Metabolic Perturbations Research Articles

Metabolic perturbation of Streptomyces albulus by introducing NADP-dependent glyceraldehyde 3-phosphate dehydrogenase.

The available resources of Streptomyces represent a valuable repository of bioactive natural products that warrant exploration. Streptomyces albulus is primarily utilized in the industrial synthesis of ε-poly-L-lysine (ε-PL). In this study, the NADP-dependent glyceraldehyde 3-phosphate dehydrogenase (GapN) from Streptococcus mutans was heterologously expressed in S. albulus CICC11022, leading to elevated intracellular NADPH levels and reduced NADH and ATP concentrations. The resulting perturbation of S. albulus metabolism was comprehensively analyzed using transcriptomic and metabolomic methodologies. A decrease in production of ε-PL was observed. The expression of gapN significantly impacted on 23 gene clusters responsible for the biosynthesis of secondary metabolites. A comprehensive analysis revealed a total of 21 metabolites exhibiting elevated levels both intracellularly and extracellularly in the gapN expressing strain compared to those in the control strain. These findings underscore the potential of S. albulus to generate diverse bioactive natural products, thus offering valuable insights for the utilization of known Streptomyces resources through genetic manipulation.

Physiological Perturbations in Combat Sports: Weight Cycling and Metabolic Function-A Narrative Review.

Combat sports athletes seeking a competitive edge often engage in weight management practices to become larger than their opponents, which ultimately includes periods of gradual weight loss, rapid weight loss, and weight regain. This pattern of weight loss and regain is known as weight cycling and often includes periods of low energy availability, making combat sports athletes susceptible to metabolic dysfunction. This narrative review represents an effort to explore the metabolic perturbations associated with weight cycling and outline the short-, medium-, and long-term effects on metabolic flexibility, function, and health. The short-term effects of rapid weight loss, such as a reduced metabolic rate and alterations to insulin and leptin levels, may prelude the more pronounced metabolic disturbances that occur during weight regain, such as insulin resistance. Although definitive support is not currently available, this cycle of weight loss and regain and associated metabolic changes may contribute to metabolic syndrome or other metabolic dysfunctions over time.

Experimental Models to Study the Pathogenesis and Treatment of Mucormycosis.

Mucormycosis presents a formidable challenge to clinicians and researchers. Animal models are an essential part of the effort to decipher the pathogenesis of mucormycosis and to develop novel pharmacotherapeutics against it. Diverse model systems have been established, using a range of animal hosts, immune and metabolic perturbations, and infection routes. An understanding of the characteristics, strengths, and drawbacks of these models is needed to optimize their use for specific research aims.

A polyphenol-rich plant extract prevents hypercholesterolemia and modulates gut microbiota in western diet-fed mice.

Totum-070 is a combination of five plant extracts enriched in polyphenols to target hypercholesterolemia, one of the main risk factors for cardiovascular diseases. The aim of this study was to investigate the effects of Totum-070 on cholesterol levels in an animal model of diet-induced hypercholesterolemia. C57BL/6JOlaHsd male mice were fed a Western diet and received Totum-070, or not, by daily gavage (1g/kg and 3g/kg body weight) for 6 weeks. The Western diet induced obesity, fat accumulation, hepatic steatosis and increased plasma cholesterol compared with the control group. All these metabolic perturbations were alleviated by Totum-070 supplementation in a dose-dependent manner. Lipid excretion in feces was higher in mice supplemented with Totum-070, suggesting inhibition of intestinal lipid absorption. Totum-070 also increased the fecal concentration of short chain fatty acids, demonstrating a direct effect on intestinal microbiota. The characterization of fecal microbiota by 16S amplicon sequencing showed that Totum-070 supplementation modulated the dysbiosis associated with metabolic disorders. Specifically, Totum-070 increased the relative abundance of Muribaculum (a beneficial bacterium) and reduced that of Lactococcus (a genus positively correlated with increased plasma cholesterol level). Together, these findings indicate that the cholesterol-lowering effect of Totum-070 bioactive molecules could be mediated through multiple actions on the intestine and gut microbiota.

Susceptibility loci identified in Han Chinese influence genetic predisposition of PCOS in Indian women.

Polycystic ovary syndrome (PCOS) is a multifactorial disorder characterized by a broad spectrum of reproductive and metabolic perturbations, necessitating early timely diagnosis and management. PCOS is a multigenic disorder and ample evidence from family based, candidate gene and genome-wide association studies (GWAS) has implicated genetic factors in development and progression of PCOS. The first GWASs in Han Chinese population revealed prominent gene loci to be strong contenders in the etiopathogenesis of PCOS. However, different ethnic and geographical settings impact the genetic association pattern of PCOS. In the current case-control replication study, we have genotyped previously identified polymorphisms viz. rs2479106 and rs10818854 of DENND1A and rs13405728 of LHCGR, rs4385527 and rs3802457 of c9orf3, rs705702 of RAB5B and rs1894116 of YAP1 in control (N = 247) and PCOS (N = 504) women by Sanger sequencing, and their association with PCOS susceptibility and its related traits was investigated. We found significant association of rs4385527 of c9orf3 and rs1894116 of YAP1 with decreased and increased PCOS susceptibility respectively in non-hyperandrogenic women. Trend towards association was also noted for rs2479106 of DENND1A and rs705702 of RAB5B. Additionally, polymorphisms also showed association with metabolic and androgen related traits in both controls and hyper- and non-hyperandrogenic women with PCOS. Thus, this study shows that some, but not all polymorphisms previously identified in Han Chinese women, could contribute to the genetic pathophysiology of PCOS in Indian women, accentuating essentiality of conducting replication studies to elucidate the genetic predisposition profile of PCOS.

Early modulation of the gut microbiome by female sex hormones alters amyloid pathology and microglial function.

It is well-established that women are disproportionately affected by Alzheimer's disease. The mechanisms underlying this sex-specific disparity are not fully understood, but several factors that are often associated-including interactions of sex hormones, genetic factors, and the gut microbiome-likely contribute to the disease's etiology. Here, we have examined the role of sex hormones and the gut microbiome in mediating Aβ amyloidosis and neuroinflammation in APPPS1-21 mice. We report that postnatal gut microbiome perturbation in female APPPS1-21 mice leads to an elevation in levels of circulating estradiol. Early stage ovariectomy (OVX) leads to a reduction of plasma estradiol that is correlated with a significant alteration of gut microbiome composition and reduction in Aβ pathology. On the other hand, supplementation of OVX-treated animals with estradiol restores Aβ burden and influences gut microbiome composition. The reduction of Aβ pathology with OVX is paralleled by diminished levels of plaque-associated microglia that acquire a neurodegenerative phenotype (MGnD-type) while estradiol supplementation of OVX-treated animals leads to a restoration of activated microglia around plaques. In summary, our investigation elucidates the complex interplay between sex-specific hormonal modulations, gut microbiome dynamics, metabolic perturbations, and microglial functionality in the pathogenesis of Alzheimer's disease.

Redox changes and cellular senescence in Alzheimer's disease

The redox process and cellular senescence are involved in a range of essential physiological functions. However, they are also implicated in pathological processes underlying age-related neurodegenerative disorders, including Alzheimer's disease (AD). Elevated levels of reactive oxygen species (ROS) are generated as a result of abnormal accumulation of beta-amyloid peptide (Aβ), tau protein, and heme dyshomeostasis and is further aggravated by mitochondria dysfunction and endoplasmic reticulum (ER) stress. Excessive ROS damages vital cellular components such as proteins, DNA and lipids. Such damage eventually leads to impaired neuronal function and cell death. Heightened oxidative stress can also induce cellular senescence via activation of the senescence-associated secretory phenotype to further exacerbate inflammation and tissue dysfunction. In this review, we focus on how changes in the redox system and cellular senescence contribute to AD and how they are affected by perturbations in heme metabolism and mitochondrial function. While potential therapeutic strategies targeting such changes have received some attention, more research is necessary to bring them into clinical application.

Exopolysaccharide secreted by Lactiplantibacillus plantarum Y12 showed inhibitory effect on the pathogenicity of Shigella flexneri in vitro and in vivo

Shigella flexneri is a prevalent foodborne and waterborne pathogen that threatens human health. Our previous research indicated that the Lactiplantibacillus plantarum Y12 exopolysaccharide (L-EPS) potentially inhibited the pathogenicity of S. flexneri. The in vitro results of this study demonstrated that L-EPS effectively mitigated the symptoms induced by S. flexneri in HT-29 cells, including inhibited gene expression levels of IL-1β, IL-6, IL-8, TNF-α, TLR 2/4, and NOD1/2; decreased apoptosis ratio; and alleviated damage degree of intestinal barrier function (Zona occludens 1, Occludin, and Claudin-1). The in vivo results demonstrated that S. flexneri treated with L-EPS elicited mild adverse physiological manifestations, an inflammatory response, and tissue damage. The infection of S. flexneri caused significant alterations in the abundance of phylum (Firmicutes, Bacteroidota, Actinobacteriota, and Proteobacteria), family (Lachnospiraceae, Muribaculaceae, Rikenellaceae, Prevotellaceaea, Ruminococcaceae, and Lactobaillaceae), and genus (Escherichia Shigella and Lachnospirillaceae NK4A136 group) within the cecal microbiota. These changes were accompanied by perturbations in taurine and hypotaurine metabolism, tricarboxylic acid (TCA) cycle activity, arginine biosynthesis, and histidine metabolic pathways. However, intervention with L-EPS attenuated the dysbiosis of cecal microbiota and metabolic disturbances. In summary, our research suggested a potential application of L-EPS as a functional food additive for mitigating S. flexneri infection.

Advances in Mass Spectrometry-Based Blood Metabolomics Profiling for Non-Cancer Diseases: A Comprehensive Review.

Blood metabolomics profiling using mass spectrometry has emerged as a powerful approach for investigating non-cancer diseases and understanding their underlying metabolic alterations. Blood, as a readily accessible physiological fluid, contains a diverse repertoire of metabolites derived from various physiological systems. Mass spectrometry offers a universal and precise analytical platform for the comprehensive analysis of blood metabolites, encompassing proteins, lipids, peptides, glycans, and immunoglobulins. In this comprehensive review, we present an overview of the research landscape in mass spectrometry-based blood metabolomics profiling. While the field of metabolomics research is primarily focused on cancer, this review specifically highlights studies related to non-cancer diseases, aiming to bring attention to valuable research that often remains overshadowed. Employing natural language processing methods, we processed 507 articles to provide insights into the application of metabolomic studies for specific diseases and physiological systems. The review encompasses a wide range of non-cancer diseases, with emphasis on cardiovascular disease, reproductive disease, diabetes, inflammation, and immunodeficiency states. By analyzing blood samples, researchers gain valuable insights into the metabolic perturbations associated with these diseases, potentially leading to the identification of novel biomarkers and the development of personalized therapeutic approaches. Furthermore, we provide a comprehensive overview of various mass spectrometry approaches utilized in blood metabolomics research, including GC-MS, LC-MS, and others discussing their advantages and limitations. To enhance the scope, we propose including recent review articles supporting the applicability of GC×GC-MS for metabolomics-based studies. This addition will contribute to a more exhaustive understanding of the available analytical techniques. The Integration of mass spectrometry-based blood profiling into clinical practice holds promise for improving disease diagnosis, treatment monitoring, and patient outcomes. By unraveling the complex metabolic alterations associated with non-cancer diseases, researchers and healthcare professionals can pave the way for precision medicine and personalized therapeutic interventions. Continuous advancements in mass spectrometry technology and data analysis methods will further enhance the potential of blood metabolomics profiling in non-cancer diseases, facilitating its translation from the laboratory to routine clinical application.

Evidence of Differences in Cellular Regulation of Wolbachia-Mediated Viral Inhibition between Alphaviruses and Flaviviruses.

The intracellular bacterium Wolbachia is increasingly being utilised in control programs to limit the spread of arboviruses by Aedes mosquitoes. Achieving a better understanding of how Wolbachia strains can reduce viral replication/spread could be important for the long-term success of such programs. Previous studies have indicated that for some strains of Wolbachia, perturbations in lipid metabolism and cholesterol storage are vital in Wolbachia-mediated antiviral activity against the flaviviruses dengue and Zika; however, it has not yet been examined whether arboviruses in the alphavirus group are affected in the same way. Here, using the reporters for the alphavirus Semliki Forest virus (SFV) in Aedes albopictus cells, we found that Wolbachia strains wMel, wAu and wAlbB blocked viral replication/translation early in infection and that storage of cholesterol in lipid droplets is not key to this inhibition. Another alphavirus, o'nyong nyong virus (ONNV), was tested in both Aedes albopictus cells and in vivo in stable, transinfected Aedes aegypti mosquito lines. The strains wMel, wAu and wAlbB show strong antiviral activity against ONNV both in vitro and in vivo. Again, 2-hydroxypropyl-β-cyclodextrin (2HPCD) was not able to rescue ONNV replication in cell lines, suggesting that the release of stored cholesterol caused by wMel is not able to rescue blockage of ONNV. Taken together, this study shows that alphaviruses appear to be inhibited early in replication/translation and that there may be differences in how alphaviruses are inhibited by Wolbachia in comparison to flaviviruses.

Real-Time Exposure to 3D-Printing Emissions Elicits Metabolic and Pro-Inflammatory Responses in Human Airway Epithelial Cells.

Three-dimensional (3D) printer usage in household and school settings has raised health concerns regarding chemical and particle emission exposures during operation. Although the composition of 3D printer emissions varies depending on printer settings and materials, little is known about the impact that emissions from different filament types may have on respiratory health and underlying cellular mechanisms. In this study, we used an in vitro exposure chamber system to deliver emissions from two popular 3D-printing filament types, acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA), directly to human small airway epithelial cells (SAEC) cultured in an air-liquid interface during 3D printer operation. Using a scanning mobility particle sizer (SMPS) and an optical particle sizer (OPS), we monitored 3D printer particulate matter (PM) emissions in terms of their particle size distribution, concentrations, and calculated deposited doses. Elemental composition of ABS and PLA emissions was assessed using scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDX). Finally, we compared the effects of emission exposure on cell viability, inflammation, and metabolism in SAEC. Our results reveal that, although ABS filaments emitted a higher total concentration of particles and PLA filaments emitted a higher concentration of smaller particles, SAEC were exposed to similar deposited doses of particles for each filament type. Conversely, ABS and PLA emissions had distinct elemental compositions, which were likely responsible for differential effects on SAEC viability, oxidative stress, release of inflammatory mediators, and changes in cellular metabolism. Specifically, while ABS- and PLA-emitted particles both reduced cellular viability and total glutathione levels in SAEC, ABS emissions had a significantly greater effect on glutathione relative to PLA emissions. Additionally, pro-inflammatory cytokines including IL-1β, MMP-9, and RANTES were significantly increased due to ABS emissions exposure. While IL-6 and IL-8 were stimulated in both exposure scenarios, VEGF was exclusively increased due to PLA emissions exposures. Notably, ABS emissions induced metabolic perturbation on amino acids and energy metabolism, as well as redox-regulated pathways including arginine, methionine, cysteine, and vitamin B3 metabolism, whereas PLA emissions exposures caused fatty acid and carnitine dysregulation. Taken together, these results advance our mechanistic understanding of 3D-printer-emissions-induced respiratory toxicity and highlight the role that filament emission properties may play in mediating different respiratory outcomes.

Obesity, Dietary Fats, and Gastrointestinal Cancer Risk-Potential Mechanisms Relating to Lipid Metabolism and Inflammation.

Obesity is a major driving factor in the incidence, progression, and poor treatment response in gastrointestinal cancers. Herein, we conducted a comprehensive analysis of the impact of obesity and its resulting metabolic perturbations across four gastrointestinal cancer types, namely, oesophageal, gastric, liver, and colorectal cancer. Importantly, not all obese phenotypes are equal. Obese adipose tissue heterogeneity depends on the location, structure, cellular profile (including resident immune cell populations), and dietary fatty acid intake. We discuss whether adipose heterogeneity impacts the tumorigenic environment. Dietary fat quality, in particular saturated fatty acids, promotes a hypertrophic, pro-inflammatory adipose profile, in contrast to monounsaturated fatty acids, resulting in a hyperplastic, less inflammatory adipose phenotype. The purpose of this review is to examine the impact of obesity, including dietary fat quality, on adipose tissue biology and oncogenesis, specifically focusing on lipid metabolism and inflammatory mechanisms. This is achieved with a particular focus on gastrointestinal cancers as exemplar models of obesity-associated cancers.

CLN3 deficiency leads to neurological and metabolic perturbations during early development.

Juvenile neuronal ceroid lipofuscinosis (or Batten disease) is an autosomal recessive, rare neurodegenerative disorder that affects mainly children above the age of 5 yr and is most commonly caused by mutations in the highly conserved CLN3 gene. Here, we generated cln3 morphants and stable mutant lines in zebrafish. Although neither morphant nor mutant cln3 larvae showed any obvious developmental or morphological defects, behavioral phenotyping of the mutant larvae revealed hyposensitivity to abrupt light changes and hypersensitivity to pro-convulsive drugs. Importantly, in-depth metabolomics and lipidomics analyses revealed significant accumulation of several glycerophosphodiesters (GPDs) and cholesteryl esters, and a global decrease in bis(monoacylglycero)phosphate species, two of which (GPDs and bis(monoacylglycero)phosphates) were previously proposed as potential biomarkers for CLN3 disease based on independent studies in other organisms. We could also demonstrate GPD accumulation in human-induced pluripotent stem cell-derived cerebral organoids carrying a pathogenic variant for CLN3 Our models revealed that GPDs accumulate at very early stages of life in the absence of functional CLN3 and highlight glycerophosphoinositol and BMP as promising biomarker candidates for pre-symptomatic CLN3 disease.

Dysregulated cysteine metabolism leads to worsened liver pathology in diabetes-tuberculosis comorbid condition

Diabetes mellitus (DM) is a risk factor for developing active tuberculosis (TB) with a 3-fold increase in susceptibility and a 4-fold higher relapse rate. With increasing DM prevalence in TB endemic regions, understanding pathophysiological changes associated with DM-TB comorbidity is imperative. In this study, streptozotocin (STZ)-induced DM C57BL/6 mice were aerosol infected with low dose (100-120 CFU) Mycobacterium tuberculosis H37Rv. At 3 weeks post infection (w.p.i.), multiple tissue mycobacterial load and metabolites were profiled. The liver proteome of DM-TB and controls were analyzed using quantitative proteomics, and multi-omics data were integrated. DM-TB mice showed dysregulated multi-tissue (lungs, liver, brain, kidney and thigh muscle) metabolism. In contrast, the mycobacterial burden in the lung, spleen and liver was similar at 3 w.p.i. in DM-TB and TB groups. Enrichment analysis of deregulated liver metabolites (n=20; log2DM-TB/TB>±1.0) showed significant perturbation in cysteine-methionine, glycine-serine, BCAA and fatty acid metabolism. Sixty out of 1660 identified liver proteins showed deregulation (log2DM-TB/TB>±1.0) and contributed from perturbed cysteine-methionine metabolism corroborating metabolomics data. In addition, amino acid biosynthesis, retinol metabolism and polyol biosynthetic process were also differentially enriched in the livers of DM-TB groups. Global correlation analysis of liver metabolome and proteome data showed a strong association between aspartic acid, pyruvic acid, leucine and isoleucine with CYP450 enzymes involved in retinol metabolism, while iminodiacetic acid, isoleucine and γ-aminobutyric acid (GABA) strong positive correlation involved in cysteine metabolism. Targeting perturbed cysteine metabolism using micro molecules, like DL-Propargylglycine, might help prevent liver damage in DM-TB comorbid conditions.

Metabolic perturbation studies using a Nash Equilibrium model of liver machine perfusion: modeling oxidative stress and effect of glutathione supplementation

The current clinical standard of Static Cold Storage (SCS) which involves preservation on ice (about +4°C) in a hypoxic state limits storage to a few hours for metabolically active tissues such as the liver and the heart. This period of hypoxia during can generate superoxide and other free radicals from purine metabolism, a well-established component of ischemia/reperfusion injury (IRI). Machine perfusion is at the cutting edge of organ preservation, which provides a functional, oxygenated preservation modality that can avoid/attenuate IRI. In clinical application, perfusion usually follows a period of SCS. This presentation of oxygen following hypoxia can lead to superoxide and hydrogen peroxide generation, but machine perfusion also allows manipulation of the temperature profiles and supply of antioxidant treatments, which could be used to minimize such issues. However, metabolomic data is difficult to gather, and there are currently no mathematical models present to allow rational design of experiments or guide clinical practice. In this article, the effects of a gradual warming temperature policy and glutathione supplementation to minimize oxidative stress are studied. An optimal gradual warming temperature policy for mid-thermic machine perfusion of a liver metabolic model is determined using a combination of Nash Equilibrium and Monte Carlo optimization. Using this optimal gradual warming temperature policy, minimum GSH requirements to maintain hydrogen peroxide concentrations in the normal region are calculated using a different Monte Carlo optimization methodology. In addition, the dynamic behavior of key metabolites and cofactors are determined. Results show that the minimum GSH requirement increases and that the ratio of GSH/GSSG decreases with increasing hydrogen peroxide concentration. In addition, at high concentrations of hydrogen peroxide it is shown that cytochrome C undergoes dysfunction leading to a decrease in useful oxygen consumption and ATP synthesis from the electron transport chain and an overall reduction in the energy charge for the liver cells.

Insights into the role of legionella effectors on host metabolic perturbations.

Legionella infection, the causative agent of Legionnaires' disease, represents a significant threat to human health. The pathogenesis of this infection is intricately linked to the complex interactions between the bacterium and its host, resulting in profound metabolic perturbations. Central to these metabolic shifts is the bacterium's modulation of lipid metabolism, with changes in lipid synthesis and breakdown modifying membrane composition and function. These alterations can influence cellular signaling and immune responses, further contributing to disease progression. It also disrupts glucose utilization and lipid metabolism, altering cellular energy production and immune responses. Additionally, Legionella infection perturbs amino acid and protein metabolism, affecting protein synthesis and degradation, leading to changes in cellular functions and immune responses. This mini-review underscores the complexity of metabolic perturbations in Legionella infection and their significance in host-pathogen interactions. Understanding these metabolic shifts provides valuable insights into the pathogenesis of Legionnaires' disease and could lead to the development of novel therapeutic strategies.

Metabolic profiling during COVID-19 infection in humans: Identification of potential biomarkers for occurrence, severity and outcomes using machine learning.

After its emergence in China, the coronavirus SARS-CoV-2 has swept the world, leading to global health crises with millions of deaths. COVID-19 clinical manifestations differ in severity, ranging from mild symptoms to severe disease. Although perturbation of metabolism has been reported as a part of the host response to COVID-19 infection, scarce data exist that describe stage-specific changes in host metabolites during the infection and how this could stratify patients based on severity. Given this knowledge gap, we performed targeted metabolomics profiling and then used machine learning models and biostatistics to characterize the alteration patterns of 50 metabolites and 17 blood parameters measured in a cohort of 295 human subjects. They were categorized into healthy controls, non-severe, severe and critical groups with their outcomes. Subject's demographic and clinical data were also used in the analyses to provide more robust predictive models. The non-severe and severe COVID-19 patients experienced the strongest changes in metabolite repertoire, whereas less intense changes occur during the critical phase. Panels of 15, 14, 2 and 2 key metabolites were identified as predictors for non-severe, severe, critical and dead patients, respectively. Specifically, arginine and malonyl methylmalonyl succinylcarnitine were significant biomarkers for the onset of COVID-19 infection and tauroursodeoxycholic acid were potential biomarkers for disease progression. Measuring blood parameters enhanced the predictive power of metabolic signatures during critical illness. Metabolomic signatures are distinctive for each stage of COVID-19 infection. This has great translation potential as it opens new therapeutic and diagnostic prospective based on key metabolites.

Analysis and Quantification of the Mitochondrial-ER Lipidome.

Mitochondria are vital organelles essential for cellular functions, but their lipid composition and response to stressors are not fully understood. Recent advancements in lipidomics reveal insights into lipid functions, especially their roles in metabolic perturbations and diseases. Previous methods have focused on the protein composition of mitochondria and mitochondrial-associated membranes. The advantage of our technique is that it combines organelle isolation with targeted lipidomics, offering new insights into the composition and dynamics of these organelles in pathological conditions. We developed a mitochondria isolation protocol for L6 myotubes, enabling lipidomics analysis of specific organelles without interference from other cellular compartments. This approach offers a unique opportunity to dissect lipid dynamics within mitochondria and their associated ER compartments under cellular stress. Key features • Analysis and quantification of lipids in mitochondria-ER fraction through liquid chromatography-tandem mass spectrometry-based lipidomics (LC-MS/MS lipidomics). • LC-MS/MS lipidomics provide precise and unbiased information on the lipid composition in in vitro systems. • LC-MS/MS lipidomics facilitates the identification of lipid signatures in mammalian cells.

THE INFLUENCE OF MESENCHYMAL STROMAL CELLS OF DIFFERENT GENESIS ON ENERGY METABOLISM IN THE RAT SOMATOSENSORY CORTEX DURING ISCHEMIA-REPERFUSION

Introduction. About 60-80% of cerebral circulation disorders are due to ischemia, that leads to high mortality, disability in working age and economic burden on society in developed countries of the world. Objective: To investigate the effect of ischemia-reperfusion on parameters of carbohydrate and energy exchanges in the rat somatosensory cortex and to determine the cerebroprotective action of mesenchymal stromal cells (MSCs) of various genesis, MSC lysate and the reference drug Citicoline. Methods. The study was performed on 200 male Wistar rats, divided into 9 groups. Group 1 included intact animals; group 2 – sham-operated rats; group 3 – control pathology (rats were subjected to ischemia-reperfusion by occlusion of the internal carotid arteries and injected with a 0.9% saline solution (2 ml/kg) into the femoral vein); group 4 – immediately after ischemia-reperfusion rats were transplanted with 106 MSC cells/animal derived from Wharton’s jelly of the human umbilical cord; group 5 – 106 cells/animal of rat embryonic fibroblasts; group 6 – 106 cells/animal derived from human adipose MSCs; group 7 – 106 cells/animal derived from rat adipose MSCs; group 8 – 0.2 ml/animal of lysate derived from Wharton’s jelly MSCs; group 9 – the reference drug Citicoline (250 mg/kg). Parameters of carbohydrate and energy metabolism in rat somatosensory cortex under the conditions of cerebral IR and on the background of correction studied on the 7th and 14th day. Results. It was found that after cerebral ischemia-reperfusion in the rat somatosensory cortex in research periods an increase in the levels of glucose, lactate, lactate/pyruvate ratio and a decrease in the content of pyruvate and succinate dehydrogenase were revealed. In the groups of experimental animals with intravenous transplantation of MSCs of various origins, MSC lysate and Citicoline, the perturbation in glucose metabolism was reduced, lactate content was decreased and the levels of pyruvate and succinate dehydrogenase were significantly increased (p<0.05), compared to rats with control pathology. A more pronounced positive effect in the recovery of disturbed energy processes and elimination of metabolic acidosis was observed with the use of human Wharton’s jelly-derived MSCs. Conclusions. The study demonstrated that experimental 20-minute model ischemia-reperfusion in rats caused a violation of the carbohydrate and energy balance in the somatosensory cortex. Human umbilical cord blood-derived MSCs contributed to the recovery of disturbed energy processes in the somatosensory cortex and eliminated metabolic acidosis at the level of Citicoline or better than it, which is one of the links of the mechanism of the cerebral protective action of MSCs. Embryonic rat fibroblasts were slightly inferior in efficiency to Citicoline and human umbilical cord Wharton’s jelly MSCs, which indicates a higher cerebroprotective activity of xenotransplantation.

Effects of a Sustained, Isometric Forearm Flexion Task to Failure on Torque and Neuromuscular Responses at 3 Elbow Joint Angles

Abstract Ortega, DG, Housh, TJ, Smith, RW, Arnett, JE, Neltner, TJ, Anders, JPV, Schmidt, RJ, and Johnson, GO. The effects of a sustained, isometric forearm flexion task to failure on torque and neuromuscular responses at 3 elbow joint angles. J Strength Cond Res 38(1): e25–e33, 2024—This study examined the effects of a sustained, isometric forearm flexion task anchored to torque to task failure on maximal voluntary isometric contraction (MVIC) and neuromuscular responses at 3 elbow joint angles. Eleven women (mean ± SD: age = 20.8 ± 2.7 years, height = 169.3 ± 7.4 cm, body mass = 67.7 ± 6.9 kg) performed two 3s forearm flexion MVICs at elbow joint angles (JAs) of 75°, 100°, and 125° before and after a sustained, isometric forearm flexion task to failure at a fatiguing joint angle of 100° anchored to a torque value that corresponded to a rating of perceived exertion of 8 (RPE = 8). The amplitude (AMP) and mean power frequency (MPF) of the electromyographic (EMG) and mechanomyographic (MMG) signals were recorded from the biceps brachii. Repeated-measures ANOVAs were used to compare mean differences for MVIC and neuromuscular parameters. Collapsed across JAs, MVIC (p < 0.001) and EMG MPF (p = 0.006) pretest values were greater than posttest values. Collapsed across time, EMG MPF at JA75 was greater than JA100 (p < 0.001) and JA125 (p < 0.001), and JA100 was greater (p = 0.007) than JA125. For EMG AMP, there was a fatigue-induced decrease at JA75 (p = 0.003). For neuromuscular efficiency (NME = normalized torque/normalized EMG AMP), there were decreases from pretest to posttest at JA100 (p = 0.002) and JA125 (p = 0.008). There were no significant interactions or main effects for MMG AMP and MMG MPF. From these findings, it was hypothesized that the decline in MVICs at JA75, JA100, and JA125 was due to fatigue-induced metabolic perturbations that resulted in JA-specific neuromuscular responses. Thus, neuromuscular parameters may provide insight into the JA-specific mechanisms of fatigue.