Role In Metabolism Research Articles

Genome-Wide Transcriptome Profiling Reveals the Mechanisms Underlying Hepatic Metabolism under Different Raising Systems in Yak.

Yak meat is nutritionally superior to beef cattle but has a low fat content and is slow-growing. The liver plays a crucial role in lipid metabolism, and in order to determine whether different feeding modes affect lipid metabolism in yaks and how it is regulated, we employed RNA sequencing (RNA-seq) technology to analyze the genome-wide differential gene expression in the liver of yaks maintained under different raising systems. A total of 1663 differentially expressed genes (DEGs) were identified (|log2FC| ≥ 0 and p-value ≤ 0.05), including 698 down-regulated and 965 up-regulated genes. According to gene ontology (GO) and KEGG enrichment analyses, these DEGs were significantly enriched in 13 GO terms and 26 pathways (p < 0.05). Some DEGs were enriched in fatty acid degradation, PPAR, PI3K-Akt, and ECM receptor pathways, which are associated with lipid metabolism. A total of 16 genes are well known to be related to lipid metabolism (e.g., APOA1, FABP1, EHHADH, FADS2, SLC27A5, ACADM, CPT1B, ACOX2, HMGCS2, PLIN5, ACAA1, IGF1, FGFR4, ALDH9A1, ECHS1, LAMA2). A total of 11 of the above genes were significantly enriched in the PPAR signaling pathway. The reliability of the transcriptomic data was verified using qRT-PCR. Our findings provide new insights into the mechanisms regulating yak meat quality. It shows that fattening improves the expression of genes that regulate lipid deposition in yaks and enhances meat quality. This finding will contribute to a better understanding of the various factors that determine yak meat quality and help develop strategies to improve yield and quality.

Antagonism of let-7c reduces atherosclerosis and macrophage lipid accumulation by promoting PGC-1α/LXRα/ABCA1/G1 pathway

Changes in circulating let-7c were significantly associated with the alter in lipid profile, but its role in intracellular lipid metabolism remains unknown. This work was conducted to explore the effects of let-7c on the lipid accumulation in macrophages and uncover the underlying mechanism. Our results showed that let-7c inhibition relieved atherosclerosis progression in apoE-/- mice. In ox-LDL-treatment macrophages, let-7c knockdown suppressed lipid accumulation but does no affect cholesterol intake. Consistent with this, overexpression of let-7c promoted lipid accumulation by reducing the expression of LXRα and ABCA1/G1. Mechanistically, let-7c targeted PGC-1α to repress the expression of LXRα and ABCA1/G1, thereby regulating cholesterol homeostasis in macrophages. Taken together, these findings suggest that antagonism of let-7c reduces atherosclerosis and macrophage lipid accumulation through the PGC-1α/LXRα/ABCA1/G1 axis.

Pyridoxal kinase gene deletion leads to impaired growth, deranged redox metabolism and cell cycle arrest in Leishmania donovani

Pyridoxal kinase (PdxK) is a vitamin B6 salvage pathway enzyme which produces pyridoxal phosphate. We have investigated the impact of PdxK deletion in Leishmania donovani on parasite survivability, infectivity and cellular metabolism. LdPdxK mutants were generated by gene replacement strategy. All mutants showed significant reduction in growth in comparison to wild type. For PdxK mediated biochemical perturbations, only heterozygous mutants and complementation mutants were used as the growth of null mutants were compromised. Heterozygous mutant showed reduction invitro infectivity and higher cytosolic and mitochondrial ROS levels. Glutathione levels decreased significantly in heterozygous mutant indicating its involvement in cellular oxidative metabolism. Pyridoxal kinase gene deletion resulted in reduced ATP levels in parasites and arrest at G0/G1 phase of cell cycle. All these perturbations were rescued by PdxK gene complementation. This is the first report to confirm that LdPdxK plays an indispensable role in cell survival, pathogenicity, redox metabolism and cell cycle progression of L. donovani parasites. These results provide substantial evidence supporting PdxK as a therapeutic target for the development of specific antileishmanial drug candidates.

Anticancer Efficacy and Folic Acid Biosensing using poly (3, 4-ethylene dioxythiophene)- Cadmium oxide Composite Platform

Abstract Monitoring vitamins is essential as they play a significant role in human metabolisms. Folic acid (FA), one type of vitamin B, is responsible for various functions, including new red blood cells, synthesis, and repair of DNA. Therefore, the detection of FA is crucial. Here, we report poly (3, 4-ethylenedioxythiophene) (PEDOT) and cadmium oxide (CdO) (PEDOT-CdO) composite for the effective sensing of FA. The PEDOT nanospheres were prepared by the wet chemical method, and CdO nanorods were synthesized using the hydrothermal technique. The sulfur groups in PEDOT connected with Cd2+ ions in CdO nanoparticles enriched their electrostatic interaction developing a robust and straightforward electrochemical FA sensor. The as-prepared PEDOT-CdO biosensor exhibited good electrocatalytic activity towards selective determination of FA in the linear range of 40 nM-1 mM with a lower detection limit of 8.4 nM. In addition, the investigation of cytotoxic nature against human breast cancer cell lines (MCF-7) reveals that, the reported composite induces apoptotic cell death and can be used as an anticancer agent. The proposed biosensor can be used for device fabrication in sensor applications as well as a vector for targeted drug delivery for cancer cell diagnosis.

Harnessing AI and Gut Microbiome Research for Precision Health

The gut microbiome's impact on physiological processes, influenced by diet and lifestyle, is profound. Dysbiosis, an imbalance in microbiota composition, is associated with diseases like obesity. This review explores the gut microbiome's role in metabolism and calorie intake, alongside recent AI advancements impacting personalized nutrition. AI has revolutionized microbiome research, especially in multi-omics data analysis. AI-driven approaches enable the integration and interpretation of diverse omics datasets, including genomics, metabolomics, and proteomics, providing comprehensive insights into the gut microbiome's functional dynamics and its impact on host metabolism. These facilitate the identification of microbial biomarkers associated with disease states and dietary interventions, paving the way for personalized nutrition strategies tailored to individual gut microbiome profiles. AI platforms can also offer tailored dietary recommendations based on microbiome composition and health objectives. Healthcare professionals leverage AI to optimize dietary interventions, promoting gut microbiome modulation and preventing chronic diseases. Challenges like data standardization and privacy persist, yet addressing them is vital for maximizing AI's benefits in health outcomes and precision medicine. Ongoing AI and microbiome research promise to revolutionize personalized nutrition and metabolic health worldwide.

Kinetic 18F-FDG PET/CT imaging of hepatocellular carcinoma: a dual input four-compartment model.

The endoplasmic reticulum plays an important role in glucose metabolism and has not been explored in the kinetic estimation of hepatocellular carcinoma (HCC) via 18F-fluoro-2-deoxy-D-glucose PET/CT. A dual-input four-compartment (4C) model, regarding endoplasmic reticulum was preliminarily used for kinetic estimation to differentiate 28 tumours from background liver tissue from 24 patients with HCC. Moreover, parameter images of the 4C model were generated from one patient with negative findings on conventional metabolic PET/CT. Compared to the dual-input three-compartment (3C) model, the 4C model has better fitting quality, a close transport rate constant (K1) and a dephosphorylation rate constant (k6/k4), and a different removal rate constant (k2) and phosphorylation rate constant (k3) in HCC and background liver tissue. The K1, k2, k3, and hepatic arterial perfusion index (HPI) from the 4C model and k3, HPI, and volume fraction of blood (Vb) from the 3C model were significantly different between HCC and background liver tissues (all P < 0.05). Meanwhile, the 4C model yielded additional kinetic parameters for differentiating HCC. The diagnostic performance of the top ten genes from the most to least common was HPI(4C), Vb(3C), HPI(3C), SUVmax, k5(4C), k3(3C), k2(4C), v(4C), K1(4C) and Vb(4C). Moreover, a patient who showed negative findings on conventional metabolic PET/CT had positive parameter images in the 4C model. The 4C model with the endoplasmic reticulum performed better than the 3C model and produced additional useful parameters in kinetic estimation for differentiating HCC from background liver tissue.

Structure of cardiac rhythm disorders in patients with obesity and associated with it dyslipidemia as an arrhythmogenic factor

Obesity is a global public health problem in the twenty-first century. The most adverse it’s effects are associated with visceral type, with accumulation of epicardial fat, showing high metabolic activity, dysfunction and important role in the development of lipotoxic cardiomyopathy linked with significant morphological and functional myocardial changes, accompanying by high risk of heart rhythm disorders. The aim of the study: to identify structure (frequency and character) of cardiac arrhythmias in men of employable age with visceral obesity, to establish the relationship of arrhythmias with features of the blood lipid spectrum of these patients. Material and methods. 98 men with abdominal obesity and 46 overweight patients were examined. The control group consisted of 40 healthy patients with normal body weight. All the patients were undergone ECG monitoring, echocardiography and analysis of serum lipid levels. Results. The presence of obesity is statistically significantly associated with the risk of supraventricular couplets, frequent ventricular extrasystoles, sinus arrhythmia and atrial fibrillation. The increase in the severity of obesity was accompanied by a tendency to a greater frequency of arrhythmias: in obesity of I degree, the frequency of atrial fibrillation was 12.3%, II–III degree — 21.2%, p = 0.25; frequent ventricular extrasystoles with similar degrees of obesity — 13.8% and 21.1%, respectively. Atrial fibrillation was significantly more often detected against the background of lipid disorders, mainly with a decrease in HDLP. Conclusion. The main type of heart rhythm disturbance in patients with obesity are supraventricular arrhythmias, mainly atrial fibrillation, the frequency of which increases in proportion to the increase in the patient's body weight. Abdominal obesity leads to an increase in ventricular ectopic activity. Dyslipidemia is the one of risk factors for arrhythmias in these patients.

Effect of riboflavin on redox balance, osmolyte accumulation, methylglyoxal generation and nutrient acquisition in indian squash (Praecitrullus fistulosus L.) under chromium toxicity.

The presence of high chromium (Cr) levels induces the buildup of reactive oxygen species (ROS), resulting in hindered plant development. Riboflavin (vitamin B2) is produced by plants, fungi, and microbes. It serves as a precursor to the coenzymes flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), which play a crucial role in cellular metabolism. The objective of this work was to clarify the underlying mechanisms by which riboflavin alleviates Cr stress in Praecitrullus fistulosus L. Further, the role of riboflavin in growth, ions homeostasis, methylglyoxal detoxification, and antioxidant defense mechanism are not well documented in plants under Cr toxicity. We found greater biomass and minimal production of ROS in plants pretreated with riboflavin under Cr stress. Results manifested a clear abridge in growth, chlorophyll content, and nutrient uptake in Indian squash plants exposed to Cr stress. Findings displayed that Cr stress visibly enhanced oxidative injury reflected as higher malondialdehyde (MDA), hydrogen peroxide (H2O2), superoxide radical (O2•‒), methylglyoxal (MG) levels alongside vivid lipoxygenase activity. Riboflavin strengthened antioxidant system, enhanced osmolyte production and improved membrane integrity. Riboflavin diminished Cr accumulation in aerial parts that led to improved nutrient acquisition. Taken together, riboflavin abridged Cr phytotoxic effects by improving redox balance because plants treated with riboflavin had strong antioxidant system that carried out effective ROS detoxification. Riboflavin protected membrane integrity that, in turn, improved nutrient uptake in plants.

Probiotics as modulators of gut-brain axis for cognitive development.

Various microbial communities reside in the gastrointestinal tract of humans and play an important role in immunity, digestion, drug metabolism, intestinal integrity, and protection from pathogens. Recent studies have revealed that the gut microbiota (GM) is involved in communication with the brain, through a bidirectional communication network known as the gut-brain axis. This communication involves humoral, immunological, endocrine, and neural pathways. Gut dysbiosis negatively impacts these communication pathways, leading to neurological complications and cognitive deficits. Both pre-clinical and clinical studies have demonstrated that probiotics can restore healthy GM, reduce intestinal pH, and reduce inflammation and pathogenic microbes in the gut. Additionally, probiotics improve cell-to-cell signaling and increase blood-brain-derived neurotrophic factors. Probiotics emerge as a potential approach for preventing and managing neurological complications and cognitive deficits. Despite these promising findings, the safety concerns and possible risks of probiotic usage must be closely monitored and addressed. This review article provides a brief overview of the role and significance of probiotics in cognitive health.

Investigating inhibitors of 1-deoxy-d-xylulose 5-phosphate synthase in a mouse model of UTI.

The rising rate of antimicrobial resistance continues to threaten global public health. Further hastening antimicrobial resistance is the lack of new antibiotics against new targets. The bacterial enzyme, 1-deoxy-d-xylulose 5-phosphate synthase (DXPS), is thought to play important roles in central metabolism, including processes required for pathogen adaptation to fluctuating host environments. Thus, impairing DXPS function represents a possible new antibacterial strategy. We previously investigated a DXPS-dependent metabolic adaptation as a potential target in uropathogenic Escherichia coli (UPEC) associated with urinary tract infection (UTI), using the DXPS-selective inhibitor butyl acetylphosphonate (BAP). However, investigations of DXPS inhibitors in vivo have not been conducted. The goal of the present study is to advance DXPS inhibitors as in vivo probes and assess the potential of inhibiting DXPS as a strategy to prevent UTI in vivo. We show that BAP was well-tolerated at high doses in mice and displayed a favorable pharmacokinetic profile for studies in a mouse model of UTI. Further, an alkyl acetylphosphonate prodrug (homopropargyl acetylphosphonate, pro-hpAP) was significantly more potent against UPEC in urine culture and exhibited good exposure in the urinary tract after systemic dosing. Prophylactic treatment with either BAP or pro-hpAP led to a partial protective effect against UTI, with the prodrug displaying improved efficacy compared to BAP. Overall, our results highlight the potential for DXPS inhibitors as in vivo probes and establish preliminary evidence that inhibiting DXPS impairs UPEC colonization in a mouse model of UTI.IMPORTANCENew antibiotics against new targets are needed to prevent an antimicrobial resistance crisis. Unfortunately, antibiotic discovery has slowed, and many newly FDA-approved antibiotics do not inhibit new targets. Alkyl acetylphosphonates (alkyl APs), which inhibit the enzyme 1-deoxy-d-xylulose 5-phosphate synthase (DXPS), represent a new possible class of compounds as there are no FDA-approved DXPS inhibitors. To our knowledge, this is the first study demonstrating the in vivo safety, pharmacokinetics, and efficacy of alkyl APs in a urinary tract infection mouse model.

Oleic acid-PPARγ-FABP4 loop fuels cholangiocarcinoma colonization in lymph node metastases microenvironment.

Lymph node metastasis is a significant risk factor for patients with cholangiocarcinoma, but the mechanisms underlying cholangiocarcinoma colonization in the lymph node microenvironment remain unclear. We aimed to determine whether metabolic reprogramming fueled the adaptation and remodeling of cholangiocarcinoma cells to the lymph node microenvironment. Here, we applied single-cell RNA sequencing of primary tumor lesions and paired lymph node metastases from patients with cholangiocarcinoma and revealed significantly reduced intertumor heterogeneity and syntropic lipid metabolic reprogramming of cholangiocarcinoma after metastasis to lymph nodes, which was verified by pan-cancer single-cell RNA sequencing analysis, highlighting the essential role of lipid metabolism in tumor colonization in lymph nodes. Metabolomics and in vivo CRISPR/Cas9 screening identified PPARγ as a crucial regulator in fueling cholangiocarcinoma colonization in lymph nodes through the oleic acid-PPARγ-fatty acid-binding protein 4 positive feedback loop by upregulating fatty acid uptake and oxidation. Patient-derived organoids and animal models have demonstrated that blocking this loop impairs cholangiocarcinoma proliferation and colonization in the lymph node microenvironment and is superior to systemic inhibition of fatty acid oxidation. PPARγ-regulated fatty acid metabolic reprogramming in cholangiocarcinoma also contributes to the immune-suppressive niche in lymph node metastases by producing kynurenine and was found to be associated with tumor relapse, immune-suppressive lymph node microenvironment, and poor immune checkpoint blockade response. Our results reveal the role of the oleic acid-PPARγ-fatty acid-binding protein 4 loop in fueling cholangiocarcinoma colonization in lymph nodes and demonstrate that PPARγ-regulated lipid metabolic reprogramming is a promising therapeutic target for relieving cholangiocarcinoma lymph node metastasis burden and reducing further progression.

The Relationship between Iron Markers, Cortisol and Insulin Resistance in Gestational Diabetes Mellitus

Background: Gestational diabetes mellitus (GDM) is a significant metabolic disorder occurring during pregnancy, associated with serious maternal and fetal complications if left untreated. The global prevalence of GDM emphasizes the urgent need for research into its pathogenesis and contributing factors, including hormonal changes, insulin resistance, and the role of iron metabolism. Objective: The aim of this study was to investigate the relationship between iron markers (hemoglobin, serum iron, and serum ferritin), cortisol, insulin resistance (measured by HOMA-IR), and the development of GDM in pregnant women between 24 and 28 weeks of gestation. Methods: This analytical cross-sectional study included 150 pregnant women, divided into GDM and non-GDM groups based on oral glucose tolerance test results. Iron markers, cortisol, fasting plasma glucose, insulin, and HOMA-IR levels were measured. Data analysis was performed using SPSS version 25, employing descriptive and inferential statistics, including the Mann-Whitney U test for non-normally distributed variables. Results: Women with GDM exhibited significantly higher mean levels of hemoglobin (12.41±0.68 g/dl), serum iron (19.57±1.14 μmol/L), serum ferritin (25.92±2.58 ng/ml), cortisol (451.32±25.20 nmol/L), fasting plasma glucose (6.83±0.46 mmol/L), insulin (12.50±1.72 μU/mL), and HOMA-IR (3.83±0.78) compared to non-GDM participants (p&lt;0.001 for all comparisons). These findings underscore the pronounced biochemical and hormonal alterations associated with GDM. Conclusion: The study identified a significant association between elevated levels of iron markers, cortisol, and insulin resistance with the development of GDM. These findings suggest that monitoring these parameters during pregnancy could be crucial for the early detection and management of GDM. Individualized iron supplementation strategies may be necessary to prevent iron overload and minimize GDM risk.

Impact of different forms of the intestinum cecum microbiome of broiler chickens

The effect of trace elements on intestinal microflora of the intestinum cecum of broiler chickens was studied. One of the causes of reduced intestinal digestive function in birds is the overgrowth of microbial flora in the intestinal lumen, resulting in decreased chyme advancement and premature deconjugation of primary bile acids. Excess microbial flora can cause damage to the small intestinal epithelium because the metabolites of some microorganisms are cytotoxic. Determination of the number of microorganisms in the intestinum cecum of broilers is an important step in monitoring the viability of the organism. The intestinal microbiota is the largest and most complex microecosystem of animals. Microflora is not only involved in various metabolic pathways to regulate metabolism, but also plays an important role as an intermediary between food and host. Gut microbiota diversity and avian body health influence and shape each other, and the gut microbiota maintains a relatively balanced state with the host under sustained environmental regulation. The gut microbiota plays an important regulatory role in nutrient metabolism and immune defense. The paper presents a study of the effect of different forms of chromium (Cr): chloride (CrCl3), ultrafine particles (UFP Cr) and picolinate (CrPic) on the intestinal microflora of the intestinum cecum of broiler chickens. In the group receiving CrPic with the diet, the genus Bacteroides occupied more than 50%, which is more than half of the total abundance of this taxon, the number of Clostridium XlVb was much less abundant at 0.6%. Collectively, the present study characterized the dynamic changes in the microbial community of the intestinum cecum of broiler chickens under exposure to different forms of Cr. The addition of CrPic to the diet of broiler chickens significantly affected the microbial diversity of the intestinum cecum and caused changes in the microbial community characterized by an increase in the phylum Bacteroidetes, where Bacteroides species was the main one.

Microbial Ecology of Granular Biofilm Technologies for Wastewater Treatment: A Review.

Nowadays, the discharge of wastewater is a global concern due to the damage caused to human and environmental health. Wastewater treatment has progressed to provide environmentally and economically sustainable technologies. The biological treatment of wastewater is one of the fundamental bases of this field, and the employment of new technologies based on granular biofilm systems is demonstrating success in tackling the environmental issues derived from the discharge of wastewater. The granular-conforming microorganisms must be evaluated as functional entities because their activities and functions for removing pollutants are interconnected with the surrounding microbiota. The deep knowledge of microbial communities allows for the improvement in system operation, as the proliferation of microorganisms in charge of metabolic roles could be modified by adjustments to operational conditions. This is why engineering must consider the intrinsic microbiological aspects of biological wastewater treatment systems to obtain the most effective performance. This review provides an extensive view of the microbial ecology of biological wastewater treatment technologies based on granular biofilms for mitigating water pollution.

Role of the Intestine and Its Gut Microbiota in Metabolic Syndrome and Obesity.

The metabolic syndrome (MetSyn) is currently one of the biggest global health challenges because of its impact on public health. MetSyn includes the cluster of metabolic disorders including obesity, high blood pressure, hyperglycemia, high triglyceride levels, and hepatic steatosis. Together, these abnormalities increase the cardiovascular risk of individuals and pose a threat to healthcare systems worldwide. To better understand and address this complex issue, recent research has been increasingly focusing on unraveling the delicate interplay between metabolic disorders and the intestines and more specifically our gut microbiome. The gut microbiome entails all microorganisms inhabiting the gastrointestinal tract and plays a pivotal role in metabolic processes and overall health of its host. Emerging evidence proves an association between the gut microbiome composition and aspects of MetSyn, such as obesity. Understanding these relationships is crucial because they offer valuable insights into the mechanisms underlying development and progression of metabolic disorders and possible treatment options. Yet, how should we interpret this relationship? This review focuses on the interplay between the gut and MetSyn. In addition, we have reviewed the existing evidence of the gut microbiome and its association with and impact on metabolic disorders, in an attempt to understand the complex interactions and nature of this association. We also explored potential therapeutic options targeting the gut to modify metabolic disorders and obesity.

Is it now appropriate to assert that creatine supplementation holds cognitive benefits for the elderly?

This paper explores the potential cognitive benefits of creatine supplementation for the elderly population. Creatine, known for its role in muscular and neuronal energy metabolism, is primarily obtained through dietary intake, particularly from meat sources. The literature underscores creatine's significance in neural tissue development and cognitive capacity, with deficiencies linked to impaired cognitive function, especially in infants. In the context of the aging global population, cognitive decline is a prevalent concern, and reduced creatine concentration is implicated in this process. While association studies suggest a connection between creatine intake and cognitive performance in the elderly, the absence of robust clinical trials calls for further investigation. Physiological plausibility supports the idea that increased creatine intake, combined with physical activities, could positively impact cognition in the elderly. However, the existing evidence remains inconclusive, and rigorous randomized placebo-controlled clinical trials are essential to establish a cause-and-effect relationship and elucidate underlying mechanisms. Confirmation of cognitive benefits could pave the way for determining optimal dosages to enhance cognitive function in the elderly.

Primary Human M2 Macrophage Subtypes Are Distinguishable by Aqueous Metabolite Profiles.

The complexity of macrophage (MΦ) plasticity and polarization states, which include classically activated pro-inflammatory (M1) and alternatively activated anti-inflammatory (M2) MΦ phenotypes, is becoming increasingly appreciated. Within the M2 MΦ polarization state, M2a, M2b, M2c, and M2d MΦ subcategories have been defined based on their expression of specific cell surface receptors, secreted cytokines, and specialized immune effector functions. The importance of immunometabolic networks in mediating the function and regulation of MΦ immune responses is also being increasingly recognized, although the exact mechanisms and extent of metabolic modulation of MΦ subtype phenotypes and functions remain incompletely understood. In this study, proton (1H) nuclear magnetic resonance (NMR) metabolomics was employed to determine the polar metabolomes of M2 MΦ subtypes and to investigate the relationship between aqueous metabolite profiles and M2 MΦ functional phenotypes. Results from this study demonstrate that M2a MΦs are most distinct from M2b, M2c, and M2d MΦ subtypes, and that M2b MΦs display several metabolic traits associated with an M1-like MΦ phenotype. The significance of metabolome differences for metabolites implicated in glycolysis, the tricarboxylic acid (TCA) cycle, phospholipid metabolism, and creatine-phosphocreatine cycling is discussed. Altogether, this study provides biochemical insights into the role of metabolism in mediating the specialized effector functions of distinct M2 MΦ subtypes and supports the concept of a continuum of macrophage activation states rather than two well-separated and functionally distinct M1/M2 MΦ classes, as originally proposed within a classical M1/M2 MΦ framework.

Quantitative MRI Evaluation of Ferritin Overexpression in Non-Small-Cell Lung Cancer.

Cancer cells frequently present elevated intracellular iron levels, which are thought to facilitate an enhanced proliferative capacity. Targeting iron metabolism within cancer cells presents an avenue to enhance therapeutic responses, necessitating the use of non-invasive models to modulate iron manipulation to predict responses. Moreover, the ubiquitous nature of iron necessitates the development of unique, non-invasive markers of metabolic disruptions to develop more personalized approaches and enhance the clinical utility of these approaches. Ferritin, an iron storage enzyme that is often upregulated as a response to iron accumulation, plays a central role in iron metabolism and has been frequently associated with unfavorable clinical outcomes in cancer. Herein, we demonstrate the successful utility, validation, and functionality of a doxycycline-inducible ferritin heavy chain (FtH) overexpression model in H1299T non-small-cell lung cancer (NSCLC) cells. Treatment with doxycycline increased the protein expression of FtH with a corresponding decrease in labile iron in vitro and in vivo, as determined by calcein-AM staining and EPR, respectively. Moreover, a subsequent increase in TfR expression was observed. Furthermore, T2* MR mapping effectively detected FtH expression in our in vivo model. These results demonstrate that T2* relaxation times can be used to monitor changes in FtH expression in tumors with bidirectional correlations depending on the model system. Overall, this study describes the development of an FtH overexpression NSCLC model and its correlation with T2* mapping for potential use in patients to interrogate iron metabolic alterations and predict clinical outcomes.

Collaborative Metabolism: Gut Microbes Play a Key Role in Canine and Feline Bile Acid Metabolism.

Bile acids, produced by the liver and secreted into the gastrointestinal tract, are dynamic molecules capable of impacting the overall health of dogs and cats in many contexts. Importantly, the gut microbiota metabolizes host primary bile acids into chemically distinct secondary bile acids. This review explores the emergence of new literature connecting microbial-derived bile acid metabolism to canine and feline health and disease. Moreover, this review highlights multi-omic methodologies for translational research as an area for continued growth in veterinary medicine aimed at accelerating microbiome science and medicine as it pertains to bile acid metabolism in dogs and cats.

The impact of some metals, molecular docking and molecular dynamic calculations on glucose 6-phosphate dehydrogenase activity in Capoeta trutta (Heckel, 1843) tissue

The first enzyme of the pentose phosphate metabolic pathway is glucose 6-phosphate dehydrogenase (d-glucose-6-phosphate: NADP + oxidoreductase EC1.1.1.49; G6PD). G6PD has essential functions such as membrane lipid synthesis, ribose 5-phosphate, and NADPH production. In this study, the G6PD enzyme was purified from kidney, liver, and gill tissues of Capoeta trutta, one of the dominant fish species in the Euphrates-Tigris River System, and the in vitro effects of some metals (Ag+, Cd2+, Cu2+, Fe2+, Ni2+, Pb2+ and Zn2+) on the enzyme activity were investigated. For this purpose, firstly, the G6PD enzyme was purified from tissues using a 2′, 5′-ADP Sepharose 4B affinity column. The purity of the enzyme was checked by the SDS-PAGE method and a single band was seen in the gel. After the purity of the enzyme was determined, the effects of metals on the enzyme activity were determined using the spectrophotometric method. As a result of the study, it was determined that the Ag+ ion was the most potent inhibitor for C. trutta gill, kidney, and liver G6PD enzymes. Lastly, calculations were made to examine the activity of the glucose 6-phosphate dehydrogenase molecule against the G6PD enzymes. Afterwards, the interaction of the glucose 6-phosphate dehydrogenase molecule with the protein (PDB ID: 5JYU and 2BH9) with the highest activity was calculated in the range of 0–100 ns. Finally, ADME/T calculation was made to predict the effects and reactions of glucose 6-phosphate dehydrogenase molecule in human metabolism. This study explores the physiological functions and environmental sensitivities of G6PD in a dominant fish species, while also investigating its potential interactions and metabolic roles in humans. Understanding these aspects can contribute to environmental monitoring, fish health management, and even pharmaceutical development.