Search Results (637)

Zinc finger proteins are frequently implicated in a wide range of neurodevelopmental disorders (NDDs). In this study, we report a case of mild intellectual disability (ID), global developmental delay (GDD), and developmental coordination disorder (DCD) in an individual with unaffected parents. Trio-based whole-exome sequencing (WES) identified a de novo variant (c.1530dup, p.Glu511ArgfsTer16) in the ZNF496 gene of the proband. According to ACMG guidelines, this novel variant is classified as pathogenic. It creates a frameshift that introduces a premature stop codon, resulting in a truncated protein of 525 amino acids (compared to the wild-type 587 residues). Notably, NMDEscPredictor analysis predicted that the transcript escapes nonsense-mediated decay (NMD) despite the frameshift. Computational analyses suggest the potential pathogenetic effects of the identified variant. As documented, ZNF496 interacts with JARID2, a gene associated with NDDs, ID and facial dysmorphism (MIM: #620098). In silico analyses suggest that the identified mutation disrupts this interaction by deleting ZNF496’s C2H2 domain, potentially dysregulating JARID2 target genes. To our knowledge, this is the first reported association between ZNF496 and NDDs, and the variant has been submitted to the ClinVar database (SCV006100880). Functional studies are imperative to validate ZNF496’s role in NDDs and confirm the mutation’s impact on ZNF496-JARID2 interactions. Full article

Background/Objectives: Cancer is a complex disease that affects patients’ nutritional and psychological status. This study aimed to assess the nutritional status of patients diagnosed with lung and gastrointestinal system cancers and evaluate its association with anthropometric measurements, nutrient intake, and psychological symptoms. Methods: This cross-sectional study was conducted with 180 patients with lung and gastrointestinal system cancers. Data were collected face-to-face by a questionnaire that included the Subjective Global Assessment-(SGA), Cachexia Assessment Criteria, 24 h Food Consumption Record, and Symptom Checklist-90-Revised-(SCL-90-R). Some anthropometric measurements were collected. Results: Body Mass Index (BMI) was found to be significantly lower (p < 0.001) in SGA-B (moderately malnourished) and SGA-C (severely malnourished) compared to those in SGA-A (well-nourished). The calf circumference was significantly lower (p = 0.002) in SGA-C compared to those in SGA-A and SGA-B. The mean SGA scores were found to be higher in cachexia-diagnosed participants (p < 0.001). The energy intake of SGA-C was significantly lower than SGA-A and SGA-B (p < 0.001). In addition, the energy intake of SGA-B was lower than SGA-A (p < 0.001). The protein intake of SGA-C was lower than SGA-A and SGA-B (p < 0.001). The protein intake of SGA-B was lower than SGA-A (p < 0.001). Regarding the intake of vitamins A, C, E, B1, and B6 and carotene, folate, potassium, magnesium, phosphorus, iron, and zinc, SGA-B and SGA-C were significantly lower than SGA-A (p < 0.001). Additionally, only phobic anxiety was found to be significantly higher in SGA-B than in SGA-A (p: 0.024). Conclusions: As the level of malnutrition increased, a reduction in some nutrient intake and anthropometric measurements was observed. No significant difference was found in any psychological symptoms except phobic anxiety. With this in mind, it is important that every cancer patient, regardless of the stage of the disease, is referred to a dietitian from the time of diagnosis. Full article

The ZC4H2 gene is the site of congenital mutations linked to neurodevelopmental and musculoskeletal pathologies collectively termed ZARD (ZC4H2-Associated Rare Disorders). ZC4H2 consists of a coiled coil and a single novel zinc finger with four cysteines and two histidines, from which the protein obtains its name. Alpha Fold 3 confidently predicts a structure for the zinc finger but also for similarly sized random sequences, providing equivocal information on its folding status. We show using synthetic peptide fragments that the zinc finger of ZC4H2 is genuine and folds upon binding a zinc ion with picomolar affinity. NMR pH titration of histidines and UV–Vis of a cobalt complex of the peptide indicate its four cysteines coordinate zinc, while two histidines do not participate in binding. The experimental NMR structure of the zinc finger has a novel structural motif similar to RANBP2 zinc fingers, in which two orthogonal hairpins each contribute two cysteines to coordinate zinc. Most of the nine ZARD mutations that occur in the ZC4H2 zinc finger are likely to perturb this structure. While the ZC4H2 zinc finger shares the folding motif and cysteine-ligand spacing of the RANBP2 family, it is missing key substrate-binding residues. Unlike the NZF branch of the RANBP2 family, the ZC4H2 zinc finger does not bind ubiquitin. Since the ZC4H2 zinc finger occurs in a single copy, it is also unlikely to bind DNA. Based on sequence homology to the VAB-23 protein, the ZC4H2 zinc finger may bind RNA of a currently undetermined sequence or have alternative functions. Full article

Trichomes are specialized epidermal structures that protect plants from environmental stresses, regulated by transcription factors integrating hormonal and environmental cues. This study investigates the roles of two C2H2 zinc finger proteins, GIS2 and ZFP8, in regulating trichome patterning in Arabidopsis thaliana. Using dexamethasone-inducible overexpression lines, transcriptomic profiling, and chromatin immunoprecipitation, we identified 142 GIS2- and 138 ZFP8-associated candidate genes involved in sterol metabolism, senescence, and stress responses. GIS2 positively and directly regulated the expression of SQE5, linked to sterol biosynthesis and drought tolerance, and repressed SEN1, a senescence marker associated with abscisic acid and phosphate signaling. ZFP8 modulated stress-related target genes, including PR-4 and SPL15, with partial functional overlap between GIS family members. Spatially, GIS2 functions in inflorescence trichomes via integrating gibberellin-cytokinin pathways, while ZFP8 influences leaf trichomes through cytokinin and abscisic acid signal. Gibberellin treatment stabilized GIS2 protein and induced SQE5 expression, whereas SEN1 repression was gibberellin-independent. Chromatin immunoprecipitation and DEX-CHX experiment confirmed GIS2 binding to SQE5 and SEN1 promoters at conserved C2H2 motifs. These findings highlight hormone-mediated transcriptional regulation of trichome development by GIS2 and ZFP8, offering mechanistic insight into signal integration. The results provide a foundation for future crop improvement strategies targeting trichome-associated stress resilience. Full article

Magenta Cherry or Eugenia (Syzygium paniculatum Gaertn) is an underutilized berry species with an interesting source of functional components. This study aimed to evaluate these berries’ morphometric, nutritional, and phytochemical characteristics at two ripening stages, CM: consumer maturity (CM) and OM: over-maturity. Morphometric analysis revealed size and weight parameters comparable to commercial berries such as blueberries. Fresh fruits were processed into pulverized material, and in this, a proximate analysis was evaluated, showing high moisture content (88.9%), dietary fiber (3.56%), and protein (0.63%), with negligible fat, indicating suitability for low-calorie diets. Phytochemical screening by HPLC identified gallic acid, chlorogenic acid, hydroxycinnamic acid, ferulic acid, quercetin, rutin, and condensed tannins. Ethanol extracts showed stronger bioactive profiles than aqueous extracts, with significant antioxidant capacity (up to 803.40 µmol _Trolox/g via Ferric Reducing Antioxidant Power (FRAP assay). Fourier-transform infrared spectroscopy (FTIR) and Raman spectroscopic analyses established structural transformations of hydroxyl, carbonyl, and aromatic groups associated with ripening. These changes were supported by observed variations in anthocyanin and flavonoid contents, both higher at the CM stage. A notable pigment loss in OM fruits could be attributed to pH changes, oxidative degradation, enzymatic activity loss, and biotic stressors. Antioxidant assays (DPPH, ABTS, and FRAP) confirmed higher radical scavenging activity in CM-stage berries. Elemental analysis identified minerals such as potassium, calcium, magnesium, iron, and zinc, although in moderate concentrations. In summary, Syzygium paniculatum Gaertn fruit demonstrates considerable potential as a source of natural antioxidants and bioactive compounds. These findings advocate for greater exploration and sustainable use of this native berry species in functional food systems. Full article

C2H2 zinc finger proteins (C2H2-ZFPs) constitute one of the largest transcription factor families in plants, playing crucial roles in growth, development, and stress responses. Here, we performed a comprehensive genome-wide analysis of C2H2-ZFPs in foxtail millet (Setaria italica v2.0), identifying 67 members that were unevenly distributed across all nine chromosomes. Most SiC2H2 proteins were predicted to be alkaline, stable, and nuclear-localized, with the exception of SiC2H2-11 and SiC2H2-66, which were chloroplast-targeted. Phylogenetic analysis with Arabidopsis thaliana and Oryza sativa (rice) homologs classified these genes into seven distinct subfamilies, each containing the characteristic motif1 domain. Evolutionary studies revealed 14 segmental duplication events and strong syntenic conservation with Triticum aestivum (wheat, 163 orthologous pairs), suggesting conserved functions during evolution. Promoter analysis identified multiple cis-acting elements associated with light responsiveness, hormone signaling, and stress adaptation. Transcriptome profiling and qPCR validation in the YuGu 56 cultivar identified several stress-responsive candidates, including SiC2H2-35 and SiC2H2-58 (salt tolerance), as well as SiC2H2-23 (5.19-fold induction under salt stress) and SiC2H2-32 (5.47-fold induction under drought). This study provides some valuable insights into the C2H2-ZFP family in foxtail millet and highlights potential genetic markers for improving stress resilience through molecular breeding approaches. Full article

Background/Objectives: Endplate lesions of the lumbar spine are often asymptomatic and frequently observed incidentally by radiological assessment. Variants in the vitamin D receptor gene (VDR) and an increase in some biochemical markers related to the osteo-cartilaginous metabolism were found in patients with endplate lesions. The aim of this study was to identify biochemical and genetic markers putatively associated with the presence of endplate lesions of the lumbar spine. Methods: Quantification of circulating bone remodeling proteins was obtained from 10 patients with endplate lesions and compared with age- and sex-matched controls. Whole exome sequencing (WES) was performed on patient genomic DNA using the Novaseq 6000 platform (Illumina, San Diego, CA, USA), obtaining a median read depth of 117×–200×, with ≥98% of regions covering at least 20×. The sequencing product was aligned to the reference genome (GRCh38.p13-hg38) and analyzed with Geneyx software. Results: We observed modifications in the levels of circulating proteins involved in bone remodeling and angiogenesis. We identified variants of interest in aggrecan (ACAN), bone morphogenetic protein 4 (BMP4), cytochrome P450 family 3 subfamily A member 4 (CYP3A4), GLI family zinc finger 2 (GLI2), heparan sulfate proteoglycan 2 (HSPG2), and mesoderm posterior bHLH transcription factor 2 (MESP2). VDR polymorphism (rs2228570) was present in nine patients, with the homozygotic ones having more severe endplate lesions and higher levels of the analyzed circulating markers in comparison with heterozygotic patients. Conclusions: These data represent interesting evidence of genetic variants, particularly in VDR, and altered levels of circulating markers of bone remodeling associated with endplate lesions, which should be confirmed in a larger population. The hypothesis suggested by our results is that the endplate lesions could be the consequence of an altered ossification mechanism at the vertebral level. Full article

Background/Objectives: Canine intervertebral disc herniation (IVDH) is an important musculoskeletal pathology. Unlike in humans, IVDH mechanisms in dogs are underinvestigated from a system-level integrative omics point of view. The aim of this study was to identify key serum molecular players in canine IVDH. Methods: An integrative multi-omics approach combining high-resolution LC-MS-based untargeted metabolomics and tandem mass tag (TMT)-based proteomics was applied. Additionally, serum zinc concentration was determined by spectrophotometry. Results: Nineteen serum metabolites were differentially abundant in IVDH dogs. Metabolite analysis highlighted dysregulation in lipoic acid and branched-chain amino acid (BCAA) metabolism, with elevated levels of valine, leucine, and isoleucine in IVDH. These findings suggest disrupted energy, nitrogen, and neurotransmitter metabolism, potentially contributing to the IVDH pathophysiology. Additionally, lower serum uridine, possibly influenced by BCAA accumulation, was observed, indicating altered neuroinflammatory responses. ELISA validation confirmed elevated serum levels of zinc-α2-glycoprotein (ZAG), alpha-1-microglobulin/bikunin precursor (AMBP), and vitronectin (VTN) in IVDH, supporting immune modulation and neuroprotective mechanisms. Serum prekallikrein (KLKB1) and Protein C inhibitor (SERPINA5), involved in fibrin cloth formation, were found to be lowered in IVDH patients. Pathway enrichment revealed disturbances in aromatic amino acid biosynthesis, with elevated phenylalanine, tyrosine, and tryptophan influencing neurotransmission and inflammation. In addition, elevated serum Zn concentration emphasized its antioxidant importance in immune response, wound healing, and neuropathic pain signaling. Conclusions: Integration with our prior CSF multi-omics data reinforced the relevance of identified molecules in IVDH-associated neurodegeneration, inflammation, and repair processes. This study offers insight into potential diagnostic biomarkers and therapeutic targets for canine IVDH through serum-based molecular profiling. Full article

Bougainvillea spp. possesses vibrantly pigmented bracts that exhibit high ornamental value. Zinc finger proteins (ZFPs), one of the most extensive transcription factor families in plants, are implicated in diverse biological functions, including plant morphogenesis, transcriptional regulation, and responses to abiotic stress. Nevertheless, their regulatory roles in bract pigmentation in Bougainvillea remain unexplored. In the present investigation, 105 BbZFP genes were identified from the Bougainvillea genome via bioinformatic analyses and subsequently categorized into five subgroups according to the quantity and arrangement of their structural domains. Analysis of physicochemical characteristics demonstrated that the BbZFP family encompasses both acidic and basic proteins, all of which are hydrophilic and predominantly classified as unstable proteins. Gene structure analysis revealed that the majority of BbZFP genes comprise between one and five– introns. Cis-regulatory element analysis suggested that BbZFP promoter regions harbor multiple elements associated with abiotic stress responses, hormonal regulation, and light responsiveness, implying their possible participation in these physiological processes. Transcriptomic data analysis revealed distinct expression patterns of BbZFP genes among bracts of different colors. A quantitative real-time polymerase chain reaction (RT-qPCR) further confirmed that Bou_68928, Bou_1096, Bou_4400, and Bou_17631 were markedly upregulated in yellow bracts relative to white bracts, suggesting their involvement in flavonoid biosynthesis regulation. Meanwhile, Bou_1096 and Bou_17631 exhibited markedly elevated expression in red-purple bracts compared to white bracts, potentially regulating betacyanin biosynthesis in Bougainvillea. These findings offer candidate genes for molecular breeding strategies aimed at enhancing floral coloration in Bougainvillea. The next step will involve elucidating the functions of these genes in bract coloration. Full article

Zinc-alpha2-glycoprotein (ZAG) is a soluble glycoprotein primarily produced in adipocytes and the liver, with key roles in lipid metabolism, including lipolysis and the browning of adipose tissue. Despite extensive studies on its role in rodents, the relationship between ZAG and insulin in humans remains unclear. Given the emerging interest in ZAG’s involvement in metabolic diseases such as metabolic-dysfunction-associated steatotic liver disease, this study aimed to investigate the acute effects of insulin on ZAG levels both in vivo and in vitro. We recruited 24 healthy, individuals who were non-obese and assessed the impact of oral glucose overload, a standardized liquid nutritional supplement, and intravenous glucagon on circulating ZAG levels. In parallel, we explored the effects of insulin on ZAG production in cultured HepG2 cells. Our findings revealed a consistent acute reduction in serum ZAG levels following all in vivo tests, coinciding with increased insulin levels. In vitro, insulin rapidly downregulated ZAG protein and mRNA levels in HepG2 cells, with significant reductions observed within 15 min, followed by partial recovery after 2 h. These results suggest a potential acute inhibitory effect of insulin on ZAG production, supporting its role in promoting energy storage by suppressing lipolysis postprandially. This study provides new insights into the complex interplay between insulin and ZAG in regulating energy balance and highlights the potential of ZAG as a therapeutic target in metabolic diseases. Full article

Background: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder caused by mutations in the SERPINA1 gene, leading to reduced levels or impaired alpha-1 antitrypsin (AAT) function. This condition predominantly affects the lungs and liver. The Z allele, a specific mutation in the SERPINA1 gene, is the most severe form and results in the production of misfolded AAT proteins. The misfolded proteins accumulate in the endoplasmic reticulum (ER) of liver cells, triggering ER stress and activating the unfolded protein response (UPR), a cellular mechanism designed to restore ER homeostasis. Currently, there is limited knowledge regarding specific nutritional recommendations for patients with AATD. The liver is essential for the regulation of zinc homeostasis, with zinc widely recognized for its hepatoprotective properties. However, the effects of AATD on zinc metabolism remain poorly understood. Similarly, the potential benefits of zinc supplementation for individuals with AATD have not been thoroughly investigated. Objective: This study explored the relationship between AATD and zinc metabolism through a combination of in vitro experiments and computational analysis. Results: The expression of the mutant Z variant of ATT (ATZ) in cultured mouse hepatocytes was associated with decreased labile zinc levels in cells and dysregulation of zinc homeostasis genes. Analysis of two data series from the Gene Expression Omnibus (GEO) revealed that mice expressing ATZ (PiZ mice), a murine model of AATD, exhibited significant differences in mRNA levels related to zinc homeostasis and UPR when compared to wildtype mice. Bayesian network analysis of GEO data uncovered novel gene-to-gene interactions among zinc transporters, as well as between zinc homeostasis, UPR, and other associated genes. Conclusions: The findings provide valuable insights into the role of zinc homeostasis genes in UPR processes linked to AATD. Full article

Rice (Oryza sativa L.) is a crucial crop for biofortification that is widely consumed and is cultivated in soils with low levels of selenium (Se) and zinc (Zn). The study evaluated how upland rice genotypes can increase Se and Zn in grains with foliar fertilization and analyzed the impact on agronomic characteristics and protein and amino acid contents. Experiments in Lambari and Lavras used a 5 × 4 factorial design with five genotypes (BRS Esmeralda, CMG 2188, CMG ERF 221-16, CMG ERF 221-19, CMG ERF 85-15) and four treatments (control, without Se; 5.22 g Se ha⁻¹; 1.42 kg Zn ha⁻¹; and combined Zn+Se) with three replicates. The study showed that CMG ERF 85-15, with Se fertilization, increased grain yield in Lambari. In Lavras, adding Zn to CMG 2188 and CMG ERF 85-15 improved grain yield. In Lambari, most variables were grouped with Zn+Se, except grain yield and free amino acids in the grain. In Lavras, variables associated with Se, proteins, free amino acids in the polished grain, hulling in whole and polished grain, and milling yield were grouped under the treatment Zn+Se. We recommend the genotype CMG ERF 85-15 based on the results for foliar biofortification with Zn+Se. Full article

“Sola dosis facit venenum” (Paracelsus). Essential trace elements, crucial for maintaining neuronal function, have their dysregulation increasingly correlated with neurodegenerative disorders, particularly Parkinson’s disease (PD). This systematic review aims to synthesize recent high-quality evidence regarding the involvement of essential trace elements, such as iron, zinc, copper, manganese, and selenium, in the pathogenesis and, consequently, as potential therapeutic targets of PD. A comprehensive literature search was conducted for articles published between 1 January 2023 and 31 December 2024. Out of an initial pool of 1231 identified studies, 63 met the methodological eligibility criteria according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. All potentially eligible interventional and observational studies were initially assessed using the Physiotherapy Evidence Database (PEDro) scale, which is commonly employed for evaluating the internal validity and statistical interpretability of clinical trials and rehabilitation-focused studies. Following the qualitative assessment using the PEDro scale, 18 studies were ultimately selected based on their scientific relevance and methodological rigor. To supplement the PEDro scoring, which is designed primarily for individual trials, we applied the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) checklist for the evaluation of the included systematic reviews or meta-analyses. The included studies employed a variety of clinical, postmortem, and experimental models to investigate trace-element concentrations and their mechanistic roles in PD. The findings revealed consistent patterns of iron accumulation in the substantia nigra, zinc’s bidirectional effects on oxidative stress and autophagy, copper-induced α-synuclein aggregation, and the neuroprotective role of selenium via antioxidant pathways. Manganese was associated with mitochondrial dysfunction and neuroinflammation. Essential trace-element disturbances contribute to PD pathology through interconnected mechanisms involving redox imbalance, protein misfolding, and impaired cellular homeostasis. These elements may serve as both biomarkers and potential therapeutic tools, warranting further investigation into personalized metal-based interventions for PD. Full article

Background/Objectives: Canada’s 2019 Food Guide (CFG) encourages the increased consumption of plant-based foods as dietary protein sources. However, the nutritional implications of replacing animal-based proteins with plant-based alternatives in children’s diets remain unclear. This study aimed to examine the association between protein food sources and nutrient intake in Canadian children aged 9–18 years. Methods: We analyzed data from 2324 children from the 2015 Canadian Community Health Survey (CCHS), using the Public-Use Microdata File (PUMF) containing 24 h dietary recalls. Participants were categorized into four groups based on the proportion of protein from plant sources: Group 1 (0–24.9%), Group 2 (25–49.9%), Group 3 (50–74.9%), and Group 4 (75–100%). Nutrient intakes were compared and assessed against the Recommended Dietary Allowances (RDAs) and Adequate Intake (AI). Results: Groups 1 and 3 had less favorable macronutrient profiles than Group 2. A 3:1 animal-to-plant protein ratio (Group 2) aligned most closely with dietary recommendations. Groups 1 and 2 exceeded RDAs for protein, iron, vitamin B12, thiamine, riboflavin, niacin, vitamin B6, and zinc by over 146% (about four SDs above the mean requirement), suggesting a low risk of inadequacy, although saturated fat intake was high. The intakes of vitamin D and folate were below 66% of the RDA, while calcium and magnesium were below 100% in some subgroups, with probabilities of inadequacy of 0.93 and 0.31, respectively. Group 4 (2.71%) was too small for reliable analysis. Conclusions: An approximate 3:1 ratio of animal-to-plant protein sources may represent an optimal balance for supporting nutrient intake and improving macronutrient profiles in the diets of Canadian children. Full article

Lifestyle and dietary modifications are unanimously suggested as the initial step to treat hypertension in the general population and in patients with chronic kidney disease (CKD). Limiting sodium intake constitutes the cornerstone of dietary interventions, but augmenting dietary potassium intake has also been associated with a significant blood pressure (BP)-lowering effect. Although there may be a consensus about restraining the daily sodium intake to <2 g per day, the target for optimal potassium intake is vague. In hypertensive patients with CKD, the desired amount of potassium in the diet remains a controversial issue, as evidence from studies concerning the effect on CKD progression is contradictory. Hence, medical societies and food authorities worldwide do not share a joint recommendation. Other dietary components, including calcium, magnesium, protein, phosphorus, zinc, and alcohol intake may play a role in BP control, but the evidence in the CKD population so far is inconclusive. Further studies are needed to establish solid evidence about the safety and efficacy of dietary interventions, particularly in CKD patients, the majority of whom suffer from hypertension. The purpose of this review is to summarize the existing recommendations and evidence concerning dietary interventions in hypertensives with CKD, with a primary focus on sodium and potassium intake. Additionally, we briefly address other dietary components that may play a role in BP regulation or kidney function. Full article