Search Results (201)

Oxidative stress overwhelms cellular antioxidant defenses, causing DNA damage and pro-tumorigenic signaling that accelerate cancer initiation and progression. Electron shuttles (ESs) from phytocompounds offer precise redox control but lack quantitative benchmarks. This study aims to give a clearer definition to electron shuttles by characterizing mulberry’s electrochemical capabilities via the three defined ES criteria and deciphering its mechanism against oxidative stress-related cancer. Using double-chambered microbial-fuel-cell power metrics, cyclic voltammetry, and compartmental fermentation modeling, we show that anthocyanin shows a significant difference (p < 0.05) in power density at ≥500 µg/mL (maximum of 2.06-fold power-density increase) and reversible redox cycling (ratio = 1.65), retaining >90% activity over four fermentation cycles. Molecular docking implicates meta-dihydroxyl motifs within the core scaffold in receptor binding, overturning the view that only ortho- and para-substituents participate in bioactivity. In vitro, anthocyanins both inhibit nitric oxide release and reduce DU-145 cell viability dose-dependently. Overall, our findings establish mulberry anthocyanins as robust electron shuttles with potential for integration into large-scale bio-electrochemical platforms and targeted redox-based cancer therapies. Full article

Calcium (Ca²⁺) is a macronutrient essential for the growth, development, yield, and quality of vegetables and fruits. It performs structural, enzymatic, and signaling functions in plants. This review examines Ca²⁺ translocation from soil to the fruit via the plant xylem network, emphasizing the importance of Ca²⁺ compartmentalization within fruit cell organelles in the development of calcium deficiency disorders such as blossom-end rot (BER). The underlying causes of BER and potential control measures are also discussed. Soil-available Ca²⁺, transported by water flow, enters the root apoplast through membrane channels and moves toward the xylem via apoplastic or symplastic routes. The transpiration force and the growth of organs determine the movement of Ca²⁺-containing xylem sap to aerial plant parts, including fruits. At the fruit level, the final step of Ca²⁺ regulation is intracellular partitioning among organelles and cellular compartments. This distribution ultimately determines the fruit’s susceptibility to Ca²⁺-deficiency disorders such as BER. Excessive sequestration of Ca²⁺ into organelles such as vacuoles may deplete cytosolic and apoplastic Ca²⁺ pools, compromising membrane integrity and leading to BER, even when overall Ca²⁺ levels are adequate at the blossom end. Effective BER management requires cultural and physiological practices that promote Ca²⁺ uptake, translocation to the fruit, and appropriate intracellular distribution. Additionally, the use of BER-resistant and Ca²⁺-efficient cultivars can help mitigate this disorder. Therefore, a comprehensive understanding of Ca²⁺ dynamics in plants is critical for managing BER, minimizing production loss and environmental impacts, and maximizing overall crop productivity. Full article

Hepatic mitochondria play critical roles in sustaining systemic nutrient balance, nitrogen detoxification, and cellular bioenergetics. These functions depend on tightly regulated mitochondrial processes, including amino acid catabolism, ammonia clearance via the urea cycle, and transport through specialized solute carriers. Genetic disruptions in these pathways underlie a range of inborn errors of metabolism, often resulting in systemic toxicity and neurological dysfunction. Here, we review the physiological functions of hepatic mitochondrial amino acid metabolism, with a focus on subcellular compartmentalization, disease mechanisms, and therapeutic strategies. We discuss how emerging genetic and metabolic interventions—including dietary modulation, cofactor replacement, and gene therapy—are reshaping treatment of liver-based metabolic disorders. Understanding these pathways offers mechanistic insights into metabolic homeostasis and reveals actionable vulnerabilities in metabolic disease and cancer. Full article

Silicon dioxide (SiO₂) foliar application offers a promising strategy for enhancing lettuce (Lactuca sativa L.) resilience under temperature extremes, salinity, and drought stress. This study investigated the effects of SiO₂ treatment on three lettuce cultivars exposed to varying temperature, salinity, and drought conditions in a controlled growth chamber environment. Silicon treatment (3.66 mM) significantly enhanced plant biomass under suboptimal (15 °C), optimal (20 °C), and salinity stress conditions. Notably, the SiO₂ effect was most positive under severe salinity stress (100 mM NaCl), where its application increased plant weight together with chlorophyll and anthocyanin content. When increasing SiO₂ concentrations from 0 to 29.30 mM were tested, optimal results to alleviate severe salinity stress were consistently observed at 3.66 mM, with peak performance in fresh weight, plant diameter, chlorophyll, and anthocyanin content. Higher SiO₂ concentrations progressively diminished these beneficial effects, with 29.30 mM treatment leading to reduced growth and increased leaf chlorosis. Comprehensive mineral composition analysis revealed complex interactions between silicon treatment and elemental profiles at 100 mM salinity stress. At 3.66 mM SiO₂, plants accumulated the highest levels of both K (20,406 mg/kg dry weight, DW) and Na (16,185 mg/kg DW) while maintaining the highest K/Na ratio (1.26). This suggests that Si enhances cellular ion compartmentalization rather than exclusion mechanisms, allowing plants to manage higher total ion content better while minimizing cytoplasmic damage. Drought stress conditions unexpectedly revealed negative impacts from 3.66 mM SiO₂ application, with decreased plant fresh weight at moderate (50% soil water content, SWC) and severe (30% SWC) water limitations, though results were statistically significant only under severe drought stress. The study highlights silicon’s potential as a stress mitigation agent, particularly under salinity stress, while emphasizing the need for concentration-specific and stress-specific approaches. These findings suggest that foliar SiO₂ application could be a valuable tool for enhancing lettuce crop productivity under both optimal and challenging environmental conditions, with future research warranting field validation and full market maturity assessments. Full article

Coacervate is a form of liquid–liquid phase separation (LLPS) in which a solution containing one or more charged components spontaneously separates into two immiscible liquid phases. Due to their ability to mimic membraneless cellular environments and their high biocompatibility, coacervates have found broad applications across various fields of life sciences. This review provides a comprehensive overview of recent advances in biomolecule-based coacervation for biotechnological and biomedical applications. Encapsulation via biomolecule-based coacervation enables high encapsulation efficiency, enhanced stability, and the sustained release of cargos. In the field of tissue engineering, coacervates not only support cell adhesion and proliferation but also serve as printable bioinks with tunable rheological properties for 3D bioprinting. Moreover, biomolecule-based coacervates have been utilized to mimic membraneless organelles, serving as experimental models to understand the origin of life or investigate the mechanisms of biochemical compartmentalization. This review discusses the mechanisms of coacervation induced by various types of biomolecules, evaluates their respective advantages and limitations in applied contexts, and outlines future research directions. Given their modularity and biocompatibility, biomolecule-based coacervates are expected to play a pivotal role in next-generation therapeutic development and the construction of controlled tissue microenvironments, especially when integrated with emerging technologies. Full article

Respiratory syncytial virus (RSV) is the leading cause of respiratory infections in children. Extracellular vesicles (EVs), released by airway epithelial cells, contain proteins and different families of non-coding RNAs (EV cargo) that can modulate the responses of target cells to viral infection. Nasal mucosa is a primary site of viral entry and the source of EVs present in the upper airway secretions. In this study we characterized proteins, including inflammatory mediators and cytokines, and the piwi-interacting RNA (piRNAs) cargo of EVs isolated from pediatric human nose organoids (HNO) and nasopharyngeal secretions (NPS) positive for RSV. Using Proximity Extension Assay (PEA) and Luminex multi-target arrays, we found significant enrichment in several chemokines and other mediators/biomarkers, including CCL2, CCL20, CXCL5, CX3CL1, CXCL6, MMP-1, MMP-10, uPA, Flt3L, ARNT and CD40 in EVs secreted by RSV-infected HNO compared to control mock HNO. Analysis of NPS samples from RSV infected children revealed that CCL3, CCL20, CXCL8, uPA, VEGFA, were concentrated in the NPS-EV fraction. LC-MS/MS and Gene Ontology indicated that RSV positive NPS-EVs originate from different cellular sources, with the most abundant proteins from neutrophils and epithelial cells. A total of 490 piRNAs were detected by NGS sequencing of small RNA libraries obtained from NPS-EVs, which has not been reported prior to this study. Identification of inflammatory mediators and small non-coding RNAs which are compartmentalized in EVs contributes to understanding mechanisms of virus-mediated pathogenesis in RSV infections. Full article

Organisms have evolved various protective mechanisms to survive in complex and dynamic environments. Phase separation is a ubiquitous mechanism in plants, animals, and microorganisms. It facilitates the aggregation of biomolecules through weak interactions, forming membrane-less organelles that help organisms respond effectively to stress signals. These biomolecular condensates include DNA, RNA, and proteins. Proteins are categorized into scaffold and client proteins, whose coordinated actions ensure the compartmentalization of cellular signals, thereby regulating various biological processes. Studies indicate that, in response to stress, phase separation modulates gene expression, signal transduction, cytoskeleton dynamics, and protein homeostasis, ensuring the precise spatiotemporal control of cellular functions. These insights underscore the crucial role of phase separation in maintaining cellular integrity and adaptability. Full article

Heavy metal toxicity leads to impaired crop growth and reduced crop yields and product quality by disrupting plant nutrient uptake, inhibiting development, inducing oxidative stress, and causing cellular toxicity. Arbuscular mycorrhizal fungi (AMF) can play a crucial role in crops’ adaptation to manganese (Mn) toxicity by regulating nutrient uptake and altering subcellular compartmentalization. The present study examines the influence of intact extraradical mycelia (ERMs) from native AMF on wheat (Triticum aestivum) grown in Mn-toxic soil, with a focus on the tissue-specific and subcellular Ca, Mg, P, and Mn distribution. Wheat cultivated in soil pre-colonized using an intact ERM associated with Lolium rigidum or Ornithopus compressus exhibited enhanced growth and improved P contents. During the first week of growth, the Mn concentrations increased in the wheat’s roots and shoots, but Mn was subsequently reduced and sequestered within the cell wall. In contrast, in the absence of an intact ERM, the Mn accumulation in wheat followed an apparent continuous time-course pattern. AMF-mediated cell wall sequestration seems to contribute to Mn detoxification by limiting excessive cytoplasmic accumulation. Furthermore, AMF-driven changes in the element distribution suggest a dynamic response, wherein an early-stage nutrient uptake transitions into a long-term protective mechanism. These findings highlight the potential of AMF in mitigating Mn stress in crops, providing insights for sustainable agriculture and soil remediation strategies. Full article

A fundamental limitation of fMRI based on the BOLD effect is its limited spatial specificity. This is because the BOLD signal reflects neurovascular coupling, leading to macrovascular changes that are not strictly limited to areas of increased neural activity. However, neuronal activation also induces microstructural changes within the brain parenchyma by modifying the diffusion of extracellular biological water. Therefore, diffusion-weighted imaging (DWI) has been applied in fMRI to overcome BOLD limits and better explain the mechanisms of functional activation, but the results obtained so far are not clear. This is because a DWI signal depends on many experimental variables: instrumental, physiological, and microstructural. Here, we hypothesize that the γ parameter of the fractional diffusion representation could be of particular interest for DW-fMRI applications, due to its proven dependence on local magnetic susceptibility and diffusion multi-compartmentalization. BOLD fMRI and DW-fMRI experiments were performed at 3T using an exemplar application to task-based activation of the human visual cortex. The results, corroborated by simulation, highlight that γ provides complementary information to conventional diffusion fMRI and γ can quantify cellular morphology changes and neurovascular regulation during neuronal activation with higher sensitivity and specificity than conventional BOLD fMRI and DW-fMRI. Full article

PE_PGRS domain proteins represent a family of proteins found in pathogenic and non-pathogenic mycobacteria such as M. smegmatis. This conserved family is characterized by two distinct regions denoted as the variable PGRS domain defined by glycine-rich repeats, and a PE domain consisting of two antiparallel alpha-helices. There are many indications that PE_PGRS proteins are involved in immunopathogenesis and virulence by evading or triggering the host immune response. However, there is not yet any information on their degree of specialization or redundancy. Computational analysis and structural annotation using AlphaFold3 combined with other tools reveals an exceptionally powerful and unprecedented ability to undergo phase separation by the PGRS domain. This suggests that PGRS’s glycine-rich, multivalent, low-complexity composition supports phase separation while adopting a structured conformation, contrary to the disordered nature typical of such domains. While previously never reported, the hypothesized role of PGRS in virulence indicates a novel window into the seemingly ubiquitous role of phase separation in cellular compartmentalization and molecular dynamics. This review aims to summarize the current understanding of the PE_PGRS family and its various biological roles in the context of bioinformatic analyses of some interesting representatives of M. marinum that are under control by host sterols. Based on the structural bioinformatics analysis, we discuss future approaches to uncover the mechanistic role of this intriguing family of mycobacterial proteins in both pathogenic and non-pathogenic mycobacteria. Full article

Mitochondria are involved in a wide array of critical cellular processes from energy production to cell death. The morphology (size and shape) of mitochondrial compartments is highly responsive to both intracellular and extracellular conditions, making these organelles highly dynamic. Nutrient levels and stressors both inside and outside the cell inform the balance of mitochondrial fission and fusion and the recycling of mitochondrial components known as mitophagy. The study of mitochondrial morphology and its implications in human disease and microbial engineering have gained significant attention over the past decade. The yeast Saccharomyces cerevisiae offers a valuable model system for studying mitochondria due to its ability to survive without respiring, its genetic tractability, and the high degree of mitochondrial similarity across eukaryotic species. Here, we review how the interplay between mitochondrial fission, fusion, biogenesis, and mitophagy regulates the dynamic nature of mitochondrial networks in both yeast and mammalian systems with an emphasis on yeast as a model organism. Additionally, we examine the crucial role of inter-organelle interactions, particularly between mitochondria and the endoplasmic reticulum, in regulating mitochondrial dynamics. The dysregulation of any of these processes gives rise to abnormal mitochondrial morphologies, which serve as the distinguishing features of numerous diseases, including Parkinson’s disease, Alzheimer’s disease, and cancer. Notably, yeast models have contributed to revealing the underlying mechanisms driving these human disease states. In addition to furthering our understanding of pathologic processes, aberrant yeast mitochondrial morphologies are of increasing interest to the seemingly distant field of metabolic engineering, following the discovery that compartmentalization of certain biosynthetic pathways within mitochondria can significantly improve chemical production. In this review, we examine the utility of yeast as a model organism to study mitochondrial morphology in both healthy and pathologic states, explore the nascent field of mitochondrial morphology engineering, and discuss the methods available for the quantification and classification of these key mitochondrial morphologies. Full article

Understanding the corpus luteum (CL) and its role in cattle reproduction is crucial, particularly as it is a progesterone source for the establishment and maintenance of pregnancy. Reduced oxygen levels significantly impact these processes. This study investigated the effects of the luteal stage on the spatio-temporal gene expression patterns of HIF1α and oxygen-sensing factors, as well as the impact of lipopolysaccharide (LPS)-induced inflammation on these factors. Endothelial inflammatory responses were also addressed. The samples included CL collected at the early, mid, and late stages, as well as biopsies from mid-luteal stage cows treated either with saline (controls) or LPS. Samples collected in subsequent cycles assessed potential carryover effects. RT-PCR revealed upregulation of HIF1α, PHD1, PHD3, FIH, and VHL encoding genes in the mid-luteal stage. In situ hybridization revealed the compartmentalization of HIF1α and its regulators within the luteal and endothelial cells, suggesting their cell-specific roles. LPS treatment affected PHD1 and PHD3 expression, while increasing endothelial pro-inflammatory factors ICAM1 and NFκB, suggesting vascular inflammation and modulated oxygen sensing. These findings reveal new insights into the spatio-temporal expression of HIF1α-regulating factors in the CL, highlighting their potential role in controlling luteal function, detailing their cellular compartmentalization, and the effects of LPS-mediated inflammatory responses. Full article

Background/Objectives: Repeat low-level blast exposure has emerged as a significant concern for military populations exposed to explosive events. Blast-Related Traumatic Brain Injury (bTBI) is a unique form of brain trauma with poorly understood molecular mechanisms. Loss of calcium homeostasis has emerged as a mediator of early neuronal dysfunction after blast injury. This review aims to examine the role of calcium signaling in bTBI, focusing on the dual function of calcium channels as mediators and modulators of injury, and to explore therapeutic strategies targeting calcium homeostasis. Methods: We conducted a review of peer-reviewed articles published between 2000 and 2024, using the databases PubMed, Scopus, and EBSCO. Search terms included “blast traumatic brain injury”, “calcium channels”, and “calcium”. Studies investigating intracellular calcium dynamics after bTBI were included. Exclusion criteria included studies lacking evaluation of calcium signaling, biomarker studies, and studies on extracellular calcium. Results: We identified 13 relevant studies, primarily using preclinical models. Dysregulated calcium signaling was consistently linked to cellular dysfunction, including plasma membrane abnormalities, cytoskeletal destabilization, mitochondrial dysfunction, and proteolytic enzyme activation. Studies highlighted spatially compartmentalized vulnerabilities across neurons and astrocytes, suggesting that targeting specific cellular regions, such as the neuronal soma or axons, could enhance the therapeutic outcome. Therapeutic strategies included pharmacological inhibitors, plasma membrane stabilizers, and modulators of secondary injury. Conclusions: Calcium signaling is implicated in the pathophysiology of bTBI. Standardized experimental approaches would reduce variability in findings and improve the understanding of the relationship between calcium channel dynamics and bTBI and help guide the development of neuroprotective interventions that mitigate injury and promote recovery. Full article

Pain and disability secondary to degenerative disc disease continue to burden the healthcare system, creating an urgent need for effective, disease-modifying therapies. Contemporary research has identified potential therapies that include protein-, cellular- and/or matrix-related approaches; however, none have yet achieved a meaningful clinical impact. The tissue-specific realities of the intervertebral disc create considerable therapeutic challenges due to the disc’s location, compartmentalization, hypovascularization and delicate physiological environment. Furthermore, the imaging modalities currently used in practice are largely unable to accurately identify sources of pain ostensibly discogenic in origin. These obstacles are considerable; however, recent research has begun to shed light on possible breakthrough technologies. Such breakthroughs include revolutionary imaging to better identify tissue sources of pain. Furthermore, novel molecular therapies have been shown to be able to mediate the progression of degenerative disc disease in some large animal studies, and even provide some insight into suppressing the development of tissue sources of discogenic pain. These potential breakthrough technologies have yet to be translated for clinical use. Full article

Nitric oxide synthases (NOS) are enzymes responsible for the cellular production of nitric oxide (NO), a highly reactive signaling molecule involved in important physiological and pathological processes. Given its remarkable capacity to diffuse across membranes, NO cannot be stored inside cells and thus requires multiple controlling mechanisms to regulate its biological functions. In particular, the regulation of endothelial nitric oxide synthase (eNOS) activity has been shown to be crucial in vascular homeostasis, primarily affecting cardiovascular disease and other pathophysiological processes of importance for human health. Among other factors, the subcellular localization of eNOS plays an important role in regulating its enzymatic activity and the bioavailability of NO. The aim of this review is to summarize pioneering studies and more recent publications, unveiling some of the factors that influence the subcellular compartmentalization of eNOS and discussing their functional implications in health and disease. Full article