Biochemical Pathways Research Articles

Effect of electrohydrodynamic drying on bee pollen biochemical pathways

The mechanism of ionic wind and electric field of electrohydrodynamic (EHD) drying dehydration stress on the biochemical and molecular basis of bee pollen is still unclear. In this study, metabolomics and proteomics were employed to analyze the changes in biochemicals and small-molecule metabolic compounds of bee pollen during the drying process using needle-to-plate and plate-to-plate electrode system. The results show that ionic wind and electric field contributed 85.0% and 15.0% respectively to the dehydration characteristics, with the electric field having a greater effect on the quality parameters. As compared to ionic wind, the ribosome, the citric acid cycle (TCA cycle), and proteasome pathway played a positive role in regulating the abiotic and biochemical responses of electric field dehydration. Both ionic wind and electric field changed the expression of functional proteins related to amino acid metabolism pathways, resulting in a decrease in the expression of characteristic metabolites such as L-phenylalanine, L-aspartic acid, and L-pyroglutamic acid from 114.27 × 107, 5.31 × 107, and 142.55 × 107 in fresh rape bee pollen to 57.46 × 107, 3.32 × 107, and 57.46 × 107 in needle-to-plate (N-P) electrode treated and 61.25 × 107, 2.47 × 107, as well as 33.82 × 107 in plate-to-plate (P-P) electrode treated samples. Additionally, the differential expression of proteasome pathway and the destruction of the structural integrity of the cell wall storing phenolic compounds resulted in the further interaction of protein-phenolic supercomplexes, which in turn changed the content of free phenolic acids in rape bee pollen. These findings elucidated the biochemical regulation strategy and protein-phenolic compound interaction mechanism of rape bee pollen during EHD drying processing, and further emphasized the synergistic mechanism of ionic wind and electric field.

Microbiological Treatment of Nitrate and Selenate from Coal Mine-Affected Water in a Subsurface,Semi-Passive, and in situ Water Treatment Facility

Metallurgical coal mining generates significant amounts of waste rock, which can release nitrate and selenate upon atmospheric exposure, with resulting changes in surface water and ground water quality. Microorganisms residing on waste rock in the local subsurface have the metabolic potential to denitrifyand reduce selenium to treat mine-affected waters and stabilize waste rock. To support these processes, waste rock facilities have been designed to inject nutrients (e.g., methanol and phosphoric acid) in semi-passive water treatment of mine-impacted waters. Microbial community data regularly collected fromsubsurface semi-passive reactors throughout the startup and operations phases showed that native heterotrophic denitrifying bacteria and selenium reducing bacteria were enriched as a result of nutrient amendment. The microbial community was stable while the source water and geochemical parameters remained unchanged; however, a significant shift in the microbial community coincided with changes in the source of water treated. Metagenomic sequencing of microbial communities within the active treatment zone revealed multiple biochemical pathways of nitrate reduction. Geochemical and water quality data indicate near complete selenate reduction, yet a low abundance of in known selenate reduction genes were recovered. This may suggest that biologically mediated selenium reduction may be more widespread, both functionally and taxonomically. Further research into these pathways and mechanisms for nitrate and selenium reduction will help to strengthen our understanding of selenium reduction mechanisms and their application in mine water waste management.

Association between Plasmodium Infection and Nitric Oxide Levels: A Systematic Review and Meta-Analysis.

Nitric oxide (NO) has been implicated in the pathology of malaria. This systematic review and meta-analysis describe the association between NO levels and malaria. Embase, Ovid, PubMed, Scopus, and Google Scholar were searched to identify studies evaluating NO levels in malaria patients and uninfected controls. Meta-regression and subgroup analyses were conducted to discern differences in NO levels between the groups. Of the 4517 records identified, 21 studies were included in the systematic review and meta-analysis. The findings illustrated significant disparities in NO levels based on geographic location and study time frames. Despite the fluctuations, such as higher NO levels in adults compared to children, no significant differences in mean NO levels between patients and uninfected controls (p = 0.25, Hedge's g: 0.35, 95% confidence interval (CI): -0.25-0.96, I2: 97.39%) or between severe and non-severe malaria cases (p = 0.09, Hedge's g: 0.71, 95% CI: -0.11-1.54, I2: 96.07%) were detected. The systematic review and meta-analysis highlighted inconsistencies in NO levels in malaria patients. Given the high heterogeneity of the results, further studies using standardized metrics for NO measurements and focusing on biochemical pathways dictating NO responses in malaria are imperative to understand the association between NO and malaria.

ZnO nanoparticles mediated by Azadirachta indica as nano fertilizer: Improvement in physiological and biochemical indices of Zea mays grown in Cr-contaminated soil

The current investigation aimed at evaluating the impact of Azadirachta indica-mediated zinc oxide nanoparticles (Ai-ZnONPs) on the growth and biochemical characteristics of maize (sweet glutinous 3000) under exposure to 50 mg kg−1Ai-ZnONPs with Cr (VI) concentrations of 50 and 100 mg kg−1. The results indicate that plants exposed to Cr (VI) only experienced a decline in growth parameters. Conversely, the inclusion of Ai-ZnONPs caused a noteworthy increase in physiological traits. Specifically, shoot and root fresh weight increased by 28.02% and 16.51%, and 63.11% and 97.91%, respectively, when compared to Cr-50 and 100 treatments. Additionally, the SPAD chlorophyll of the shoot increased by 91.08% and 15.38% compared to Cr-50 and 100 treatments, respectively. Moreover, the antioxidant enzyme traits of plant shoot and root, such as superoxide dismutase (SOD 7.44% and 2.70%, and 4.45% and 3.53%), catalase (CAT 1.18% and 3.20%, and 5.03% and 5.78%), and peroxidase (POD 0.31% and 5.55%, and 4.72% and 3.61%), exhibited significant increases in Cr 50 and 100 treatments, respectively. The addition of Ai-ZnONPs to the soil also enhanced soil nutrient status and reduced Cr (VI) concentrations by 40.69% and 19.82% compared to Cr-50 and 100 treated soils. These findings suggest that Ai-ZnONPs can trigger the activation of biochemical pathways that enable biomass accumulation in meristematic cells. Further investigations are required to elucidate the mechanisms involved in growth promotion.

Understanding of effect and mechanism of abiotic stress tolerance in legumes and recent development

The present changing climatic conditions are affecting crop productivity worldwide. The crop growth and productivity are adversely hit by perturbed climatic conditions and climate change. Being sessile, plants are openly exposed to biotic and abiotic stresses which limit the crop productivity. Crop plants exhibit tolerance and susceptibility under adverse conditions through various attributes at different levels like morphological, physiological, biochemical and genetic level, although their magnitude of response varies. Crops responses toward abiotic stresses have increased in the recent years by advancement of technology and understanding of physiology, molecular and genetic level of crops response to these stresses. In the processes of development of stress-tolerant plants, several genes associated tolerance and adaptation get activated leading to modulate several biochemical, physiological and metabolic pathways. Stress also induces the production of reactive oxygen species (ROS) and subsequently change in signal transduction in the plants switches towards enhancement of antioxidant system. Both abiotic and biotic stresses affect all the physiological processes of the legume plants, especially photosynthesis, respiration, water use efficiency, nutrient use efficiency etc. The activity of cell organelles like mitochondria, chloroplast and vacuoles is also affected by stress. The present study is focusing on the impact of diverse abiotic stresses at different levels in legume crops and changes at physiological, biochemical and molecular level. It also discusses the opportunities to ameliorate the ability of the legumes to enhance abiotic stress tolerance for crop improvement and agriculture sustainability.

From Pain Relief to Cancer Defense: The Promise of NSAIDs

NSAIDs (Non-Steroidal Anti-inflammatory Drugs) are commonly used to treat various types of pain and inflammation. In recent decades, extensive scientific research has been conducted to examine the use of NSAIDs in the treatment and prevention of cancer. Chronic inflammation has been linked to various cancer types, suggesting that prolonged inflammation can promote genetic mutations and accelerate their accumulation within cells. The COX pathway, short for Cyclooxygenase pathway, is a critical biochemical pathway in the human body involved in the production of important signaling molecules called prostaglandins. Key factors like COX enzymes and cytokines are important in the development and progression of inflammation-induced cancer. Angiogenesis occurs during inflammation, and it plays a major role in cancer development and metastasis. NSAIDs inhibit this process, which may also contribute to their anticancer effects. This review highlights the potential of NSAIDs, particularly aspirin, ibuprofen, and celecoxib, to influence various aspects of tumor behavior. Although promising, further rigorous studies are needed to establish their clinical efficacy and safety in diverse cancer scenarios. The use of NSAIDs as adjunctive therapies along with conventional treatments presents a promising avenue for enhancing cancer management strategies.

Melatonin Modulates the SIRT1-Related Pathways via Transdermal Cryopass-Laser Administration in Prostate Tumor Xenograft.

Melatonin displays antitumor activity in several types of malignancies; however, the best delivery route and the underlying mechanisms are still unclear. Alternative non-invasive delivery route based on transdermal administration of melatonin by cryopass-laser treatment demonstrated efficiency in reducing the progression of LNCaP prostate tumor cells xenografted into nude mice by impairing the biochemical pathways affecting redox balance. Here, we investigated the impact of transdermal melatonin on the tumor dimension, microenvironment structure, and SIRT1-modulated pathways. Two groups (vehicle cryopass-laser and melatonin cryopass-laser) were treated for 6 weeks (3 treatments per week), and the tumors collected were analyzed for hematoxylin eosin staining, sirius red, and SIRT1 modulated proteins such as PGC-1α, PPARγ, and NFkB. Melatonin in addition to simple laser treatment was able to boost the antitumor cancer activity impairing the tumor microenvironment, increasing the collagen structure around the tumor, and modulating the altered SIRT1 pathways. Transdermal application is effective, safe, and feasible in humans as well, and the significance of these findings necessitates further studies on the antitumor mechanisms exerted by melatonin.

Cross-study analyses of microbial abundance using generalized common factor methods

BackgroundBy creating networks of biochemical pathways, communities of micro-organisms are able to modulate the properties of their environment and even the metabolic processes within their hosts. Next-generation high-throughput sequencing has led to a new frontier in microbial ecology, promising the ability to leverage the microbiome to make crucial advancements in the environmental and biomedical sciences. However, this is challenging, as genomic data are high-dimensional, sparse, and noisy. Much of this noise reflects the exact conditions under which sequencing took place, and is so significant that it limits consensus-based validation of study results.ResultsWe propose an ensemble approach for cross-study exploratory analyses of microbial abundance data in which we first estimate the variance-covariance matrix of the underlying abundances from each dataset on the log scale assuming Poisson sampling, and subsequently model these covariances jointly so as to find a shared low-dimensional subspace of the feature space.ConclusionsBy viewing the projection of the latent true abundances onto this common structure, the variation is pared down to that which is shared among all datasets, and is likely to reflect more generalizable biological signal than can be inferred from individual datasets. We investigate several ways of achieving this, demonstrate that they work well on simulated and real metagenomic data in terms of signal retention and interpretability, and recommend a particular implementation.

Selected phenolic compounds in the modulation of biochemical pathways involved in aging

Graphical abstract Abstract The use of phenolic compounds, derived by plants, has recently emerged as a promising approach to prolong the lifespan by modulating metabolic pathways involved in aging. Phenolic compounds possess a broad spectrum of biochemical and pharmacological effects beneficial to human health such as modulating cellular senescence processes by interacting with molecular targets that regulate aging-related pathways. Phenolic compounds represent the major phytochemicals in our diet and possess several biological activities such as antioxidant and anti-inflammatory effects; protection against aging-related diseases (cancer, diabetes and cardiovascular diseases) with potential therapeutic applications and this could suggest that these compounds could be used as anti-aging nutraceutical support. In this review, we have considered the possible effects of some phenolic compounds in different aging pathways, to provide an overview of recent knowledge on their anti-aging mechanism of action.

FRI135 Differential Expression Of Circulating MicroRNAs In Primary Aldosteronism: Potential Biomarkers For Improved Diagnosis

Abstract Disclosure: S. Lamprou: None. S.M. MacKenzie: None. J.D. McClure: None. S. Robertson: None. A. Riddell: None. J.C. van Kralingen: None. A. Gimenez-Roqueplo: None. P. Reel: None. S. Reel: None. G. Assié: None. A. Laurence: None. F. Beuschlein: None. G. Rossi: None. J. Deinum: None. M. Reincke: None. G. Eisenhofer: None. E. Jefferson: None. M. Zennaro: None. E. Davies: None. Primary Aldosteronism (PA) is the most common endocrine hypertension subtype, caused by autonomous aldosterone secretion. While readily treatable, accurate diagnosis of PA – particularly its differentiation from primary hypertension (PHT) – is a complex and protracted process that can entail delays in effective treatment and lead to more severe comorbidities. Given the established role of microRNAs (miRNA) in regulating aldosterone biosynthesis, we hypothesize that circulating miRNAs are potentially viable biomarkers for PA that could inform more accurate and rapid diagnosis. To detect changes in circulating miRNA profiles specific to PA, we analyzed plasma levels of 172 selected microRNAs in a retrospectively-generated cohort of PHT (n=111) and PA patients (n=109). The dataset consisted of ΔCt values for each miRNA (normalized to multiple endogenous miRNAs), as determined by real time RT-qPCR assay. Two-sample t-tests were used to assess whether the means of the two disease groups are equal, corrected using False Discovery Rate (FDR; significance level q < 0.05). Ingenuity Pathway Analysis software (QIAGEN) was employed to analyze the miRNAs bioinformatically and identify mRNA targets involved in blood pressure regulation. Pathway analysis was performed to discover associations between PA and differentially-expressed miRNAs. We identified 83 circulating microRNAs that showed significant differential expression: 27 were upregulated and 56 downregulated in PA relative to PHT. The upregulated miRNA demonstrating the greatest fold change was hsa-miR-451a (FC:1.8, q=0.001), while the most downregulated was hsa-miR-409-3p (FC:0.5, q=0.001). Bioinformatics analysis predicted several dysregulated miRNAs to target mRNAs in PA-related pathways. For example, the most upregulated miRNA, hsa-miR-451a, is predicted to target mRNAs in biochemical pathways relevant to PA pathophysiology, including SGK1 and MAP3K1. SGK1 contributes to the signaling cascade induced by the mineralocorticoid receptor-aldosterone complex that stimulates Na+ reabsorption in the kidney, while MAP3K1 participates in the Renin-Angiotensin system, a key regulator of aldosterone secretion, as part of a signaling cascade that leads to the activation of the AP1 complex in the nucleus. In addition to hsa-miR-451a, other differentially-expressed miRNAs were also revealed to target multiple mRNAs with direct and indirect connections to PA. In summary, analysis has identified miRNAs that are significantly differentially expressed in the plasma of PA patients compared to PHT patients, indicating promise for a biomarker-based approach to PA diagnosis utilizing distinctive circulating microRNA signatures. Further analysis is now being conducted to validate our findings in an independent population of hypertensive patients. Presentation: Friday, June 16, 2023

RNA Sequencing and Related Differential Gene Expression Analysis in a Mouse Model of Emphysema Induced by Tobacco Smoke Combined with Elastin Peptides.

To establish a model of emphysema induced by tobacco smoke combined with elastin peptides (EP), explore the biochemical metabolic processes and signal transduction pathways related to emphysema occurrence and development at the transcriptional level, and identify new targets and signaling pathways for emphysema prevention and treatment. Mice were randomly divided into the air pseudoexposure group (NORMAL group) and the tobacco smoke + EP group (EP group). The differentially expressed genes (DEGs) in lung tissue between the two groups were identified by RNA-seq, and functional annotation and Gene Ontology (GO)/ Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. The differential expression of the selected genes were verified using qRT‒PCR and immunohistochemistry (IHC). EP group mice showed emphysema-like changes. The expression levels of 1159 genes in the EP group differed significantly (529 up-regulated and 630 down-regulated) from those in the NORMAL group. GO enrichment analysis showed that the DEGs were significantly enriched in the terms immune system, adaptive immune response, and phosphorylation, while KEGG pathway enrichment analysis showed that the DEGs were enriched mainly in the pathways cytokine‒cytokine receptor interaction, T-cell receptor signaling pathway, MAPK signaling pathway, Rap1 signaling pathway, endocytosis, chemokine signaling pathway, Th17 cell differentiation, and Th1 and Th2 cell differentiation. The differential expression of the selected DEGs were verified by qRT‒PCR and IHC, and the expression trends of these genes were consistent with those identified by RNA-seq. Emphysema may be related to the inflammatory response, immune response, immune regulation, oxidative stress injury, and other biological processes. The Bmp4-Smad-Hoxa5/Acvr2a signaling pathway may be involved in COPD/ emphysema occurrence and development.

Chemical Inductors of Proximity Associating DNA Damage-Binding Protein 2 and XIAP as Targeted Therapy for General Cancers

While all cancers are classified as uncontrolled proliferations of cells, they manifest in many forms and may arise from a wide range of cellular anomalies. It has thus made finding a universal targeted cancer therapy a highly desirable goal. Several common biochemical changes associated with oncogenesis have been described in literature across all cancers, namely the Warburg effect (Heiden et al., 2009) (Warburg, 1925) and resistance to apoptosis (Hanahan & Weinburg, 2011). These hallmarks possess high potential to be used as targeting mechanisms in cancer treatment. Recent findings by Gourlsankar et al. have shown a promising new technique of linking the activity of a frequently activated cancer driver (B cell lymphoma 6) with an apoptosis promotor, allowing the creation of a synthetic biochemical pathway which rewires cancer driver activity to induce cell death, done through using a drug to covalently link two molecules that bond to each protein (Gourlsankar et al., 2023). While this approach specifically targeted diffuse large B cell lymphoma, it shows high promise for new strategies to approach eliminating cancer cells, namely in the artificial activation of tumor suppressor function through protein linkage and the consequent association in protein location within the cytosol. This paper aims to review the strategy of Gourlsankar et al., identifying ways to expand its concept towards generalized treatments using the hallmarks of cancer, and proposing a new theoretical drug mechanism using the linkage of DNA damage-binding protein 2 (DDB2) with X-linked inhibitor of apoptosis (XIAP) to induce cell death.

The Use of Enzyme Inhibitors in Drug Discovery: Current Strategies and Future Prospects

Abstract: Enzyme inhibitors are an important therapeutic agent in drug discovery, as they can be used to manipulate biochemical pathways to treat a wide range of diseases. Current strategies for enzyme inhibition involve the use of small molecule inhibitors, natural products, or peptide-based inhibitors. These inhibitors can be used to target and modulate the activity of enzymes, which in turn can affect the progression of a particular disease. The future of enzyme inhibitor-based drug discovery lies in the development of more selective and potent inhibitors, as well as the ability to target enzymes that are involved in multiple pathways. Additionally, there is significant potential for the use of enzyme inhibitors in combination with other therapeutic strategies, such as gene therapy. Finally, the development of novel computational strategies for the design and optimization of enzyme inhibitor-based drugs is an exciting area of research. Such strategies could lead to the discovery of new and more effective inhibitors, which would facilitate the development of improved treatments for a variety of diseases. Hence, this review focuses on some techniques for the discovery of enzyme inhibitors and their applications as various therapeutic agents.

Differential voluntary feed intake and whole transcriptome profiling in the hypothalamus of young sheep offered CP and phosphorus-deficient diets.

A reduction in voluntary feed intake is observed in ruminants consuming nutrient-deficient diets, such as those with a low CP or P content, and has been attributed to active metabolic regulation, rather than a physical constraint. The hypothalamus is the key integrator of feed intake regulation in mammals. The objectives of this experiment were to (1) establish a model of metabolic feed intake regulation in ruminants consuming diets of variable CP and P content, and (2) determine key biochemical pathways and influential points of regulation within the hypothalamus. Merino wethers [n=40; 23.7±1.4kg liveweight (mean±SD)] were fed one of five dietary treatments (n=8/treatment) for 63days in individual pens. The treatments included targeted combinations of high (H) and low (L) CP (110 and 55g/kg DM) and high and low P (2.5 and 0.7g/kg DM) with 9MJ metabolisable energy (ME) per kg DM which were fed ad libitum (UMEI; unrestricted ME intake) resulting in four experimental diets (HCP-HP-UMEI, LCP-HP-UMEI, HCP-LP-UMEI and LCP-LP-UMEI). An additional nutritional treatment (HCP-HP-RMEI) restricted intake of the HCP-HP diet to an equivalent ME intake of wethers consuming the LCP-LP-UMEI treatment. Wethers offered the LCP-HP-UMEI, HCP-LP-UMEI and LCP-LP-UMEI treatments consumed 42, 32 and 49% less total DM (P≤0.05), respectively than the HCP-HP-UMEI treatment, and this was not attributable to any physical limitation of the rumen. Plasma concentrations of urea nitrogen and inorganic phosphate indicated that these nutrient deficiencies were successfully established. To assess potential mechanisms, RNA-seq was conducted on samples from the arcuate nucleus (ARC), ventromedial hypothalamus and lateral hypothalamus of the wethers, yielding a total of 301, 8 and 148 differentially expressed genes across all pairwise comparisons, respectively. The expression of NPY, AGRP and CARTPT, known for their regulatory role in mammalian feed intake regulation, had a similar transcriptional response in the ARC of wethers consuming nutrient-deficient treatments and those consuming a ME-restricted treatment, despite these wethers expressing behaviours indicative of satiated and hungry states, respectively. In addition, genes involved with glycolysis (TPI1), the citric acid cycle (CS, OGDH, GLUD1, GOT1) and oxidative phosphorylation (COX5A, ATP5MC1, ATP5F1B, ATP5MC3) were downregulated in the ARC of wethers fed a nutrient deficient (LCP-LP-UMEI) relative to the non-deficient (HCP-HP-UMEI) treatment. In summary, a model for voluntary feed intake restriction was established to determine genome-wide molecular changes in the hypothalamus of young ruminants.

Metabolomic Signatures of Alzheimer's Disease Indicate Brain Region-Specific Neurodegenerative Progression.

Pathological mechanisms contributing to Alzheimer's disease (AD) are still elusive. Here, we identified the metabolic signatures of AD in human post-mortem brains. Using 1H NMR spectroscopy and an untargeted metabolomics approach, we identified (1) metabolomic profiles of AD and age-matched healthy subjects in post-mortem brain tissue, and (2) region-common and region-unique metabolome alterations and biochemical pathways across eight brain regions revealed that BA9 was the most affected. Phenylalanine and phosphorylcholine were mainly downregulated, suggesting altered neurotransmitter synthesis. N-acetylaspartate and GABA were upregulated in most regions, suggesting higher inhibitory activity in neural circuits. Other region-common metabolic pathways indicated impaired mitochondrial function and energy metabolism, while region-unique pathways indicated oxidative stress and altered immune responses. Importantly, AD caused metabolic changes in brain regions with less well-documented pathological alterations that suggest degenerative progression. The findings provide a new understanding of the biochemical mechanisms of AD and guide biomarker discovery for personalized risk prediction and diagnosis.

The oxidoreductase activity of Rnf balances redox cofactors during fermentation of glucose to propionate in Prevotella

Propionate is a microbial metabolite formed in the gastrointestinal tract, and it affects host physiology as a source of energy and signaling molecule. Despite the importance of propionate, the biochemical pathways responsible for its formation are not clear in all microbes. For the succinate pathway used during fermentation, a key enzyme appears to be missing—one that oxidizes ferredoxin and reduces NAD. Here we show that Rnf [ferredoxin—NAD+ oxidoreductase (Na+-transporting)] is this key enzyme in two abundant bacteria of the rumen (Prevotella brevis and Prevotella ruminicola). We found these bacteria form propionate, succinate, and acetate with the classic succinate pathway. Without ferredoxin:NAD+ oxidoreductase, redox cofactors would be unbalanced; it would produce almost equal excess amounts of reduced ferredoxin and oxidized NAD. By combining growth experiments, genomics, proteomics, and enzyme assays, we point to the possibility that these bacteria solve this problem by oxidizing ferredoxin and reducing NAD with Rnf [ferredoxin—NAD+ oxidoreductase (Na+-transporting)]. Genomic and phenotypic data suggest many bacteria may use Rnf similarly. This work shows the ferredoxin:NAD+ oxidoreductase activity of Rnf is important to propionate formation in Prevotella species and other bacteria from the environment, and it provides fundamental knowledge for manipulating fermentative propionate production.

An insight into the importance of B vitamins and melatonin in the prevention of diabetes through modulation of the brain energy metabolism- a comprehensive review

Energy metabolism is the biochemical pathway of converting macronutrients (carbohydrates, protein, and fat) to cellular energy for the maintenance of cell homeostasis. The brain is an organ that consumes unproportional energy compared to its size. Glucose (glycogen, in storage form of glucose) is the principal source of brain energy. Impairment in brain energy metabolism results in neuronal loss and subsequent neurodegenerative diseases including AD, PD, amyotrophic lateral sclerosis, Huntington’s disease, etc. However, metabolic disorders such as chronic hyperglycemia, and insulin resistance are also linked with neuronal activity. Dysregulation in neuronal transmission is associated with oxidative stress and brain insulin resistance. Diabetes mellitus jeopardizes brain function through various mechanisms including glucose toxicity, BBB damage, neuroinflammation, and gliosis. B vitamins as antioxidants and neuroprotective agents, can improve brain glucose metabolism. Melatonin is a potent free radical scavenger and it can also modulate cellular cytokine levels and prevent insulin resistance. The neuroprotective and antihyperglycemic effects of melatonin improve the brain's antioxidant defense system, decrease brain NOS activity, and prevent glucose toxicity. Hence this review suggests a therapeutic use of a combination of melatonin and  B vitamins to improve brain functioning disrupted by diabetes. 

Effect of strigolactone on growth, photosynthetic efficiency, antioxidant activity, and osmolytes accumulation in different maize (Zea mays L.) hybrids grown under drought stress

ABSTRACT Drought alters plant physiology, morphology, and biochemical pathways, necessitating effective mitigation strategies. Strigolactones (SLs) are phytohormones known to enhance plant growth under abiotic stress. However, their specific impact on drought stress in maize remains unclear. This study aimed to determine the optimal SL concentration for mitigating drought stress in two maize hybrids (HY-1898, FH-1046). Maize plants were subjected to 60% field capacity drought stress in a pot experiment. After 40 d, different concentrations (0, 0.001, 0.01, and 0.1 mg L−1) of the synthetic SL analogue GR24 were applied to evaluate their effects on growth features, photosynthesis attributes, and osmolyte accumulation in the maize hybrids. Results showed that exogenous SL application significantly increased photosynthetic pigments in maize hybrids under drought stress. Chlorophyll content, gas exchange characteristics, net CO2 assimilation rate, stomatal conductance, water use efficiency, and antioxidant activities were enhanced by GR24. Leaf ascorbic acid and total phenolics also increased with SL application. Organic osmolytes, such as glycine betaine and free proline, were elevated in both maize hybrids under drought stress. Yield-related parameters, including cob diameter, cob weight, number of seeds per cob, and number of seeds per plant, were significantly increased by GR24 under drought stress. Our findings highlight the potential of GR24 foliar application to mitigate drought stress and promote maize growth and grain yield in a concentration-dependent manner. The minimum effective SL concentration against drought stress was determined to be 0.01 mg L−1. Overall, foliar application of GR24 could serve as a sustainable approach for drought tolerance in agriculture.

Targeted quantitative metabolic profiling of brain-derived cell cultures by semi-automated MEPS and LC-MS/MS

The accurate characterisation of metabolic profiles is an important prerequisite to determine the rate and the efficiency of the metabolic pathways taking place in the cells. Changes in the balance of metabolites involved in vital processes such as glycolysis, tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), as well as in the biochemical pathways related to amino acids, lipids, nucleotides, and their precursors reflect the physiological condition of the cells and may contribute to the development of various human diseases. The feasible and reliable measurement of a wide array of metabolites and biomarkers possesses great potential to elucidate physiological and pathological mechanisms, aid preclinical drug development and highlight potential therapeutic targets. An effective, straightforward, sensitive, and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach was developed for the simultaneous quali-quantitative analysis of 41 compounds in both cell pellet and cell growth medium obtained from brain-derived cell cultures. Sample pretreatment miniaturisation was achieved thanks to the development and optimisation of an original extraction/purification approach based on digitally programmed microextraction by packed sorbent (eVol®-MEPS). MEPS allows satisfactory and reproducible clean-up and preconcentration of both low-volume homogenate cell pellet lysate and cell growth medium with advantages including, but not limited to, minimal sample handling and method sustainability in terms of sample, solvents, and energy consumption. The MEPS-LC-MS/MS method showed good sensitivity, selectivity, linearity, and precision. As a proof of concept, the developed method was successfully applied to the analysis of both cell pellet and cell growth medium obtained from a line of mouse immortalised oligodendrocyte precursor cells (OPCs; Oli-neu cell line), leading to the unambiguous determination of all the considered target analytes. This method is thus expected to be suitable for targeted, quantitative metabolic profiling in most brain cell models, thus allowing accurate investigations on the biochemical pathways that can be altered in central nervous system (CNS) neuropathologies, including e.g., mitochondrial respiration and glycolysis, or use of specific nutrients for growth and proliferation, or lipid, amino acid and nucleotide metabolism.

Pathomechanism of Pruritus in Psoriasis and Atopic Dermatitis: Novel Approaches, Similarities and Differences.

Pruritus is defined as an unpleasant sensation that elicits a desire to scratch. Nearly a third of the world's population may suffer from pruritus during their lifetime. This symptom is widely observed in numerous inflammatory skin diseases-e.g., approximately 70-90% of patients with psoriasis and almost every patient with atopic dermatitis suffer from pruritus. Although the pathogenesis of atopic dermatitis and psoriasis is different, the complex intricacies between several biochemical mediators, enzymes, and pathways seem to play a crucial role in both conditions. Despite the high prevalence of pruritus in the general population, the pathogenesis of this symptom in various conditions remains elusive. This review aims to summarize current knowledge about the pathogenesis of pruritus in psoriasis and atopic dermatitis. Each molecule involved in the pruritic pathway would merit a separate chapter or even an entire book, however, in the current review we have concentrated on some reports which we found crucial in the understanding of pruritus. However, the pathomechanism of pruritus is an extremely complex and intricate process. Moreover, many of these signaling pathways are currently undergoing detailed analysis or are still unexplained. As a result, it is currently difficult to take an objective view of how far we have come in elucidating the pathogenesis of pruritus in the described diseases. Nevertheless, considerable progress has been made in recent years.