Search Results (2,934)

Molar pregnancy (MP) is a gestational disorder resulting from abnormal fertilization, leading to atypical trophoblastic proliferation and the formation of a complete or partial hydatidiform mole. This condition represents the most common form of gestational trophoblastic disease (GTD) and carries a significant risk of progression to gestational trophoblastic neoplasia (GTN). Although rare in high-income countries, MP remains up to ten times more prevalent in low-income and developing countries, contributing to preventable maternal morbidity and mortality. This narrative review provides an updated, practical overview of the clinical presentation, diagnosis, treatment, and follow-up of MP. A key focus is the challenge of early diagnosis, particularly given the increasing frequency of first-trimester detection, where classical histopathological criteria may be subtle, leading to diagnostic errors. The review innovates by integrating advanced diagnostic methods—combining histopathology, immunohistochemistry using p57Kip2, Ki-67, and p53 markers, along with cytogenetic analysis—to improve diagnostic accuracy in early gestation. The central role of referral centers is also emphasized, not only in facilitating timely treatment and access to chemotherapy, but also in implementing standardized post-molar follow-up protocols that reduce progression to GTN and maternal mortality. By focusing on both advanced diagnostic strategies and the organization of care through referral centers, this review offers a comprehensive, practice-oriented perspective to optimize patient outcomes in GTD and address persistent care gaps in high-burden regions. Full article

Type 10 17β-hydroxysteroid dehydrogenase (17β-HSD10) is the HSD17B10 gene product. It plays an appreciable part in the carcinogenesis and pathogenesis of neurodegeneration, such as Alzheimer’s disease and infantile neurodegeneration. This mitochondrial, homo-tetrameric protein is a central hub in various metabolic pathways, e.g., branched-chain amino acid degradation and neurosteroid metabolism. It can bind to other proteins carrying out diverse physiological functions, e.g., tRNA maturation. It has also previously been proposed to be an Aβ-binding alcohol dehydrogenase (ABAD) or endoplasmic reticulum-associated Aβ-binding protein (ERAB), although those reports are controversial due to data analyses. For example, the reported k_m value of some substrate of ABAD/ERAB was five times higher than its natural solubility in the assay employed to measure k_m. Regarding any reported “one-site competitive inhibition” of ABAD/ERAB by Aβ, the k_i value estimations were likely impacted by non-physiological concentrations of 2-octanol at high concentrations of vehicle DMSO and, therefore, are likely artefactual. Certain data associated with ABAD/ERAB were found not reproducible, and multiple experimental approaches were undertaken under non-physiological conditions. In contrast, 17β-HSD10 studies prompted a conclusion that Aβ inhibited 17β-HSD10 activity, thus harming brain cells, replacing a prior supposition that “ABAD” mediates Aβ neurotoxicity. Furthermore, it is critical to find answers to the question as to why elevated levels of 17β-HSD10, in addition to Aβ and phosphorylated Tau, are present in the brains of AD patients and mouse AD models. Addressing this question will likely prompt better approaches to develop treatments for Alzheimer’s disease. Full article

Triple-negative breast cancer (TNBC) is a clinically and molecularly heterogeneous subtype defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. In this study, tumor specimens from 104 TNBC patients were analyzed to characterize molecular and clinicopathological features and to assess the expression and therapeutic potential of four key surface markers: epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCAM), tissue factor (TF), and trophoblast cell surface antigen (TROP2). Multiplex immunofluorescence (mIF) demonstrated elevated EGFR and TROP2 expression in the majority of samples. Significant positive correlations were observed between EGFR and TF, as well as between TROP2 and both TF and EpCAM. Expression analyses revealed increased EGFR and TF levels with advancing tumor stage, whereas EpCAM expression declined in advanced-stage tumors. TROP2 and TF expression were significantly elevated in higher-grade tumors. Additionally, EGFR and EpCAM levels were significantly higher in patients with elevated Ki-67 indices. Binding specificity assays using single-chain variable fragment (scFv-SNAP) fusion proteins confirmed robust targeting efficacy, particularly for EGFR and TROP2. These findings underscore the therapeutic relevance of EGFR and TROP2 as potential biomarkers and targets in TNBC. Full article

Background/Objectives: Degenerative processes of the hip joint increasingly affect not only the articular cartilage but also periarticular structures such as the joint capsule and acetabular labrum. This study aimed to investigate the structural and molecular changes occurring in these tissues during advanced hip osteoarthritis. Methods: A combined analysis using immunohistochemistry (IHC), scanning electron microscopy (SEM), and micro-computed tomography (microCT) was conducted on tissue samples from patients undergoing total hip arthroplasty and from controls with morphologically normal joints. Markers associated with proliferation (Ki67), inflammation (CD68), angiogenesis (CD31, ERG), chondrogenesis (SOX9), and lubrication (Lubricin) were evaluated. Results: The pathological group showed increased expression of Ki67, CD68, CD31, ERG, and SOX9, with a notable decrease in Lubricin. SEM analysis revealed ultrastructural disorganization, collagen fragmentation, and neovascular remodeling in degenerative samples. A significant correlation between structural damage and molecular expression was identified. Conclusions: These results suggest that joint capsule and acetabular labrum degeneration are interconnected and reflect a broader pathophysiological continuum, supporting the use of integrated IHC and SEM profiling for early detection and targeted intervention in hip joint disease. Full article

Prostate cancer (PCa) is the second leading cause of cancer-related death among men in most Western countries. Current therapies for PCa are limited, often ineffective, and associated with significant side effects. As a result, there is a growing interest in exploring new therapeutic agents, particularly from the polyphyletic group of algae, which offers a promising source of compounds with anticancer properties. Our research group has focused on investigating the effects of a novel oleoresin from Gracilaria chilensis, known as Gracilex^®, as a potential therapeutic agent against PCa using both in vitro and in vivo models. Our findings indicate that Gracilex^® exhibits a time- and dose-dependent inhibitory effect on cell survival in LNCaP and PC-3 PCa, reducing viability by over 50% and inducing apoptosis, as evidenced by a significant increase in activated caspase-3 expression in both cell lines. Moreover, Gracilex^® significantly reduces the proliferation rate of both LNCaP and PC-3 prostate cancer cell lines, as evidenced by a marked decrease in the growth curve slope (p = 0.0034 for LNCaP; p < 0.0001 for PC-3) and a 40–50% reduction in the proportion of Ki-67-positive PCa cells. In addition, Gracilex^® significantly reduces in vitro cell migration and invasion in LNCaP and PC-3 cell lines. Lastly, Gracilex^® inhibits tumor growth in an in vivo xenograft model, an effect that correlates with the reduced PCa cell proliferation observed in tumor tissue sections. Collectively, our data strongly support the broad antitumoral effects of Gracilex^® on PCa cells in vitro and in vivo. These findings advance our understanding of its potential therapeutic role in PCa and highlight the relevance of further investigating algae-derived compounds for cancer treatment. Full article

Background/Objectives: The 2019 WHO classification redefined high-grade gastrointestinal neuroendocrine neoplasms (GI NENs), encompassing not only poorly differentiated neuroendocrine carcinomas (NECs), but also well-differentiated grade 3 neuroendocrine tumors (NETs G3). Since both subtypes share a Ki-67 index > 20%, distinguishing them based solely on morphology is challenging. Prior studies have shown TP53 alterations in NECs but not in NETs. This study aimed to evaluate clinico-morphological parameters and the immunohistochemical (IHC) expression of p53 in high-grade GI NENs to identify relevant correlations. Methods: Tumors were stratified by Ki-67 index into two groups: >20–50% and >50%. p53 IHC expression was assessed as “wild-type” (1–20% positive tumor cells) or “non-wild-type” (absence or >20% positivity). Correlations were analyzed between Ki-67, p53 status, and various pathological features. Results: Significant correlations were found between the Ki-67 index and maximum tumor size, pT stage, lymphovascular invasion, perineural infiltration, and diagnostic classification. Similarly, p53 immunohistochemical status was significantly associated with lymphovascular invasion, lymph node metastasis, and tumor classification (NET G3 versus NEC, including NEC components of MiNENs). Conclusions: The findings support the value of Ki-67 and p53 as complementary biomarkers in the pathological evaluation of high-grade GI NENs. Their significant associations with key morphological parameters support their utility in differentiating NETs G3 from NECs, particularly in cases showing overlapping histological features. The immunohistochemical profile of p53 may serve as a useful diagnostic adjunct in routine practice. Full article

Skin aging is characterized by compromised epidermal homeostasis and dermo-epidermal junction (DEJ) integrity, resulting in reduced stem cell potential and impaired tissue regeneration. This study investigated the effects of Andrographis paniculata extract (APE) on keratinocyte stem cells (KSCs) and DEJ composition in human skin. Using human skin explants and cell culture models, we demonstrated that APE treatment enhances DEJ composition by increasing Collagen IV and Laminin production while decreasing MMP-9 expression, without altering epidermal structure or differentiation. In the same model, APE preserved stemness potential by upregulating markers related to niche components (collagen XVII and β1-integrin), proliferation (Ki-67 and KRT15), and stem cell capacity (Survivin and LRIG1). In vitro studies revealed that APE selectively stimulated KSC proliferation without affecting transit amplifying cells and promoted Collagen IV and Laminin secretion, particularly in KSCs. Furthermore, in a co-culture model simulating a compromised DEJ (UVB-induced), APE increased Laminin production in KSCs, suggesting a protective effect against photo-damage. These findings indicate that APE enhances DEJ composition and preserves stem cell potential, highlighting its promise as a candidate for skin anti-aging strategies targeting stem cell maintenance and extracellular matrix stability to promote skin regeneration and repair. Full article

Background/Objectives: Eph receptor A5 (EphA5) is a receptor tyrosine kinase that is implicated in multiple malignancies, although its role in endometrial cancer (EC) remains unclear. The aim of this study was to investigate the clinicopathological significance of EphA5 expression in EC and explore its association with proliferative and metabolic markers. Methods: We retrospectively analyzed 75 EC tissue samples from treatment-naïve patients by using immunohistochemistry and H-score quantification. Associations between EphA5 expression and clinicopathological parameters were assessed through logistic regression analysis. Kaplan–Meier analysis was used to evaluate survival outcomes. Correlation analysis, stratified according to cancer stage, was used to explore biomarker interactions. Results: High EphA5 expression levels were significantly associated with elevated Ki-67 expression (adjusted odds ratio (aOR): 1.08 per 1-point H-score increase, p = 0.024) and decreased pAMPK expression (aOR: 0.89 per 1-point H-score increase, p = 0.024), indicating its involvement in proliferative and metabolic pathways. Paradoxically, patients with high EphA5 levels had significantly better overall survival probabilities (H-score > 105, log-rank p = 0.007). Stage-specific analyses suggested that EphA5 levels correlated with proliferation in early-stage disease and epithelial–mesenchymal transition in advanced stages. Conclusions: EphA5 may act as a context-dependent biomarker in EC. Despite its positive correlation with proliferation and negative association with metabolic stress signaling, high EphA5 expression levels were predictive of a favorable prognosis. Full article

Membrane technology is primarily used for the separation and purification of biotechnological products, which contain proteins and enzymes. Membrane fouling during crossflow filtration remains a significant challenge. This study aims to initially validate crossflow filtration models, particularly related to pore-blocking mechanisms, through a comparative analysis with dead-end filtration models. One crossflow microfiltration (MF) and six consecutive ultrafiltration (UF) stages were implemented to concentrate laccase extracts from Pleurotus ostreatus 202 fungi. The complete pore-blocking mechanism significantly impacts the MF, UF 1000, UF 100 and UF 10 stages, with the highest related filtration constant (Kb_F) estimated at 12.60 × 10⁻⁴ (m⁻¹). Although the intermediate pore-blocking mechanism appears across all filtration stages, UF 100 is the most affected, with an associated filtration constant (Ki_F) of 16.70 (m⁻¹). This trend is supported by the highest purification factor (6.95) and the presence of 65, 62 and 56 kDa laccases in the retentate. Standard pore blocking occurs at the end of filtration, only in the MF and UF 1000 stages, with filtration constants (Ks_F) of 29.83 (s^−0.5m^−0.5) and 31.17 (s^−0.5m^−0.5), respectively. The absence of cake formation and the volume of permeate recovered indicate that neither membrane was exposed to exhaustive fouling that could not be reversed by backwashing. Full article

Obesity and metabolic dysfunction are established risk factors for luminal breast cancer, yet current preclinical models inadequately recapitulate the complex metabolic and immune interactions driving tumorigenesis. To develop and characterize an immunocompetent rat model of luminal breast cancer induced by chronic exposure to a cafeteria diet mimicking Western obesogenic nutrition, female rats were fed a cafeteria diet or standard chow from weaning. Metabolic parameters, plasma biomarkers (including leptin, insulin, IGF-1, adiponectin, and estrone), mammary gland histology, tumor incidence, and gene expression profiles were longitudinally evaluated. Gene expression was assessed by PCR arrays and qPCR. A subgroup underwent dietary reversal to assess the reversibility of molecular alterations. Cafeteria diet induced significant obesity (mean weight 426.76 g vs. 263.09 g controls, p < 0.001) and increased leptin levels without altering insulin, IGF-1, or inflammatory markers. Histological analysis showed increased ductal ectasia and benign lesions, with earlier fibroadenoma and luminal carcinoma development in diet-fed rats. Tumors exhibited luminal phenotype, low Ki67, and elevated PAI-1 expression. Gene expression alterations were time point specific and revealed early downregulation of ID1 and COX2, followed by upregulation of MMP2, THBS1, TWIST1, and PAI-1. Short-term dietary reversal normalized several gene expression changes. Overall tumor incidence was modest (~12%), reflecting early tumor-promoting microenvironmental changes rather than aggressive carcinogenesis. This immunocompetent cafeteria diet rat model recapitulates key metabolic, histological, and molecular features of obesity-associated luminal breast cancer and offers a valuable platform for studying early tumorigenic mechanisms and prevention strategies without carcinogen-induced confounders. Full article

This study explores a series of 3,4-dihydroisocoumarins as potential inhibitors of fatty acid oxidation through rational design, synthesis and in vitro evaluation. The compounds studied were designed as structural analogs of the natural substrates of carnitine acetyltransferase (CAT) and other enzymes in the carnitine transferase family, which play a crucial role in fatty acid metabolism. Comparative in vitro analyses revealed that the presence of an alkyl substituent at position 3 of the heterocyclic core, along with its chain length, significantly influences inhibitory activity, yielding IC₅₀ values in the micromolar range. Kinetic studies of one of the most potent compounds—cis- and trans-3-decyl-6,7-dimethoxy-3,4-dihydroisocoumarin-4-carboxylic acids—demonstrated mixed inhibition of CAT, with K_i values of 130 μM and 380 μM, respectively. These findings underscore the therapeutic potential of the compounds under investigation in modulating fatty acid catabolism, with possible applications in treating metabolic disorders. Full article

This study presents a detailed analysis of the combustion dynamics of stoichiometric H₂–air and CH₄–air mixtures in a 20 L closed vessel over an initial temperature range of 298–423 K. We integrate experimental pressure–time P(t) measurements with numerical analysis to extract laminar burning velocity (LBV) and deflagration index (K_G) values, and we assess three independent kinetic mechanisms (KiBo_MU, University of San Diego, Lund University) via simulations. For H₂–air, LBV increases from 0.50 m/s at 298 K to 0.94 m/s at 423 K (temperature exponent α ≈ 1.79), while for CH₄–air, LBV rises from 0.36 m/s to 0.96 m/s (α ≈ 2.82). In contrast, the deflagration index K_G decreases by ca. 20% for H₂–air and ca. 30% for CH₄–air over the same temperature span. The maximum explosion pressure (P_max) and peak pressure rise rate ((dP/dt)_max) also exhibit systematic increases with temperature. A comparison with model predictions shows agreement within experiments, providing data for safety modeling and kinetic mechanism validation in H₂- and CH₄-based energy systems. Full article

Background/Objectives: Doxorubicin is a chemotherapeutic agent whose clinical use is limited by side effects (SEs). The most common SE is doxorubicin-induced cardiotoxicity (DIC), for which there is still no prevention. The hypothesis arises that active substances of natural origin could influence DIC prevention by affecting several pathways of DIC occurrence. Methods: Thirty Wistar rats were divided into six groups (control, NADES (C8:C10) solvent, pumpkin pulp extract, doxorubicin, NADES (C8:C10) solvent–doxorubicin, and pumpkin pulp extract–doxorubicin). During the experiment, parameters of general condition, body, and heart weight were observed. Heart function parameters were monitored by measuring the levels of serum NT-pro-BNP, CK-MB, and hsTnT. Tissue damage was evaluated by determining the doxorubicin damage score and the expression of anti-cardiac troponin I, anti-Nrf2, anti-Bcl-2, anti-caspase-3, anti-COX2, and anti-Ki67 antibodies. Results: Doxorubicin administration led to impaired general condition of animals and increased the levels of NT-proBNP, CK-MB, hsTnT, and myocardium tissue damage of medium grade. Its administration induced apoptosis (as evidenced by elevated Casp3), reduced antiapoptotic Bcl-2 and troponin I expression in cardiomyocytes. Reduced Nrf2 expression due to doxorubicin administration was restored when pumpkin pulp extract containing carotenoids was coadministered, which led to the normalization of Casp3, Bcl-2, and troponin I expression. Consequently, the general condition and body weight were better in animals treated with both doxorubicin and the other treatment compared to those treated with doxorubicin alone. Conclusions: The results of this study strongly suggest that pumpkin pulp extract containing carotenoids has a cardioprotective effect, possibly by regulating the Nrf2 pathway. Full article

Sepsis remains a leading global cause of mortality, with delayed recognition and empirical antibiotic overuse fueling poor outcomes and rising antimicrobial resistance. This systematic scoping review evaluates the current landscape of artificial intelligence (AI) and machine learning (ML) applications in sepsis care, focusing on early detection, personalized antibiotic management, and resistance forecasting. Literature from 2019 to 2025 was systematically reviewed following PRISMA-ScR guidelines. A total of 129 full-text articles were analyzed, with study quality assessed via the JBI and QUADAS-2 tools. AI-based models demonstrated robust predictive performance for early sepsis detection (AUROC 0.68–0.99), antibiotic stewardship, and resistance prediction. Notable tools, such as InSight and KI.SEP, leveraged multimodal clinical and biomarker data to provide actionable, real-time support and facilitate timely interventions. AI-driven platforms showed potential to reduce inappropriate antibiotic use and nephrotoxicity while optimizing outcomes. However, most models are limited by single-center data, variable interpretability, and insufficient real-world validation. Key challenges remain regarding data integration, algorithmic bias, and ethical implementation. Future research should prioritize multicenter validation, seamless integration with clinical workflows, and robust ethical frameworks to ensure safe, equitable, and effective adoption. AI and ML hold significant promise to transform sepsis management, but their clinical impact depends on transparent, validated, and user-centered deployment. Full article

The present study investigated the neuroprotective potential of the Murraya carbazole derivatives murrayanol, mahanimbine, murrayafoline A, and 9-methyl-9H-carbazole-2-carbaldehyde using in silico and in vitro assays. The pharmacokinetic properties and potential toxicity (ADME/T) of the carbazole derivatives were assessed to evaluate their prospects as up-and-coming drug candidates. Molecular docking was used to investigate the interactions of the compounds with Aβ (PDB: 1IYT, 2BEG, and 8EZE) and AChE receptors (PDB: 4EY7 and 1C2B). The results from the in vitro assays were used to validate and support the findings from the in silico assays. The compounds demonstrated significant inhibition of acetylcholinesterase (AChE), a key target in neurodegenerative disorders. Murrayanol and mahanimbine presented superior inhibitory activity (IC₅₀ ~0.2 μg/mL), outperforming the reference drug, galantamine. The inhibition mechanisms were competitive (murrayanol, murrayafoline A, and 9-methyl-9H-carbazole-2-carbaldehyde) and non-competitive (mahanimbine), supported by low Ki values and strong docking affinities. The compounds also proved effective in reducing Aβ fibrillization (murrayanol: 40.83 ± 0.30%; murrayafoline A: 33.60 ± 0.55%, mahanimbine: 27.68 ± 2.71%). These findings highlight Murraya carbazoles as promising scaffolds for multifunctional agents in AD therapy. Further optimization and mechanistic studies are warranted to advance their development into clinically relevant neuroprotective agents. Full article