Search Results (79)

Soil degradation resulting from intensive agricultural practices, the excessive use of agrochemicals, and climate-induced stresses has significantly impaired soil fertility, disrupted microbial diversity, and reduced crop productivity. Plant growth-promoting bacteria (PGPB) represent a sustainable biological approach to restoring degraded soils by modulating plant physiology and soil function through diverse molecular mechanisms. PGPB synthesizes indole-3-acetic acid (IAA) to stimulate root development and nutrient uptake and produce ACC deaminase, which lowers ethylene accumulation under stress, mitigating growth inhibition. They also enhance nutrient availability by releasing phosphate-solubilizing enzymes and siderophores that improve iron acquisition. In parallel, PGPB activates jasmonate and salicylate pathways, priming a systemic resistance to biotic and abiotic stress. Through quorum sensing, biofilm formation, and biosynthetic gene clusters encoding antibiotics, lipopeptides, and VOCs, PGPB strengthen rhizosphere colonization and suppress pathogens. These interactions contribute to microbial community recovery, an improved soil structure, and enhanced nutrient cycling. This review synthesizes current evidence on the molecular and physiological mechanisms by which PGPB enhance soil restoration in degraded agroecosystems, highlighting their role beyond biofertilization as key agents in ecological rehabilitation. It examines advances in nutrient mobilization, stress mitigation, and signaling pathways, based on the literature retrieved from major scientific databases, focusing on studies published in the last decade. Full article

To explore the potential seed compounds from natural products as anticancer agents against small-cell lung cancer (SCLC), the underground parts of Agapanthus africanus, a plant commonly used for ornamental purposes, were investigated. Three spirostan-type steroidal glycosides (1–3) were isolated and identified by nuclear magnetic resonance spectral analysis. Compounds 1–3 exhibited cytotoxicity against SBC-3 human SCLC cells, with IC₅₀ values of 0.56, 1.4, and 7.4 µM, respectively. Compound 1, also known an agapanthussaponin A, demonstrated the most potent cytotoxicity among the isolated compounds and was evaluated for its apoptosis- and ferroptosis-inducing activities. Compound 1 arrested the cell cycle of SBC-3 cells in the G₂/M phase and induced apoptosis primarily via the mitochondrial pathway, characterized by caspases-3 and -9 activation, loss of mitochondrial membrane potential, and overproduction of reactive oxygen species. Additionally, 1 triggered ferroptosis via a dual mechanism consisting of enhanced cellular iron uptake through upregulation of transferrin and transferrin receptor 1 expression and impaired glutathione synthesis via downregulation of both xCT and glutathione peroxidase 4 expression. Compound 1 induces cell death via the apoptosis and ferroptosis pathways, suggesting its promise as a seed compound for the development of anticancer therapeutics against SCLC. Full article

Doxorubicin-induced cardiotoxicity (DIC) significantly constrains the clinical efficacy of anthracycline chemotherapy, primarily through the induction of ferroptosis, an iron-dependent, regulated cell death driven by oxidative stress and lipid peroxidation. However, the upstream regulators of ferroptosis in DIC remain incompletely defined. Cold-inducible RNA-binding protein (CIRBP) exhibits cardioprotective effects in various pathological contexts, but its precise role in ferroptosis-related cardiotoxicity is unknown. This study investigated whether CIRBP mitigates DIC by modulating the ferroptosis pathway via the SLC7A11 (Solute carrier family 7 member 11)/GPX4 (Glutathione peroxidase 4) axis. We observed marked downregulation of CIRBP in cardiac tissues and cardiomyocytes following doxorubicin exposure. CIRBP knockout significantly exacerbated cardiac dysfunction, mitochondrial damage, oxidative stress, and lipid peroxidation, accompanied by increased mortality rates. Conversely, CIRBP overexpression alleviated these pathological changes. Molecular docking and dynamics simulations, supported by transcriptomic analyses, revealed direct binding of CIRBP to the 3′-UTR of Slc7a11 mRNA, enhancing its stability and promoting translation. Correspondingly, CIRBP deficiency markedly suppressed SLC7A11 and GPX4 expression, impairing cystine uptake, glutathione synthesis, and antioxidant defenses, thus amplifying ferroptosis. These ferroptotic alterations were partially reversed by ferroptosis inhibitor ferrostatin-1 (Fer-1). Collectively, this study identifies CIRBP as a critical regulator of ferroptosis in DIC, elucidating a novel post-transcriptional mechanism involving Slc7a11 mRNA stabilization. These findings offer new insights into ferroptosis regulation and highlight CIRBP as a potential therapeutic target for preventing anthracycline-associated cardiac injury. Full article

Background/Objectives: Endometriosis and high-grade serous ovarian cancer (HGS-OC) share common features within the peritoneal immune microenvironment, yet they exhibit divergent clinical outcomes. This study aimed to dissect the immune–metabolic landscape of the peritoneal cavity in patients with endometriosis and ovarian cancer by evaluating macrophage polarization, intracellular signaling pathways, and iron-driven oxidative stress. Methods: A prospective cohort study enrolled 40 patients with endometriosis, 198 with ascitic ovarian cancer (178 HGS-OC), and 200 controls with benign gynecological conditions. Peritoneal and peripheral blood samples were analyzed via flow cytometry for macrophage (M1/M2) polarization markers, mTOR/AKT expression, and glucose uptake. Inflammatory markers (IL-6, CRP), oxidative stress (ROS), and iron metabolism parameters (hepcidin, ferritin, transferrin, serum/free iron) were quantified. Results: HGS-OC displayed a predominance of M1-polarized tumor-associated macrophages (TAMs) (CD14⁺/CD80⁺/Glut1⁺) and a high M1/M2 ratio (2.5 vs. 0.8 and 0.9; p = 0.019), correlating positively with IL-6 (p = 0.015), ROS (p = 0.023), hepcidin (p = 0.038), and ferritin (p = 0.043). Conversely, endometriosis showed a dominant M2 profile (CD14⁺/CD163⁺), elevated intracellular mTOR and AKT expression in both TAMs and epithelial cells (p < 0.01), and significantly higher ascitic ROS and free iron levels (p = 0.047 and p < 0.0001, respectively). In endometriosis, the M1/M2 ratio correlated inversely with free iron (p = 0.041), while ROS levels were directly associated with iron overload (p = 0.0034). Conclusions: Endometriosis exhibits a distinct immune–metabolic phenotype characterized by M2 macrophage predominance and iron-induced oxidative stress, contrasting with the inflammatory, M1-rich profile of HGS-OC. These findings suggest that iron metabolism and macrophage plasticity contribute to disease persistence in endometriosis and may inform future immunomodulatory strategies. Full article

Age-related neurodegeneration is characterized by oxidative stress and iron-dependent cell death, yet the neuroprotective mechanisms of folic acid in modulating ferroptosis remain unclear. This study systematically investigated the role of folic acid in inhibiting ferroptosis and attenuating neuronal damage in aging, with a focus on the solute carrier family 7 member 11 (SLC7A11)-glutathione (GSH)-glutathione peroxidase 4 (GPX₄) antioxidant pathway, using aged rats supplemented with folic acid (<0.1, 2.0, and 4.0 mg/kg·diet) for 22 months, with young adult rats as controls. Brain iron accumulation and ferroptosis-related proteins (SLC7A11, GPX₄, Ferritin heavy chain 1 (FTH1)) were evaluated. In vitro, HT-22 hippocampal neuronal cells were pre-treated with folic acid (0, 10, 20 μmol/L) for 72 h before combining with Erastin (10 μmol/L)-induced ferroptosis for an additional 24 h. Intracellular Fe²⁺, lipid peroxidation (LPO), malondialdehyde (MDA), reactive oxygen species (ROS), along with cystine, GSH, and ferroptosis-related protein levels were quantified. Stable sh-SLC7A11 knockdown and control (sh-NC) cell lines were used to validate the dependency of folic acid’s protective effects on SLC7A11 expression. Folic acid supplementation in aged rats dose-dependently reduced aging-related brain iron accumulation and enhanced the expression of SLC7A11, GPX₄, and FTH1. In Erastin-induced HT-22 cells, folic acid significantly mitigated ferroptosis hallmarks. Mechanistically, folic acid increased extracellular cystine uptake and intracellular GSH synthesis, thereby activating the SLC7A11-GSH-GPX₄ antioxidant pathway. Notably, molecular docking technique suggested that compared to GPX₄, folic acid stabilized SLC7A11’s active conformation. sh-SLC7A11 knockdown completely abolished folic acid-mediated protection against ferroptosis, as evidenced by restored loss of cystine, GSH and GPX₄ production. This study innovatively emphasized the critical role of folic acid supplementation in inhibiting ferroptosis by up-regulating the SLC7A11-GSH-GPX₄ antioxidant pathway, primarily through enhancing cystine availability and SLC7A11 expression. These findings established folic acid as a potential dietary intervention for aging-related neurodegenerative diseases characterized by neuronal ferroptosis, providing preclinical evidence for folic acid based neuroprotection. Full article

Microelement deficiencies, often termed “hidden hunger”, represent a significant global health challenge. Optimal human health relies on adequate dietary intake of essential microelements, including selenium (Se), zinc (Zn), copper (Cu), boron (B), manganese (Mn), molybdenum (Mo), iron (Fe), nickel (Ni), and chlorine (Cl). In recent years, there has been a growing focus on vitality and longevity, which are closely associated with the sufficient intake of essential microelements. This review focuses on these nine elements, whose bioavailability in the food chain is critically determined by their geochemical behavior in soils. There is a necessity for an understanding of the sources, soil–plant transfer, and plant uptake mechanisms of these microelements, with particular emphasis on the influence of key soil properties, including pH, redox potential, organic matter content, and mineral composition. There is a dual challenge of microelement deficiencies in agricultural soils, leading to inadequate crop accumulation, and the potential for localized toxicities arising from anthropogenic inputs or geogenic enrichment. A promising solution to microelement deficiencies in crops is biofortification, which enhances nutrient content in food by improving soil and plant uptake. This strategy includes agronomic methods (e.g., fertilization, soil amendments) and genetic approaches (e.g., marker-assisted selection, genetic engineering) to boost microelement density in edible tissues. Moreover, emphasizing the need for advanced predictive modeling techniques, such as ensemble learning-based digital soil mapping, enhances regional soil microelement management. Integrating machine learning with digital covariates improves spatial prediction accuracy, optimizes soil fertility management, and supports sustainable agriculture. Given the rising global population and the consequent pressures on agricultural production, a comprehensive understanding of microelement dynamics in the soil–plant system is essential for developing sustainable strategies to mitigate deficiencies and ensure food and nutritional security. This review specifically focuses on the bioavailability of these nine essential microelements (Se, Zn, Cu, B, Mn, Mo, Fe, Ni, and Cl), examining the soil–plant transfer mechanisms and their ultimate implications for human health within the soil–plant–human system. The selection of these nine microelements for this review is based on their recognized dual importance: they are not only essential for various plant metabolic functions, but also play a critical role in human nutrition, with widespread deficiencies reported globally in diverse populations and agricultural systems. While other elements, such as cobalt (Co) and iodine (I), are vital for health, Co is primarily required by nitrogen-fixing microorganisms rather than directly by all plants, and the main pathway for iodine intake is often marine-based rather than soil-to-crop. Full article

Plasma non-transferrin-bound iron (NTBI) comprises multiple subspecies, classified by their composition, chemical reactivity, and susceptibility to chelation. The redox-active and chelatable fraction of NTBI is referred to as labile plasma iron (LPI). The pathophysiological significance of NTBI and LPI lies in their ability to enter cells via alternative transport pathways that are not regulated by the transferrin receptor system or by cellular iron levels. Several mechanisms have been proposed for their cellular entry, including the hijacking of divalent metal transporters and passive diffusion. This unregulated uptake can lead to iron accumulation in vulnerable tissues such as the liver and the heart. NTBI and LPI bypassing normal cellular control mechanisms can rapidly exceed the cell’s capacity to safely store excess iron, leading to toxicity. Both NTBI and LPI contribute to oxidative stress by participating in free-radical-generating reactions. However, LPI concentration in the bloodstream may be differentially affected by the mode and extent of iron overload, the presence of residual serum iron-binding activity, and the antioxidant capacity of individual sera. In summary, both NTBI and LPI contribute to iron-mediated toxicity but differ in terms of reactivity, availability, and pathogenic potential depending on the pathophysiological conditions that influence the degree of toxicity. Full article

The uptake and utilization of iron by bacteria must be strictly controlled. The ferric uptake regulator (Fur) is a global transcription factor widely present in bacteria that can perceive cellular iron levels and adjust the expressions of various genes accordingly. Our earlier research demonstrated that the knockdown of the fur gene in Vibrio splendidus significantly reduced its lethality to Apostichopus japonicus. Although the functions and mechanisms of Fur in regulating bacterial virulence genes have been extensively studied, its virulence regulatory network during V. splendidus pathogenesis in A. japonicus remains unclear. In this article, transcriptome sequencing analysis of V. splendidus under different iron conditions reveals substantial differential gene expressions in the simulated pathogenic environments, identifying 1185 differentially expressed genes, including 198 downregulated and 987 upregulated genes. Comparative analysis between wild-type and Vsfur knockdown strains shows that Vsfur knockdown altered the expression of 3593 genes in V. splendidus, with the most significant differential expression observed under simulated pathogenic conditions (1030 upregulated and 72 downregulated). KEGG enrichment analysis indicates that Vsfur knockdown caused significant gene enrichment in the flagellar assembly pathway and bacterial secretion system, critically impairing flagellar synthesis and secretion system function in V. splendidus. Eight genes selected for qRT-PCR validation showed expression levels in line with the RNA-seq results. Consistent with the transcriptomic results, Vsfur knockdown resulted in reduced antioxidant capacity, bacterial competitiveness, and cytotoxicity in V. splendidus. These findings elucidate the virulence regulatory mechanism of Fur in V. splendidus and provide a reference for understanding the occurrence of A. japonicus skin ulcer syndrome. Full article

Iron is essential for vital biological processes, with its metabolism closely linked to host–pathogen interactions. Pseudomonas donghuensis HYS, with its superior iron uptake capacity, demonstrates pronounced virulence toward Caenorhabditis elegans. However, the virulence mechanisms remain unexplored. Ferric uptake regulator (Fur) regulates iron homeostasis and pathogenicity in bacteria, yet its role in HYS-mediated C. elegans pathogenesis requires systematic investigation. In this study, comparing the pathogenic processes of HYS and P. aeruginosa PA14 revealed that HYS causes stronger, irreversible toxicity via distinct mechanisms. Transcriptomics revealed that HYS infection disrupts C. elegans iron metabolism pathways, specifically iron transport, and iron–sulfur cluster utilization. Fur was identified as a pivotal regulator in HYS virulence and was indispensable for its colonization. Specifically, Fur was critical for disrupting nematode iron metabolism, as fur deletion eliminated this effect. While Fur regulated two HYS siderophores, neither of them mediated in the iron metabolism disruption of C. elegans. Screening identified Fur-regulated virulence factors to further investigate the function of Fur in HYS virulence, particularly alkaline proteases, and type II secretion system components. This study highlight that HYS can disrupt the iron metabolism pathway in C. elegans; Fur serves as a pivotal positive regulator in HYS-induced damage, particularly in disrupting iron metabolism through a siderophore-independent pathway. These findings expand the understanding of Pseudomonas pathogenicity and Fur-mediated virulence regulation. Full article

The myogenic differentiation of muscle satellite cells (MuSCs) is an important biological process that plays a key role in the regeneration and repair of skeletal muscles. However, the mechanisms regulating myoblast myogenesis require further investigation. In this study, we found that STEAP3 is involved in myogenic differentiation based on the Yunan black pig MuSCs model in vitro using cell transfection and other methods. Furthermore, the expression of myogenic differentiation marker genes MyoG and MyoD and the number of myotubes formed by the differentiation of cells from the si-STEAP3 treated group were significantly decreased but increased in the STEAP3 overexpression group compared to that in the control group. STEAP3 played a role in iron ion metabolism, affecting myogenic differentiation via the uptake of iron ions and enhancing IRP-IRE homeostasis. STEAP3 also activated the PI3K/AKT pathway, thus promoting myoblast differentiation of Yunan black pig MuSCs. The results of this study showed that STEAP3 overexpression increased intracellular iron ion content and activated the homeostatic IRP-IRE system to regulate intracellular iron ion metabolism. Full article

The growing threat of antibiotic resistance has made treating bacterial and fungal infections increasingly difficult. With the discovery of new antibiotics slowing down, alternative strategies are urgently needed. Siderophores, small iron-chelating molecules produced by microorganisms, play a crucial role in iron acquisition and serve as virulence factors in many pathogens. Because iron is essential for microbial survival, targeting siderophore biosynthesis and transport presents a promising approach to combating drug-resistant infections. This review explores the key genetic and biochemical mechanisms involved in siderophore production, emphasizing potential drug targets within these pathways. Three major biosynthetic routes are examined: nonribosomal peptide synthetase (NRPS)-dependent, polyketide synthase (PKS)-based, and NRPS-independent (NIS) pathways. Additionally, microbial iron uptake mechanisms and membrane-associated transport systems are discussed, providing insights into their role in sustaining pathogenic growth. Recent advances in inhibitor development have shown that blocking critical enzymes in siderophore biosynthesis can effectively impair microbial growth. By disrupting these pathways, new antimicrobial strategies can be developed, offering alternatives to traditional antibiotics and potentially reducing the risk of resistance. A deeper understanding of siderophore biosynthesis and its regulation not only reveals fundamental microbial processes but also provides a foundation for designing targeted therapeutics. Leveraging these insights could lead to novel drugs that overcome antibiotic resistance, offering new hope in the fight against persistent infections. Full article

Pore-forming peptides are promising antimicrobial and anticancer agents due to their membrane selectivity and biodegradability. Our prior work identified peptide M159, which permeabilized synthetic phosphatidylcholine liposomes without mammalian cell toxicity. Here, we report that the D-type variant (D-M159) induces apoptosis in HeLa cells under starvation. To explore its anticancer mechanism, we analyzed D-M159 cytotoxicity, intracellular uptake, and apoptotic pathways via flow cytometry, confocal microscopy, and Western blot. Calcium dynamics and mitochondrial function were examined via specific labeling and functional assays. Results revealed that D-M159 exhibited starvation-dependent, dose-responsive cytotoxicity and triggered apoptosis in HeLa cells. Mechanistic studies indicated that D-M159 entered the cells via caveolin-dependent and caveolae-dependent endocytosis pathways and induced endoplasmic reticulum stress in HeLa cells by up-regulating proteins such as ATF6, p-IRE1, PERK, GRP78, and CHOP. Meanwhile, D-M159 promoted the expression of IP3R1, GRP75, and VDAC1, which led to mitochondrial calcium iron overload, decreased mitochondrial membrane potential, and increased reactive oxygen species (ROS) generation, thereby activating the mitochondrial apoptotic pathway and inducing the aberrant expression of Bax, Bcl-2, Caspase-9, and Caspase-3. This study showed that D-M159 synergistically induced apoptosis in starved HeLa cells through endoplasmic reticulum stress and mitochondrial dysfunction, demonstrating its potential as a novel anticancer agent. Full article

Brassinosteroids (BRs) are crucial plant hormones that play a significant role in regulating various physiological processes, including micronutrient homeostasis. This review delves into the complex roles of BRs in the uptake, distribution, and utilization of essential micronutrients such as iron (Fe), zinc (Zn), manganese (Mn), copper (Cu), and boron (B). BRs influence the expression of key transporter genes responsible for the absorption and internal distribution of these micronutrients. For iron, BRs enhance the expression of genes related to iron reduction and transport, improve root architecture, and strengthen stress tolerance mechanisms. Regarding zinc, BRs regulate the expression of zinc transporters and support root development, thereby optimizing zinc uptake. Manganese homeostasis is managed through the BR-mediated regulation of manganese transporter genes and chlorophyll production, essential for photosynthesis. For copper, BRs influence the expression of copper transporters and maintain copper-dependent enzyme activities crucial for metabolic functions. Finally, BRs contribute to boron homeostasis by regulating its metabolism, which is vital for cell wall integrity and overall plant development. This review synthesizes recent findings on the mechanistic pathways through which BRs affect micronutrient homeostasis and discusses their implications for enhancing plant nutrition and stress resilience. Understanding these interactions offers valuable insights into strategies for improving micronutrient efficiency in crops, which is essential for sustainable agriculture. This comprehensive analysis highlights the significance of BRs in micronutrient management and provides a framework for future research aimed at optimizing nutrient use and boosting plant productivity. Full article

This study investigates the content of some metals and metalloids in the flowers of three Aesculus cultivars (AHP, Aesculus hippocastanum pure species, with white flowers; AHH, Aesculus hippocastanum hybrid species, with pink flowers; and AXC, Aesculus × carnea, with red flowers) over a four-year period (2016–2019) using inductively coupled plasma optical emission spectrometry (ICP OES) and principal component analysis (PCA). The research focuses on assessing macro- and micro-elemental compositions, identifying variations in mineral uptake, and exploring potential correlations with soil composition. Results highlight significant differences in elemental profiles among the three species, despite similar total ash content. Potassium and phosphorus emerged as dominant macroelements, with AXC showing lower magnesium levels compared to AHP and AHH. Particularly intriguing was the detection of antimony in all cultivars, raising questions about its role and bioaccumulation pathways in floral tissues. Iron and aluminum concentrations varied significantly across species, indicating species-specific metal transport mechanisms. Nickel content showed temporal fluctuations, potentially influenced by climatic conditions and soil properties. PCA revealed distinct clustering patterns, linking elemental concentrations to specific species and years. This comprehensive analysis enhances understanding of metal absorption and distribution in ornamental plants, providing insights into their metabolic processes and potential implications for environmental monitoring and phytoremediation strategies. Full article

Vibrio ordalii is the causative agent of atypical vibriosis in salmonids cultured in Chile. While extensive research provides insights into V. ordalii through phenotypic, antigenic, and genetic typing, as well as various virulence mechanisms, proteomic characterization remains largely unexplored. This study aimed to advance the proteomic knowledge of Chilean V. ordalii Vo-LM-18 and its OMVs, which have known virulence. Using Nano-UHPLC-LC-MS/MS, we identified 2242 proteins and 1755 proteins in its OMVs. Of these, 644 unique proteins were detected in V. ordalii Vo-LM-18, namely 156 unique proteins in its OMVs and 1596 shared proteins. The major categories for the OMVs were like those in the bacteria (i.e., cytoplasmic and cytoplasmic membrane proteins). Functional annotation identified 37 biological pathways in V. ordalii Vo-LM-18 and 28 in its OMVs. Proteins associated with transport, transcription, and virulence were predominant in both. Evident differences in protein expression were found. OMVs expressed a higher number of virulence-associated proteins, including those related to iron- and heme-uptake mechanisms. Notable pathways in the bacteria included flagellum assembly, heme group-associated proteins, and protein biosynthesis. This proteomic analysis is the first to detect the RTX toxin in a V. ordalii strain (Vo-LM-18) and its vesicles. Our results highlight the crucial role of OMVs in the pathogenesis and adaptation of V. ordalii, suggesting use as potential diagnostic biomarkers and therapeutic targets for bacterial infections. Full article