Search Results (395)

MicroRNAs (miRNAs) are small non-coding RNA molecules approximately 20–22 nucleotides in length that regulate gene expression at the post-transcriptional level. By binding to target messenger RNAs (mRNAs), miRNAs inhibit translation or induce degradation, thus influencing a wide array of biological processes including development, inflammation, apoptosis, and tissue remodeling. Owing to their remarkable stability and tissue specificity, miRNAs have emerged as promising biomarkers in both clinical and forensic settings. In recent years, increasing evidence has demonstrated their utility in cardiovascular diseases, where they may serve as diagnostic, prognostic, and therapeutic tools. This systematic review aims to comprehensively summarize the role of miRNAs in cardiovascular pathology, focusing on their diagnostic potential in myocardial infarction, sudden cardiac death (SCD), and cardiomyopathies, and their applicability in post-mortem investigations. Following PRISMA guidelines, we screened PubMed, Scopus, and Web of Science databases for studies up to December 2024. The results highlight several miRNAs—including miR-1, miR-133a, miR-208b, miR-499a, and miR-486-5p—as robust markers for ischemic injury and sudden death, even in degraded or formalin-fixed autopsy samples. The high stability of miRNAs under extreme post-mortem conditions reinforces their potential as molecular tools in forensic pathology. Nevertheless, methodological heterogeneity and limited standardization currently hinder their routine application. Future studies should aim to harmonize analytical protocols and validate diagnostic thresholds across larger, well-characterized cohorts to fully exploit miRNAs as reliable molecular biomarkers in both clinical cardiology and forensic medicine. Full article

Each year, around 23 million miscarriages occur worldwide, which have a substantial emotional impact on parents, and impose significant societal costs. While medical care accounts for most expenses, work productivity loss contributes significantly. Addressing underlying causes of miscarriage could improve parents’ mental health and potentially their economic impact. In most countries, investigations into miscarriage causes are only recommended after recurrent cases, focusing mainly on maternal factors. Fetal and placental tissue are rarely examined, as current guidelines do not advise routine genetic analyses of pregnancy tissue, because the impact of further clinical decision making and individual prognosis is unclear. However, this leaves over 90% of all miscarriage cases unexplained and highlights the need for alternative methods. We therefore conducted a narrative review on genetic analysis, autopsy, and imaging of products of conception (POC). Karyotyping, QF-PCR, SNP array, and aCGH were reviewed in different research settings, with QF-PCR being the most cost-effective, while obtaining the highest technical success rate. Karyotyping, historically being considered the gold standard for POC examination, was the least promising. Post-mortem imaging techniques including post-mortem ultrasound (PMUS), ultra-high-field magnetic resonance imaging (UHF-MRI), and microfocus computed tomography (micro-CT) show promising diagnostic capabilities in miscarriages, with micro-CT achieving the highest cost-effective performance. In conclusion, current guidelines do not recommend diagnostic testing for most cases, leaving the majority unexplained. Although genetic and imaging techniques show promising diagnostic potential, they should not yet be implemented in routine clinical care and require thorough evaluation within research settings—assessing not only diagnostic and psychosocial outcomes but also economic implications. Full article

Background/Objectives: Snakebite envenoming remains a critical yet frequently under-recognized cause of mortality in many parts of the world, particularly in tropical and rural areas where access to timely medical care and accurate post-mortem investigation is limited. While clinical and epidemiological data on snakebites have been extensively studied, the forensic characterization of fatal envenomations remains fragmentary and inconsistently documented. This review aims to synthesize the existing literature on autopsy-confirmed snakebite deaths, focusing on the pathological and toxicological evidence that supports cause-of-death determinations in forensic settings. Methods: A comprehensive search of the PubMed NCBI databases identified nine relevant studies, including case reports, retrospective analyses, and systematic reviews. Results: Across these reports, a range of lethal mechanisms were identified, including venom-induced consumption coagulopathy (VICC), acute renal failure (frequently in the setting of rhabdomyolysis and acute tubular necrosis), neurotoxic respiratory arrest, multi-organ necrosis, and myocardial infarction. Histological findings frequently revealed glomerular and tubular necrosis, pulmonary edema and/or hemorrhage, pituitary and adrenal hemorrhage, and cerebral ischemic changes. Toxicological confirmation was achieved in several cases using ELISA and liquid chromatography–mass spectrometry (LC–MS/MS), underscoring the importance of biochemical validation in post-mortem diagnosis and the value of analytical tools beyond ELISA (e.g., immunoaffinity LC–MS/MS, venom-specific immunohistochemistry, zymography for SVMP activity). Conclusions: Our findings highlight the variability in venom effects across snake families—particularly Viperidae, Elapidae, and Lamprophiidae/Atractaspididae—and emphasize the indispensable role of forensic autopsy in distinguishing snakebite envenoming from other causes of sudden or unexplained death. However, significant limitations persist, including inconsistent autopsy protocols, lack of species-specific venom assays, and poor integration of toxicological methods in routine forensic practice. Addressing these gaps through standardized forensic guidelines and improved access to diagnostic tools is essential for enhancing the accuracy of death investigations in envenoming-endemic regions. Full article

Sudden cardiac death (SCD) remains a major challenge in forensic medicine, representing a leading cause of natural mortality and frequently occurring in individuals without antecedent symptoms. Although conventional autopsy and histology remain the cornerstones of investigation, up to 10–15% of cases are classified as “autopsy-negative sudden unexplained death,” underscoring the need for complementary diagnostic tools. In recent years, post-mortem biochemistry and molecular approaches have become essential to narrowing this gap. Classical protein markers of myocardial necrosis (cardiac troponins, CK-MB, H-FABP, GPBB) continue to play a fundamental role, though their interpretation is influenced by post-mortem interval and sampling site. Peptide biomarkers reflecting hemodynamic stress (BNP, NT-proBNP, copeptin, sST2) offer additional insight into cardiac dysfunction and ischemic burden, while inflammatory and immunohistochemical markers (CRP, IL-6, fibronectin, desmin, C5b-9, S100A1) assist in detecting early ischemia and myocarditis when routine histology is inconclusive. Beyond these traditional markers, molecular signatures—including cardiac-specific microRNAs, exosomal RNA, proteomic alterations, and metabolomic fingerprints—provide innovative perspectives on metabolic collapse and arrhythmic mechanisms. Molecular autopsy through next-generation sequencing has further expanded diagnostic capability by identifying pathogenic variants associated with channelopathies and cardiomyopathies, enabling both cause-of-death clarification and cascade screening in families. Emerging multi-omics and artificial intelligence frameworks promise to integrate these heterogeneous data into standardized and robust interpretive models. Pre- and post-analytical considerations, together with medico-legal implications ranging from malpractice evaluation to the management of genetic information, remain essential components of this evolving field. Overall, the incorporation of validated biomarkers into harmonized international protocols, increasingly supported by AI, represents the next frontier in forensic cardiology. Full article

Epstein-Barr virus (EBV) infection shows the strongest causative association with multiple sclerosis (MS), but its contribution to disease progression and the mechanisms allowing for viral persistence in the MS brain are still elusive. Studies in post-mortem MS brain tissue indicate an ongoing yet ineffective antiviral immune reaction in advanced stages of the disease. EBV has evolved strategies to evade immune recognition and clearance by the host immune system during both the latency and lytic phase of its life cycle. Recent evidence demonstrates that cells expressing EBV latent membrane protein (LMP) 2A exploit the PD-1/PDL1 inhibitory immune checkpoint to escape immune surveillance and maintain a persistent latent infection in the MS brain. This study investigated whether the virus also utilizes this inhibitory mechanism during other phases of the viral life cycle. By using multiple immunostainings on highly inflamed MS brain tissues containing meningeal tertiary lymphoid structures (TLSs), we analyzed PD-L1 expression on EBV-infected cells expressing EBNA2, five EBV lytic gene products, BZLF1, BHRF1, BMRF1, BALF2, and gp350/220, as well as on follicular dendritic cells within the TLSs. This is the first study describing in secondary progressive MS brain tissue the expression and the cellular and tissue distribution of PD-L1 on EBV-infected cells being in different stages of the viral life cycle, and confirms the meningeal TLSs as immune-permissive habitats favoring the maintenance of an intracerebral EBV reservoir. Full article

Accurate post-mortem diagnosis of sepsis remains a critical challenge in forensic pathology, as conventional morphological findings often lack specificity. Circulating microRNAs (miRNAs) have been proposed as stable molecular biomarkers, yet their diagnostic value in cadaveric samples is still unclear. This exploratory study investigated the expression of three candidate miRNAs (miR-122-5p, miR-125b-5p, and miR-27a-3p) in post-mortem peripheral whole blood to assess their association with sepsis-related death versus non-infective controls. Out of 58 cases, 45 met quality-control criteria (26 sepsis-related deaths and 19 controls). miRNA expression was quantified by qRT-PCR, normalized to miR-320, and analyzed using ΔCt values. Group differences were evaluated using linear regression models with adjustment for age, sex, and post-mortem interval, with Benjamini–Hochberg correction for multiple testing. In adjusted models, miR-125b-5p and miR-27a-3p showed evidence of association with sepsis status, whereas miR-122-5p did not. These results support the feasibility of miRNA quantification in post-mortem samples and motivate validation in larger, independent cohorts and within multimodal post-mortem diagnostic frameworks. Full article

The paper presents the experimental results of applying a novel protective coating made from Mn_1.7Cu_1.3-xFe_xO₄, compared to commercial spinels Mn_1.5Co_1.5O₄ and MnCo₂O₄, as a key component responsible for preventing chromium diffusion and slowing the increase in area-specific resistance (ASR) in solid oxide fuel cells (SOFCs). The layers of selected materials were deposited on Crofer 22APU steel by electrophoretic deposition (EPD) on small samples and by roll painting on full-scale interconnects. The coatings were evaluated by measuring the ASR of small samples for short and long runs (1000 h), as well as real-scale interconnects assembled in a SOFC stack composed of three cells, measuring 11 × 11 cm², which operated for 1000 h at 670 °C. The collected data on the electrochemical performance of the stack allowed for estimation of the degradation rates of all the repeating units, revealing benefits from using (Mn,Cu,Fe)₃O₄ as a coating. The results are compared to the literature reports. Post-mortem analysis by the SEM-EDS technique allowed for investigation of Cr diffusion levels. Full article

Background/Objectives: Immunohistochemistry (IHC) is a critical diagnostic tool in forensic pathology, enabling molecular-level assessment of wound vitality, post-mortem interval, and cause of death. However, IHC interpretation is subject to variability due to its reliance on human expertise. This study investigates whether artificial intelligence (AI), specifically a generative model, can assist in the diagnostic evaluation of IHC slides and replicate expert-level scoring, thereby improving consistency and reproducibility. Methods: A total of 225 high-resolution IHC images were classified into five immunoreactivity categories. The AI model (ChatGPT-4V) was trained on 150 labeled images and tested blindly on 75 unseen slides. Performance was assessed using confusion matrices, per-class precision/recall/F1, overall accuracy, Cohen’s κ (unweighted and weighted), and binary metrics (sensitivity, specificity, MCC). Results: Overall accuracy was 81.3% (95% CI: 71.1–88.5%), with substantial agreement (κ = 0.767 unweighted; 0.805 linear-weighted; 0.848 quadratic-weighted). Binary classification achieved a sensitivity of 98.3%, specificity of 93.3%, MCC of 0.92. Accuracy was highest in extreme categories (− and +++, 93.3%), while intermediate classes (+ and ++) showed reduced performance (error rates up to 33%). Evaluation was rapid and consistent but lacked interpretative reasoning and struggled with borderline cases. Conclusions: AI-assisted diagnostic evaluation of IHC slides demonstrates promising accuracy and consistency, particularly in well-defined staining patterns. While not a replacement for human expertise, AI can serve as a valuable adjunct in forensic pathology, supporting rapid and standardized assessments. Ethical and legal considerations must guide its implementation in medico-legal contexts. Full article

Background/Objectives: Suicide is a significant public health concern with a multifactorial etiology. The biological background of suicide is not sufficiently explored, which encumbers suicide prevention. Epigenetic mechanisms may mediate environmental influences on suicide risk. Recent studies have suggested that protein aggregation occurs in the brains of patients with chronic psychiatric disorders and suicidality, which may influence disease trajectory. However, the intersection between epigenetics and proteinopathy in suicide remains unexplored. Our pilot study investigated whether aggregation-related genes show epigenetic and transcriptional alterations in the post-mortem brains of individuals who had died by suicide. Methods: Brain tissue from 69 male subjects (32 suicide by hanging, 37 sudden cardiac death controls) was collected at autopsy. Genome-wide hippocampal DNA methylation data from our previous reduced representation bisulfite sequencing (RRBS) study were reanalyzed to identify differentially methylated cytosines (DMCs) in candidate aggregation-related genes. The expression of nine candidate and three reference genes in the hippocampus and Brodmann area 46 was assessed by qPCR. Statistical analyses were performed using Student’s t-test or Mann–Whitney U test (p < 0.05 was considered significant). Results: Reanalysis revealed hypomethylation in suicide cases within CRMP1, DISC1, MAPT, SOD1, PRKN, GABARAPL1, GRIN2A, and GRIN2B. In the hippocampus, suicides exhibited increased expression of CRMP1, SOD1, PRKN, GABARAPL1, and GRIN2A, and decreased MAPT expression. The GRIN2A/GRIN2B ratio was significantly elevated. In Brodmann area 46, altered expression was limited to increased GRIN2A and decreased DISC1. Conclusions: This is the first study to implicate epigenetic and transcriptional dysregulation of protein aggregation-associated genes in suicide. The findings suggest a possible role for proteostasis disturbances in suicidality, particularly within the hippocampal pathways related to stress response and synaptic signaling. Validation in larger cohorts and protein-level studies are warranted to determine the functional significance of these findings. Full article

Background: Starvation represents a specific pathological entity characterized by severe nutritional deprivation leading to multi-organ failure. Despite its forensic relevance, a comprehensive synthesis of autopsy findings remains lacking. Methods: This systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed, Scopus, and Google Scholar were searched from inception to June 2025 using a pre-specified Boolean query. Eligible studies included case reports, case series and cohort investigations reporting post-mortem evidence of starvation or starvation-related malnutrition. Data extracted encompassed demographic, contextual, macroscopic, histological, and ancillary findings. Results: Fourteen studies were included, comprising 20 individual cases and two population-based cohorts (totaling 1647 deaths). Most cases (75%) involved children, predominantly victims of domestic neglect; adults accounted for 25%, mainly due to anorexia nervosa or voluntary fasting. Six cadavers were severely decomposed or mummified. Across studies, consistent autopsy findings included extreme emaciation, near-total loss of subcutaneous and visceral fat, empty gastrointestinal tract, and diffuse organ atrophy, especially of the liver, heart, thymus, and pancreas. Histology revealed hepatic steatosis, myocardial fibrosis, thymic involution and gelatinous transformation of adipose tissue. Ancillary methods (dual-energy X-ray absorptiometry, stable isotope and anthropological analyses) confirmed malnutrition in decomposed or skeletonized remains. Conclusions: This review delineates the morphological and histopathological hallmarks of starvation and suggests the possible diagnostic value of ancillary techniques in advanced decomposition. The predominance of neglect-related pediatric cases underscores starvation as a forensic indicator of social and caregiving failure. Establishing reproducible morphological and histological indicators may improve the consistency of forensic diagnosis and strengthen the evidentiary basis for determining starvation as a cause of death. Full article

Background: The potential long-term effects of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection on the brain structure have not yet been fully elucidated. Even though existing studies have reported structural changes in the post-COVID-19 period, the results remain highly inconsistent and controversial. As such, identifying an imaging biomarker for post-COVID brains is still under investigation. This review aims to comprehensively summarize the structural MRI (sMRI) studies that focus on volumetric brain changes at least two weeks following COVID-19 infection. Methods: A systematic literature search was conducted on PubMed, SCOPUS, Web of Science, EMBASE, and Google Scholar up to 9 September 2025. Studies that utilized sMRI to assess volumetric brain changes post-COVID at greater than two weeks following infection were included. Exclusion criteria encompassed research involving pediatric or adolescent populations and imaging modalities other than sMRI. Preprints, reviews, case reports, case series and post-mortem studies were also excluded. Results: Forty-one studies satisfied the inclusion criteria and consisted of 2895 patients and 1729 healthy controls. Despite the wide variability in image acquisition protocols, data processing methods, and comorbidities between studies, multiple studies reported statistically significant volumetric reductions in the hippocampus, amygdala, thalamus, basal ganglia, nucleus accumbens and the cerebellum months to years after infection, especially in older hospitalized patients with severe COVID-19. Conclusions: The emerging literature reports long-term volume changes across various brain regions in individuals previously infected with COVID-19; however, the evidence is inconsistent. Specific imaging biomarkers following exposure to SARS-CoV-2 infection and the underlying mechanisms of these changes are yet to be identified. Future studies with harmonized imaging protocols, longitudinal designs, and integrated biomarker and clinical data are needed to define robust biomarkers and elucidate the pathophysiology of these findings. Full article

Ionic liquid (IL)-based electrolytes have garnered significant interest for enhancing lithium-ion battery (LIB) safety due to their non-flammability, thermal stability, high conductivity, and broad electrochemical stability. We propose novel pyrrolinium-based ionic liquids to enhance lithium-ion mobility and address safety concerns in LIBs. This study investigated LiTFSI in [Pyr13] [FSI] ionic liquid for Li-ion batteries. The cyclic stability and rate performance of single-layer full cells with commercial graphite anode and NMC532 cathode were examined for the electrolyte required per cell and compared to those using a carbonate electrolyte (LP30). Electrolytes containing LiTFSI/[Pyr13] [FSI] exhibited satisfactory rate performance and stable cycling for 100 cycles. The reversible capacity was maintained at over 22 mAh for a cycle period of 100 cycles with an electrolyte loading of 161.8 µL/cm². These electrolytes exhibited the highest oxidation stability, surpassing 5.3 V compared to that of the Li⁺/Li reference electrode. Long cycle life of up to 1000 cycles was conducted, showing 80% capacity retention. Post-mortem analysis using scanning electron microscopy (SEM) and micro-Raman spectroscopy allowed observation of LiTFSI/ [Pyr13] [FSI] effects on cathode and anode active particle stability, and reduced formation of secondary reactions between the IL and battery electrodes. Full article

Post-mortem interval (PMI) analysis plays a crucial role in forensic investigations, providing essential insights into the time since death. This study examined histological changes and ribonucleic acid (RNA) quantification across major organs to identify molecular indicators for PMI estimation. Because RNA gradually degrades after death, understanding its stability under different tissue, temperature, and PMI conditions provides valuable forensic insights. We analyzed post-mortem changes in total RNA from the heart, kidney, liver, and lung tissues of Sprague Dawley rats stored at 4 °C and 26 °C. Tissue samples were collected at various PMIs and evaluated histologically for cellular integrity. Total RNA concentration and purity were measured, and complementary DNA (cDNA) was synthesized for molecular analysis. Expression levels of 5S rRNA, B2m, Gapdh, and Sort1 were quantified using reverse transcription quantitative PCR (RT-qPCR). The results showed that PMI and organ type significantly affected total RNA concentration, whereas temperature exerted only a minor effect. Among the four target genes, 5S rRNA exhibited the lowest Ct values, indicating the highest stability. Notably, RNA degradation patterns varied with temperature, particularly in kidney and liver tissues. These findings suggest that RNA-based molecular markers, particularly 5S rRNA, may serve as promising indicators for accurate PMI estimation. Full article

This study investigates all-solid-state batteries employing multifunctional metallic current collectors/electrodes that remain electrochemically inert toward an alkali-based Na ion solid electrolyte. Inconel 625 was evaluated as the positive current collector in combination with aluminum as the negative electrode and the ferroelectric electrolyte Na2.99Ba0.005OCl. The inertness of both electrodes enabled the construction of a robust device architecture that behaved as a true battery, exhibiting a two-phase equilibrium discharge plateau at ~1.1 V despite the absence of traditional Faradaic reactions. After a one-month rest period, the cell was sequentially discharged through external resistors and retained full functionality for one year. Cyclic voltammetry confirmed a stable electrochemical response over repeated cycling. The final long-term discharge under a 9.47 kΩ load produced a steady ~0.92 V plateau and delivered a total capacity of 35 mAh (~2.3 mAh·cm⁻²). Post-mortem analyses revealed excellent chemical and mechanical stability of Inconel 625 after extended operation, while aluminum showed superficial surface degradation attributed to residual moisture, with X-ray diffraction indicating the formation of aluminum hydroxide. Scanning Kelvin probe measurements guided electrode selection and provided insight into interfacial energetics, whereas scanning electron microscopy confirmed interface integrity. Complementary density functional theory simulations optimized the crystalline bulk and surfaces of Inconel, demonstrating interfacial stability at the atomic scale. Overall, this work elucidates the fundamental driving forces underlying traditional battery operation by studying a “capacity-less” system, highlighting the central role of interfacial electrostatics in sustaining battery-like discharge behavior in the absence of redox-active electrodes. Full article

Feline calicivirus (FCV) is widespread in multi-cat environments and typically causes acute upper respiratory tract disease (URTD). FCV also causes outbreaks of virulent systemic disease (VSD), mainly in adults, with multiple organ involvement. In this study, an FCV-VSD infection was described in a less-one-month-old Maine Coon kitten originating from a cattery where an outbreak of FCV-URTD had previously been reported. After spontaneous death, post-mortem examination as well as histopathological, immunohistochemical, bacteriological and virological investigations were carried out. Pathological findings were consistent with severe pneumonia and cutaneous oedema of the footpads. No concomitant bacterial infection was detected. FCV RNA was detected in several organs and the highest amount of viral RNA was observed in the lung sample, in which the presence of the FCV antigen was confirmed by immunohistochemistry. With the same immunohistochemical technique, the IBA-1 antibody detected sparse alveolar macrophages, the main viral target cell and pulmonary replication site. The nucleotide sequences of the viral ORF2 gene amplified from all positive tissues were identical with each other and phylogeny confirms that highly virulent FCV strains are not distinguishable from FCV-URTD phenotypes. Our findings reinforce the hypothesis that VSD outbreaks can occur even in small populations, due to the high genetic variability of FCV. Full article