Search Results (644)

Cadmium (Cd) is a toxic environmental heavy metal that exerts harmful effects on multiple tissues, including the kidney, liver, lung, and bone, and is also associated with the development of anemia. However, the precise molecular mechanisms underlying Cd-induced toxicity remain incompletely understood. In this paper, we review the recent molecular mechanisms of Cd-induced toxicity and its modification, with a particular emphasis on our recent findings. Using a combination of DNA microarray analysis, protein–DNA binding assays, and siRNA-mediated gene silencing, we identified several transcription factors, YY1, FOXF1, ARNT, and MEF2A, as novel molecular targets of Cd. The downregulation of their downstream genes, including UBE2D2, UBE2D4, BIRC3, and SLC2A4, was directly associated with the expression of cytotoxicity. In addition, PPARδ plays a pivotal role in modulating cellular susceptibility to Cd-induced renal toxicity, potentially by regulating apoptosis-related signaling pathways. In addition to apoptosis pathways, Cd toxicity through ROS generation, ferroptosis and pyroptosis were summarized. Furthermore, it has been revealed that Cd suppresses the expression of iron transport-related genes in duodenal epithelial cells leading to impaired intestinal iron absorption as well as decreased hepatic iron levels. These findings provide a mechanistic basis for Cd-induced iron deficiency anemia, implicating disrupted iron homeostasis as a contributing factor. Full article

Background: Influenza A viruses (IAV) cause seasonal flu and occasional pandemics. In addition, the potential for the emergence of new strains presents unknown challenges for public health. Face masks and other personal protective equipment (PPE) can act as barriers that prevent the spread of these viruses. Metal ions embedded into PPE have been demonstrated to inactivate respiratory viruses, but the underlying mechanism of inactivation and potential for resistance is presently not well understood. Methods: In this study, we used hemagglutination assays to quantify the effect of zinc ions on IAV sialic acid receptor binding. We varied the zinc concentration, incubation time, incubation temperature, and passaged IAV in the presence of zinc ions to investigate if resistance to zinc ions could evolve. Results: We found that zinc ions impact the ability of IAV particles to hemagglutinate and observed inhibition within 1 min of exposure. Maximum inhibition was achieved within 1 h and sustained for at least 24 h in a concentration-dependent manner. Inhibition was also temperature-dependent, and optimal above room temperature. Serial passaging of IAV in the presence of zinc ions did not result in resistance. Conclusions: e conclude that zinc ions prevent IAV hemagglutination in a concentration and temperature-dependent manner for at least 24 h. Overall, these findings are in line with previous observations indicating that zinc-embedded materials can inactivate the IAV hemagglutinin and SARS-CoV-2 spike proteins, and they support work toward developing robust, passive, self-cleaning antiviral barriers in PPE. Full article

Reducing the application of chemical fertilizers and remediating heavy metal pollution in soil are important directions in current agricultural research. Utilizing the plant-growth-promoting and remediation capabilities of bacteria can provide more environmentally friendly assistance to agricultural production. In this study, the Burkholderia alba YIM B08401 strain was isolated and identified from rhizospheric soil, subjected to whole-genome sequencing and analysis, and its Cd²⁺ adsorption efficiency and characteristics were confirmed using multiple experimental methods, including atomic absorption spectrometry (AAS), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS). The results showed that the genome of strain YIM B08401 has a total length of 7,322,157 bp, a GC content of 66.39%, and predicts 6504 protein-coding sequences. It contains abundant functional genes related to nutrient conversion (phosphate solubilization, sulfur metabolism, zinc solubilization, siderophore production), plant hormone regulation (indole-3-acetic acid secretion, ACC deaminase production), phenolic acid degradation, root colonization, heavy metal tolerance, pathogen antagonism, and the production of antagonistic secondary metabolites. Additionally, strain YIM B08401 can specifically bind to Cd²⁺ through various functional groups on the cell surface, such as C-O-C, P=O, and O-H, enabling biosorption. In conclusion, strain YIM B08401 is an excellent strain with plant-growth-promoting, disease-resistant, and bioremediation capabilities, warranting further development as a biofertilizer for agricultural applications to promote green and sustainable agricultural development. Full article

A novel ruthenium(II) complex, [RuCl₂(η⁶-p-cymene)(bph-κN)] (1), was synthesized and structurally characterized using FTIR and NMR spectroscopy. Density functional theory (DFT) calculations supported the proposed geometry and allowed for comparative analysis of experimental and theoretical spectroscopic data. The interaction of complex 1 with human serum albumin (HSA) and calf thymus DNA was investigated through fluorescence quenching experiments, revealing spontaneous binding driven primarily by hydrophobic interactions. The thermodynamic parameters indicated mixed quenching mechanisms in both protein and DNA systems. Ethidium bromide displacement assays and molecular docking simulations confirmed DNA intercalation as the dominant binding mode, with a Gibbs free binding energy of −34.1 kJ mol⁻¹. Antioxidant activity, assessed by EPR spectroscopy, demonstrated effective scavenging of hydroxyl and ascorbyl radicals. In vitro cytotoxicity assays against A375, MDA-MB-231, MIA PaCa-2, and SW480 cancer cell lines revealed selective activity, with pancreatic and colorectal cells showing the highest sensitivity. QTAIM analysis provided insight into metal–ligand bonding characteristics and intramolecular stabilization. These findings highlight the potential of 1 as a promising candidate for further development as an anticancer agent, particularly against multidrug-resistant tumors. Full article

In this research, the proteomic landscape of 100 kDa protein extract sourced from rabbit brain was compared to extracts from liver and from organ mixture (OM). Our aim was to compare the efficacy of Nanomised Organo Peptides (NOP) ultrafiltrates from two different tissues and a tissue mixture for inducing neurite outgrowth, and subsequently to identify the molecular networks and proteins that could explain such effects. Proteins were isolated by gentle homogenization followed by crossflow ultrafiltration. Proteomic evaluation involved gel electrophoresis, complemented by mass spectrometry and bioinformatics. GO (Gene Ontology) and protein analysis of the mass spectrometry results identified a diverse array of proteins involved in critical specific biological functions, including neuronal development, regulation of growth, immune response, and lipid and metal binding. Data from this study are accessible from the ProteomeXchange repository (identifier PXD051701). Our findings highlight the presence of small proteins that play key roles in metabolic processes and biosynthetic modulation. In vitro outgrowth experiments with neural stem cells (NSCs) showed that 100 kDa protein extracts from the brain resulted in a greater increase in neurite length compared to the liver and organ mixture extracts. The protein networks identified in the NOP ultrafiltrates may significantly improve biological therapeutic strategies related to neural differentiation and outgrowth. This comprehensive proteomic analysis of 100 kDa ultrafiltrates revealed a diverse array of proteins involved in key biological processes, such as neuronal development, metabolic regulation, and immune response. Brain-specific extracts demonstrated the capacity to promote neurite outgrowth in NSCs, suggesting potential application for neuroregenerative therapies. Our findings highlight the potential of small proteins and organ-specific proteins in the development of novel targeted treatments for various diseases, particularly those related to neurodegeneration and aging. Full article

Metal ions and ligand binding are crucial in various biological processes, and their rational design can be used to develop novel therapeutic drugs and diagnostic tools. Metal atoms are soluble in biological fluids due to their ability to easily lose electrons and form positively charged ions. Because of their electron deficiency, they can interact with electron-rich biomolecules like proteins and DNA, and potentially participate in catalytic mechanisms or stabilize their tertiary or quaternary structures. Antibacterial resistance has become a major global concern and requires novel strategies to combat resistance mechanisms in infectious microbes. Full article

Paddlewheel dirhodium complexes are cytotoxic compounds that are also used as catalysts and in the formation of Rh-based artificial metalloenzymes. Low-temperature structures of adducts formed by the model protein hen egg white lysozyme (HEWL) with dirhodium tetraacetate ([Rh₂(μ-O₂CCH₃)₄]) when crystals of the protein were treated with the metal compound at 20 °C demonstrated that [Rh₂(μ-O₂CCH₃)₄] in part breaks down upon reaction with HEWL; dimeric Rh-Rh units bind the side chains of Asp18 and the C-terminal carboxylate, and monometallic fragments coordinate the side chains of Arg14 and His15 in 20% ethylene glycol, 0.100 M sodium acetate at pH 4.5 and 0.600 M sodium nitrate, while dimeric Rh-Rh units bind the side chains of Asn93 and Lys96, the C-terminal carboxylate and Asp101, with monometallic fragments that bind the side chains of Lys33 and His15 in 0.010 M HEPES pH 7.5 and 2.00 M sodium formate. To verify whether the binding of this metallodrug to proteins also occurs at body temperature, crystals of HEWL were grown in 0.010 M HEPES pH 7.5 and 2.00 M sodium formate at 37 °C and soaked with [Rh₂(μ-O₂CCH₃)₄] at the same temperature. X-ray diffraction data collected on these crystals at 37 °C demonstrate that [Rh₂(μ-O₂CCH₃)₄] reacts with proteins at body temperature. The structures of the Rh/HEWL adduct formed at 20 °C (obtained from data collected at 100 K) and at 37 °C under the same experimental conditions are very similar, with metal binding sites that are conserved. However, metal-containing fragment occupancy is higher in the structure obtained at 37 °C, suggesting a role of temperature in defining the protein metalation process. Full article

Calprotectin, the most abundant cytosolic protein in neutrophils, is a S100A8/S100A9 heterodimer released during immune activation. It inhibits bacterial growth by binding to essential metal ions and contributes to inflammation and leukocyte migration. This review highlights calprotectin’s potential as a diagnostic marker for bacterial infections and inflammation. Clinical trials demonstrate that calprotectin is at least as effective as C-reactive protein, procalcitonin, and white blood cell counts in predicting bacterial infections. The rapid elevation of calprotectin levels in the early stages of sepsis, pneumonia, brain injury, and transplant complications underscores its diagnostic value. Predictive use of calprotectin may reduce ICU stays, mortality, and costs. However, challenges remain, including assay standardization and bacterial–viral differentiation. Advanced methods, such as the particle-enhanced turbidimetric immunoassay, enable faster and more reliable measurements. While calprotectin shows promise, further standardization and clinical validation are necessary to optimize its diagnostic utility. Full article

Microalgae-based bioremediation is increasingly recognized as a sustainable, efficient, and straightforward technology. Despite this growing interest, the potential of Parachlorella hussii for metal biosorption remains underexplored. This study is the first report evaluating the metal biosorption activity in Parachlorella hussii ACOI 1508 (N9), highlighting the impact of the culture age on the monosaccharide composition and its correlation to the metal binding capacity. The capsular strain (N9) was isolated from the hypersaline ecosystem—Lake Chott Aïn El-Beida—in southeastern Algeria. Cultivated in Bold’s Basal medium, the strain produced 0.807 ± 0.059 g L⁻¹ of RPSs and 1.975 ± 0.120 g L⁻¹ of CPSs. Biochemical analysis of the extracts revealed a high total sugar content (% w/w) that ranged from 62.98 ± 4.87% to 95.60 ± 87% and a low protein content (% w/w) that ranged from 0.49 ± 0.08% to 1.35 ± 0.69%, with RPS-D7 and RPS-D14 having high molecular weight (≥2 MDa). HPLC-based monosaccharide characterization demonstrated compositional differences between the exponential and stationary phases, with rhamnose dominating (~55%) in RPS-D14 and with the presence of uronic acids comprising 7–11.3%. Metal removal efficiency was evaluated using the whole biomass in two growth phases. Copper uptake exhibited the highest capacity, reaching 18.55 ± 0.61 mg Cu g⁻¹ DW at D14, followed by zinc removal with 6.52 ± 0.61 mg Zn g⁻¹ DW. Interestingly, removal efficiencies increased to about twofold during the stationary phase, reaching 51.15 ± 1.14% for Cu, 51.08 ± 3.35% for Zn, and 36.55 ± 3.09% for Ni. The positive results obtained for copper/zinc removal highlight the biosorption potential of P. hussii, and notably, we found that the metal removal capacity significantly improved with culture age—a parameter that has been poorly investigated in prior studies. Furthermore, we observed a growth phase-dependent modulation in monosaccharide composition, which correlated with enhanced functional properties of the excreted biomolecules involved in biosorption. This metabolic adjustment suggests an adaptive response that may contribute to the species’ effectiveness in heavy metal uptake, underscoring its novelty and biotechnological relevance. Full article

Copper (Cu) is an essential micronutrient for cyanobacteria, where it functions as a cofactor in key proteins involved in photosynthesis and antioxidant defense. However, at elevated concentrations, Cu becomes toxic, exhibiting algicidal effects by disrupting metal homeostasis and competing for metal-binding sites on critical cellular proteins. Due to the considerable morphological and physiological diversity within the phylum Cyanobacteria, the thresholds for Cu deficiency or toxicity vary considerably among strains. Maintaining Cu homeostasis in cyanobacterial cells is a complex process involving multiple layers of regulation. It begins at the extracellular polysaccharide layer, involves specialized membrane-bound proteins (in the outer, plasma, and thylakoid membranes), and results in transcriptional regulation in response to intracellular Cu status. This review summarizes the current understanding of Cu uptake and efflux pathways in cyanobacteria and explores how these mechanisms contribute to maintaining cellular Cu balance. The knowledge gained may contribute to the application of cyanobacteria in bioremediation strategies and/or the targeted use of Cu in the control of harmful cyanobacterial blooms. Full article

Background: Phytoremediation is an efficient approach for remediating heavy metal-contaminated soils. Heavy metal-associated isoprenylated plant proteins (HIPPs)—crucial for metal ion homeostasis—are unique to vascular plants, featuring a heavy metal-associated (HMA) domain and an isoprenylated CaaX motif. However, ZmHIPP genes have not been systematically or functionally characterized in maize. Methods: This study characterizes ZmHIPP at the genome-wide level, including phylogenetic classification, motif/gene structure, chromosome location, gene duplication events, promoter elements, and tissue expression patterns. Cadmium (Cd) responses were evaluated by specific ZmHIPP expression and Cd accumulation in shoots and roots under Cd treatment. Results: A total of 66 ZmHIPPs were distributed unevenly across ten chromosomes, classified into five phylogenetic groups phylogenetically. Gene collinearity revealed 26 pairs of segmental duplications in ZmHIPPs. Numerous synteny genes were detected in rice and sorghum, but none in Arabidopsis, suggesting high conservation of HIPP genes in crop evolution. Transcriptomic analysis revealed tissue-specific expression patterns of ZmHIPP members in maize. Cis-acting element analysis linked several binding elements to abscisic acid, MeJA response, and MYB and MYC transcription factors. Under Cd stress, 53 out of 66 ZmHIPP genes were significantly induced, exhibiting three expression patterns. Cd exposure confirmed that the expression of ZmHIPP11, ZmHIPP30, and ZmHIPP48 was generally higher in shoots than roots, while ZmHIPP02 and ZmHIPP57 exhibited the opposite. Cd accumulation was higher in roots than shoots, peaking at 72 h (96 mg/kg) in shoots and exceeding 1000 mg/kg in roots after 120 h. Conclusions: This study not only provides fundamental genetic and molecular insights into HIPP function in maize but also identifies specific ZmHIPP genes as promising genetic resources for breeding Cd-tolerant maize, aiding in phytoremediation of Cd-contaminated soils. Full article

The ReAV enzyme from Rhizobium etli, a representative of Class 3 L-asparaginases, is sequentially and structurally different from other known L-asparaginases. This distinctiveness makes ReAV a candidate for novel antileukemic therapies. ReAV is a homodimeric protein, with each subunit containing a highly specific zinc-binding site created by two cysteines, a lysine, and a water molecule. Two Ser-Lys tandems (Ser48-Lys51, Ser80-Lys263) are located in the close proximity of the metal binding site, with Ser48 hypothesized to be the catalytic nucleophile. To further investigate the catalytic process of ReAV, site-directed mutagenesis was employed to introduce alanine substitutions at residues from the Ser-Lys tandems and at Arg47, located near the Ser48-Lys51 tandem. These mutational studies, along with enzymatic assays and X-ray structure determinations, demonstrated that substitution of each of these highly conserved residues abolished the catalytic activity, confirming their essential role in enzyme mechanism. Full article

Understanding the mechanisms of protein preservation in extreme environments is essential for identifying potential molecular biosignatures on Mars. In this study, we investigated five sabkha sedimentary samples from the Abu Dhabi coast, spanning from the present day to ~11,000 years before present (BP), to assess how mineralogy and environmental conditions influence long-term protein stability. Using LC-MS/MS and direct Data-independent Acquisition (DIA) proteomic analysis, we identified 722 protein groups and 1300 peptides, revealing a strong correlation between preservation and matrix composition. Carbonate- and silica-rich samples favored the retention of DNA-binding and metal-coordinating proteins via mineral–protein interactions, while halite- and gypsum-dominated facies showed lower recovery due to extreme salinity and reduced biomass input. Functional profiling revealed a shift from metabolic dominance in modern samples to genome maintenance strategies in ancient ones, indicating microbial adaptation to prolonged environmental stress. Contrary to expectations, some ancient samples preserved large, multi-domain proteins, suggesting that early mineral encapsulation can stabilize structurally complex biomolecules over millennial timescales. Taxonomic reconstruction based on preserved proteins showed broad archaeal diversity, including Thaumarchaeota and thermophilic lineages, expanding our understanding of microbial ecology in hypersaline systems. These findings highlight sabkhas as valuable analogs for Martian evaporitic environments and suggest that carbonate–silica matrices on Mars may offer optimal conditions for preserving ancient molecular traces of life. Full article

The Spodoptera litura, a Lepidopteran pest known for its high fecundity, undergoes a complete metamorphosis, including a distinctive process during which the male testes fuse from two separate organs into a single entity, significantly enhancing its fertility. To elucidate the molecular mechanisms underlying this testicular fusion, this study employed an integrated multi-omics approach to investigate concurrent changes at the transcriptomic and proteomic levels. We identified a series of synchronized alterations on the peritestic larval membrane, including heme binding, peptidase activity, hydrolase activity, metal ion transport, redox reactions, and chitin metabolism, all of which are substantially enriched at specific temporal points during testicular fusion. Nine genes/proteins co-expressed at the mRNA and protein levels were selected for targeted quantitative proteomics (PRM) and quantitative PCR (qPCR) validation, leading to the identification of five genes potentially involved in the testicular fusion process: Sl3030, ARCP, PSLRE, Obstructor-E, and Osris9B. Notably, the gene Sl3030, once knocked out, not only disrupted the normal fusion process but also resulted in reduced testis size, thickened peritestic membranes, and abnormal sperm development. Transcriptomic sequencing of the Sl3030 knockout mutant revealed its primary influence on the fusion process by affecting the assembly of the microtubule system and cytoskeleton. This research, for the first time, provides a multi-omics perspective on the response of key signaling pathways and molecular changes during the testicular fusion of S. litura and validates the role of the previously uncharacterized gene Sl3030 in this process, offering valuable insights into the complex mechanisms of testicular fusion in this species. Full article

All beta- and gamma-herpesviruses utilize a set of six viral proteins to facilitate transcription from specific promoters that become active late in the viral life cycle. These proteins form a complex that interacts with a TA-rich sequence upstream of the late transcription start sites and recruits RNA polymerase II (Pol II). The structure of any of the late transcription factors (LTFs) alone or in complexes has not been solved by standard means yet, but a fair amount is known about how the proteins interact and where the complex is positioned over the late promoters. Here, AlphaFold3 was used to predict and analyze the LTF complex using proteins from the beta-herpesviruses HCMV, MCMV, HHV6, and HHV7, and from the gamma-herpesviruses EBV and KSHV. The predicted structures had high levels of confidence and were remarkably similar even though there is little sequence conservation in the LTFs across the viruses. The results are consistent with most of the previously determined information concerning the interaction of the factors with each other and with DNA. A conserved threonine phosphorylation in one of the subunits that is critical to the function of the LTFs is predicted to be at the junction of five subunits. AlphaFold 3 predicts seven metal ion binding sites in each of the four beta-herpesviruses and either five or six in the gamma-herpesviruses created by conserved residues in three of the subunits. The structures also provide insights into the function of the subunits and which host general transcription factors (GTFs) may or may not be utilized during initiation. Full article