Regulation Of Metabolism Research Articles

Metabolic regulation of the immune system in health and diseases: mechanisms and interventions.

Metabolism, including glycolysis, oxidative phosphorylation, fatty acid oxidation, and other metabolic pathways, impacts the phenotypes and functions of immune cells. The metabolic regulation of the immune system is important in the pathogenesis and progression of numerous diseases, such as cancers, autoimmune diseases and metabolic diseases. The concept of immunometabolism was introduced over a decade ago to elucidate the intricate interplay between metabolism and immunity. The definition of immunometabolism has expanded from chronic low-grade inflammation in metabolic diseases to metabolic reprogramming of immune cells in various diseases. With immunometabolism being proposed and developed, the metabolic regulation of the immune system can be gradually summarized and becomes more and more clearer. In the context of many diseases including cancer, autoimmune diseases, metabolic diseases, and many other disease, metabolic reprogramming occurs in immune cells inducing proinflammatory or anti-inflammatory effects. The phenotypic and functional changes of immune cells caused by metabolic regulation further affect and development of diseases. Based on experimental results, targeting cellular metabolism of immune cells becomes a promising therapy. In this review, we focus on immune cells to introduce their metabolic pathways and metabolic reprogramming, and summarize how these metabolic pathways affect immune effects in the context of diseases. We thoroughly explore targets and treatments based on immunometabolism in existing studies. The challenges of translating experimental results into clinical applications in the field of immunometabolism are also summarized. We believe that a better understanding of immune regulation in health and diseases will improve the management of most diseases.

Sestrin 2 as a new biomarker in obesity and diabetes mellitus: A new key player in the metabolic regulation

Sestrin 2 as a new biomarker in obesity and diabetes mellitus: A new key player in the metabolic regulation

Efficient conversion of hemicellulose into high-value product and electric power by enzyme-engineered bacterial consortia

As an abundant agricultural and forestry biomass resource, hemicelluloses are hard to be effectively degraded and utilized by microorganisms due to the constraints of membrane and metabolic regulations. Herein, we report a synthetic extracellular metabolic pathway with hemicellulose-degrading-enzymes controllably displayed on Escherichia coli surface as engineered bacterial consortia members for efficient utilization of xylan, the most abundant component in hemicellulose. Further, we develop a hemicellulose/O2 microbial fuel cell (MFC) configuring of enzyme-engineered bacterial consortia based bioanode and bacterial-displayed laccase based biocathode. The optimized MFC exhibited an open-circuit voltage of 0.71 V and a maximum power density (Pmax) of 174.33 ± 4.56 µW cm−2. Meanwhile, 46.6% (w/w) α-ketoglutarate was produced in this hemicellulose fed-MFC. Besides, the MFC retained over 95% of the Pmax during 6 days’ operation. Therefore, this work establishes an effective and sustainable one-pot process for catalyzing renewable biomass into high-value products and electricity in an environmentally-friendly way.

Exploring serum bile acids as potential noninvasive biomarkers for nonalcoholic fatty liver disease

BackgroundBile acids are vital regulators of liver metabolism, and their dysregulation is closely linked with the progression of nonalcoholic fatty liver disease (NAFLD). Profiling these bile acids may provide valuable diagnostic and prognostic markers for these conditions. This study aimed to evaluate bile acid profiles in NAFLD patients and assess their potential as biomarkers for diagnosing and predicting disease progression. Serum levels of 14 bile acids were measured in 25 normal healthy controls (NHC), 35patients with metabolic dysfunction–associated steatotic liver disease (MASLD), and 40 patients with NASH, categorized by the NAFLD Activity Score (NAS). Quantification was performed using high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS).ResultsPrimary unconjugated bile acids, CA and CDCA, along with conjugated acids GCA, GCDCA, TCA, and TCDCA, were significantly elevated in both MASLD and NASH compared to NHC (all p < 0.05). While levels increased progressively from NHC to MASLD to NASH, no significant differences were observed between MASLD and NASH except for GCA and TCA (P < 0.05). Similarly, secondary bile acids LCA, TLCA, GUDCA, and TUDCA were higher in MASLD and NASH compared to NHC (all p < 0.05).Logistic regression identified CA (odds ratio = 2.05, p = 0.02), CDCA (odds ratio = 1.58, p = 0.04), GCA (odds ratio = 1.92, p = 0.03) and DCA (odds ratio = 2.06, p = 0.04) as significant predictors of fibrosis. For active inflammation, GCA (odds ratio = 2.04, p = 0.04), and TCA (odds ratio = 1.94, p = 0.04) were significant predictors. In steatosis, CA, CDCA, GCA, DCA, TDCA, TLCA, and UDCA were notable predictors, with high odds ratios.ConclusionThe study highlights significant alterations in bile acid profiles associated with NAFLD progression. Specific bile acids, such as CA, GCA, TCA, and TCDCA are strong predictors of disease severity, indicating their potential as biomarkers for NAFLD treatment and prognosis.

Fibroblast growth factor 1 (FGF1) improves glucose homeostasis, modulates gut microbial composition, and reduces inflammatory responses in rainbow trout (Oncorhynchus mykiss) fed a high-fat diet

High-fat diets (HFDs) are widely used in aquaculture due to their lipid and protein-conserving effects, thereby reducing feed costs. However, prolonged feeding of HFD often leads to metabolic disorders in fish, such as disruption of hepatic lipid homeostasis, liver injury, and disruption of glucose homeostasis. Fibroblast growth factor 1 (FGF1) plays an essential role in controlling glucose levels in the body and dampening immune reactions. However, its impact on teleosts remains poorly researched. The therapeutic potential of recombinant FGF1 (rFGF1) was examined in a 6-week culture experiment involving rainbow trout (Oncorhynchus mykiss) that were fed an HFD. The results revealed that rFGF1 significantly reduced serum glucose levels and hepatic PEPCK and G6PC activities, but improved hepatic glycogen (P < 0.05), compared to the HFD + PBS group. Further experiments indicated that the inhibitory effect of rFGF1 on hepatic gluconeogenesis was mediated by the cAMP signaling pathway and was dependent on the high expression of PDE4D. In addition, rFGF1 increased hepatic glycogen content, which involves the AKT-GSK3β axis. Despite this increase, rFGF1 did not lead to glycogen storage disease, as shown by reduced hepatic inflammation as a result of decreased GOT (glutamic oxaloacetic transaminase), GPT (glutamic pyruvic transaminase), and elevated SOD (superoxide dismutase) in the rFGF1-treated group, accompanied by decreased il-1β, il-6, and xbp-1, and elevated nrf2 and number of hepatocyte autophagosomes. Alterations in gut microbes and short-chain fatty acids (SCFAs) were noted, indicating that rFGF1 caused a notable rise in intestinal Lactobacillus, acetic acid, and butyric acid levels. This study investigated the molecular mechanisms of rFGF1 on glucose metabolism and inflammatory responses in an HFD-fed rainbow trout model, providing new insights to improve the regulation of glucose metabolism in carnivorous fish.

Potential Anti-Obesity Effect of Hazel Leaf Extract in Mice and Network Pharmacology of Selected Polyphenols

Background: Obesity is gradually becoming a widespread health problem, and treatment using natural compounds has seen an increasing trend. As a by-product of hazelnut, hazel leaf is usually disposed of as waste, but it is widely used in traditional and folk medicines around the world. Aim of this study: Based on previous studies, the effects of the regulation of lipid metabolism and the mechanism of hazel leaf polyphenol extraction obesity were investigated. Methods: In this study, a high-fat diet-fed mouse model of obesity and 3T3-L1 preadipocytes were established. The ameliorative effects of the hazel leaf polyphenol extract on obesity and the regulating lipid metabolisms were explored based on network pharmacology, gut microbiota, and molecular docking. Results: Network pharmacology showed that hazel leaf polyphenols may play a role by targeting key targets, including PPARγ, and regulating the PPAR signaling pathway. They significantly improved body weight gain, the liver index, and adiposity and lipid levels; regulated the gut microbiota and short-chain fatty acid contents; down-regulated the expression of lipid synthesis proteins SREBP1c, PPARγ, and C/EBP-α; and up-regulated the expression of p-AMPK in obese mice. They inhibited the differentiation of 3T3-L1 cells, and the expression of related proteins is consistent with the results in vivo. The molecular docking results indicated that gallic acid, quercetin-3-O-beta-D-glucopyranoside, quercetin, myricetin, and luteolin-7-O-glucoside in the hazel leaf polyphenol extract had strong binding activities with PPARγ, C/EBP-α, and AMPK. Conclusions: The results demonstrate that the hazel leaf polyphenol extract can improve obesity by regulating lipid metabolism, which provides a valuable basis for developing health products made from hazel leaf polyphenols in the future.

Growth and metabolism regulation of cinnamic acid and its derivatives to Auxenochlorella pyrenoidosa

Auxenochlorella pyrenoidosa's industrial utility is closely associated with the concentration of high-value products. This study focuses on the effects of cinnamic acid (CA) and its derivatives, which known as secondary metabolites in higher plants and effective plant growth regulators, on the growth and metabolic profiles of A. pyrenoidosa. It was discovered that CA and its derivatives significantly enhance the biomass of A. pyrenoidosa under conditions of 10 mg/L over 48 h or 100 mg/L over 120 h. Cells treated with 10 mg/L CA exhibited lower oxidative stress and maintained robust metabolic activity. Metabolic pathways, including those for carbohydrates, lipids, small peptides, and cofactors, were stimulated, leading to the accumulation of a wide array of bio-products, notably high-value products such as α-linolenic acid, cis-4,7,10,13,16,19-docosahexaenoic acid (DHA), nicotinamide adenine dinucleotide plus hydrogen (NADH), glutathione, and vitamins B2/B3. This study demonstrates that CA and its derivatives are good nutritional enhancers for cultivating A. pyrenoidosa, highlighting their potential for broad application in biotechnological industries.

Leonurine Inhibits Hepatic Lipid Synthesis to Ameliorate NAFLD via the ADRA1a/AMPK/SCD1 Axis.

Leonurine is a natural product unique to the Lamiaceae plant Leonurus japonicus Houtt., and it has attracted attention due to its anti-oxidative stress, anti-apoptosis, anti-fibrosis, and metabolic regulation properties. Also, it plays an important role in the prevention and treatment of nonalcoholic fatty liver disease (NAFLD) through a variety of biological mechanisms, but its mechanism of action remains to be elucidated. Therefore, this study aims to preliminarily explore the mechanisms of action of leonurine in NAFLD. Mice were randomly divided into four groups: the normal control (NC) group, the Model (M) group, the leonurine treatment (LH) group, and the fenofibrate treatment (FB) group. The NAFLD model was induced by a high-fat high-sugar diet (HFHSD) for 12 weeks, and liver pathological changes and biochemical indices were observed after 12 weeks. Transcriptomic analysis results indicated that leonurine intervention reversed the high-fat high-sugar diet-induced changes in lipid metabolism-related genes such as stearoyl-CoA desaturase 1 (Scd1), Spermine Synthase (Sms), AP-1 Transcription Factor Subunit (Fos), Oxysterol Binding Protein Like 5 (Osbpl5), and FK506 binding protein 5 (Fkbp5) in liver tissues. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results suggest that leonurine may exert its lipid-lowering effects through the AMP-activated protein kinase (AMPK) signaling pathway. Liver lipidomic analysis showed that leonurine could alter the abundance of lipid molecules related to fatty acyl (FAs) and glycerophospholipids (GPs) such as TxB3, carnitine C12-OH, carnitine C18:1-OH, and LPC (20:3/0:0). Molecular biology experiments and molecular docking techniques verified that leonurine might improve hepatic lipid metabolism through the alpha-1A adrenergic receptor (ADRA1a)/AMPK/SCD1 axis. In summary, the present study explored the mechanism by which leonurine ameliorated NAFLD by inhibiting hepatic lipid synthesis via the ADRA1a/AMPK/SCD1 axis.

Selective-Integrative Technology for the Separation of Colostrum Into Components and the Possibilities of Obtaining Protein Substances From Different Sources

Background. Obtaining biologically active natural compounds involved in the regulation of metabolism is an important goal in biotechnology. Colostrum is a unique natural source of various biologically active compounds. However, the extremely high natural variability of colostrum composition does not meet the existing requirements for standardization in pharmaceutical preparations. Objective. To develop a method for separating colostrum into its basic components (lipids, casein, and protein fractions), thereby reducing the variability of whole colostrum composition, obtaining several target products, and demonstrating the possibility of acquiring new protein substances from different sources. Methods. Colostrum separation was carried out through centrifugation and membrane filtration. Plant proteins (sunflower) and milk proteins were used to obtain protein substances from different sources. The composition of proteins, carbohydrates, and nucleic acids was determined using mass spectrometry, centrifugation, and membrane filtration. Results. The proposed method for obtaining basic substances from colostrum significantly reduced the vari­ability in composition compared to whole colostrum. The efficiency of protein sedimentation in concentrated protein solutions by centrifugation and ultrafiltration was shown to depend on protein concentration. Additionally, the formation of non-specific protein aggregates in the centrifugal field allowed the extraction of protein substances from various natural sources, which is relevant for functional nutrition. Conclusions. The proposed selective-integrative technology for obtaining different substances from colostrum significantly reduces the high variability of whole colostrum composition. It increases the efficiency of component separation into lipid, casein fractions, low molecular weight protein fractions, and ultrafiltrate, while also enabling the acquisition of protein substances from diverse sources.

Unraveling the role of long non-coding RNAs in chronic heat stress-induced muscle injury in broilers

BackgroundChronic heat stress (CHS) is a detrimental environmental stressor with a negative impact on the meat quality of broilers. However, the underlying mechanisms are not fully understood. This study investigates the effects of CHS on long non-coding RNA (lncRNA) expression and muscle injury in broilers, with a focus on its implications for meat quality.ResultsThe results showed that CHS diminished breast muscle yield, elevated abdominal fat deposition, induced cellular apoptosis (P < 0.05), and caused myofibrosis. Transcriptomic analysis revealed 151 differentially expressed (DE) lncRNAs when comparing the normal control (NC) and HS groups, 214 DE lncRNAs when comparing the HS and PF groups, and 79 DE lncRNAs when comparing the NC and pair-fed (PF) groups. After eliminating the confounding effect of feed intake, 68 lncRNAs were identified, primarily associated with cellular growth and death, signal transduction, and metabolic regulation. Notably, the apoptosis-related pathway P53, lysosomes, and the fibrosis-related gene TGF-β2 were significantly upregulated by lncRNAs.ConclusionsThese findings indicate that chronic heat stress induces cellular apoptosis and muscle injury through lncRNA, leading to connective tissue accumulation, which likely contributes to reduced breast muscle yield and meat quality in broilers.

E!Canasta: A card game to teach ATP synthesis and metabolic regulation in biochemistry classes.

Understanding ATP formation is essential for learning metabolism and is central to grasping metabolic processes as a whole. However, due to the high level of abstraction, the number of intermediate substrates, the connections, and integrated regulation, its comprehension often poses a challenge. This and the fact that traditional teaching methods struggle when dealing with highly abstract concepts, game-based strategies present a more concrete and dynamic alternative, which led to the creation of E!Canasta (card game). Developed based on Canasta and adapted in order to improve the learning of concepts, including some of pathway's regulation and integration, E!Canasta motivates students and promotes engagement in a fun activity. Students assemble a sequence of cards representing the glycolysis, acetyl-CoA, Krebs cycle, and electron transport chain, which correspond to the card suits. Strategically, some of the cards hold special feats that simulate some aspects of metabolic regulation and integration (to give or take away points). At the end of the game, points are added up for sequences and cards with positive or negative effects. The game was played with two classes of students enrolled in biochemistry as part of their graduations (86 players). Student perception on gameplay, motivation and understanding was measured through an anonymous Likert scale questionnaire, with very positive results in all questions. Statistically significant correlations were observed regarding the perceived comprehension of pathways and their regulation, and in linking motivation with a positive gaming experience, showcasing that E!Canasta demonstrates considerable educational potential, along with an enjoyable experience for learning ATP synthesis.

Glucocorticoid chrono-pharmacology promotes glucose metabolism in heart through a cardiomyocyte-autonomous transactivation program.

Circadian time-of-intake gates the cardioprotective effects of glucocorticoid administration in both healthy and infarcted hearts. The cardiomyocyte-specific glucocorticoid receptor (GR) and its co-factor, Krüppel-like factor (Klf15), play critical roles in maintaining normal heart function in the long-term and serve as pleiotropic regulators of cardiac metabolism. Despite this understanding, the cardiomyocyte-autonomous metabolic targets influenced by the concerted epigenetic action of GR-Klf15 axis remain undefined. Here, we demonstrate the critical roles of the cardiomyocyte-specific GR and Klf15 in orchestrating a circadian-dependent glucose oxidation program within the heart. Combining integrated transcriptomics and epigenomics with cardiomyocyte-specific inducible ablation of GR or Klf15, we identified their synergistic role in the activation of adiponectin receptor expression (Adipor1) and the mitochondrial pyruvate complex (Mpc1/2), thereby enhancing insulin-stimulated glucose uptake and pyruvate oxidation. Furthermore, in obese diabetic (db/db) mice exhibiting insulin resistance and impaired glucose oxidation, light-phase prednisone administration, as opposed to dark-phase prednisone dosing, effectively restored cardiomyocyte glucose oxidation and improved diastolic function towards control-like levels in a sex-independent manner. Collectively, our findings uncover novel cardiomyocyte-autonomous metabolic targets of the GR-Klf15 axis. This study highlights the circadian-dependent cardioprotective effects of glucocorticoids on cardiomyocyte glucose metabolism, providing critical insights into chrono-pharmacological strategies for glucocorticoid therapy in cardiovascular disease.

Histone-like transcription factor Hfl1p in Candida albicans harmonizes nuclear and mitochondrial genomic network in regulation of energy metabolism and filamentation development

ABSTRACT Candida albicans is an opportunistic fungal pathogen known for surviving in various nutrient-limited conditions within the host and causing infections. Our prior research revealed that Hfl1p, an archaeal histone-like or Hap5-like protein, is linked to mitochondrial ATP generation and yeast-hyphae morphogenesis. However, the specific roles of Hfl1p in these virulence behaviours, through its function in the CBF/NF-Y complex or as a DNA polymerase II subunit, remain unclear. This study explores Hfl1p’s diverse functions in energy metabolism and morphogenesis. By combining proteomic analysis and phenotypic evaluations of the hfl1Δ/hfl1Δ mutant with ChIP data, we found that Hfl1p significantly impacts mitochondrial DNA-encoded CI subunits, the tricarboxylic acid (TCA) cycle, and morphogenetic pathways. This influence occurs either independently or alongside other transcription factors recognizing a conserved DNA motif (TAXXTAATTA). These findings emphasize Hfl1p’s critical role in linking carbon metabolism and mitochondrial respiration to the yeast-to-filamentous form transition, enhancing our understanding of C. albicans’ metabolic adaptability during morphological transition, an important pathogenic trait of this fungus. This could help identify therapeutic targets by disrupting the relationship between energy metabolism and cell morphology in C. albicans.

Resveratrol's bibliometric and visual analysis from 2014 to 2023.

Resveratrol (RSV) is a natural polyphenolic compound derived from a variety of plants that possesses a wide range of biological activities, including antioxidant, anti-inflammatory, antitumor, antibacterial, antiviral, anti-aging, anti-radiation damage, anti-apoptosis, immune modulation, regulation of glucolipid metabolism, inhibition of lipid deposition, and anti-neuro. It is therefore considered a promising drug with the potential to treat a wide range of diseases. In this study, using Web of Science Core Collection (WoSCC) and CiteSpace bibliometric tool, VOSviewer quantitatively visualized the number of countries, number of authors, number of institutions, number of publications, keywords, and references of 16,934 resveratrol-related papers from 2014-2023 for quantitative and qualitative analysis. The results showed that an average of 1693.4 papers were published per year, with a general upward trend. China had the most publications with 5877. China Medical University was the institution with the largest number of publications and the highest number of citations in the field. The research team was mainly led by Prof. Richard Tristan, and the journal with the highest number of published papers was Molecular. Dietary polyphenols, oxidative stress, and antioxidant and anti-inflammatory effects are the most frequently cited articles. Oxidative stress, apoptosis, expression, and other keywords play an important role in connecting other branches of the field. Our analysis indicates that the integration of nanoparticles with RSV is poised to become a significant trend. RSV markedly inhibits harmful bacteria, fosters the proliferation of beneficial bacteria, and enhances the diversity of the intestinal flora, thereby preventing intestinal flora dysbiosis. Additionally, RSV exhibits both antibacterial and antiviral properties. It also promotes osteogenesis and serves a neuroprotective function in models of Alzheimer's disease. The potential applications of RSV in medicine and healthcare are vast. A future research challenge lies in modifying its structure to develop RSV derivatives with superior biological activity and bioavailability. In the coming years, innovative pharmaceutical formulations of RSV, including oral, injectable, and topical preparations, may be developed to enhance its bioavailability and therapeutic efficacy.

Differential Regulation of L-Arginine Metabolism through NOS2 and Arginases during Infection with Trypanosoma cruzi.

L-arginine metabolism through arginases and inducible nitric oxide synthase (NOS2) constitutes a fundamental axis for the resolution or progression of Chagas disease. Infection with Trypanosoma cruzi can cause a wide spectrum of disease, ranging from acute forms contained by the host immune response to chronic ones, such as the chronic chagasic cardiomyopathy. Here, we analyzed, in an in vitro model, the ability of two T. cruzi isolates, with different degrees of virulence, to regulate the metabolism of L-arginine through arginase 1 (Arg-1) and NOS2 in macrophages and through arginase 2 (Arg-2) and NOS2 in cardiomyocytes. Stimulation of bone marrow-derived macrophages (BMMΦ), obtained from CD1 mice, with TNF-α + IFN-γ induced their polarization into classically activated macrophages (CAMΦ), which expressed functional NOS2, while stimulation with IL-4 induced their polarization into alternatively activated macrophages (AAMΦ), which expressed functional Arg-1. Interestingly, stimulation of cardiomyocytes, obtained from hearts of CD1 neonatal mice, with TNF-α + IFN-γ or IL-4 also resulted in functional NOS2 and arginase expression, as observed in CAMΦ and AAMΦ, but Arg-2 was the arginase isoform expressed instead of Arg-1. We observed that infection of BMMΦ with the more virulent T. cruzi isolate (QRO) importantly diminished NOS2 expression and nitric oxide (NO) production in CAMΦ, allowing parasite survival, while infection with the less virulent isolate (CI2) did not diminish NOS2 activity and NO production in CAMΦ to a great extent, which resulted in parasite killing. Regarding Arg-1, infection of BMMΦ with the QRO isolate significantly induced Arg-1 expression and activity in AAMΦ, which resulted in a higher parasite load than the one in the unstimulated BMMΦ. Even though infection with CI2 isolate did not increase Arg-1 expression and activity in AAMΦ, the parasite load was higher than the one in the unstimulated BMMΦ but at a lesser magnitude than that observed during infection with the QRO isolate. On the other hand, infection of cardiomyocytes with either QRO or CI2 isolates and further stimulation with TNF-α + IFN-γ inhibited NOS2 expression and NO production, leading to amelioration of infection. Surprisingly, infection of cardiomyocytes with either QRO or CI2 isolates and further stimulation with IL-4 strongly inhibited Arg-2 expression and function, which resulted in parasite loads similar to those observed in unstimulated cardiomyocytes. Our results suggest that T. cruzi isolates that exhibit variable virulence or pathogenicity degrees differentially regulate L-arginine metabolism through Arg-1/2 and NOS2 in macrophages and cardiomyocytes.

A first-in-human phase 1 study of BXQ-350, a first-in-class sphingolipid metabolism regulator, in patients with advanced/recurrent solid tumors or high-grade gliomas.

BXQ-350, a nanovesicle formulation of Saposin C, is an allosteric sphingolipid metabolism regulator that increases pro-apoptotic ceramide and decreases oncogenic sphingosine-1-phosphate (S1P) levels. We conducted a first-in-human, phase 1 study of BXQ-350. Adults (≥18 years old) with advanced/recurrent, treatment-refractory solid tumors or high-grade gliomas received BXQ-350 intravenously in five dose cohorts (0.7-2.4 mg/kg) in a 3+3 dose-escalation and expansion design. Primary endpoints during dose escalation were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD); primary objective in expansion parts was assessment of anti-tumor activity (RECIST v1.1/RANO criteria). Eighty-six patients were enrolled. DLTs were not observed during dose escalation (n=18), and a MTD was not identified. An additional 68 patients received the 2.4 mg/kg dose. Nine patients (10%) discontinued due to adverse events (AEs). The most common treatment-related AEs were nausea (24%) and fatigue (23%). Eight patients had a progression-free survival (PFS) ≥6 months. Two of these achieved a partial response, and six had stable disease, among whom three had a reduction in ≥1 target lesion. Of those with PFS ≥6 months, seven remained on study for >12 months, five for >24 months, and after seven years, two remained on study without disease progression. BXQ-350 was well tolerated as monotherapy at doses up to 2.4 mg/kg. It provided some lasting clinical benefit in patients with recurrent solid malignancies across several tumor types, consistent with a decreased systemic S1P/ceramide metabolic rheostat. BXQ-350 warrants further clinical investigation alone and combined with standard-of-care for advanced solid tumors.

Role of phosphorus-calcium metabolism regulators in cardiorenal syndrome development

Role of phosphorus-calcium metabolism regulators in cardiorenal syndrome development

Bioorthogonal Regulated Metabolic Balance for Promotion of Ferroptosis and Mild Photothermal Therapy.

The nanozyme with NADPH oxidase (NOX)-like activity can promote the consumption of NADPH and the generation of free radicals. In consideration of that the upregulation of glucose-6-phosphate dehydrogenase (G6PD) would accelerate the compensation production of NADPH, for inhibition of G6PD activity, our designed bioorthogonal nanozyme can in situ catalyze pro-DHEA to produce G6PD inhibitor and dehydroepiandrosterone (DHEA) drugs to inhibit G6PD activity. Therefore, the well-defined platform can disrupt NADPH homeostasis, leading to the collapse of the antioxidant defense system in the tumor cells. The enzyme-like activity of PdCuFe is further enhanced when irradiated by NIR-II light. The destruction of NADPH homeostasis can promote ferroptosis and, in turn, facilitate mild photothermal therapy. Our design can realize NADPH depletion and greatly improve the therapeutic effect through metabolic regulation, which may provide inspiration for the design of bioorthogonal catalysis.

Animal and plant protein intake association with mental health, tryptophan metabolites pathways, and gut microbiota in healthy women: a cross-sectional study

Mental health is affected by tryptophane (TRP) metabolism regulation. Diet-influenced gut microbiome regulates TRP metabolism. Thus, the present study aimed to explore the relationship between type of dietary protein intake, gut microbiota, TRP metabolites homeostasis, and mental well-being in healthy women. 91 healthy females aged 18–50 were recruited based on the study protocol. Validate and reliable questionnaires assessed dietary intake and mental health. Biochemical tests and gut microbiota composition were analyzed following the manufacturer’s instructions for each enzyme-linked immune sorbent assay (ELISA) kit and Real-time quantitative polymerase chain reaction (qPCR) methods respectively. Regression methods were used to estimate the considered associations. The results show that in the fully adjusted model, plant protein consumption was partially inversely associated with depression risk (OR = 0.27; 95% CI: 0.06, 1.09; P = 0.06). Higher dietary animal protein intake was marginally associated with psychological distress (OR = 2.59; 95% CI: 0.91, 7.34; P = 0.07). KYN to serotonin ratio was inversely associated with animal protein consumption (ß = 1.10; 95% CI: -0.13, 2.33; P = 0.07). Firmicutes/Bacteriodetes ratio (β = -1.27 × 103, SE = 5.99 × 102, P = 0.03) was lower in the top tertile of plant protein. A partially negative correlation was found between dietary animal protein and Prevotella abundance (β = -9.20 × 1018, SE = 5.04 × 1018, P = 0.06). Overall, significant inverse associations were found between a diet high in plant protein with mental disorders, KYN levels, and Firmicutes to Bacteroidetes ratio while adhering to higher animal protein could predispose women to psychological stress.

Mitochondria in tumor immune surveillance and tumor therapies targeting mitochondria.

Mitochondria play a central role in cellular energy production and metabolic regulation, and their function has been identified as a key factor influencing tumor immune responses. This review provides a comprehensive overview of the latest advancements in understanding the role of mitochondria in tumor immune surveillance, covering both innate and adaptive immune responses. Specifically, it outlines how mitochondria influence the function of the tumor immune system, underscoring their crucial role in modulating immune cell behavior to either promote or inhibit tumor development and progression. Additionally, this review highlights emerging drug interventions targeting mitochondria, including novel small molecules with significant potential in cancer therapy. Through an in-depth analysis, it explores how these innovative strategies could improve the efficacy and outlook of tumor treatment.