Search Results (361)

Background: Trace elements and heavy metals can provide valuable forensic information for individual identification, lifestyle reconstruction, and association with the scene or time of death and may also assist in linking objects to criminal activities. However, the lack of standardized guidelines and post-mortem reference values represents a significant limitation in forensic investigations. Methods: This review was conducted in accordance with the PRISMA statement. We performed a comprehensive literature study over the last ten years focusing on the analysis of trace elements and heavy metals in post-mortem tissues. Results: The search results from the databases yielded 247 records. The screening, according to PRISMA criteria, allowed us to select and include 19 articles. The results showed the need for standardized guidelines and reference values. Although post-mortem trace element analysis shows high potential for forensic applications, substantial methodological heterogeneity persists. Some studies have proposed preliminary reference values for cadmium (Cd) in kidneys and mercury (Hg) in hair but validated post-mortem reference ranges remain largely unavailable. Conclusions: The current literature demonstrates the forensic potential of trace element and heavy metals analysis including Cd, Hg, lead (Pb), Manganese (Mn), Aluminum (Al), Copper (Cu), Zinc (Zn), Iron (Fe), Thallium (Tl), Polonium (²¹⁰Po) but also underlines the urgent need for standardized protocols and validated post-mortem reference values to improve interpretability and reliability in forensic contexts. Full article

Micronutrients and nutraceuticals play crucial roles in wound healing and tissue regeneration, supporting various physiological processes. This review aims to synthesize and evaluate the functions of various micronutrients and nutraceuticals, emphasizing the synergistic interactions among different nutrients that facilitate wound healing processes. A thorough literature review was performed using electronic databases, including PubMed, Scopus, Web of Science, Embase, Google Scholar, and Cochrane Library, to identify molecular studies, animal models, randomized controlled trials, and observational human studies published up to January 2000. Two independent reviewers screened the articles, extracted data, and evaluated the Risk of Bias using the Risk of Bias 2 (RoB 2) tool for the 190 studies that met the inclusion criteria. Evidence suggests that bioactive compounds found in functional foods and dietary supplements can help prevent chronic conditions and promote wellness beyond basic nutrition. Vitamins A, C, and E, as well as minerals such as zinc, selenium, and iron, are essential for cell proliferation and the formation of new tissues. Additionally, nutraceuticals, including omega-3 fatty acids, glutamine, arginine, and polyphenols, exhibit anti-inflammatory and antioxidant properties, which promote healing and reduce the risk of infection. Probiotics and other bioactive compounds in nutraceuticals contribute to maintaining the balance of microbiota, reducing inflammation, and stimulating cell regeneration. Significant variability was noted in study design, sample size, intervention dosage, and outcome measures. This evidence underscores the necessity for further well-designed clinical trials to determine the optimal dosages and combinations for specific wound types across diverse patient populations. This systematic review was prospectively registered in PROSPERO (ID: 1072091). Full article

Background: Histone deacetylase 6 (HDAC6) is a unique class IIb HDAC isozyme characterized by two catalytic domains and a zinc finger ubiquitin-binding domain. It plays critical roles in various cellular processes, including protein degradation, autophagy, immune regulation, and cytoskeletal dynamics. Due to its multifunctional nature and overexpression in several cancer types, HDAC6 has emerged as a promising therapeutic target. Methods: In this study, we employed a ligand-based pharmacophore modeling approach using a structurally diverse set of known HDAC6 inhibitors. This was followed by the virtual screening of over 140,000 commercially available compounds from both the MolPort and Asinex databases. The screening workflow incorporated pharmacophore filtering, molecular docking, and molecular dynamic (MD) simulations. Binding free energies were estimated using Molecular Mechanics Generalized Born Surface Area (MM-GBSA) analysis to prioritize top candidates. A fluorometric enzymatic assay was used to measure HDAC6 activity, while cell viability assay by Cell Titer Glo was used to assess the anti-tumor activity against drug-sensitive and -resistant multiple myeloma (MM) cells. Western blotting was used to evaluate the acetylation of tubulin or histone H4 after treatment with selected compounds. Results: Three promising compounds were identified based on stable binding conformations and favorable interactions within the HDAC6 catalytic pocket. Among them, Molecular Mechanics Generalized Born Surface Area (MM-GBSA) analysis identified Compound 10 (AKOS030273637) as the top theoretical binder, with a ΔG_bind value of −45.41 kcal/mol. In vitro enzymatic assays confirmed its binding to the HDAC6 catalytic domain and inhibitory activity. Functional studies on MM cell lines, including drug-resistant variants, showed that Compound 10 reduced cell viability. Increased acetylation of α-tubulin, a substrate of HDAC6, likely suggested on-target mechanism of action. Conclusions: Compound 10, featuring a benzyl 4-[4-(hydroxyamino)-4-oxobutylidene] piperidine-1-carboxylate scaffold, demonstrates potential drug-like properties and a predicted bidentate zinc ion coordination, supporting its potential as an HDAC6 inhibitor for further development in hematologic malignancies. Full article

Background and Objective: Thyroid cancer (TC) represents the most common group of endocrine tumors, and its incidence has increased over the last four decades. The imbalance of trace elements, such as zinc (Zn), has been investigated due to the thyroid’s sensitivity to these elements. Zn is essential for thyroid hormone action and may be involved in the pathogenesis of TC. This systematic review and meta-analysis aim to contribute to the discussion on the association between low serum Zn concentrations and the occurrence of TC. Materials and Methods: The search was carried out in the PubMed/MEDLINE, Scopus, Embase, LILACS and Web of Science databases, including observational studies published until December 2024. The primary outcome was low serum Zn concentration and the occurrence of TC. Three independent reviewers selected the studies and extracted the data from the original publications. The risk of bias was assessed using the Newcastle–Ottawa Quality Assessment Scale. Data analysis was performed using R software (V.4.3.1), and heterogeneity was calculated using the I² statistic, with results based on random effects models. Results: A total of 10 studies (n = 7 case–control and n = 3 cross-sectional) with sample sizes ranging from 44 to 294 individuals were included. The results indicated that serum Zn levels were not significantly lower in patients with TC compared with healthy controls (mean difference: −251.77; 95% confidence interval: −699.09, 195.54; I² = 100%, very low certainty). Conclusions: Further investigations, including rigorously designed observational studies with representative samples and improved control of potential confounding variables are indispensable. Full article

Background: Cardiomyocyte death is a key factor in myocardial ischemia–reperfusion injury (MI/RI), and the expression patterns and molecular mechanisms of pyroptosis-related genes (PRGs) in ischemia–reperfusion injury are poorly understood. Methods: The mouse MI/RI injury-related datasets GSE61592 and GSE160516 were obtained from the Gene Expression Omnibus database, and differential expression analysis was performed on each to identify differentially expressed genes (DEGs). The DEGs were intersected with the PRGs obtained from GeneCards to identify differentially expressed PRGs in MI/RI. Enrichment analysis identified key pathways, while PPI network analysis revealed hub genes. The expression patterns and immune cell infiltration of hub genes were also investigated. The molecular docking prediction of key genes was performed using MOE software in conjunction with the ZINC small molecular compounds database. Key gene expression was validated in an external dataset (GSE4105), a mouse MI/RI model, and an HL-1 cell hypoxia/reoxygenation model via RT-qPCR. Results: A total of 29 differentially expressed PRGs were identified, which are primarily associated with pathways such as “immune system process”, “response to stress”, “identical protein binding”, and “extracellular region”. Seven key genes (Fkbp10, Apoe, Col1a2, Ppic, Tlr2, Fstl1, Serpinh1) were screened, all strongly correlated with immune infiltration. Seven FDA-approved small molecule compounds exhibiting the highest docking potential with each key gene were selected based on a comprehensive evaluation of S-scores and hydrogen bond binding energies. Apoe, Tlr2, and Serpinh1 were successfully validated across external datasets, the mouse MI/RI model, and the cardiomyocyte H/R model. Conclusions: Apoe, Tlr2, and Serpinh1 may be key genes involved in MI/RI-related pyroptosis. Targeting these genes may provide new insights into the treatment of MI/RI. Full article

Liver fibrosis (LF) poses significant challenges in diagnosis and treatment. This study aimed to identify effective biomarkers for diagnosis and therapy, as well as to gain deeper insights into the immunological features associated with LF. LF-related datasets were retrieved from the Gene Expression Omnibus (GEO) database. Two datasets were merged to generate a metadata cohort for bioinformatics analysis and machine learning, while another dataset was reserved for external validation. Seventy-eight machine learning algorithms were employed to screen signature genes. The diagnostic performance of these genes was evaluated using receiver operating characteristic (ROC) curves, and their expression levels were validated via qRT-PCR experiments. The R language was utilized to delineate the immune landscape. Finally, correlation analysis was conducted to investigate the relationship between the signature genes and immune infiltration. Through the intersection of GEO datasets and Weighted Gene Co-expression Network Analysis (WGCNA), 42 genes were identified. Machine learning methods further narrowed down 13 signature genes (alpha-2-macroglobulin (A2M), ankyrin-3 (ANK3), complement component 7 (C7), cadherin 6 (CDH6), cysteine-rich motor neuron protein 1 (CRIM1), dihydropyrimidinase-like 3 (DPYSL3), F3, gamma-aminobutyric acid (GABA) receptor subunit epsilon (GABRE), membrane metalloendopeptidase (MME), solute carrier family 38 member 1 (SLC38A1), tropomyosin alpha-1 chain (TPM1), von Willebrand factor (VWF), and zinc finger protein 83 (ZNF83)), and qRT-PCR confirmed these genes’ expression patterns. Furthermore, these signature genes demonstrated strong correlations with multiple immune cell populations. In conclusion, the 13 genes (A2M, ANK3, C7, CDH6, CRIM1, DPYSL3, F3, GABRE, MME, SLC38A1, TPM1, VWF, and ZNF83) represent robust potential biomarkers for the diagnosis and treatment of LF. Among these genes, we first identified Gabre as related to LF and expressed in hepatocytes and cholangiocytes. The immune response mediated by these signature biomarkers plays a pivotal role in the pathogenesis and progression of LF through dynamic interactions between the biomarkers and immune-infiltrating cells. Full article

Background: Hydroxycarboxylic acid receptor 3 (HCAR3) is a receptor that is mainly expressed in human adipose tissue. It can inhibit lipolysis through the inhibition of adenylyl cyclase; thus, it is closely related to the regulation of lipids in the human body. This makes HCAR3 a compelling target for developing drugs against dyslipidemia. Notably, the reported active compounds for HCAR3 are all carboxylic acids. This observation is in line with the fact that ARG111 has been reported as the key residue to anchor the active compound in a closely related homologous protein—HCAR2. Methods: In this study, we aim to discover new chemicals, through virtual screening, that may bind with HCAR3. As there are several choices for the receptor conformation, cross-docking was conducted and the root-mean-square deviation of the docking pose from the conformation of the crystal ligand was employed to determine the best receptor conformation for screening. Ligands from the ZINC20 database were screened through molecular docking, and 30 candidates were subjected to 100 ns MD simulations. Six stable complexes were further assessed by umbrella sampling to estimate binding affinity. Results: The homology model (HCAR3_homology) was selected as the receptor. Following the protocol determined by the retrospective docking process, prospective docking was conducted to screen the ligands from the ZINC20 database. Subsequently, the top 30 compounds with a good docking score and a good interaction with ARG111 were subjected to 100 ns molecular dynamics (MD) simulations, and their binding stability was analyzed based on the resulting trajectories. Finally, six compounds were chosen for binding free energy calculation using umbrella sampling; all showed negative binding affinities. Conclusions: All six compounds selected for umbrella sampling showed negative binding affinities, suggesting their potential as novel HCAR3 ligands for the development of drugs against dyslipidemia. Full article

Verticillium wilt (VW), caused by Verticillium dahliae, poses a significant threat to global cotton production. Through analysis of public transcriptome databases, this study identified GhSTZ, a C2H2 zinc finger protein transcription factor gene, which was significantly induced by V. dahliae. Suppressing GhSTZ expression via virus-induced gene silencing significantly enhanced cotton resistance to VW. This resistance manifested as a 1.2-fold increase in lignin deposition, optimized ROS (reactive oxygen species) homeostasis, and a 1.3-fold elevation in glucose levels. Transcriptome analysis revealed 338 differentially expressed genes in GhSTZ-silenced plants, with 97 upregulated and 241 downregulated. Key downregulated genes included PME (pectin methylesterase) and PG1-pec (polygalacturonase) in the pentose phosphate pathway, while the key upregulated genes comprised C4H (cinnamate 4-hydroxylase) and C3H (p-coumarate 3-hydroxylase) in the phenylpropanoid biosynthesis pathway. Notably, in the plant–pathogen interaction signaling pathway, approximately half of the genes exhibited upregulated expression while the other half showed downregulation. Protein–protein interaction network analysis further revealed cooperative interaction between PME and the secoisolariciresinol dehydrogenase SIRD. This study is the first to elucidate GhSTZ as a negative regulator that compromises cotton disease resistance through a tripartite mechanism. These findings offer a novel approach to enhancing crop disease resistance by targeting the negative regulatory genes. Full article

This review examines the emerging role of manganese-based nanoparticles (Mn-NPs) in detecting heavy metal pollutants in environmental matrices. Heavy metals such as cadmium, lead, zinc, and copper pose serious environmental and health concerns due to their tendency to persist in ecosystems and accumulate in living organisms. As a result, there is a growing need for reliable methods to detect and remove these pollutants. Manganese nanoparticles offer unique advantages that scientists could consider as replacing other metal nanoparticles, which may be more expensive or more toxic. The physicochemical properties of Mn-NPs—including their multiple oxidation states, magnetic susceptibility, catalytic capabilities, and semiconductor conductivity—enable the development of multi-modal sensing platforms with exceptional sensitivity and selectivity. While Mn-NPs exhibit inherently low electrical conductivity, strategies such as transition metal doping and the formation of composites with conductive materials have successfully addressed this limitation. Compared to noble metal nanoparticles (Au, Ag, Pd) and other base metal nanoparticles (Bi, Fe₃O₄), Mn-NPs demonstrate competitive performance without the drawbacks of high cost, complex synthesis, poor distribution control, or significant aggregation. Preliminary studies retrieved from the Scopus database highlight promising applications of manganese-based nanomaterials in electrochemical sensing of heavy metals, with recent developments showing detection limits in the sub-ppb range. Future research directions should focus on addressing challenges related to scalability, cost-effectiveness, and integration with existing water treatment infrastructure to accelerate the transition from laboratory findings to practical environmental applications. Full article

Background: Anaplastic lymphoma kinase (ALK) is a validated oncogenic driver in non-small cell lung cancer and other malignancies, making it a clinically relevant target for small-molecule inhibition. Methods: Here, we report a computational discovery pipeline integrating structure-based virtual screening, machine learning-guided prioritization, molecular dynamics simulations, and binding free energy analysis to identify potential ALK inhibitors from a natural product-derived subset of the ZINC20 database. We trained and benchmarked eleven machine learning models, including tree-based, kernel-based, linear, and neural architectures, on curated bioactivity datasets of ALK inhibitors to capture nuanced structure-activity relationships and prioritize candidates beyond conventional docking metrics. Results: Six compounds were shortlisted based on binding affinity, solubility, bioavailability, and synthetic accessibility. Molecular dynamics simulations over 100 ns revealed stable ligand engagement, with limited conformational fluctuations and consistent retention of the protein’s structural integrity. Key catalytic residues, including GLU105, MET107, and ASP178, displayed minimal fluctuation, while hydrogen bonding and residue interaction analyses confirmed persistent engagement across all ligand-bound complexes. Binding free energy estimates identified ZINC3870414 and ZINC8214398 as top-performing candidates, with ΔG_total values of –46.02 and –46.18 kcal/mol, respectively. Principal component and dynamic network analyses indicated that these compounds restrict conformational sampling and reorganize residue communication pathways, consistent with functional inhibition. Conclusions: These results highlight ZINC3870414 and ZINC8214398 as promising scaffolds for further optimization and support the utility of integrating machine learning with dynamic and network-based metrics in early-stage kinase inhibitor discovery. Full article

Background/Objectives: Previous studies assessing dietary intake have used self-report methods, prone to misreporting. Using researcher-conducted weighed food records, we assessed rural and urban mothers’ energy and nutrient intakes of concern and compared them to recommended nutrient intakes (RNIs). Methods: This cross-sectional study was conducted in rural (Asaase Kokoo) and urban (University of Ghana Staff Village) communities. Dietary data were collected from fifty-four mothers (26 rural, 28 urban) on 2 weekdays and 1 weekend day, analyzed with software, and programmed with West African, FNDDS, Kenyan, Ugandan, and USDA food composition databases. Results: Mean (SD) ages (years) were 35.8 (11.6) and 44.4 (7.6), and mean energy intakes (kcal) were 2026 (461) and 1669 (385) for rural and urban mothers, respectively. Mean percentage contributions of macronutrients to energy intake were within recommended ranges for rural and urban mothers. All participants met or exceeded vitamin A RNI, irrespective of location. While all rural mothers met or exceeded iron RNI, some urban mothers (14.3%) did not. Few rural (7.7%) and urban mothers (10.7%) did not meet zinc RNI. About half of rural (46.2%) and urban mothers (53.6%) did not meet folate RNI. Most rural (96.1%) and urban mothers (92.8%) met or exceeded fiber RNI. Conclusions: Overall, rural mothers had higher energy and nutrient intakes than urban mothers. While most met RNIs, there were some micronutrient inadequacies, particularly folate, where almost half of rural and urban mothers consumed below RNI. Our findings indicate the need for tailored interventions to prevent nutrient deficiencies or excesses in Ghanaian mothers. Full article

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

Transcription factors play crucial roles in regulating gene expression, and any dysregulation in their levels could be involved in cancer progression. The role of androgen receptors (AR) and zinc finger (ZNF) proteins in tumors, like prostate cancer (PC), remains poorly understood. Moreover, due to the multifaceted transcriptional behavior of ARs and ZNFs, their biological role in cancer progression may also depend on the interplay with micro-RNAs (miRNAs). Based on The Cancer Genome Atlas (TCGA) database, we analyzed the expression levels of zinc finger transcripts and ARs in PC. Specifically, exploring their involvement in cancer progression and regulation by miRNAs. The analysis relied on several tools to create a multivariate combination of the original biomarkers to improve their diagnostic efficacy. Multidimensional Scaling (MDS) identified two new dimensions that were entered into a regression analysis to determine the best predictors of overall survival (OS) and disease-free interval (DFI). A combination of both dimensions predicted almost 50% (R² = 0.46) of the original variance of OS. Kaplan–Meier survival analysis also confirmed the significance of these two dimensions regarding the clinical output. This study showed preliminary evidence that several transcription factor expression levels belonging to the zinc family and related miRNAs can effectively predict patients’ overall PC survivability. Full article

Background: Developments in biology, genetics, soil science, plant breeding, engineering, and agricultural microbiology are driving advances in soil microbiology and microbial biotechnology. Material and methods: The literature for this review was collected by searching leading scientific databases such as Embase, Medline/PubMed, Scopus, and Web of Science. Results: Recent advances in soil microbiology and biotechnology are discussed, emphasizing the role of microorganisms in sustainable agriculture. It has been shown that soil and plant microbiomes significantly contribute to improving soil fertility and plant and soil health. Microbes promote plant growth through various mechanisms, including potassium, phosphorus, and zinc solubilization, biological nitrogen fixation, production of ammonia, HCN, siderophores, and other secondary metabolites with antagonistic effects. The diversity of microbiomes related to crops, plant protection, and the environment is analyzed, as well as their role in improving food quality, especially under stress conditions. Particular attention was paid to the diversity of microbiomes and their mechanisms supporting plant growth and soil fertility. Conclusions: The key role of soil microorganisms in sustainable agriculture was highlighted. They can support the production of natural substances used as plant protection products, as well as biopesticides, bioregulators, or biofertilizers. Microbial biotechnology also offers potential in the production of sustainable chemicals, such as biofuels or biodegradable plastics (PHA) from plant sugars, and in the production of pharmaceuticals, including antibiotics, hormones, or enzymes. Full article

Background: Micronutrient deficiencies, particularly among pregnant women and children under five years old, remain a significant public health challenge in Nigeria. Despite existing policies and programmes, national data on prevalence and risk factors are fragmented. Objective: To synthesise the current evidence on the prevalence of key micronutrient deficiencies and associated risk factors among pregnant women and children under five years old in Nigeria. Methods: A systematic review and meta-analysis were conducted using peer-reviewed studies that were published between 2008 and 2024. The databases searched included PubMed, Scopus, and African Journals Online. After screening 1207 studies, 37 studies were included: 27 were conducted among pregnant women and 10 were among children. A meta-analysis was conducted to estimate the anaemia prevalence using a random-effects model. A narrative synthesis was conducted to synthesise evidence on other micronutrients (i.e., magnesium, copper, and vitamins C and E) due to the limited data and risk factors. Results: The pooled prevalence of anaemia was 56% among children and 54% among pregnant women. The prevalence of other micronutrient deficiencies varied widely, with a high prevalence of zinc (86.4%), magnesium (94%), and vitamin D (73.3%) deficiencies in certain regions. The identified risk factors included poor dietary diversity, lower socioeconomic status, low maternal education, infection burden, and early or high parity. Most studies were facility-based and sub-national, limiting the generalisability. Conclusions: This review highlights a high prevalence of anaemia and micronutrient deficiencies among pregnant women and children in Nigeria. Key risk factors included a poor diet, low maternal education, infections, and reproductive health challenges. Targeted, multisectoral policies are urgently needed to address these gaps and improve health outcomes. Full article