Metabolic Processes Research Articles

The effects of muscle factors irisin on lipid metabolism in breast cancer: A possible mechanism anti-tumor mechanism of physical activity

Breast cancer is the most prevalent cancer in the female population and is a significant cause of global cancer deaths in this group. Obesity increases a woman’s risk of developing breast cancer and has a negative impact on prognosis. Metabolic alterations are an important part of the process of cancer migration; invasion and proliferation, with lipids being a major metabolic substrate for rapid cancer progression, capable of influencing the metabolic crosstalk between tumor cells and other cells in the tumor microenvironment. Physical activity-induced irisin affects the progression of obesity-associated breast cancer and is a new indicator for breast cancer diagnosis. Existing evidence suggests a potential inhibitory effect of physical activity-induced irisin on the progression of breast cancer. A strong association exists between obesity and breast cancer progression and outcomes. This paper discusses how physical activity-induced irisin may achieve cancer suppression by affecting lipid metabolic processes between breast cancer cells and cancer-associated adipocytes, and elucidates the molecular pathways involved in the effects of irisin on cancer lipid reprogramming, thereby helping to prevent the metastatic progression of breast cancer, and ultimately improving the survival rate of this patient group.

Abstract PR015: Decoding RNA metabolism by RNA-linked CRISPR screening in human cells

Abstract RNAs undergo a complex choreography of metabolic processes in human cells that are regulated by thousands of RNA-associated proteins. While the effects of individual RNA-associated proteins on RNA metabolism have been extensively characterized, the full complement of regulators for most RNA metabolic events remain unknown. Here we present a massively parallel RNA-linked CRISPR (ReLiC) screening approach to measure the responses of diverse RNA metabolic events to knockout of 2,092 human genes encoding all known RNA-associated proteins. ReLiC screens highlight modular interactions between gene networks regulating splicing, translation, and decay of mRNAs. When combined with biochemical fractionation of polysomes, ReLiC reveals striking pathway-specific coupling between growth fitness and mRNA translation. Perturbing different components of the translation and proteostasis machineries have distinct effects on ribosome occupancy, while perturbing mRNA transcription leaves ribosome occupancy largely intact. Isoform-selective ReLiC screens capture differential regulation of intron retention and exon skipping by SF3b complex subunits. Chemogenomic screens using ReLiC decipher translational regulators upstream of mRNA decay and uncover a role for the ribosome collision sensor GCN1 during treatment with the anti-leukemic drug homoharringtonine. Our work demonstrates ReLiC as a versatile platform for discovering and dissecting regulatory principles of human RNA metabolism. Citation Format: Patrick J Nugent, Heungwon Park, Arvind Rasi Subramaniam. Decoding RNA metabolism by RNA-linked CRISPR screening in human cells [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr PR015.

Abstract PR013: Highly accurate detection of early-stage colorectal cancer using tumor and immune extracellular vesicles biomarkers

Abstract Introduction: Colorectal cancer (CRC) is one of the most common cancers worldwide, and early detection is critical for successful treatment and improved survival rates. However, precancerous and early-stage CRC present significant diagnostic challenges due to the small size of lesions and the very low expression of tumor-specific biomarkers in the bloodstream. Current genomics-based diagnostic methods struggle to detect these lesions, making it imperative to develop more sensitive and specific approaches. Circulating extracellular vesicles (EVs) are emerging as a promising solution for early-stage CRC detection, since EVs are produced by tumor cells as well as the tumor microenviroment and host immune cells. Thus, EVs may offer the means to detect and monitor small early-stage tumors through both direct detection of tumor- associated biomarkers as well through tumor specific host response and tumor microenvironment biomarkers. Methods: To identify novel early-stage CRC specific biomarkers, we performed proteomics analysis on EVs purified from patient plasma using size exclusion chromatography and a proprietary buffer system that enhances EV and corona protein recovery. TrueDiscovery™ Data-independent acquisition (DIA) mass spectrometry (MS) analysis was conducted on 24 pre- cancer/stage 0 and 25 stage 1 CRC patients and 75 normal patient plasma samples. An in-house developed machine learning pipeline was used to identify differentially expressed proteins and model candidate multiplexes to identify those with extremely high diagnostic accuracy (> 0.99). Results: An average of ∼2,500 proteins were identified per sample and included in bioinformatics analysis. Comparative analysis between control patient EVs and either pre- cancerous/Stage 0, or Stage 1 colon cancer EVs using an in-house Machine Learning pipeline identified 336 and 493 differentially expressed proteins for each group (FDR adjusted p-value < 0.001). Of these, the best 17 pre/stage 0 proteins and 53 stage 1 proteins were trained and tested using Support Vector Machine to assess all potential 3-plexes in order to identify those with mean diagnostic accuracy > 99%. This yielded 5 3-plexes in precancer/stage 0 and 34 3-plexes in stage 1 with near perfect diagnostic accuracy. These plexes are currently being assessed in single analyte and multiplex immunoassays with the goal of translating candidate 3-plexes to the clinical. Conclusions: Key biomarkers from CRC patient EVs indicate the potential to detect and diagnose early-stage and low tumor burden cancers using our methods. Interestingly, the most accurate 3-plexes consist of proteins from immune, inflammatory and metabolic processes, suggesting that for the detection of early stage cancer it may be critical to include both tumor and host specific biomarkers. Citation Format: Poorva Mudgal, Cheryl Bandoski, Zachary Opheim, Martin Mehnert, Valesca Anschau, Issa Isaac, Alan Ezrin, Todd Hembrough. Highly accurate detection of early-stage colorectal cancer using tumor and immune extracellular vesicles biomarkers [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr PR013.

Effect of micronutrients on growth and bulb production of LA hybrid lilium (Lilium longiflorum) cv. pavia

The experiment was conducted during the 2021–22 at ICAR-Indian Agricultural Research Institute, New Delhi to determine the effect of micronutrients on the growth and bulb production of LA hybrid lilium cv. pavia. The experiment's findings showed that applying micronutrients topically in combination was more beneficial than doing so topically alone. In contrast, a combination of ZnSO4 + MnSO4 @6 g/litre each sprayed at 40 and 60 days after planting performed better in terms of growth attributes, such as net assimilation rate (4.07 g/m2 leaf area/day), relative growth rate (9.46 mg/g/day), and specific leaf area (46.68 m2/kg). Bulb attributes included number of bulblets/plant (4.60), bulb circumference (14.97 cm), bulblets circumference (3.77 cm), weight of bulb (30.44 g), and bulblets (2.64 g) in LA hybrid lilium cv. pavia, whereas the control group showed the lowest interaction effect levels. This demonstrates that the growth of bulbous ornamental crops such as lilium benefits more from the combined administration of micronutrients. It results from the application of the ideal concentration of micronutrients at regular intervals, which increases photosynthetic rate. These micronutrients help plants accumulate biosynthates through a variety of activities and control metabolic processes that occur in plants. Additionally, they activate enzymes that enhance development and better distribute carbohydrates to various regions of the plant, such as carbonic dehydrogenase, peroxidase, tryptophan synthase, and catalase. Micronutrients are essential for all cellular and metabolic processes, and their optimal utilization enhances the quality of the crop.

Comprehensive analysis of molecular mechanisms underlying kidney stones: gene expression profiles and potential diagnostic markers

BackgroundThe study aimed to investigate the molecular mechanisms underlying kidney stones by analyzing gene expression profiles. They focused on identifying differentially expressed genes (DEGs), performing gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, and screening optimal feature genes using various machine learning algorithms.MethodsData from the GSE73680 dataset, comprising normal renal papillary tissues and Randall’s Plaque (RP) tissues, were downloaded from the GEO database. DEGs were identified using the limma R package, followed by GSEA and WGCNA to explore functional modules. Functional enrichment analysis was conducted using KEGG and Disease Ontology. Various machine learning algorithms were used for screening the most suitable feature genes, which were then assessed for their expression and diagnostic significance through Wilcoxon rank-sum tests and ROC curves. GSEA and correlation analysis were performed on optimal feature genes, and immune cell infiltration was assessed using the CIBERSORT algorithm.Results412 DEGs were identified, with 194 downregulated and 218 upregulated genes in kidney stone samples. GSEA revealed enriched pathways related to metabolic processes, immune response, and disease states. WGCNA identified modules correlated with kidney stones, particularly the yellow module. Functional enrichment analysis highlighted pathways involved in metabolism, immune response, and disease pathology. Through machine learning algorithms, KLK1 and MMP10 were identified as optimal feature genes, significantly upregulated in kidney stone samples, with high diagnostic value. GSEA further elucidated their biological functions and pathway associations.ConclusionThe study comprehensively analyzed gene expression profiles to uncover molecular mechanisms underlying kidney stones. KLK1 and MMP10 were identified as potential diagnostic markers and key players in kidney stone progression. Functional enrichment analysis provided insights into their roles in metabolic processes, immune response, and disease pathology. These results contribute significantly to a better understanding of kidney stone pathogenesis and may inform future diagnostic and therapeutic strategies.

Advancements and Challenges in Nanoscale Zero-Valent Iron-Activated Persulfate Technology for the Removal of Endocrine-Disrupting Chemicals

Endocrine-disrupting chemicals are a new class of pollutants that can affect hormonal metabolic processes in animals and humans. They can enter the aquatic environment through various pathways and gradually become enriched, thus posing a serious threat to the endocrine and physiological systems of both animals and humans. Nano zero-valent iron has promising applications in endocrine disruptor removal due to its excellent reducing properties and high specific surface area. However, given the dispersed focus and fragmented results of current studies, a comprehensive review is still lacking. In this paper, it was analyzed that the types of endocrine disruptors and their emission pathways reveal the sources of these compounds. Then, the main technologies currently used for endocrine disruptor treatment are introduced, covering physical, chemical, and biological treatment methods, with a special focus on persulfate oxidation among advanced oxidation technologies. Also, the paper summarizes the various activation methods of persulfate oxidation technology and proposes the nZVI-activated persulfate technology as the most promising means of treatment. In addition, this paper reviews the research progress of different modification methods of nZVI in activating persulfate for the removal of EDCs. Finally, the discussion includes recycling studies of nZVI/PS technology and emphasizes the urgency and importance of endocrine disruptor treatment. The review of this paper provides further scientific basis and technical support for nZVI/PS technology in the field of endocrine disruptor management.

Association Between Zinc Status and Insulin Resistance/Sensitivity Check Indexes in Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is considered the most common metabolic disorder of the pregnancy period. It is characterized by pancreatic beta-cell dysfunction in the setting of chronic insulin resistance. Zinc is a nutrient involved in numerous metabolic processes and shows a relationship with glycometabolic disorders and GDM. The latest data have demonstrated the association of zinc with insulin sensitivity and resistance. The exact role of zinc in the connection with indexes of insulin resistance and insulin sensitivity is still not fully clarified. The aim of the study is to analyze the newly calculated indexes Glu/Zn, Ins/Zn, and HOMA-IR/Zn as surrogate markers to explore the correlation between serum zinc status and some indexes of insulin sensitivity and insulin resistance. The possible role of these indexes as markers of insulin resistance in pregnant women was analyzed too. An ROC analysis demonstrated that HOMA-IR/Zn with AUC 0.989, p < 0.001 (95% CI 0.967–1.000) and Ins/Zn with AUC 0.947, p < 0.001 (95% CI 0.889–1.000) in the GDM group, and only HOMA-IR/Zn index with AUC 0.953, p < 0.001 (95% CI 0.877–1.000) in healthy pregnant women, have good power as markers of insulin resistance in both groups. We speculate that these new ratios could be suitable for the assessment of pregnant women at high risk of insulin resistance development and, probably, for the evaluation of the specific pathophysiologic characteristics of women with GDM.

The circulatory levels and bone expression of MIR21, 34a, 155 and their target genes in a section of Egyptian Population

AbstractBone tissue is constantly regenerated and repaired through a finely balanced process known as bone remodeling. Many miRNAs act as regulators of the signaling pathways involved in bone metabolic processes to maintain tissue homeostasis. This study aimed to assess the circulating levels of MIR21, MIR34a, and MIR155 in human serum and their bone expression, and the expression of bone turnover-related genes which can reflect the bone quality. This prospective study was conducted on 60 patients (30 males and 30 females) indicated for surgical interventions for neural decompression +/- fixation. Relative quantification of expression of MIR21, miR34a, and MIR155 and bone related genes was assayed using PCR. The serum levels of osteocalcin and Serum Bone Alkaline Phosphatase (sBAP) were assayed using a human ELISA kit. The main finding of the present work was the strong positive association between the circulating levels of only miR21 and MIR155 and their bone expression in the population under study and with bone markers and target genes Also, a positive association was found between both bone expression and circulating MIR21 levels with age and sBAP. These results suggest that the circulating levels of these microRNAs as early markers for the predication of bone quality.

Motion and magnetic field inhomogeneity correction techniques for chemical exchange saturation transfer (CEST) MRI: A contemporary review

AbstractChemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) has emerged as a powerful imaging technique sensitive to tissue molecular composition, pH, and metabolic processes in situ. CEST MRI uniquely probes the physical exchange of protons between water and specific molecules within tissues, providing a window into physiological phenomena that remain invisible to standard MRI. However, given the very low concentration (millimolar range) of CEST compounds, the effects measured are generally only on the order of a few percent of the water signal. Consequently, a few critical challenges, including correction of motion artifacts and magnetic field (B0 and B1+) inhomogeneities, have to be addressed in order to unlock the full potential of CEST MRI. Motion, whether from patient movement or inherent physiological pulsations, can distort the CEST signal, hindering accurate quantification. B0 and B1+ inhomogeneities, arising from scanner hardware imperfections, further complicate data interpretation by introducing spurious variations in the signal intensity. Without proper correction of these confounding factors, reliable analysis and clinical translation of CEST MRI remain challenging. Motion correction methods aim to compensate for patient movement during (prospective) or after (retrospective) image acquisition, reducing artifacts and preserving data quality. Similarly, B0 and B1+ inhomogeneity correction techniques enhance the spatial and spectral accuracy of CEST MRI. This paper aims to provide a comprehensive review of the current landscape of motion and magnetic field inhomogeneity correction methods in CEST MRI. The methods discussed apply to saturation transfer (ST) MRI in general, including semisolid magnetization transfer contrast (MTC) and relayed nuclear Overhauser enhancement (rNOE) studies.

Physio-Metabolic Mechanisms Behind Postharvest Quality Deterioration in Broccoli (Brassica oleracea var. Italica) and Swiss Chard (Beta vulgaris L. var. Cicla): A Review

Leafy vegetables are among the potential foods that can combat food insecurity in developing countries. Their major drawback is a short shelf life, which limits their supply chain and is commonly associated with their high metabolic activities. Leafy vegetables have a high water content, which determines their freshness. Moisture loss through respiration and transpiration at postharvest storage is one quality attribute that leads to rapid quality deterioration. Little has been carried out in studying the mechanisms associated with the quality deterioration of leafy vegetables; however, understanding these mechanisms may aid in developing effective preservation measures. Furthermore, recent literature reviews that focus on discussing the mechanisms that lead to quality loss in leafy vegetables are scarce. The current paper aims to review the physiological and biochemical processes associated with quality deterioration in leafy vegetables. The respiration, ethylene production, moisture loss, colour, and texture are highly associated with the quality deterioration of fresh produce and, thus will be discussed critically in selected leafy vegetables, namely: broccoli and Swiss chard. The findings from this review indicate that the quality deterioration in leafy vegetables is primarily enzymatic. Understanding the mechanisms of quality deterioration involves identifying the specific enzymes responsible for each metabolic process and examining the internal and external factors that influence enzyme activities.

Biodegradation of Polyethylene Using Bacillus tropicus Isolated from Sewage Wastewater Treatment Plant

One of the most pressing environmental problems contemporary civilizations confront is the ever-increasing amount of plastic waste. Because of their impact on every living thing, these wastes are seen as a major issue on a global scale. To counteract the harmful environmental effects caused by conventional disposal methods, it is critical to show that eco-friendly alternatives are viable. Biodegradation is one of the best eco-friendly methods for removing plastic waste. In this study, we aimed to identify bacteria from sewage wastewater treatment plants (SWWs) that could degrade low-density polyethylene (LDPE). Bacterial strains isolated from sewerage wastewater were incubated for 120 days in 50 mL of minimal salt media (MSM) containing 60 mg of low-density polyethylene (LDPE). After four months, our research revealed that Bacillus tropicus (SH4) demonstrated significant potential, degrading the LDPE up to 21.6%. We observed the changes after biodegradation using FTIR, GC-MS, and SEM analysis. In conclusion, microorganisms extracted from sewage wastewater possess the ability to mitigate plastic contamination in aquatic ecosystems. Future proteomics and genome investigations are necessary to elucidate the enzymes and metabolic processes implicated in plastic breakdown.

Expression profile of tsRNAs in white adipose tissue of vitamin D deficiency young male mice with or without obesity

The expression of tsRNA in white adipose tissue (WAT) of VD deficiency male mice with obesity has not been reported. The healthy male C57BL/6J mice aged 4-6 weeks were divided into 4 groups according to the VD3 and fat energy supplement in daily diets. The qPCR verification further demonstrated that tRF5-20-HisGTG-3 were significantly up-regulated and mt-tRF3a-ProTGG was significantly down-regulated not only in HFVDD vs HFVDS, but aslo in HFVDD vs ConVDS. tRF5-22-CysGCA-27 were significantly up-regulated and mt-5'tiRNA-32-SerTGA, mt-5'tiRNA-33-SerTGA and mt-5'tiRNA-33-AlaTGC was significantly down-regulated only in HFVDD vs ConVDS. Enrichment analysis of the qPCR verified DE tsRNAs showed that the 3 up-regulated tsRNAs seemed to be associated with FoxO signaling pathway, GnRH secretion, 2−Oxocarboxylic acid metabolism, Autophagy-animal, Glucagon and insulin signaling pathway, while 4 down-regulated tsRNA seemed to be associated with cell communication, primary metabolic process, metabolic process, response to stimulus, multicellular organismal process, cellular metabolic process, cellular process and biological regulation. The tsRNAs were differentially expressed in VD deficiency with obesity, especially tRF5-20-HisGTG-3, tRF5-22-CysGCA-27, tRF3a-GlyGCC-1, mt-5'tiRNA-33-AlaTGC, mt-5'tiRNA-33-SerTGA, mt-5'tiRNA-32-SerTGA and mt-tRF3a-ProTGG. These tsRNAs seemed to be associated with FoxO signaling pathway, GnRH secretion, 2−oxocarboxylic acid metabolism, autophagy, glucagon and insulin signaling pathway, metabolic process and biological regulation.

Glyphosate contact alters the expression of genes in the head of africanized Apis mellifera bees

The increase in the world population results in a greater demand for food, intensifying the dependence on pesticides use. Glyphosate, a pesticide widely used in crops, can contaminate resources collected by bees. In this context, this study aimed to analyze the transcriptome of the head of Africanized Apis mellifera bees during the foraging phase to determine whether contact with the herbicide glyphosate, in lethal and sublethal doses, causes changes in the gene expression profile. For this, 180 marked bees were collected from their hives, aged 21 days, and distributed into three treatment groups: 1) bees in contact with the lethal dose of glyphosate (255.73 µg/bee); 2) bees in contact with the sublethal dose of glyphosate (2.5573 µg/bee); 3) control group with distilled water. Transcriptome analysis was performed on 12 bees from each treatment after one and four hours of exposure. The results show that one hour of contact with glyphosate resulted in 57 genes presenting differential expression in relation to the control (11 lethal and 53 sublethal), interfering in the signaling, communication and metabolism processes, while four hours of exposure, 38 genes (32 lethal and 11 sublethal) related, mainly, to the stimulation of the immune response. In summary, glyphosate affects the gene expression of honey bees during the foraging phase, at both doses, resulting in negative effects on behavior, metabolism and immune system, which compromises the health, activity and development of the colonies, also compromising the process of pollination.

Investigation of the Effects of Biotinidase Deficiency on Plasma Cholinesterase Activity

Purpose: Biotinidase deficiency (BD) is a rare autosomal recessive metabolic disorder that impairs the body's ability to recycle biotin, a crucial coenzyme for carboxylase enzymes involved in various metabolic processes. This study aims to evaluate the effects of biotinidase deficiency on cholinesterase activity in plasma, hypothesizing that the metabolic disruptions caused by inadequate biotin recycling may lead to alterations in cholinesterase function. Materials and methods: Plasma samples were collected from 73 individuals categorized into four genetic groups: wild type (n = 12), heterozygous (n = 30), homozygous (n = 19), and compound heterozygous (n = 12). Cholinesterase activity was measured using a colorimetric method. Results: The study discovered that the cholinesterase activity of the Heterozygous group was higher than the homozygous group (p = 0.0356). Additionally, cholinesterase activity was significantly lower in homozygous and compound heterozygous people than in wild and heterozygous groups (p = 0.0272). The statistically significant changes suggested a relationship between biotinidase deficiency and altered cholinergic activity. Conclusion: The findings indicate that biotinidase deficiency, particularly in its severe variants, may cause considerable reductions in cholinesterase activity, contributing to the neurological symptoms found in affected patients. More studies are needed to investigate the processes behind this association and develop strategies for reducing the effects of BD on cholinesterase activity and neurological health.

N-Carbamoyl Glutamate Prevents Ammonia Intoxication in Piglets with Reduced Liver Function

Ammonia as the end product of protein catabolism has a depressing effect on neurons. Ammonia neutralization in mammals occurs in the ornithine cycle, the activity of which is regulated mainly at the level of synthesis of N-Carbamoyl phosphate. The Krebs cycle is coupled with the ornithine cycle through a common substrate—arginine succinate. Therefore, the effects of ammonia neutralization and the processes of amino acid and energy metabolism are largely interrelated. This study is aimed at evaluating the efficacy of an N-carbamoyl glutamate additive in terms of optimizing metabolic processes and improving ammonia neutralization in suckling piglets. The experiment was conducted on two groups of piglets (n=15) formed at the age of 24 hours. Piglets in the experimental group were fed with an aqueous solution of the drug at a dose of 10 mg/kg of body weight once daily. The duration of feeding the supplement was 30 days; the average daily gain in body weight was determined at weaning at the age of 30 days. An analysis of the blood biochemical composition was carried out on the 30th day from the onset of the experiment. At the end of feeding the supplement in the experimental group, a decrease in the content of ammonia (p<0.05) and urea in blood plasma, an increase in the concentration of arginine (p<0.05) and triacylglycerols (p<0.05) in comparison with the control group was revealed. The N-carbamoyl glutamate additive under study stimulates the endogenous production of the arginine essential amino acid, neutralizes ammonia formed in metabolic processes, and optimizes the amount of metabolic energy spent on binding ammonia in the urea cycle.

INDICATORS OF FREE RADICAL OXIDATION AND ANTIOXIDANT PROTECTION IN THE ORAL FLUID OF CHILDREN WITH CHRONIC CATARRHAL GINGIVITIS AND DIABETIS MELLITUS

Failure of antioxidant mechanisms leads to an increase in lipid peroxidation products in the body, resulting in a non-specific cascade of cellular membrane damage. Proteins play a crucial role in metabolic processes, but when lipid peroxidation intensifies, protein modifications occur, leading to fragmentation, denaturation, and loss of biological activity. This disruption impairs tissue regenerative processes. The objective of this study was to analyze indicators of free radical oxidation and antioxidant protection in the oral fluid of children with chronic catarrhal gingivitis and type I diabetes mellitus. Materials and methods. A total of 170 children aged 12 to 16 were observed, including 130 who were examined and treated at the Endocrinology Department of the Regional Municipal Non-Profit Institution “Chernivtsi Regional Pediatric Clinical Hospital” for type 1 diabetes mellitus. Among them, 74 children had a disease duration of less than 5 years, including 65 with chronic catarrhal gingivitis. Sixty five children had diabetes for more than 5 years, with 44 of them diagnosed to have chronic catarrhal gingivitis. The children with chronic catarrhal gingivitis were further divided into groups based on their level of glycemic control: 1 child with optimal glycemic control, 66 with suboptimal glycemic control, and 42 with glycemic control at a high risk to life. The control group included 40 practically healthy children: 22 of them had clinically healthy periodontal tissues, and 18 children were diagnosed to suffer from chronic catarrhal gingivitis. Results. The study performed found out that children with chronic catarrhal gingivitis present increased indicators of lipid peroxide oxidation (protein oxidative modification, diene conjugates, malondialdehyde) and decreased activity of the enzyme in the antioxidant protective system of the oral fluid (whole protein, НS-groups, ceruloplasmin, activity of supermutase and catalase) in comparison with indicators of children without dental pathology. The most considerable changes were found in patients with chronic catarrhal gingivitis and type 1 diabetes mellitus, especially when the disease lasted more than 5 years (р<0,05).

Exploring non-canonical targets in Alzheimer’s disease: a departure from the norm

AbstractAlzheimer’s disease (AD), a progressive neurodegenerative disorder, is characterized by neurological impairments such as visual and sensory difficulties, motor dysfunction, sphincter issues, incoordination, gait abnormalities, and cognitive decline. Despite advances in understanding AD pathophysiology and the expansion of therapeutic options over the past three decades, the disease remains incurable. Current therapies, even those specifically targeting AD, often fail to significantly alter its progression, underscoring the need for innovative treatment approaches beyond symptomatic relief. This calls for a re-examination of AD pathology to identify potential therapeutic targets that go beyond conventional strategies. This review highlights four of the most promising non-canonical therapeutic targets: oligodendrocytes, the blood–brain barrier (BBB), neuroimmunometabolism, and the coagulation system. These components are crucial for maintaining the integrity and proper function of neurons and the brain, playing key roles in the progression of AD. Oligodendrocytes, for example, are essential for myelination and neuronal support, while BBB dysfunction can lead to impaired clearance of toxic proteins. Neuroimmunometabolism offers insights into how metabolic processes influence immune responses in the brain and dysregulation of the coagulation system has been linked to increased neuroinflammation and vascular abnormalities in AD. Recent discoveries in these fields provide new avenues for understanding the disease and identifying potential therapeutic targets. By exploring these non-canonical pathways, future research may offer breakthroughs in treating AD, moving beyond symptomatic management towards disease-modifying strategies.

Pressure-tolerant survival mechanism of Schizophyllum commune 20R-7-F01 isolated from deep sediments 2 kilometers below the seafloor

In anaerobic high hydrostatic pressure (HHP) sedimentary environments below the seafloor, fungi are found to dominate the eukaryotic communities, playing crucial ecological roles. However, the specific mechanisms by which fungi adapt to anaerobic HHP environments remain unclear. In this study, we investigated Schizophyllum commune 20R-7-F01 isolated from coal-bearing sediments at a depth of 2 km below the seafloor. By assessing the cell viability, biomass, and cell wall thickness changes of strain 20-7-1 under different HHP conditions, we observed that, compared to 0.1 MPa, strain 20-7-1 exhibited slower growth rates and decreased cell viability at 15 MPa and 35 MPa, yet demonstrated significant pressure tolerance. Transcriptomic and metabolomic analyses revealed that this strain activated the carbohydrate metabolic process to simultaneously utilize ethanol and lactic acid fermentation pathway. Additionally, it activates the oxidoreductase activity and hydrolase activity pathways to detoxify intracellular reactive oxygen species (ROS). Activation of the metal ion binding pathway increases the proportion of unsaturated fatty acids in the cell membrane, while instigation of the integral component of membrane pathway maintains cell wall structural stability. Furthermore, activation of the DNA repair pathway repairs DNA damage, demonstrating its comprehensive adaptive mechanisms against the HHP stress. These research findings deepen our understanding of fungal survival strategies and adaptation mechanisms in extreme environments, laying the groundwork for further exploration of their roles in cycling of carbon, nitrogen, sulfur, and other elements in the deep biosphere.

Study of anti-inflammatory, antioxidant, antimicrobial and mineralizing effects of an N-isopropenylimidazole zinc metal complex derivative in experimental endodontic-periodontal lesions in rats

Introduction: The combination treatment of patients with dentition problems including endodontic-periodontal lesions (EPL) is known to widely involve anti-inflammatory drugs, including non-steroidal anti-inflammatory agents, and antimicrobial drugs, in particular antibiotics and antiseptics, from which the former often lead to the development of gastro- and neuropathy, lesions of kidneys and liver, as well as the cardiovascular system, and the latter, in addition to serious side effects, lead to the development of steady resistance of pathogenic microorganisms and dysbacteriosis. This necessitates search for and development of new molecules with a wide range of therapeutic effects aimed to block the infectious and inflammatory process and to restore the functional ability of teeth in EPLs as much as possible (depending on a lesion severity). The aim of the study was to examine the anti-inflammatory, antioxidant, antimicrobial and mineralizing effects of an N-isopropenylimidazole zinc metal complex derivative in experimental endodontic-periodontal lesions in rats. Materials and Methods: EPL simulation in experiments on the anesthetized rats was conducted in the following way: first, the pulp cavity of lower incisors was opened and left exposed to infection; then periodontal inflammation was induced using a ligature. Thirty days later, EPL developed in the animals. An N-isopropenylimidazole zinc metal complex derivative (laboratory code Pilim-1, prepared in form of gel), reference drug Metrogyl Denta® (M-D, dental gel), as well as the combination Pilim-1 + M-D were applied daily for 14 days on the lower incisors and appropriate gums, and also placed in the gingival pockets and pulp cavities, with pulp partially removed beforehands. After euthanasia of the animals on the 15th day of the experiments, gingival homogenates were assayed for the activity of elastase, urease, catalase, the level of malondialdehyde, and the antioxidant-prooxidant index was calculated, while pulp homogenates were assayed for the activity of elastase, urease, alkaline and acidic phosphatases, and the mineralizing index was calculated. Results and Discussion: In the gum in EPL, Pilim-1 and, especially, the combination Pilim-1+M-D more significantly than M-D have a pronounced anti-inflammatory, antioxidant and antimicrobial (reduce a microbial content level) effects. In the pulp in EPL, Pilim-1 and, to a greater extent, the combination Pilim-1 + M-D in a more pronounced way than M-D have anti-inflammatory, antimicrobial (reduce a microbial content level) and mineralizing effects. In the therapeutic action mechanisms of Pilim-1 and, especially, the combination Pilim-1 + M-D in EPL conditions, their ability to have an antihypoxic effect and an inhibitory effect on cyclooxygenase and 5-lipoxygenase is likely to play a very important role, in addition to their identified effect on the examined metabolic processes. Besides, a certain role may be played by the presence of zinc and imidazole in the structure of Pilim-1, as they have a wide range of biological activity. Conclusion: The presented results of studying Pilim-1 and its combination with M-D indicate their high therapeutic efficiency, especially when using the latter in the experimental EPL in rats, which makes it possible to consider Pilim-1 and Pilim-1 + M-D as potential therapeutic agents to treat EPL.

Metabolic regulation of 5-oxoproline for enhanced heat tolerance in perennial ryegrass

Pyroglutamic acid [(5-oxoproline (5-oxp)], a non-protein amino acid, can be converted to glutamate to regulate amino acid metabolism in plants. Its roles in plant adaptation to abiotic stresses, including heat stress, are not well understood. The objectives of this study were to determine whether exogenous application of 5-oxp could promote heat tolerance in cool-season perennial grass species and identify the major metabolic pathways that could be activated or responsive to 5-oxp for enhancing heat tolerance. Perennial ryegrass (Lolium perenne L.) plants were foliar-sprayed with 5-oxp or water (untreated control) prior to and during the exposure to heat stress (35/33 ℃, day/night temperature) or ambient temperature (25/22 ℃, day/night temperature, non-stress control) in controlled-environment growth chambers. Application of 5-oxp improved the heat tolerance of perennial ryegrass, as manifested by the chlorophyll content, photochemical efficiency, cell membrane stability, and antioxidant enzyme activities increasing by 31.2%, 25.7%, 37.2%, and 57.1-258.3%, as well as the reduction in hydrogen peroxide production by 36.8%. Metabolic profiling identified metabolites up-regulated by 5-oxp that are involved in the metabolic pathways of carbon assimilation in photosynthesis, glycolysis and the tricarboxylic acid cycle of respiration, proteinogenic amino acid metabolism, glutathione metabolism, and nucleotide metabolism for DNA or RNA synthesis and ATP generation. The up-regulation or activation of those metabolic processes could contribute to 5-oxp-mediated enhancement in the heat tolerance of perennial ryegrass.