Search Results (8,095)

Background/Objectives: Obesity remains a major global health burden, with metabolic–bariatric surgery being the most efficient long-term treatment strategy. However, both variability in perioperative care and postoperative complications persist. To address these challenges, the EUropean PErioperative MEdical Networking (EUPEMEN) protocol for bariatric surgery was developed to standardize care and enhance perioperative outcomes across European healthcare settings. Methods: The protocol was formulated through close collaboration among experts from multiple disciplines, involving surgeons, anesthetists, nurses, and nutritionists. Its development included a literature review, expert consensus, and the creation of structured perioperative guidelines covering the preoperative, intraoperative, and postoperative phases. Focus areas include patient education, nutritional optimization, early mobilization, opioid-sparing analgesia, and minimally invasive surgical techniques, supported by educational materials and manuals. Technical activities included the development of detailed multimodal rehabilitation manuals translated into five languages, the creation of an open-access online learning platform, training of future educators through a “train the trainer” approach, organization of multiplier promotional events, international collaboration meetings to refine the protocol, and revision and standardization of existing perioperative care guidelines to ensure evidence-based, unified practices across Europe. Results: Implementation of the EUPEMEN protocol aims to reduce postoperative complications, enhance recovery, and decrease hospitalization time. Standardized rehabilitation pathways and access to free educational platforms promote consistent care delivery across diverse healthcare environments. Key strategies include early oral intake, limited use of invasive devices, and comprehensive patient preparation. Conclusions: The EUPEMEN protocol introduces an evidence-based, multidisciplinary framework for optimizing perioperative management in bariatric surgery. While variability in resources and adherence may present potential obstacles, its application holds significant promise for improving perioperative outcomes. Future studies are necessary to assess its long-term impact and adaptability in different healthcare settings. Full article

Background: Oral squamous cell carcinoma often develops from oral potentially malignant disorders and is frequently diagnosed at an advanced stage. Conventional oral examination is limited by moderate sensitivity, observer variability, and poor discrimination between benign and dysplastic lesions. Adjunctive light-based screening technologies have been introduced, but their diagnostic value remains uncertain. Methods: This systematic review followed PRISMA 2020 guidelines and was registered in PROSPERO. MEDLINE (PubMed), Embase, Scopus, and the Cochrane Database were searched through December 2025. Studies assessing adjunctive light-based screening technologies for detecting oral potentially malignant disorders or squamous cell carcinoma were included. Histopathology served as the reference standard. Diagnostic accuracy outcomes were extracted, and risk of bias was assessed using Cochrane-based criteria. Results: Eleven studies were included. Autofluorescence imaging showed consistently high sensitivity but low and variable specificity. Chemiluminescence demonstrated similar or lower sensitivity with poor specificity. False-positive results were frequent, particularly in inflammatory or benign lesions. Marked heterogeneity across studies limited quantitative synthesis. Conclusions: Adjunctive light-based technologies can increase detection sensitivity when used with conventional oral examination but lack sufficient specificity for standalone use. Histopathological confirmation remains mandatory. Standardized, multicenter diagnostic accuracy studies are needed to clarify their clinical role. Full article

Background/Objectives: Poor oral bioavailability and limited intestinal permeation restrict the clinical translation of phytochemicals for colorectal cancer (CRC) therapy. The present preliminary study explored the development of a nanoparticle-based combinatorial formulation of resveratrol (Resv), acetyl-11-keto-β-boswellic acid (AKBA), and quercetin (Quer), to improve intestinal permeation and anti-cancer efficacy. Methods: A triple phytochemical nano formulation (designated as 3X) was developed and evaluated for morphology, particle size, zeta potential, encapsulation efficiency, and in vitro pharmaceutical characteristics. Safety was evaluated using in vitro cytotoxicity assays, while anticancer efficacy and apoptotic potential were preliminarily evaluated in Caco-2 CRC cell lines. Gene expression analysis was performed to examine the modulation of inflammation and cancer-related markers. Results: The 3X formulation exhibited a particle size of 198.5 nm with a polydispersity index of 0.492 and a zeta potential of −32.7, indicating good nanoscale stability. The encapsulation efficiencies were 90% for AKBA, 80% for Resv, and 75% for Quer. In vitro permeation studies demonstrated a controlled release mechanism. The formulation showed minimal hemolysis (3%) and had acceptable in vitro safety. The IC50 of the formulation was found to be 365 µg in the cytotoxicity assay. Treatment with the 3X nanoformulation significantly modulated anti-inflammatory and cancer-related gene expression in Caco2 cells, evidenced by downregulation of TGFβ (Transforming Growth Factor-beta) and COX-2 (cyclooxygenase-2), and upregulation of TNFα (Tumor necrosis factor-alpha) and nitric oxide (NO) and reduced IL-1β (Interleukins-1 beta) expression compared with control cells. Conclusions: The findings demonstrate that the developed 3X nano formulation exhibits favorable permeation characteristics and exerts anticancer activity against CRC. Based on preliminary findings, the formulation represents a promising phytochemical-based combination strategy for CRC, warranting further in vivo studies to validate its efficacy and elucidate the underlying molecular mechanisms. Full article

Background: The oral delivery of biopharmaceuticals remains a major challenge for researchers and the pharmaceutical industry. Therefore, extensive research is ongoing to develop a viable delivery method, hence self-emulsifying drug delivery systems (SEDDSs) are being investigated because of their ability to protect the carried macromolecules in the gastrointestinal environment and facilitate absorption through the intestinal barrier. Objectives: To systematically investigate this promising method for the oral delivery of lysozyme (LYZ) and to model oral peptide/protein administration. Methods: LYZ/sodium dodecyl sulfate (SDS) hydrophobic ion pairs (HIPs) were prepared to enhance protein solubility and stability in SEDDSs. Different surfactants (Tween^® 20 and 80) and as co-surfactants (Span^® 20 and 80) were combined for the preparation of liquid SEDDSs according to a 2² full factorial design and samples of each combination were formulated based on a three-factor-constrained mixture design. The critical quality attributes (CQAs), droplet size, polydispersity index (PDI), and zeta potential were measured by dynamic light scattering (DLS). The process design space was determined by response surface methodology (RSM) and two-dimensional ternary contour plots. An in vitro release test was performed using the sample-and-separate approach. Results: Emulsions of SEDDSs with the optimal properties of droplet size < 200 nm, PDI < 0.4 and zeta potential < −10 mV were prepared. Consequently, a HIP load of 10 mg/g was achievable, exhibiting apparent first-order kinetics, with approximately 80% of the loaded LYZ released within 6 h. Conclusions: This study may contribute to better understanding of the effects and interactions of formulating materials for SEDDSs and their possible role in the oral delivery of biopharmaceuticals. Full article

Background: Early detection of dental caries is essential for effective oral health management. Current diagnostic workflows rely heavily on radiographic imaging, which involves infrastructure requirements, workflow coordination, and resource considerations that may limit frequent use in high-throughput or resource-constrained settings. These contextual factors motivate exploration of adjunct screening concepts that could support front-end triage decisions within existing care pathways. This study evaluates, in simulation, whether modeled tooth-percussion response signals contain sufficient discriminative information to justify further translational and managerial investigation. Implementation costs, workflow optimization, and economic outcomes are not evaluated directly; rather, the objective is to assess whether the technical preconditions for a potentially scalable screening concept are satisfied under controlled in silico conditions. Methods: An in silico model of tooth percussion was developed in which enamel, dentin, and pulp/root structures were represented as a simplified layered mechanical system. Impulse responses generated from simulated tapping were used to compute the modeled surface-vibration response (enamel-layer displacement), which served as a proxy for a measurable percussion-related signal (e.g., contact vibration), rather than a recorded acoustic waveform. Carious conditions were simulated through depth-dependent reductions in stiffness and effective mass and increases in damping to represent enamel and dentin demineralization. A synthetic dataset of labeled simulated signals was generated under varying structural parameters and measurement-noise assumptions. Machine-learning models using Mel-frequency cepstral coefficient (MFCC) features were trained to classify healthy teeth, enamel caries, and dentin caries at a screening (triage) level. Results: Under baseline simulation conditions, the classifier achieved an overall accuracy of 0.97 with balanced macro-averaged F1-score (0.97). Misclassifications occurred primarily between healthy and enamel-caries categories, whereas dentin-caries cases were most consistently identified. When measurement noise and structural variability were increased, performance declined gradually, reaching approximately 0.90 accuracy under the most challenging simulated scenario. These results indicate that discriminative information is present within the modeled signals at a screening (triage) level, meaning that higher-risk categories can be distinguished probabilistically rather than with definitive diagnostic certainty. Sensitivity and specificity trade-offs were not optimized in this study, as the objective was to assess separability rather than to define clinical decision thresholds. Conclusions: Within the constraints of the in silico model, simulated tooth-percussion response signals demonstrated discriminative patterns between healthy, enamel caries, and dentin caries categories at a screening (triage) level. These findings establish technical plausibility under controlled simulation conditions and support further investigation of percussion-based screening as a potential adjunct to clinical assessment. From a healthcare management perspective, the present results address a prerequisite question—whether such signals contain sufficient information to justify translational research, rather than demonstrating workflow optimization, cost reduction, or system-level impact. Clinical validation, threshold optimization, and implementation studies are required before managerial or operational benefits can be evaluated. Full article

Background/Objectives: Postoperative early hypocalcemia (PEH) is a key postoperative issue after parathyroidectomy in primary hyperparathyroidism. It often leads to long-lasting hypocalcemia, requiring more calcium and active vitamin D supplements. This study aimed to determine whether the extent of intraoperative parathyroid hormone (PTH) decline, measured 15 min after parathyroid tumor excision, could serve as a reliable intraoperative rule-out marker for PEH. Methods: We conducted a retrospective review of 88 adult patients who underwent surgical intervention for a solitary parathyroid tumor at a single institution. Postoperative early hypocalcemia (PEH) was defined as a total serum calcium level <8.5 mg/dL within the postoperative 6th hour or on postoperative day 1, requiring clinical calcium supplementation (oral and/or intravenous), with active vitamin D when appropriate. The percentage decrease in PTH at 15 min post-excision was calculated using morning-of-surgery preoperative PTH values alongside the 15-min post-excision levels. Additional variables assessed included preoperative alkaline phosphatase (ALP), parathyroid tumor weight, and serum concentrations of calcium, phosphate, magnesium, and 25-hydroxyvitamin D. Predictive factors were identified by logistic regression, and the diagnostic accuracy of the 15-min PTH decline was evaluated using receiver operating characteristic (ROC) curve analysis, optimizing cutoff selection with Youden’s index. Odds ratios were standardized per 10-unit increments for ALP and parathyroid tumor weight for interpretability. Results: Of the studied cohort, 10 patients (11.4%) developed PEH. The intraoperative 15-min PTH decline was notably greater in those who developed PEH compared to those who did not (81.2 ± 4.4% vs. 69.9 ± 8.3%; p < 0.001). Univariate logistic regression showed a significant association between the 15-min PTH decline and PEH (OR 1.22 per 1% increment; 95% CI 1.08–1.38). That said, when we added ALP and parathyroid tumor weight to the multivariate models, PTH decline no longer predicted independently. In contrast, ALP (OR 3.11 per 10 U/L; 95% CI 1.34–7.93; p = 0.011) and parathyroid tumor weight (OR 1.22 per 10 mg; 95% CI 1.10–1.48; p = 0.004) stayed significant. Thus, the incremental prognostic contribution of the 15-min PTH decline beyond ALP and parathyroid tumor weight appears limited. The ROC curve for the 15-min PTH decline produced an AUC of 0.883, with an optimal cutoff of 75% providing 100% sensitivity and 74.4% specificity. No patients with a PTH decline below 75% developed PEH. Conclusions: Preoperative ALP and parathyroid tumor weight showed the strongest independent associations with PEH following parathyroid tumor surgery. An intraoperative PTH decline of less than 75% at 15 min may serve as a practical rule-out tool for PEH, although further validation in larger patient populations is warranted. Full article

Background: Saliva has been identified as a valuable diagnostic biofluid due to its non-invasive collection and its capacity to reflect oral and systemic biological processes. Advances in analytical chemistry, biosensing technologies, and artificial intelligence (AI)-assisted data integration have broadened the applications of salivary diagnostics. Among salivary exposome components, heavy metals such as lead, cadmium, mercury, nickel, chromium, arsenic, and aluminum serve as biologically and clinically relevant indicators of environmental exposure, toxic burden, and disease-associated molecular disorders. Methods: This structured review integrates clinical, experimental, and translational studies published between January 2020 and January 2026 that examined salivary heavy metal profiling in relation to oral health. Evidence was identified using systematic searches of PubMed/MEDLINE and supplementary sources. Studies were qualitatively assessed regarding analytical methodologies, reported concentration ranges, biological mechanisms, disease associations, and the development of digital and AI-assisted diagnostic applications. Results: Thirteen human clinical studies and six animal or in vivo investigations met the inclusion criteria. Across these studies, altered salivary metal profiles were linked to oxidative stress, inflammatory signaling, immune dysregulation, microbiome disturbances, and genotoxic markers relevant to periodontal disease, oral mucosal pathology, and the risk of oral squamous cell carcinoma. Inductively coupled plasma mass spectrometry was the predominant analytical platform, while emerging biosensor technologies showed potential for rapid detection and monitoring. Digital and AI-based approaches were identified as promising tools for integrating metallomic data with clinical and molecular biomarkers to support exposure-informed risk stratification. Conclusions: Salivary heavy metal profiling represents a biologically informative, non-invasive method for exposure-aware risk assessment in oral health. Although current clinical translation is limited by methodological variability, small cohort sizes, and the lack of standardized reference ranges, integration with digital biosensing platforms and explainable AI frameworks might facilitate scalable, precision-oriented salivary diagnostics. Full article

Background and Objectives: Psychosocial symptoms and oral behaviors can complicate routine dental care, yet available screeners yield multiple separate scores. Explainable artificial intelligence offers a pragmatic way to integrate such multidomain measures into a single, auditable output that can support screening-oriented stratification and standardized documentation (non-diagnostic). Therefore, we aimed to develop an interpretable, deterministic Mamdani fuzzy inference system (FIS) integrating GAD-7, PHQ-9, and OBC-21 into a 0–10 psychobehavioral composite score (PCS) to support screening-oriented stratification and standardized documentation (non-diagnostic). Materials and Methods: Cross-sectional multicenter study in 18 private dental clinics in Romania (October 2024–March 2025; n = 460). A rule-based Mamdani Type-1 FIS was specified a priori (48 rules; triangular membership functions; centroid defuzzification) without supervised training. Internal evaluation assessed coherence across severity strata, robustness to predefined input perturbations (±1 point; ±5%) and membership-function variation (±10%), and benchmarking against linear composites (Z-mean; PCA PC1). Results: Median PCS was 2.30 (IQR 2.03–3.56). PCS correlated with GAD-7 (Spearman ρ = 0.886), PHQ-9 (ρ = 0.792), and OBC-21 (ρ = 0.687) (all p < 0.001), increased monotonically across anxiety and depression severity strata, and was higher in high OBC-21 risk. Robustness was excellent under input perturbations (ICC(3,1) = 0.983 for ±1 point; 0.992 for ±5%) and high under ±10% membership-function variation (ICC(3,1) = 0.959). Concordance with linear baselines was high (Spearman ρ = 0.956 for Z-mean; 0.955 for PCA PC1), with a small systematic nonlinearity at higher scores. Conclusions: PCS provides a fully auditable, rule-based integration of three patient-reported measures with coherent internal behavior and robustness to plausible measurement noise and specification changes. This study reports internal evaluation of a deterministic, rule-based aggregation; external clinical validation against independent outcomes is required before any clinical utility claims. Full article

Background/Objectives: Oral and oropharyngeal cancers are highly prevalent and associated with a high mortality. The primary treatment modality is surgery with free flap reconstruction becoming the gold standard. Our study aimed to assess the anthropometric and metabolic predictors of the occurrence of postoperative complications after free flap reconstruction, and to present a PRISM (Predictive Reconstructive Index for Soft-tissue Microflaps) scoring system. Methods: This retrospective cohort study included 92 patients with advanced oral and oropharyngeal squamous cell carcinoma who underwent primary surgical treatment with microvascular free flap reconstruction between 2020 and 2024. Clinical, surgical, and biochemical parameters (operative and flap ischemia time, BMI; serum albumin, total protein, and calcium) were analyzed in relation to postoperative complications. Associations were assessed using correlation analyses and binary logistic regression. Based on the key predictive variables, the PRISM scoring system was developed to estimate perioperative risk. Results: Underweight or overweight patients showed higher complication rates (Kruskal–Wallis, p = 0.019). Longer surgeries were associated with a higher incidence of SIRS, which in turn correlated with increased flap ischemia (Man-Whitney, p = 0.032 and 0.039). Lower albumin and total protein levels on the second postoperative day were linked to more complications (Kruskal–Wallis, p = 0.001 and 0.010), as were lower calcium levels on the first postoperative day (p = 0.033). Additionally, longer hospitalization was significantly associated with complication severity (p = 0.031). The PRISM score stratified patients into low-, moderate-, and high-risk groups. Conclusions: Free flap outcomes in oral and oropharyngeal cancer are influenced by SIRS, nutritional status, and surgical factors. Longer surgeries, flap ischemia, low albumin, protein, calcium, and abnormal BMI increased the complication risk. Careful preoperative assessment, optimization of patient condition, and strategies to minimize operative time and ischemia are essential. The PRISM score may help stratify patients and guide clinical decisions. Full article

Background/Objective: Human papillomavirus (HPV) represents the most widespread sexually transmitted infection globally, with high-risk strains such as HPV16 driving a rising incidence of oropharyngeal squamous cell carcinoma (OPSCC), particularly in developed countries like the United States and United Kingdom. In the U.S., HPV16-associated OPSCC has surpassed cervical cancer as the most common HPV-related malignancy. Despite the availability of preventive vaccines, uptake remains suboptimal among adolescents and shifting sexual behaviors have contributed to increased disease burden. Early detection remains a major clinical challenge due to the absence of defined precursor lesions and the extended latency between viral exposure and disease onset. Most patients present with advanced-stage disease and no prior clinical history of pre-malignancy, limiting access to early-stage samples and hindering biomarker discovery. Methods: To address these limitations, we developed an in vitro HPV16 oral cancer model, using the three-dimensional organotypic raft culture system that simulates the progression of HPV16-transfected oral epithelium from precancerous states to malignant phenotypes. Results: Using HPV16-transfected human tonsil keratinocytes, we generated stratified and differentiated epithelia that mimic the biochemical and structural changes observed in vivo. This system enables detailed monitoring of epithelial differentiation, biochemical shifts, viral genome status, and key oncogenic and metabolic markers associated with HPV16-driven OPSCC. By aligning expression profiles with clinical datasets, we validated the model through the measurement of virologic markers linked to infection and progression, as well as tissue markers indicative of carcinogenic transformation. Conclusions: This model offers a promising tool for refining early detection strategies and evaluating potential clinical biomarkers, ultimately aiming to improve diagnostic precision and therapeutic outcomes in HPV-associated OPSCC. Full article

Texture perception in extruded snacks is commonly evaluated using force-based measurements, although crispness-related oral sensations arise from fracture, sound emission, and lubrication during mastication. This study developed a mechanistically grounded framework for texture characterization of fiber-enriched extruded snacks by integrating instrumental and sensory analyses within an oral-processing context. Extruded snack samples containing soybean residue (okara; 0%, 29%, and 40%) and commercial benchmarks were evaluated using synchronized mechanical–acoustic testing (five-blade Allo-Kramer shear and three-point bending tests), oral tribology, and sensory evaluation combining intensity rating and ranking. Increasing okara content shifted fracture behavior from brittle, sound-emitting failure toward damped, progressive deformation with approximately 3–5-fold lower acoustic envelope amplitudes and smoother force–time profiles. These changes corresponded to lower perceived Crunchiness and Sound Intensity, reflecting diminished crispness-related perception, and higher Hardness and Grittiness/Coarseness attributes (increases of ~25–45%). Oral tribology revealed cohesive, poorly lubricated boli for okara-rich snacks, requiring higher entrainment parameters (Uη₀ ≈ 1.0 × 10⁵–3.5 × 10⁵) to transition from boundary to mixed lubrication compared with commercial benchmarks (Uη₀ ≈ 7.0 × 10⁴–2.0 × 10⁵). Convergent multivariate analyses established instrumentally defined texture phenotypes that translate mechanical–acoustic and tribological signatures into sensory-interpretable texture categories, providing a practical framework for discriminating and optimizing nutritionally enhanced extruded snack products. Full article

NOTCH1 is associated with various tumors, including oral squamous cell carcinoma (OSCC), with a complex role depending on cellular contexts. Our aim was to analyze the expression of NOTCH1, several stem cell markers, and selected microRNAs in preneoplastic lesion of the oral cavity, oral epithelial dysplasia (OAD). Our study included formalin-fixed paraffin-embedded biopsy samples of 36 cases of OAD and 15 cases of normal oral mucosa. Expression of NOTCH1, stem cell markers (AGR2, KLF4, NANOG, OCT4, SOX2), and miR-27a, miR-34a, miR-128, miR-145, miR-150, and miR-335 was analyzed by quantitative PCR (qPCR). Expression of NOTCH1 protein was analyzed by immunohistochemistry. In OAD compared to normal mucosa, we found a significant increase in mRNA levels of NOTCH1, stem cell markers AGR2, NANOG, OCT4, and SOX2, and miR-150 and miR-128. NOTCH1 mRNA positively correlated with all five stem cell markers’ mRNA levels and miR-150. Immunohistochemistry showed variable expression patterns of NOTCH1 in OAD and normal mucosa. Our results support the role of NOTCH1 in early phases of OSCC development, with a potential contributory role in stemness, in association with AGR2, NANOG, OCT4, and SOX2, miR-150 and miR-128. These results support a complex role of NOTCH1 in carcinoma development, i.e., from oncogenic to tumor suppressor roles and stemness maintenance, not only in invasive OSCC but also in its precursor—OED. Full article

Senecavirus A (SVA) is a picornavirus that causes vesicular disease in swine and has been associated with increased neonatal mortality. Although SVA had only been detected sporadically in the United States since the 1980s, there was a sharp increase in cases in the United States and around the world starting in 2015. The cause of this shift in SVA epidemiology remains unknown; however, changes in the virus that have resulted in enhanced infectivity may have contributed. The aim of this research was to establish the infectious dose of a post-2015 SVA isolate in neonatal pigs and compare its infectivity to previous work with a 2011 SVA isolate. A 2018 SVA isolate (SVA/KS/2018) was serially 10-fold diluted to generate six inoculums. Animals were individually housed with four pigs inoculated with 2 mL orally per dilution. Detection of SVA RNA in serum and swabs, as well as the presence of neutralizing antibodies, were used to classify the infection status of animals. The minimum infectious dose for SVA/KS/2018 in neonates was 10^2.5 TCID₅₀/mL (2 × 10^2.5 or 632 TCID₅₀/pig). This value is similar to the infectious dose determined for SVA/CAN/2011, thus providing evidence that the increase in SVA detections was not due to increases in infectivity of contemporary isolates. Neonatal mortality has not been experimentally reproduced; however, pigs inoculated with higher doses of SVA/KS/2018 developed diarrhea and mortality, suggesting increased virulence, which should be investigated further. Full article

This study aimed to develop dissolving microneedles (MNs) for the buccal delivery of cannabidiol (CBD). CBD is a non-psychotomimetic phytocannabinoid with anti-inflammatory and anxiolytic properties. The MN arrays were produced using micromolding, which has the ability of scalability. However, this approach lacks the ability to customize needle geometry; thus, additive manufacturing was implemented in the study. Digital Light Processing (DLP) printing is a promising way to produce molds with customized MN architecture. In the present study, molds were fabricated from 3D-printed MN arrays to prepare dissolving MNs for buccal administration. Polymeric needles based on Eudragit L100-55 and Eudragit RSPO were produced from reverse molds and they were evaluated regarding their physiochemical and mechanical properties, followed by in vitro and ex vivo studies using porcine buccal mucosa. Visualization studies were conducted using confocal scanning laser microscopy, whereas the membrane integrity of the porcine mucosa upon application of the MNs was assessed by histological evaluation. Our results suggest that the needles can be effectively inserted into the buccal tissue and release the active pharmaceutical ingredient (API) in a controlled manner. This approach offers a patient-friendly alternative to oral CBD delivery, bypassing first-pass metabolism. Full article

The toxic actions of 2-monochloropropane-1,3-diol (2-MCPD) are still less well understood than those of 3-monochloropropane-1,2-diol (3-MCPD). The toxic effects of 2-MCPD on the heart, especially at the proteomic level, were recently investigated by researchers in a subacute (28 days, in 2017) and in a subchronic (90 days, in 2024) oral toxicity rat study. Here, we set out to perform an updated analysis and re-evaluation of these proteomic in vivo data in a comparative manner and in the context of 2-MCPD metabolism, focusing in particular on mitochondrial energy metabolism and the maintenance of the structural integrity and function of the heart. The aim of our project was to develop further reasonable, toxicologically relevant research hypotheses for future studies addressing this topic in order to shed more light on the—so far—rather limited knowledge of the toxicological properties and modes of action of 2-MCPD. Our updated data analysis and comparative re-evaluation revealed strong indications of cytoskeletal protein deregulation, indicative of cardiomyocyte degeneration, and the deregulation of enzyme proteoforms linked to carbohydrate utilization and mitochondrial functions. This led us to hypothesize that reactive metabolites of 2-MCPD, other than those formed from 3-MCPD, could impair mitochondrial pyruvate utilization and mitochondrial energy production, potentially resulting in cardiac functional heart failure in rats at doses slightly higher than 10 mg 2-MCPD per kg bw/day. Thus, we postulate the intermediate formation of some putative aldehydic and acidic metabolites following oral 2-MCPD exposure that might be causative of cardiotoxicity in rats. Full article