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Search Results (249)

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Keywords = Zn2+-binding proteins

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0 pages, 3474 KB  
Article
A Marine Anticancer Cinnamyloxyl Derivative with Unique Binding Sites at Carbonic Anhydrase IX (CAIX) Inhibits Adenocarcinomic A549 Cells
by Shailaja Vommi Lakshmipathy, Christina Vijayaraghavan Sathyanathan, Mohanapriya Dandapani Chinambedu, Mohanraj Gopikrishnan, Abhinand Ponneri Adithavarman, Sadras Panchatcharam Thyagarajan and Mary Elizabeth Gnanambal Krishnan
Pharmaceuticals 2026, 19(1), 132; https://doi.org/10.3390/ph19010132 - 12 Jan 2026
Viewed by 239
Abstract
Background: Many inhibitors have been discovered to target hypoxia-induced carbonic anhydrase IX (CAIX) due to its critical role in lung cancers. This study discovers a novel compound, 3-(E-3,4-dihydroxycinnamaoyloxyl)-2-hydroxypropyl-9Z,12Z-octadeca-9,12-dienoate, which is produced by the seagrass Cymodocea serrulata and has binding sites at CAIX that [...] Read more.
Background: Many inhibitors have been discovered to target hypoxia-induced carbonic anhydrase IX (CAIX) due to its critical role in lung cancers. This study discovers a novel compound, 3-(E-3,4-dihydroxycinnamaoyloxyl)-2-hydroxypropyl-9Z,12Z-octadeca-9,12-dienoate, which is produced by the seagrass Cymodocea serrulata and has binding sites at CAIX that are distinct from those of current inhibitors. Methods: Compound and reference drug treatment for cell lines; Cell viability: MTT; Staining: Ao/PI/DAPI; MMP shifts and cell cycle: FACS; Gene and protein expression of CAIX, BAX, BAD: qPCR and Western blotting. Results: The compound binds to the CAIX protein, raises extracellular pH, and kills A549 cells [IC50: 11.61 µM], producing results that are lower than those of the reference drug doxorubicin [13.7 µM]. The substance depolarised the electrical potential of the mitochondrial membrane, caused S-phase arrest, and fragmented DNA. Additionally, it downregulated CAIX by 0.9 times while increasing apoptotic mRNA, BAX and BAD by 5.2 and 3.08 times, respectively, as demonstrated by qPCR. Between 0 and 24 h, the untreated hypoxic cells had a ΔpHe of 0.15, but the compound-treated cells had a ΔpHe of 0.6 indicative of intracellular acidosis. MD simulations verify the stability of the CAIX–C1 complex for more than 100 ns, and in silico studies show a strong binding affinity of the molecule to CAIX [−7.55 kcal/mol]. Conclusions: This implies that the amount of extracellular alkalosis was increased by the combination of treatment and hypoxia induction. As a result, when the cells were deprived of O2, the compound provided less defense against ROS. The compound binds to the glutamine and alanine amino acids at positions 242 and 392, respectively, at the central Zn atom of CAIX, which sets it apart from conventional sulphonamide CAIX inhibitors. This naturally occurring compound may be a potent CAIX inhibitor with newer binding sites, which could help treat hypoxic lung cancers. Full article
(This article belongs to the Special Issue Identification and Extraction of Bioactive Compounds from Marine Life)
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18 pages, 2586 KB  
Article
Novel ACE-Inhibitory Peptides from Royal Jelly Proteins: Comprehensive Screening, Mechanistic Insights, and Endothelial Protection
by Wanyu Yang, Xinyu Zou, Tianrong Zhang, Qingqing Liu, Ziyan Liu, Fan Li, Yuhong Luo, Yiwen Wang, Zhijun Qiu and Bin Zhang
Foods 2026, 15(1), 84; https://doi.org/10.3390/foods15010084 - 26 Dec 2025
Viewed by 329
Abstract
This study aimed to identify novel angiotensin-converting enzyme (ACE)-inhibitory peptides from royal jelly proteins (RJPs) by integrating in silico digestion, virtual screening, and in vitro evaluation. Three major royal jelly proteins (MRJP1-3) were subjected to in silico digestion using 16 enzymatic systems, yielding [...] Read more.
This study aimed to identify novel angiotensin-converting enzyme (ACE)-inhibitory peptides from royal jelly proteins (RJPs) by integrating in silico digestion, virtual screening, and in vitro evaluation. Three major royal jelly proteins (MRJP1-3) were subjected to in silico digestion using 16 enzymatic systems, yielding 1411 unique peptides. Virtual screening based on predicted bioactivity, toxicity, water solubility, and ADMET profiles resulted in the selection of 27 candidate peptides. Molecular docking revealed strong binding affinities for these peptides compared with the positive control captopril, among which PYPDWSFAK and RPYPDWSF exhibited potent ACE-inhibitory activity, with IC50 values of 110 ± 1.02 μmol/L and 204 ± 0.61 μmol/L, respectively. Kinetic analysis indicated that PYPDWSFAK acts as a mixed-type ACE inhibitor. Docking visualization demonstrated that PYPDWSFAK forms multiple hydrogen bonds with key residues in the ACE active pocket and directly coordinates with the catalytic Zn2+ ion. Cellular assays showed that PYPDWSFAK was non-cytotoxic, suppressed Ang II–induced endothelial cell migration, restored NO and ET-1 balance, and enhanced SOD and GSH-Px activities. Overall, this study enriches the repertoire of ACE-inhibitory peptides derived from royal jelly proteins. Furthermore, PYPDWSFAK is identified as a promising ACE-inhibitory peptide with potential for incorporation into natural antihypertensive ingredients or functional foods. Full article
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15 pages, 2572 KB  
Article
Transcriptome Assembly and Comparative Analysis of the Superoxide Dismutase (SOD) Gene Family in Three Hyotissa Species
by Xiangjie Kong, Sheng Liu, Shan Zhang, Youli Liu, Zhihua Lin and Qinggang Xue
Biology 2026, 15(1), 4; https://doi.org/10.3390/biology15010004 - 19 Dec 2025
Viewed by 465
Abstract
The genus Hyotissa (family Gryphaeidae) comprises ecologically and economically important marine bivalves, yet their molecular biology remains poorly characterized. This study presents de novo transcriptome sequencing of three Hyotissa species—H. sinensis, H. inaequivalvis, and Hyotissa sp.—to systematically identify and characterize [...] Read more.
The genus Hyotissa (family Gryphaeidae) comprises ecologically and economically important marine bivalves, yet their molecular biology remains poorly characterized. This study presents de novo transcriptome sequencing of three Hyotissa species—H. sinensis, H. inaequivalvis, and Hyotissa sp.—to systematically identify and characterize the superoxide dismutase (SOD) gene family, a crucial component of the antioxidant defense system. We identified 46 SOD genes, including both Cu/Zn-SOD and Fe/Mn-SOD types, which exhibited considerable variation in molecular properties, domain architecture, and potential phosphorylation sites. Phylogenetic analysis revealed both evolutionary conservation and diversification of SODs across species. Notably, we identified homologs of two specialized SOD types: Dominin, which showed mutations in metal-binding sites suggestive of functional divergence, and copper-only SOD repeat proteins (CSRPs), which retained copper-binding residues but lost zinc-binding capacity. These findings suggest that the SOD family in Hyotissa has undergone significant functional diversification, potentially as an adaptive response to their high-oxygen, high-ultraviolet reef habitats. This study provides foundational transcriptomic resources for Hyotissa and offers new insights into the evolution and environmental adaptation of SOD genes in marine bivalves. Full article
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17 pages, 2967 KB  
Article
Identification, Molecular Docking Mechanism and Cellular Activity of Selenium-Enriched ACE Inhibitory Peptides from Oysters
by Zhuangzhuang Yue, Zhen Xia, Fei Xu, Bingbing Chen, Shufei Jiao, Xingtang Liang, Yanzhen Yin and Jianyin Miao
Molecules 2025, 30(24), 4818; https://doi.org/10.3390/molecules30244818 - 18 Dec 2025
Viewed by 419
Abstract
Selenium-enriched oyster proteins were hydrolyzed using trypsin to obtain peptides with angiotensin-I-converting enzyme (ACE) inhibitory activity. The hydrolysate was purified by ultrafiltration and two-step reversed-phase high-performance liquid chromatography (RP-HPLC), yielding the most active fraction M4-2 (selenium content: 37.00 ± 0.56 mg/kg; IC50 [...] Read more.
Selenium-enriched oyster proteins were hydrolyzed using trypsin to obtain peptides with angiotensin-I-converting enzyme (ACE) inhibitory activity. The hydrolysate was purified by ultrafiltration and two-step reversed-phase high-performance liquid chromatography (RP-HPLC), yielding the most active fraction M4-2 (selenium content: 37.00 ± 0.56 mg/kg; IC50: 0.774 mg/mL, significantly lower than the IC50 of the crude hydrolysate, 2.801 mg/mL). This fraction was further analyzed by LC-MS/MS and molecular docking, leading to the identification of 91 selenium-containing peptide sequences. Two novel peptides, SeMFRTSSK and QASeMNEATGGK, showing strong binding affinities (−9.8 and −9.0 kcal/mol, respectively), were selected. Molecular docking revealed that SeMFRTSSK bound to key residues in the ACE active pocket via hydrogen bonds, whereas QASeMNEATGGK interacted with the Zn2+ active center. Cellular assays using EA.hy926 cells demonstrated that both peptides were non-cytotoxic at concentrations up to 0.25 mg/mL. At 0.025 mg/mL, SeMFRTSSK and QASeMNEATGGK enhanced cellular NO release by 202.65% and 273.45%, respectively, while suppressing Endothelin-1 (ET-1) secretion by 18.03% and 27.86%, compared to the blank control group. Notably, these peptides induced higher levels of NO release and greater suppression of ET-1 secretion than those in the captopril-treated positive control group. These findings support selenium-enriched oyster-derived peptides as potential natural antihypertensive ingredients. Full article
(This article belongs to the Section Food Chemistry)
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34 pages, 2440 KB  
Review
Protective Functions of β-Alanyl-L-Histidine and Glycyl-L-Histidyl-L-Lysine Glycoconjugates and Copper in Concert
by Irina Naletova and Enrico Rizzarelli
Antioxidants 2025, 14(12), 1512; https://doi.org/10.3390/antiox14121512 - 17 Dec 2025
Viewed by 1038
Abstract
Two endogenous peptides, β-alanyl-L-histidine, named carnosine (Car), and glycyl-L-histidyl-L-lysine (GHK), derived from the matricellular protein Secreted Protein Acidic and Rich in Cysteine (SPARC), share many beneficial functions. The hydrolytic enzyme carnosinase for Car and the low stability for GHK can put into question [...] Read more.
Two endogenous peptides, β-alanyl-L-histidine, named carnosine (Car), and glycyl-L-histidyl-L-lysine (GHK), derived from the matricellular protein Secreted Protein Acidic and Rich in Cysteine (SPARC), share many beneficial functions. The hydrolytic enzyme carnosinase for Car and the low stability for GHK can put into question their antioxidant, antiaggregating, and anti-inflammatory properties. The glycoconjugates of Car with a di- (trehalose, Tre) or polysaccharide (hyaluronan, HA) inhibit carnosinase, while the synthesis of HAGHK derivatives increases the tripeptide stability and protects/delays the biopolymer degradation. A synergic effect between the two components of the glycoconjugates is evident in their consequently preserved protective features. TreCar, HACar, and HAGHK maintain the copper-binding ability of the peptides alone, and the saccharides potentiate the Cu,Zn-superoxide dismutase-like ability of the copper(II) complexes with the glycoconjugates. These peptide derivatives behave as copper ionophores, utilizing Cu2+ present in the culture medium; also, an increase in the metal intracellular level occurs with a consequent stimulation of the copper-driven signaling pathways that produce the expression/release of trophic (Brain-Derived Neurotrophic Factor, BDNF, and Bone Morphogenetic Protein 2, BMP-2) and angiogenic (Vascular Endothelial Growth Factor, VEGF) proteins. Copper chaperons for SOD1, CCS, and Antioxidant 1 (Atox-1) are the copper chaperones that act as transcription factors. Full article
(This article belongs to the Special Issue Oxidative Stress and Its Mitigation in Neurodegenerative Disorders)
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19 pages, 10931 KB  
Article
Computational Biocompatibility and Safety Evaluation of Metal-Doped PET-Carbon Quantum Dots via Multi-Target Molecular Docking and ADMET Analysis on Human Proteins
by Christian Ebere Enyoh, Tochukwu Oluwatosin Maduka, Qingyue Wang, Miho Suzuki and Ifunanya Scholastica Enyoh
Physchem 2025, 5(4), 55; https://doi.org/10.3390/physchem5040055 - 10 Dec 2025
Viewed by 682
Abstract
Polyethylene terephthalate-derived fluorescent carbon quantum dots (PET-CQDs) are promising nanomaterials for sensing and biomedical uses, yet their biological interactions after metal doping require careful evaluation. Here, we report an in silico assessment of pristine and dual-site (via graphitic [G] and carbonyl [O]) metal-doped [...] Read more.
Polyethylene terephthalate-derived fluorescent carbon quantum dots (PET-CQDs) are promising nanomaterials for sensing and biomedical uses, yet their biological interactions after metal doping require careful evaluation. Here, we report an in silico assessment of pristine and dual-site (via graphitic [G] and carbonyl [O]) metal-doped PET-CQDs (Ca, Mg, Fe, Zn) using molecular docking against eight human proteins: HSA (distribution), CYP3A4 (metabolism), hemoglobin (systemic biocompatibility), transferrin (uptake), GST (detoxification), ERα (endocrine regulation), IL-6 (inflammation), and caspase-3 (cytotoxic signaling) together with ADMET profiling and DFT–docking correlation analysis. Docking affinities were compared with controls and ranged from −7.8 to −10.4 kcal·mol−1 across systems, with binding stabilized by π–π stacking, hydrogen bonding and metal–ligand coordination involving residues such as arginine, tyrosine and serine. Importantly, top-performing CQD variants differed by target: PET-CQDs, MgG_PET-CQDs and FeG_PET-CQDs were best for GST; ERα interacted favorably with all doped variants; IL-6 bound best to CaO_PET-CQDs and FeO_PET-CQDs (≈−7.1 kcal·mol−1); HSA favored CaG_PET-CQDs (−10.0 kcal·mol−1) and FeO_PET-CQDs (−9.9 kcal·mol−1); CYP3A4 bound most strongly to pristine PET-CQDs; hemoglobin favored MgG_PET-CQDs (−9.6 kcal·mol−1) and FeO_PET-CQDs (−9.3 kcal·mol−1); transferrin favored FeG_PET-CQDs; caspase-3 showed favored binding overall (pristine −6.8 kcal·mol−1; doped −7.4 to −7.6 kcal·mol−1). ADMET predictions indicated high GI absorption, improved aqueous solubility for some dopants (~18.6 mg·mL−1 for Ca-O/Mg-O), low skin permeability and no mutagenic/carcinogenic flags. Regression analysis showed frontier orbital descriptors (HOMO/LUMO) partially explain selective affinities for ERα and IL-6. These results support a target-guided selection of PET-CQDs for biomedical applications, and they call for experimental validation of selected dopant–target pairs. Full article
(This article belongs to the Section Theoretical and Computational Chemistry)
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22 pages, 4293 KB  
Article
Immobilized Sinirhodobacter sp. 1C5-22 for Multi-Metal Bioremediation: Molecular Resistance Mechanisms and Operational Validation in Industrial Wastewater Systems
by Yue Qiao, Xiaojun Huang, Si Chen, Zuye Zhang, Ying Xu, Xiaorui Zhang, Runmei Jia, Song Zhang, Wenting Lin, Xian Jiao, Huirong Chen, Zhipeng Guo, Xiao Ye, Zefeng Wu and Zhongmei Lin
Water 2025, 17(24), 3450; https://doi.org/10.3390/w17243450 - 5 Dec 2025
Viewed by 605
Abstract
A novel heavy metal-resistant bacterium with significant bioremediation capabilities, Sinirhodobacter sp. 1C5-22 was isolated from moderately polluted Shenzhen Futian mangrove rhizosphere sediments. This strain showed exceptional tolerance (MIC ≥ 600 mg/L for Cu/Zn; > 500 mg/L for Ni). Analyses revealed distinct metal-specific distribution [...] Read more.
A novel heavy metal-resistant bacterium with significant bioremediation capabilities, Sinirhodobacter sp. 1C5-22 was isolated from moderately polluted Shenzhen Futian mangrove rhizosphere sediments. This strain showed exceptional tolerance (MIC ≥ 600 mg/L for Cu/Zn; > 500 mg/L for Ni). Analyses revealed distinct metal-specific distribution strategies: Cd and Ni were predominantly bound extracellularly (>80%); Cu was bound intracellularly (~60%); and Zn exhibited balanced partitioning. Integrated omics analysis identified a molecular defense mechanism coordinated by the CreB transcriptional regulator. This Adsorption–Sequestration–Efflux (ASE) system integrates extracellular polymer binding, periplasmic sequestration via stable metal-binding proteins, and efflux pump activity, resolving the apparent adsorption-tolerance paradox at elevated concentrations. For bioremediation applications, we developed a polyvinyl alcohol–sodium alginate immobilized consortium (PVA-SA 1C5-22). The engineered agent displayed significantly enhanced biosorption capacity compared to free cells and effectively mitigated heavy metal-induced oxidative damage, evidenced by stabilized malondialdehyde levels. It demonstrated robust reusability, maintaining high metal enrichment across five adsorption–desorption cycles in multi-metal wastewater with efficient HCl-driven desorption (55–70%). Critically, it achieved stable nickel removal performance (~20% adsorption, >50% desorption) from authentic electroplating wastewater (1850 mg/L Ni2+) through successive multiple cycles. Our integrated approach bridges microbial ecology and environmental biotechnology, establishing this immobilized system as a highly sustainable strategy for complex industrial effluent remediation. Full article
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14 pages, 1736 KB  
Article
Zinc-Related Proteasome Variants in Type 1 Diabetes: An in Silico-Guided Case-Control Study
by Raif Gregorio Nasre-Nasser, Anna Carolina Meireles Vieira, Felipe Mateus Pellenz, Luciane Moretto, Eliandra Girardi, Taís Silveira Assmann, Chih-Hao Lu, Luís Henrique Canani, Cristine Dieter and Daisy Crispim
Metabolites 2025, 15(12), 772; https://doi.org/10.3390/metabo15120772 - 28 Nov 2025
Viewed by 474
Abstract
Introduction: The proteasome is a multicatalytic complex responsible for protein degradation and regulation of immune responses, and has been implicated in type 1 diabetes mellitus (T1DM) pathogenesis. Zinc (Zn2+) is essential for insulin granule biogenesis and modulates proteasomal activity. This study [...] Read more.
Introduction: The proteasome is a multicatalytic complex responsible for protein degradation and regulation of immune responses, and has been implicated in type 1 diabetes mellitus (T1DM) pathogenesis. Zinc (Zn2+) is essential for insulin granule biogenesis and modulates proteasomal activity. This study investigated associations between single-nucleotide polymorphisms (SNPs) in proteasomal subunits predicted to bind Zn2+ and T1DM susceptibility or related traits. Methods: This case–control study included 654 patients with T1DM and 573 subjects without DM from Southern Brazil. SNPs were selected through in silico analysis using MIB docking platform to identify Zn2+-interacting residues in proteasomal subunits. Five SNPs in proteasomal subunit genes—PSMA6 (rs1048990), PSMB6 (rs2304975), PSMB9 (rs17587), PSMC6 (rs2295825), and PSMD3 (rs3087852)—were genotyped using TaqMan assays. Results: The PSMC6 rs2295825C allele was associated with lower T1DM (OR = 0.77, 95% CI 0.61–0.97; p = 0.028) and diabetic retinopathy (DR; OR = 0.65; 95% CI 0.42–0.99; p = 0.048) risk, and a more favorable lipid profile (higher HDL-C, lower triglycerides) compared to the G/G genotype. The PSMB9 rs17587A/A genotype was linked to higher total cholesterol and HbA1c levels. The PSMA6 rs1048990G allele was linked to increased prevalence of diabetic kidney disease (DKD; OR = 1.75, 95% CI 1.02–2.99; p = 0.042), and the PSMD3 rs3087852A allele was associated with lower urinary albumin excretion. No significant associations were observed for the PSMB6 rs2304975 SNP. Conclusions: The PSMC6 rs2295825 SNP may confer protection against T1DM. The PSMC6 rs2295825, PSMB9 rs17587, PSMA6 rs1048990, and PSMD3 rs3087852 SNPs appear to influence lipid metabolism and diabetic microvascular complications. Full article
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29 pages, 870 KB  
Review
Epigenomics and Non-Coding RNAs in Soybean Adaptation to Abiotic Stresses
by Kinga Moskal, Bartosz Tomaszewski and Maja Boczkowska
Int. J. Mol. Sci. 2025, 26(23), 11527; https://doi.org/10.3390/ijms262311527 - 27 Nov 2025
Viewed by 685
Abstract
This review presents soybean responses to drought, heat, and salinity within a signal–transcript–chromatin framework. In this framework, calcium/reactive oxygen species and abscisic acid cues converge on abscisic acid-responsive element binding factor (ABF/AREB), dehydration-responsive element binding protein (DREB), NAC, and heat shock factor (HSF) [...] Read more.
This review presents soybean responses to drought, heat, and salinity within a signal–transcript–chromatin framework. In this framework, calcium/reactive oxygen species and abscisic acid cues converge on abscisic acid-responsive element binding factor (ABF/AREB), dehydration-responsive element binding protein (DREB), NAC, and heat shock factor (HSF) families. These processes are modulated by locus-specific chromatin and non-coding RNA layers. Base-resolved methylomes reveal a high level of CG methylation in the gene body, strong CHG methylation in heterochromatin, and dynamic CHH ‘islands’ at the borders of transposable elements. CHH methylation increases over that of transposable elements during seed development, and GmDMEa editing is associated with seed size. Chromatin studies in soybean and model species implicate the reconfiguration of salt-responsive histone H3 lysine 27 trimethylation (H3K27me3) in G. max and heat-linked H2A.Z dynamics at thermoresponsive promoters characterized in Arabidopsis and other plants, suggesting that a conserved chromatin layer likely operates in soybean. miR169–NF-YA, miR398–Cu/Zn Superoxide Dismutases(CSD)/copper chaperone of CSD(CCS), miR393–transporter inhibitor response1/auxin signaling F-box (TIR1/AFB), and miR396–growth regulating factors (GRF) operate across leaves, roots, and nodules. Overexpression of lncRNA77580 enhances drought tolerance, but with context-dependent trade-offs under salinity. Single-nucleus and spatial atlases anchor these circuits in cell types and microenvironments relevant to stress and symbiosis. We present translational routes, sentinel epimarkers (bisulfite amplicons, CUT&Tag), haplotype-by-epigenotype prediction, and precise cis-regulatory editing to accelerate marker development, genomic prediction and the breeding of resilient soybean varieties with stable yields. Full article
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24 pages, 3083 KB  
Article
Can the Quality of Semen Affect the Fertilisation Indices of Turkey Eggs?
by Aleksandra Orzołek, Anna Dziekońska, Paulina Skorynko and Joanna Ner-Kluza
Int. J. Mol. Sci. 2025, 26(22), 11000; https://doi.org/10.3390/ijms262211000 - 13 Nov 2025
Viewed by 572
Abstract
Several factors, including semen quality, can influence fertilisation success. Poor semen parameters may necessitate more frequent inseminations or the removal of males with consistently low fertility. This study evaluated turkey ejaculates (n = 37) with good fertility (GF) and impaired fertility (IF). [...] Read more.
Several factors, including semen quality, can influence fertilisation success. Poor semen parameters may necessitate more frequent inseminations or the removal of males with consistently low fertility. This study evaluated turkey ejaculates (n = 37) with good fertility (GF) and impaired fertility (IF). The analyses included sperm motility parameters (total motility—TMOT, progressive motility—PMOT, curvilinear velocity—VCL, straight-line velocity—VSL, average path velocity—VAP, linearity—LIN, straightness—STR, amplitude of lateral head displacement—ALH, and beat cross frequency—BCF), plasma membrane integrity (PMI), mitochondrial membrane potential (MMP), and nitric oxide (NO) production, as well as enzymatic and biochemical assays of semen, such as superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) activities, glutathione (GSH) content, malondialdehyde (MDA) levels, and zinc (Zn2+) concentration. In parallel, the proteomes of seminal plasma and spermatozoa were separated using SDS- and Tricine-PAGE, and selected proteins were identified by nano LC-MS/MS. Spermatozoa derived from IF ejaculates exhibited significantly reduced TMOT (p = 0.002), VCL (p = 0.028), and PMI (p = 0.000), accompanied by elevated STR (p = 0.000) and NO production (p = 0.044). In the seminal plasma of IF males, a significant decrease was noted in SOD (p = 0.000) and GPx (p = 0.001) activities, whereas CAT activity was markedly higher (p = 0.014). Seminal fluid from IF ejaculates was also characterised by increased GSH (p = 0.014) and MDA (p = 0.014) concentrations, accompanied by reduced Zn2+ content (p = 0.014). In contrast, IF spermatozoa exhibited elevated SOD activity (p = 0.001), but reduced GPx (p = 0.000) and CAT (p = 0.012) activities. Sperm cells from IF ejaculates also had lower GSH levels (p = 0.000), higher MDA concentrations (p = 0.000), and increased Zn2+ content (p = 0.018) compared with those from GF ejaculates. A proteomic analysis revealed differences in fertility-associated proteins: peroxiredoxin 6 (PRDX6) was detected exclusively in GF semen, whereas alpha-enolase (ENO1), fatty acid-binding protein (FABP7), cytoplasmic aspartate aminotransferase (GOT1), and L-lactate dehydrogenase B (LDHB) were detected only in IF semen. Overall, the results demonstrate that both semen parameters and proteome composition may potentially affect the fertilisation outcomes in turkeys. Full article
(This article belongs to the Section Molecular Biology)
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18 pages, 8401 KB  
Article
Identification of the Metallocarboxypeptidase M14 Gene Family in Lysiosquillina maculata, Odontodactylus scyllarus and Oratosquilla oratoria Based on the Full-Length Transcriptome
by Jiantong Zhang, Xiuqiang Dong, Xinyan Hu, Xiaowen Duan, Bin Xu and Fangrui Lou
Fishes 2025, 10(10), 515; https://doi.org/10.3390/fishes10100515 - 10 Oct 2025
Viewed by 509
Abstract
Metallocarboxypeptidase (MCP) is a crucial protein enzyme involved in food digestion and absorption in animals, which has a potential influence on the differentiation of the trophic niche. Considering that stomatopods have raptorial appendage-specific trophic niches, the present study screened and compared [...] Read more.
Metallocarboxypeptidase (MCP) is a crucial protein enzyme involved in food digestion and absorption in animals, which has a potential influence on the differentiation of the trophic niche. Considering that stomatopods have raptorial appendage-specific trophic niches, the present study screened and compared the MCP M14 gene family of three stomatopods (Lysiosquillina maculata, Odontodactylus scyllarus, and Oratosquilla oratoria) with different raptorial appendage morphologies based on full-length transcriptome information. There are 13 and 17 MCP M14 gene family members identified in L. maculata and O. scyllarus, respectively, which are classified as M14A, M14B, and M14D subfamilies. However, 15 MCP M14 family members have been identified in O. oratoria, all belonging to the M14A subfamily. The physicochemical properties, phylogenetic relationships, conserved motifs, and secondary and tertiary structures of the MCP M14 amino acid sequences were also analyzed in the present study. The results revealed that each amino acid sequence had unique physicochemical properties. Ten conserved motifs were further characterized across the MCP M14 amino acid sequences, and the type and number of motifs from the same subfamily remained highly conserved. Meanwhile, we found that most of the MCP M14 gene family members have critical residues (including Zn2+ binding sites [His69, Glu72, and His196], substrate-binding residues [Arg124, Arg127, and Arg145], and disulfide bond-forming residues [Cys138 and Cys161]) involved in disulfide bond formation and enzyme activity stabilization. Furthermore, the random coil is the predominant structural feature of the MCP M14 amino acid sequence. In conclusion, these results are undoubtedly valuable for exploring the evolution and regulation mechanisms of the trophic niche in stomatopods. Full article
(This article belongs to the Section Genetics and Biotechnology)
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33 pages, 5369 KB  
Review
Zinc-Mediated Defenses Against Toxic Heavy Metals and Metalloids: Mechanisms, Immunomodulation, and Therapeutic Relevance
by Roopkumar Sangubotla, Shameer Syed, Anthati Mastan, Buddolla Anantha Lakshmi and Jongsung Kim
Int. J. Mol. Sci. 2025, 26(19), 9797; https://doi.org/10.3390/ijms26199797 - 8 Oct 2025
Viewed by 2290
Abstract
Zinc (Zn), a naturally occurring trace element ubiquitous in the Earth’s crust, soil, and water, is indispensable for human health due to its physiological and nutritive benefits. In this scenario, Zn is pivotal for maintaining homeostasis against toxic effects exerted by heavy metals [...] Read more.
Zinc (Zn), a naturally occurring trace element ubiquitous in the Earth’s crust, soil, and water, is indispensable for human health due to its physiological and nutritive benefits. In this scenario, Zn is pivotal for maintaining homeostasis against toxic effects exerted by heavy metals (HMs) through bioaccumulation and metabolic interference. Zinc is an enticing cofactor for miscellaneous biochemical enzymes such as Zn metalloenzymes, which mediate crucial cellular processes, including cell proliferation, protein synthesis, immune modulation, epigenetic regulation, and nucleic acid synthesis. Recently, several research studies have focused on the thorough investigation of Zn supplementation in controlling HM toxicity by competing for binding sites and boosting protective mechanisms in humans. The current article discusses the upper limits for various toxic HMs in staple crop foods, as provided by globally recognized organizations. Clinical studies recommend a daily dose of 11 mg of Zn for healthy men and 8–12 mg for women in healthy and pregnancy conditions. However, during Zn deficiency, therapeutic supplementation is expected to be adjustable, and the dosage is increased from 15 to 30 mg daily. This review discusses the dysregulation of specific Zn importers and transporters (ZIPs/ZnTs) due to their clinical significance in immune system dysfunction as well as the progression of a myriad of cancers, including prostate, breast, and pancreas. Moreover, this review emphasizes indispensable in vitro and in vivo studies, as well as key molecular mechanisms related to Zn supplementation for treating toxicities exacerbated by HMs. Full article
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21 pages, 2754 KB  
Article
Exploring Growth Phase Effect on Polysaccharide Composition and Metal Binding Properties in Parachlorella hussii
by Karima Guehaz, Zakaria Boual, Giulia Daly, Matilde Ciani, Hakim Belkhalfa and Alessandra Adessi
Polysaccharides 2025, 6(3), 58; https://doi.org/10.3390/polysaccharides6030058 - 2 Jul 2025
Cited by 1 | Viewed by 1150
Abstract
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), [...] Read more.
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
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11 pages, 1407 KB  
Article
Molecular Dynamics Study on Complexation of Uranyl and Zinc Ions with Fatty Acid Bound Human Serum Albumin
by Vijayakriti Mishra, Pramilla D. Sawant and Arup Kumar Pathak
Liquids 2025, 5(2), 14; https://doi.org/10.3390/liquids5020014 - 16 May 2025
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Abstract
Nuclear technology, while offering significant benefits across various sectors, poses potential health risks due to uranium (U) contamination, particularly through its internalization and subsequent interactions with biological systems. This study investigates the binding of uranyl (UO22+) and zinc (Zn2+ [...] Read more.
Nuclear technology, while offering significant benefits across various sectors, poses potential health risks due to uranium (U) contamination, particularly through its internalization and subsequent interactions with biological systems. This study investigates the binding of uranyl (UO22+) and zinc (Zn2+) ions to Human Serum Albumin (HSA) that is already bound to fatty acids (FAs), using all-atom molecular dynamics (MD) simulations. The analysis focuses on the structural and dynamic alterations in the protein’s multi-metal binding site (MBS-A) caused by FA binding. Results reveal that FA binding induces a conformational change in HSA, disrupting the pre-formed MBS-A binding site, while still allowing uranyl and zinc ions to interact with residue D249 through strong Coulombic interactions. Secondary binding sites, associated with calcium and zinc binding, remain largely unaffected by FAs, providing alternative coordination for metal ions. This study also explores the binding and unbinding pathways of the metal ions using well-tempered meta-dynamics (WT-MtD), showing that while FA binding disrupts the primary metal binding site, it does not completely inhibit the binding of both uranyl and zinc ions. These findings offer new insights into the nature of uranium’s interactions with blood serum proteins and the role of fatty acids in modulating these interactions, which may help in designing future strategies for managing uranium contamination in biological systems. Full article
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14 pages, 2399 KB  
Article
Purification of Human Immunoglobulin G with Bathophenanthroline–Zn2+, –Fe2+, or –Cu2+ Complexes
by Thisara Jayawickrama Withanage, Ron Alcalay, Olga Krichevsky, Ellen Wachtel, Ohad Mazor and Guy Patchornik
Antibodies 2025, 14(2), 40; https://doi.org/10.3390/antib14020040 - 12 May 2025
Viewed by 1328
Abstract
Background/Objectives: Pharmaceutical companies are aware of the ongoing effort to satisfy the increasing global demand for therapeutic-grade monoclonal antibodies (mAbs), an especially difficult challenge for poor and developing countries. We present a simple, economical, single-step purification approach at neutral pH for polyclonal human [...] Read more.
Background/Objectives: Pharmaceutical companies are aware of the ongoing effort to satisfy the increasing global demand for therapeutic-grade monoclonal antibodies (mAbs), an especially difficult challenge for poor and developing countries. We present a simple, economical, single-step purification approach at neutral pH for polyclonal human IgG (hIgG), which does not require any expensive ligands, chromatography columns, polymers, or membranes. Methods/Results: Instead, porous precipitates of commercial, recyclable aromatic [bathophenanthroline:cation] complexes were found to efficiently capture impurity proteins from CHO cells or E. coli lysate while maintaining the majority of the highly concentrated hIgG (5–15 mg/mL) in the supernatant. [(Batho)3:Zn2+] complexes were the most promising, resulting in hIgG with a purity of ≈95%, by SDS-PAGE. This purified hIgG is monomeric (by dynamic light scattering, DLS) and preserves the native secondary structure (by far UV circular dichroism spectroscopy, CD). The process yield is >90% (by densitometry) and is maintained after a 100-fold increase in the reaction volume, which required only proportional increases in reagents. Conclusions: Although Protein A chromatographic columns, the industry gold standard, have a limited binding capacity, are costly, and require familiarity with column maintenance, we are attempting, by our efforts, to help to produce a more efficient, simple, and economical purification platform. Full article
(This article belongs to the Section Antibody-Based Therapeutics)
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