Search Results (266)

Atherosclerosis is a chronic inflammatory and metabolic disease driven by endothelial dysfunction, immune activation, vascular smooth muscle cell remodeling and aging-associated mitochondrial decline. Although lipid lowering remains the cornerstone of therapy, substantial residual inflammatory risk persists, highlighting the need for integrative regulatory targets. Sirtuin 1 (SIRT1), a NAD⁺-dependent deacetylase, has emerged as a central metabolic sensor linking energy availability to transcriptional control of inflammation, oxidative stress, mitochondrial biogenesis and cellular senescence. Experimental studies across endothelial cells, macrophages and vascular smooth muscle cells consistently demonstrate that SIRT1 activation preserves nitric oxide bioavailability, suppresses ROS-dependent inflammasome signaling, modulates macrophage polarization, inhibits ferroptosis and maintains mitochondrial integrity. These cell-type-specific effects converge to reduce plaque progression and enhance fibrous cap stability in preclinical models. However, SIRT1 activity is hierarchically regulated by AMPK signaling and NAD⁺ availability and is influenced by aging, metabolic dysfunction and environmental stressors, underscoring its context-dependent function. Despite promising mechanistic data, clinical translation remains limited, suggesting that precision modulation strategies may be required. This review synthesizes current evidence and proposes that SIRT1 functions as a metabolic–inflammatory integrator within the atherosclerotic arterial wall, representing a potential but context-sensitive target for future cardiovascular therapies. Full article

In the context of research aimed at identifying the causes of the progressive decline in cellular and tissue functions characteristic of aging, in recent decades, increasing attention has been devoted to the sirtuin family. Sirtuins are named after the Sir2 protein of Saccharomyces cerevisiae, a product of the SIR gene family, known as “silent information regulator 2”. Sirtuins are NAD⁺-dependent protein deacetylases and deacylases characterized by a conserved catalytic domain of approximately 275 amino acids. The removal of acetyl groups from acetyl-lysine residues on proteins is critical in regulating a wide range of biological functions, including gene silencing, genome stability, longevity, metabolism, and cellular physiology. In humans, the sirtuin family comprises seven isoforms (SIRT1–SIRT7), each with specific substrate preferences and primarily, but not exclusively, localized in the nucleus (SIRT1, SIRT6, and SIRT7), cytoplasm (SIRT2), and mitochondria (SIRT3, SIRT4, and SIRT5). Sirtuins may regulate numerous cellular processes associated with survival and longevity, including transcription and DNA repair, inflammation, glucose and lipid metabolism, oxidative stress, mitochondrial function, apoptosis, autophagy, and stress resistance. Sirtuins’ dependence on NAD⁺ allows them to function as cellular energy sensors, linking metabolic demands to selective lysine deacylation in various subcellular organelles. The aim of this review is to provide an update on this family of molecules, describing their molecular structures, physiological functions, roles in aging processes, and potential to be modulated to serve as a strategy for promoting healthy aging. Full article

In our previous study, a taste sensor employing a lipid/polymer membrane modified with 2,6-dihydroxyterephthalic acid (2,6-DHTPA) enabled the detection of the umami substances monosodium glutamate (MSG) and inosinate monophosphate (IMP). The taste sensor was also able to evaluate the synergistic effect, an umami enhancement phenomenon that occurs between MSG and IMP. However, the structural requirements for modifiers capable of detecting IMP have not yet been clarified. In the present study, to elucidate these requirements, nine different modifiers were prepared, and taste sensor measurements for IMP were conducted in combination with ¹H-NMR analysis. As a result, three distinct patterns were observed: (1) modifiers that exhibited chemical shift changes and generated a potential response in the positive direction (i.e., a positive potential response); (2) modifiers that showed chemical shift changes but produced either an almost zero or a negative potential response; and (3) modifiers that exhibited neither chemical shift changes nor any potential response. For receptor membranes that did not exhibit a positive response, the corresponding modifiers either lacked two carboxyl groups or did not possess intramolecular hydrogen bonding involving hydroxyl groups. From these results, it was clarified that the essential conditions for obtaining a positive potential response to IMP are that the modifier (1) contains two carboxyl groups and (2) possesses intramolecular hydrogen bonding. Full article

Membrane fusion is fundamental to intracellular transport and signal transduction, with its dysregulation implicated in various diseases. Deciphering its transient, microscale dynamics requires advanced sensing technologies. This review systematically evaluates optical and electrochemical sensing platforms for in vitro studies of membrane fusion. Optical sensing platforms provide greater intuitive readout of membrane fusion events, whereas electrochemical sensing platforms enable label-free, single-event resolution. We revisit classical fluorescence resonance energy transfer (FRET) strategies for lipid and content mixing, tracing their evolution from ensemble measurements to real-time, multiparameter, single-vesicle analysis. We further examine electrochemical platforms based on nanodisc-black lipid membranes (ND-BLMs) and solid-supported lipid bilayers (SLBs), highlighting their unique capabilities in characterizing fusion pore kinetics and virus–host membrane fusion. ND-BLM-based systems are irreplaceable for probing fusion pore kinetics, owing to their sub-millisecond temporal resolution and being essentially free from ion saturation and depletion effects. Meanwhile, SLB-based electrochemical sensing platforms excel at high-throughput detection of viral membrane fusion events by virtue of their excellent compatibility and facile integration. These sensors provide powerful tools for elucidating the molecular mechanisms underlying SNARE-mediated membrane fusion and viral fusion processes. Finally, this review outlines future directions centered on the integration of multimodal sensing and the construction of physiomimetic membranes, emphasizing the critical role of cross-scale, multiparameter sensing in bridging molecular mechanisms with biological functions and advancing the diagnosis and treatment of membrane fusion-related diseases. Full article

Accurate prediction of progression to Alzheimer’s disease (AD) is crucial for early intervention and personalized patient management. In this study, we developed a robust, data-driven survival analysis pipeline to model time-to-progression from cognitively normal (CN) and mild cognitive impairment (MCI) at baseline to AD, integrating cognitive, clinical, MRI and PET neuroimaging biomarkers, and biospecimen features from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. The ADNI cohort can be regarded as a multi-center platform for multimodal data integration that jointly captures cognitive performance, MRI/PET imaging-sensor biomarkers, and biofluid biosensing assays within a unified prognostic framework. Accordingly, our pipeline is designed to be robust to cross-site and cross-instrument variability through harmonized preprocessing and quality-check aware integration of heterogeneous multimodal data. Indeed, we employed eXtreme Gradient Boosting (XGBoost) for predicting survival data, which allows for the native handling of missing values that are frequently observed in real-world clinical datasets. Our results confirm that strong predictive performance can be achieved using a minimal set of features, obtaining a concordance index (C-index) of 0.92 using 13 features and 0.90 using only 4 features. These findings underscore the importance of multi-domain feature integration, transparent feature selection, and the inclusion of underexplored biomarkers such as lipid metabolites for prognostic modeling. Full article

The design and optimization of microalgae processes are usually focused on maximizing biomass productivity, neglecting the impact of cell-to-cell heterogeneity. Flow cytometry (FCM) represents a powerful and high-throughput tool for analyzing and examining microalgae intrinsic characteristics, such as their physiology, metabolism and response at the single-cell level. The aim of this work is to develop a novel FCM sensor-based single-cell analysis method to monitor and study the effect of several process conditions, mainly variations of light spectral composition (blue, red and green), nitrogen depletion and moderate osmotic stress conditions (0.2 M NaCl), on the subpopulation structure and dynamics of the green microalgae Chromochloris zofingiensis, a natural source for lipids, proteins and carotenoids. The FCM procedures developed in this study proved to be effective for monitoring the population dynamics of microalgae, demonstrating how the process conditions have a direct and significant impact on population heterogeneity of C. zofingiensis on a single-cell level. Cell division was found to be adversely affected by the moderate osmotic stress (N⁺S⁺), nitrogen depletion (N⁻), and their combined occurrence (N⁻S⁺), independent of the light spectral composition used for culture illumination. In terms of cell-to-cell heterogeneity, a higher proportion of large cells (~20 µm) was observed under green light across all conditions with 21%, 29%, 35% and 52% under N⁻, N⁻S⁺, N⁺S⁺ and N⁺ conditions, respectively, followed by red light combined with osmotic stress (46%), whereas blue light consistently led to a predominance of smaller cells (≤4 µm) with 30%, 47%, 50% and 55% under N⁺S⁺, N⁺, N⁻S⁺ and N⁻ conditions, respectively. Full article

Mitochondria are a key organelle in maintaining metabolic homeostasis. It not only generates most of the cell’s energy through oxidative phosphorylation but also acts as a complex sensor of the redox state and oxygen in the cell. This review thoroughly analyzes the interactions among mitochondrial iron metabolism, mitochondrial reactive oxygen species (mtROS), and lipid peroxidation (LPO), the triggering factors of ferroptosis, an iron-dependent form of programmed cell death. We point out research showing that intrinsic mitochondrial machinery, such as iron–sulfur (Fe-S) cluster assembly and heme metabolism, is both an important cofactor and a master regulator. If these processes are disrupted, they can lead to ferroptosis. Unlike views that focus on the cytosol, we explain that the stability of Fe-S clusters in complexes such as aconitase and respiratory Complex I is crucial for preventing electron leakage and excessive mtROS formation. The Fenton reaction and its direct effect on cardiolipin (CL) oxidation in the inner membrane of mitochondria is a central event in cardiometabolic diseases. Its peroxidation and breakdown make the organelle very unstable and lead to cell death though Ca²⁺ overload and a significantly decreased reduced/oxidized glutathione ratio. Additionally, the functions of essential iron transporters and glutathione homeostasis are examined, and their dysregulation is correlated with ferroptosis-associated progression of cardiometabolic and neurodegenerative disorders, such as obesity and Alzheimer’s disease. This review focused on the need to revisit the classic bioenergetic core of the mitochondria as a key player in the pathophysiology of metabolic and neurodegenerative diseases. Full article

Herein, we present a comprehensive single-cell investigation of the biochemical and metabolic responses of normal human colon fibroblasts (CCD-18Co) and colorectal adenocarcinoma cells (Caco-2) to supplementation with the amino acids leucine, threonine, and arginine, employing State-of-the-Art Raman spectroscopy and Raman imaging. This fully label-free and noninvasive methodology enabled high-spatial-resolution mapping of intracellular components, providing unprecedented insight into subcellular biochemical organization and metabolic remodeling associated with colorectal carcinogenesis. By synergistically integrating Raman spectroscopic data with advanced chemometric methods, we demonstrate robust, reproducible discrimination between normal and malignant colon cells, both in their native state and after amino acid treatment, based solely on their intrinsic vibrational fingerprints. Partial Least Squares Discriminant Analysis (PLS-DA) and one-way ANOVA revealed that perturbations in lipid metabolism and protein composition constitute key molecular determinants underlying the observed phenotypic divergence between control and amino acid–supplemented cells. Notably, detailed analysis of diagnostic Raman band intensity ratios (2845/3015, 2845/2930, 3015/2888, and 1444/1256) uncovered pronounced amino acid–driven alterations in metabolic pathways at the single-cell level. Raman imaging further enabled spatially resolved visualization of these biochemical shifts and changes in Raman band intensities, highlighting distinct lipid- and protein-rich subcellular domains that respond differentially to amino acid exposure in normal versus cancerous cells. Collectively, our findings establish Raman spectroscopy combined with chemometric analysis as a powerful and sensitive platform for decoding amino acid–induced metabolic reprogramming in colorectal cells. This approach deepens the mechanistic understanding of nutrient–cancer cell interactions and opens new avenues for the development of Raman-based strategies in cancer diagnostics and therapeutic response assessment. Full article

Lysophosphatidic acid (LPA) is a cell-signaling lipid that has been proposed as an early-stage biomarker for ovarian cancer (OC). Diagnosing OC in Stage I is critical to improving patient outcomes, increasing the survival rate from 30% (when diagnosed in late stages of the disease) to over 90%. This significant improvement is due to the success of early interventions; however, current diagnostic methods are not as effective at early-stage detection, with only 15% of cases diagnosed in Stage I and over 70% diagnosed in Stage III or IV. There is a strong need for LPA detection that is sensitive, specific, rapid, low-cost, and automated to truly validate its effectiveness as a diagnostic characteristic for OC. We report the preliminary development and characterization of one such biosensor, which makes use of the advantages of magnetic particles and chemiluminescence for quick, sensitive detection of LPA. The sensor has proven to be viable, with a positive response to LPA concentration, a measurement time of 5 s after incubation, and an LOD of 3.5 nM. Full article

Dietary fats are consumed as mixtures, yet it remains unclear whether fatty acid composition, independent of fat content, dictates human macrophage polarization. We compared two defined mixtures containing identical fatty acids (palmitic, oleic, and linoleic acids) in different ratios: a palmitate-enriched mixture (4:3:3) and an unsaturated fat-dominant mixture (2:4:4). In primary human monocyte-derived macrophages, palmitate enrichment increased CD14+CD11b+HLA-DR+ pro-inflammatory polarization, whereas the unsaturated fat-dominant mixture increased CD14+CD11b+CD163+ anti-inflammatory polarization. Mechanistic studies in THP-1-derived macrophages recapitulated these phenotype shifts and identified a reciprocal nuclear-receptor program: palmitate enrichment induced peroxisome proliferator-activated receptor gamma (PPARγ), together with ER-stress mediators EIF2AK3 and DDIT3, while the unsaturated fat-dominant mixture preferentially induced PPARα and IRF4. Pharmacologic modulation demonstrated functional dependence on PPARγ: GW9662 attenuated palmitate-driven M1-like polarization, whereas rosiglitazone disrupted the protective program under unsaturated fat-dominant conditions. These findings show that fatty acid composition, at equivalent total lipid concentration, is a dominant determinant of human macrophage inflammatory fate and highlight PPARγ as a context-dependent lipid sensor. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) involves early disturbances such as excessive lipid accumulation, sterile inflammation, and hepatocellular stress. The results of recent studies have highlighted extracellular ATP and its metabolite adenosine (Ado) as damage-associated molecular patterns (DAMPs) that drive inflammation, endoplasmic reticulum (ER) stress, and steatosis, contributing to MASLD progression. Although vitamin E is clinically used for its antioxidant and anti-inflammatory properties, it remains unclear whether its therapeutic effects involve modulation of DAMP-associated signaling. To address this gap, we used transgenic zebrafish expressing a liver-specific G-protein-coupled receptor activation-based adenosine sensor (GRAB_Ado). We found that a high-cholesterol diet markedly increased hepatic extracellular Ado levels, combined with inflammatory and ER stress-associated gene expression. Vitamin E significantly reduced extracellular Ado levels and hepatic lipid accumulation. Based on RNA sequencing results, vitamin E restored the expression of genes encoding calcium-handling proteins, including atp2a1 and atp1b1b. These genes encode components of the sarco/ER Ca²⁺-ATPase (SERCA) machinery, which is essential for maintaining ER Ca²⁺ homeostasis and preventing stress-induced hepatic injury. CDN1163-mediated SERCA activation phenocopied the protective effect of vitamin E, supporting a Ca²⁺-dependent mechanism. Together, these findings highlight extracellular Ado signaling and impaired SERCA-mediated Ca²⁺ regulation as early drivers of MASLD and demonstrate that vitamin E ameliorates steatosis by targeting both pathways. Full article

Maternal nutrition during gestation profoundly influences fetal growth, organogenesis, and long-term offspring performance through developmental programming. Among the molecular mechanisms responsive to maternal nutrient availability, one-carbon metabolism plays a central role by integrating folate, methionine, choline, and vitamin B₁₂ pathways that regulate methylation, nucleotide synthesis, and antioxidant defense. These processes link maternal nutritional status to epigenetic remodeling, cellular proliferation, and redox balance during fetal development. Mitochondria act as nutrient sensors that translate maternal metabolic cues into bioenergetic and oxidative signals, shaping tissue differentiation and metabolic flexibility. Variations in maternal diet have been associated with shifts in fetal amino acid, lipid, and energy metabolism, suggesting adaptive responses to constrained intrauterine environments. This review focuses on the molecular interplay between one-carbon metabolism, mitochondrial function, and metabolomic adaptation in developmental programming of ruminant livestock. Understanding these mechanisms offers opportunities to design precision nutritional strategies that enhance fetal growth, offspring productivity, and long-term resilience in livestock production systems. Full article

Microproteins are small polypeptides translated from short open reading frames (sORFs) that typically encode < 100 amino acids. Advances in ribosome profiling, mass spectrometry, and computational prediction have revealed a growing number of microproteins that play important roles in cellular metabolism, organelle function, and stress adaptation; however, these were considered non-coding or functionally insignificant. At the mitochondrial level, microproteins, such as MTLN (also known as mitoregulin/MOXI) and BRAWNIN, contribute to lipid oxidation, oxidative phosphorylation efficiency, and respiratory chain assembly. Other microproteins at the endoplasmic reticulum–mitochondria interface, including PIGBOS and several muscle-resident regulators of calcium cycling, show diverse biological contexts in which these microproteins act. A subset of microproteins responds to nutrient availability. For example, SMIM26 modulates mitochondrial complex I translation under serine limitation, and non-coding RNA expressed in mesoderm-inducing cells encoded with peptides facilitates glucose uptake during differentiation, indicating that some microproteins can affect metabolic adaptation through localized translational- or organelle-level mechanisms. Rather than functioning as primary nutrient sensors, these microproteins complement classical nutrient-responsive pathways such as AMP-activated protein kinase-, peroxisome proliferator-activated receptor-, and carbohydrate response element binding protein-mediated signaling. As the catalog of microproteins continues to expand, integrating proteogenomics, nutrient biology, and functional studies will be central to defining their physiological relevance; these integrative approaches will also help reveal their potential applications in metabolic health. Full article

Pharmacological compounds can disrupt glucose homeostasis, leading to impaired glucose tolerance, hyperglycemia, or newly diagnosed diabetes, as well as worsening glycemic control in patients with pre-existing diabetes. Traditional risk factors alone cannot explain the rapidly growing global incidence of diabetes. Therefore, prevention of insulin resistance could represent an effective strategy. Achieving this goal requires a deeper understanding of the mechanisms underlying the development of insulin resistance, with particular attention to the aryl hydrocarbon receptor (AhR). AhR, a transcription factor functioning as a xenobiotic sensor, plays a key role in various molecular pathways regulating normal homeostasis, organogenesis, and immune function. Activated by a range of exogenous and endogenous ligands, AhR is involved in the regulation of glucose and lipid metabolism as well as insulin sensitivity. However, current findings remain contradictory regarding whether AhR activation exerts beneficial or detrimental effects. This narrative review summarizes recent studies exploring the role of the AhR pathway in insulin secretion and glucose homeostasis across different tissues, and discusses molecular mechanisms involved in this process. Considering that several drugs act as AhR ligands, the review also compares how these ligands affect metabolic pathways of glucose and lipid metabolism and insulin sensitivity, producing either positive or negative effects. Full article

Tilapia is a cornerstone species in global aquaculture, yet the impact of saline-alkaline adaptive breeding on its flavor-related volatile organic compounds (VOCs) remains unclear. Herein, we compared VOCs in freshwater-cultured tilapia (FW) and 7th-generation tilapia subjected to long-term selective breeding for saline-alkaline tolerance (SAW_G7) using an electronic nose (E-nose), gas chromatography-ion mobility spectrometry (GC-IMS), and headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS). The aim was to identify flavor differentiation and assess the effect of saline-alkaline acclimation. E-nose analysis revealed distinct odor profiles, with SAW_G7 showing higher sensor responses for aldehydes, ketones, and alcohols. GC-IMS detected 32 VOCs, highlighting significant increases in alcohols, aldehydes, and heterocyclics in SAW_G7. GC-MS identified 43 VOCs, with orthogonal partial least-squares discriminant analysis (OPLS-DA) confirming 18 discriminant compounds, including elevated ketones (2-undecanone), aldehydes ((E)-2-octenal), alcohols (2,7-Octadien-1-ol), and furans (2-ethyl-Furan) in SAW_G7, linked to lipid oxidation under saline-alkaline stress. These findings demonstrate that long-term saline-alkaline breeding achieves a potentially more diverse VOC profile in tilapia by altering its volatile profiles. The study provides insights for optimizing aquaculture practices to improve product quality in marginal environments. Full article