to reach the mature milk stage differs between taxa and species, as do the final concentrations of all the components. The white rhinoceros belongs to the family Perissodactyla, of which the milk and milk metabolome of the domesticated Equidae have been studied to some detail. Metabolomic information on the colostrum and milk of the Rhinocerotidae is lacking.
The Action of Colchicine in Patients with Metabolic Syndrome and Obesity: Perspectives and Challenges
Colchicine is an alkaloid traditionally used to treat inflammatory conditions such as gout and familial Mediterranean fever. Currently, there are proposals for the use of this drug in several other situations, such as cardiovascular and liver diseases and diabetes. In this study, the current literature on the potential of colchicine in the treatment of obesity and metabolic syndrome (MS) was evaluated. The inhibitory action of the NLRP3 inflammasome and other processes, such as reductions in the migration and activation of immune system cells, are effects observed in both in vitro studies and animal models related to colchicine, as well as the promotion of mechanisms of the intensification of lipid metabolism, the reduction of tissue fibrosis, and the reduction of serum glucose and triglycerides. These factors are associated with changes in the prognoses of patients with MS, which, together with obesity, has a high association with inflammatory mechanisms for its maintenance and secondary impairments to homeostasis. In humans, clinical research has rarely addressed the use of colchicine in obesity and MS, with only one pilot randomized clinical trial having been conducted, which identified a beneficial anti-inflammatory effect on endothelial function and the process of insulin resistance in this population. However, it is not yet possible to extrapolate its findings and apply its results to a broader context. Given the potential of this "ancient drug" in various pathological contexts and its good tolerability, it is important that its properties continue to be investigated and that more clinical studies be conducted to expand the therapeutic applications of this low-cost substance in patients with obesity and MS.
Strategy for Optimizing Vitamin B12 Production in KT2440 Using Metabolic Modeling
: Vitamin B is very important for human health, as it is a cofactor for enzymatic activities and plays various roles in human physiology. It is highly valued in the pharmaceutical, food, and additive production industries. Some of the bacteria currently used for the vitamin production are difficult to modify with gene-editing tools and may have slow growth. We propose the use of the bacteria KT2440 for the production of vitamin B because it has a robust chassis for genetic modifications. The present wok evaluates KT2440 as a host for vitamin B production and explore potential gene-editing optimization strategies. : We curated and modified a genome-scale metabolic model of KT2440 and evaluated different strategies to optimize vitamin B production using the knockin and OptGene algorithms from the COBRA Toolbox. Furthermore, we examined the presence of riboswitches as cis-regulatory elements and calculated theoretical biomass growth yields and vitamin B production using a flux balance analysis (FBA). : According to the flux balance analysis of KT2440 under culture conditions, the biomass production values could reach 1.802 gDW·h·L, and vitamin B production could reach 0.359 µmol·gDW·h·L. The theoretical vitamin B synthesis rate calculated using KT2040 with two additional reactions was 14 times higher than that calculated using the control, , which has been used for the industrial production of this vitamin. : We propose that, with the addition of aminopropanol linker genes and the modification of riboswitches, KT2440 may become a suitable host for the industrial production of vitamin B.
Lipid Abundance and Metabolism Aberrations in Skin Diseases
This Special Issue of , entitled "Lipid Abundance and Metabolism Aberrations in Skin Diseases" broadly discusses the issue of lipids that are engaged in pathogenesis, as well as in the clinical course and treatment of dermatoses [...].
Associations Between Cardiorespiratory Fitness and Metabolic Syndrome in Adolescents: A Systematic Review and Meta-Analysis
Low levels of cardiorespiratory fitness (CRF) are associated with a greater risk of metabolic syndrome (MetS) in adolescence. In this sense, it is important to verify the strength of this association and the certainty that this evidence can be recommended. The objective of this paper is to summarize, through a systematic review and meta-analysis, the evidence available to verify the association between CRF and MetS in adolescents. PubMed, Embase, CINAHL, SPORTDiscus, LILACS, and Web of Science were searched until 20 August 2024. The risk of bias in each study was assessed via the AXIS tool, and the certainty of the evidence was assessed via the GRADE system. For the meta-analysis, the odds ratio (OR) was calculated with a 95% confidence interval. Nine studies (7077 participants), all with a low risk of bias, were included in the systematic review. There was a high certainty of evidence that adolescents with low CRF have significantly greater odds of developing MetS (OR = 3.63 [CI 95%, 2.54 to 5.20]). The odds increase for low vs. moderate (OR = 4.23 [CI 95%, 2.64 to 6.78]) and low vs. high (OR = 8.03 [CI 95%, 3.20 to 20.18]) CRF are considered separately. The effect does not change according to the type of test used to assess CRF ( = 0.51). There is high certainty of evidence that adolescents with low CRF levels have significantly greater odds of developing MetS; therefore, it is essential that intervention strategies be designed to increase CRF in this population.
Hepatic Transcriptomics of Broilers with Low and High Feed Conversion in Response to Caloric Restriction
In broiler chickens, the efficient utilization of macro- and micronutrients is influenced by various metabolic pathways that are closely linked to feed efficiency (FE), a critical metric in poultry industry, with residual feed intake (RFI) as the preferred proxy. Feed restriction is considered an approach to address the underlying molecular mechanisms of feed conversion. We hypothesized that broiler chickens with divergent RFI subjected to quantitative feed restriction differ in their pattern of molecular pathways for efficient nutrient utilization in liver as post-absorptive tissue.
Type 1 Diabetes and Cataracts: Investigating Mediating Effects of Serum Metabolites Using Bidirectional Mendelian Randomization
To investigate the causal relationship between type 1 diabetes (T1D) and cataracts and to explore the mediating role of serum metabolites.