Search Results (2,172)

Type 2 diabetes mellitus (T2DM) is a chronic disease that has become a serious health problem worldwide. Moreover, increased systemic and cerebrovascular inflammation is one of the major pathophysiological features of T2DM, and a growing body of evidence emphasizes T2DM with memory and executive function decline. Bioactive sphingolipids regulate a cell’s survival, inflammatory response, as well as glucose and insulin signaling/metabolism. Moreover, current research on the role of sphingosine kinases (SPHKs) and sphingosine-1-phosphate receptors (S1PRs) in T2DM is not fully understood, and the results obtained often differ. The aim of the present study was to evaluate the effect of metformin (anti-diabetic agent, MET) on the brain’s sphingosine-1-phosphate-related signaling and ultrastructure in diabetic mice. Our results revealed elevated mRNA levels of genes encoding sphingosine kinase 2 (SPHK2) and sphingosine-1-phosphate receptor 3 (S1PR3), which was accompanied by downregulation of sphingosine-1-phosphate receptor 1 (S1PR1) in the hippocampus of diabetic mice. Simultaneously, upregulation of genes encoding pro-inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) was observed. Administration of MET significantly reversed changes in mRNA levels in the hippocampus and reduced Sphk2, Il6, and Tnf, with concomitant upregulation of S1pr1 gene expression. Ultrastructural analysis of diabetic mice hippocampus revealed morphological alterations in neurons, neuropil, and capillaries that were manifested as mitochondria swelling, blurred synaptic structure, and thickened basal membrane of capillaries. The use of MET partially reversed those changes. Our research emphasizes the important role of insulin sensitivity modulation by metformin in the regulation of SPHKs and S1PRs and inflammatory gene expression in a murine model of T2DM. Full article

Camels have developed unique adaptive mechanisms, one of which is the active accumulation of lipids. This metabolic feature has a direct influence on the liver ultrastructure. Its analysis reveals how exactly the hepatocytes have evolved to effectively store fat and neutralize toxins, which is crucial for survival in the desert. Considering the latter, the aim of this research is to establish the features of the microstructural organization of the liver of the Bactrian camel (Camelus bactrianus). This study was conducted using 15 liver tissue fragments from 5 healthy Bacterian camels (3 pieces from each animal) via biopsy. The sections were examined using a JEM-1011 electron microscope at magnifications of 2500–8000. Electron microscopic analysis of hepatocytes revealed a significantly larger hepatocyte diameter (25–30 µm), suggesting an adaptation for metabolites and water storage. Hepatocytes exhibited fewer, medium-sized (0.5–2 µm) lipid droplets, present in only 12–15% of cells. A high density of specialized Kupffer (15–20 cells per 10,000 µm²) and activated Ito cells was observed, indicating enhanced detoxification and immune functions. These specific ultrastructural features provide a model for studying metabolic resistance and inform veterinary diagnostics and husbandry practices for this species. Full article

Eosinophils are innate immune cells that infiltrate tissues in response to cell proliferation and necrosis, which occurs during normal injury repair, parasitic infections, allergies, and cancer. Their involvement in cancer is controversial particularly with regard to tumor-associated tissue eosinophilia (TATE) and a recently defined mechanism of extracellular trap cell death (ETosis), a particular type of eosinophil cell death that is distinct from both apoptosis and necrosis. This narrative review synthesizes the literature regarding the prognostic significance of TATE, focusing on eosinophil ETosis and the important role of transmission electron microscopy (TEM) in its detection and morphological characterization. The prognostic role of TATE is contradictory: in certain tumors, it is a favorable prognostic marker, while in others, it is unfavorable. However, recent research reveals that TATE is associated with a better prognosis in non-viral neoplasms, but it may correlate with a poor prognosis in virus-related neoplasms, such as human T-lymphotropic virus type 1 (HTLV-1)-associated lymphomas and HPV-positive carcinomas. Our ultrastructural investigations revealed distinct phases of eosinophil ETosis in gastric cancer, which were defined by chromatin decondensation, plasma membrane disruption, granule discharge, and development of extracellular traps. We observed synapse-like interactions between eosinophils, exhibiting ETosis or compound exocytosis, and tumor cells, which showed various degrees of cellular damage, ultimately leading to colloid-osmotic tumor cell death. TEM provides important insights into eosinophil-mediated cytotoxicity, requiring further investigation as potential immune effector mechanisms in non-viral tumors. TATE evaluation, together with the viral status of the neoplasia, may be useful to confirm its prognostic significance and consequently its therapeutic implication in specific cancers. Full article

Angiogenesis, the formation of new blood vessels from existing vasculature, is regulated by a balance between pro- and anti-angiogenic factors. In adults, this process typically occurs in response to inflammation, wound healing, and neoplastic growth. Uniquely, the female reproductive system undergoes cyclical and repetitive angiogenesis with folliculogenesis, decidualization, implantation, and embryo development throughout the reproductive cycle. Ovarian angiogenesis involves a coordinated network of signaling pathways and molecular factors. Vascular endothelial growth factor (VEGF) is the primary driver of this process, supported by other regulators such as fibroblast growth factor (FGF) and hypoxia-inducible factor (HIF). Understanding the molecular mechanisms that govern ovarian angiogenesis is essential for developing new diagnostic and therapeutic approaches in reproductive medicine. Vascular dysfunction and impaired angiogenesis are key contributors to various ovarian disorders and infertility, including polycystic ovary syndrome (PCOS). Therefore, in-depth studies of ovarian vascularization are crucial for identifying the pathophysiology of these conditions and guiding the development of effective treatments. Advancing knowledge in this area holds significant potential for innovation in both medicine and biotechnology. Full article

Leprosy is a chronic infectious disease that targets the peripheral nervous system, leading to peripheral neuropathy. Mycobacterium leprae primarily infects Schwann cells, adipocytes, and macrophages, altering their metabolism and gene expression. This study investigates the metabolic interaction between M. leprae and Schwann cells, with a focus on indoleamine 2,3-dioxygenase (IDO), a key enzyme in tryptophan catabolism via the kynurenine pathway. We found that M. leprae induces IDO expression in Schwann cells, suggesting a role in immune modulation and neuropathy. Inhibition of IDO with 1-methyl-L-tryptophan (1-MT) reduced Schwann cell viability and metabolic activity in response to M. leprae. After 24 h of infection, M. leprae impaired mitochondrial membrane potential, although no significant changes in autophagy or mitochondrial ultrastructure were observed by electron microscopy. Interestingly, IDO1 inhibition upregulated the expression of antioxidant genes, including GPX4, NFE2L2, and HMOX1. In conclusion, these findings highlight a central role for IDO in shaping the metabolic and immunological response of Schwann cells to M. leprae infection. IDO induction contributes to immune regulation and cellular stress, while its inhibition disrupts cell viability and promotes antioxidant gene expression. These results position IDO as a potential therapeutic target for modulating host–pathogen interactions and mitigating nerve damage in leprosy. Full article

This study distinguished male and female individuals by wing morphology (males with long wings, females with short wings) and investigated sexual dimorphism in the chemosensory system of Blaptica dubia through integrated ultrastructural and transcriptomic analyses. Scanning electron microscopy (SEM) was used to characterize the type, number, and distribution of antennal sensilla, while Illumina HiSeq sequencing, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) annotation, and Quantitative Real-time Reverse Transcription Polymerase Chain Reaction (qRT-PCR) validation were employed to analyze sex-specific gene expression profiles. Both sexes exhibited Böhm’s bristles, chaetic, trichoid, and basiconic sensilla. Males showed significantly more chaetic sensilla on the pedicel and longer type I/II chaetic sensilla on the flagellum, whereas females had longer ST2 sensilla. Basiconic sensilla were predominantly flagellar-distributed and more abundant/longer in males. No sexual differences were observed in Böhm’s bristles. Transcriptomics revealed 5664 differentially expressed genes (DEGs) (2541 upregulated; 3123 downregulated), enriched in oxidation-reduction, extracellular space, lysosome, and glutathione metabolism. KEGG analysis identified five key pathways: lysosome, glutathione metabolism, cytochrome P450-mediated xenobiotic/drug metabolism, and ascorbate/aldarate metabolism. Among 11 chemosensory-related DEGs, chemosensory proteins (CSPs) and odorant binding proteins (OBPs) were downregulated in males, while gustatory receptors (GRs), olfactory receptors (Ors), and ionotropic receptors (IRs) were upregulated. These results demonstrate profound sexual dimorphism in both antennal sensilla morphology and chemosensory gene expression, suggesting divergent sex-specific chemical communication strategies in Blaptica dubia, with implications for understanding adaptive evolution in Blattodea. Full article

Supplement use has increased in recent years, despite limited evidence for its broad health benefits. Furthermore, exogenous antioxidants may determine pro-oxidant effects, depending on various factors such as dose, circadian window, and presence of metal ions. Although the effects of sleep deprivation (SD) on the brain are well-documented, its impact on peripheral organs remains relatively underexplored. The goal of this study was to evaluate the effects of a Cornus mas (C. mas) fruit extract on multiple peripheral sites in rats undergoing paradoxical sleep deprivation (PSD). Male Wistar rats were randomly distributed in four groups, including control, C. mas (CM), sleep deprivation (SD), and sleep deprivation and C. mas (SD+CM) (n = 7/group). Seven days of PSD were associated with ultrastructural liver injury and evidence of oxidative dysfunction in several organs: liver, kidney, spleen, and aorta. These alterations were accompanied by marked increases in the evaluated cytokines, including testicular Interleukin-1β, hepatic Interleukin-6, and aortic Interleukin-4. Although the C. mas extract largely maintained hepatic ultrastructure, its effects on other organs were limited. In the aorta, it normalized GSSG values but was also associated with a significant increase in lipid peroxidation. These findings highlight both the systemic impact of SD and caution against assuming uniform benefits of exogenous antioxidants across organ systems in this context. Full article

Scientific awareness is rising regarding fish and sea invertebrates’ sensitivity to the sound field’s particle motion component. The AquaVib, a distinctive laboratory setup, provides a practical methodology for controlled sound exposure experiments on small aquatic organisms, enabling a separate assessment of their acoustic pressure- and particle motion-elicited responses across a range of realistic scenarios. The chosen facility design permits the reproduction of realistic sound exposures at different kinetic-to-potential energy ratios, with characteristics similar to underwater-radiated noise from human activities such as shipping or offshore installations (<1 kHz). It provides a cost-efficient multimodal approach to investigate potential physiological, pathological, and ultrastructural effects on small aquatic organisms at any stage of maturity. This study details the vibroacoustic characterization of the AquaVib system, identifies key challenges, and outlines planned improvements. The ultimate goal of the presented approach is to contribute to the scientific community and competent authorities in covering the main gaps in current knowledge on the sensitivity of aquatic organisms to the particle motion component and to identify and quantify potential acute and long-term detrimental effects arising from human activities. Full article

Serpulids are among the few annelid groups capable of building skeletal structures by secreting calcium carbonate. Compared with other biomineralizing organisms, their control over tube construction is relatively limited, making them vulnerable to environmental changes. To distinguish between intrinsic biological regulation and extrinsic environmental influence in tube formation, we examine the calcareous tube of Hydroides elegans, focusing on the tube ultrastructure, mineral composition, elemental distribution, organic-inorganic constituents, and biomineralization mechanism. The results show that the tube consists of three superimposed layers: an innermost organic sheet, an intermediate lamello-fibrillar calcite layer, and an outermost spherulitic prismatic calcite layer. The outer spherulitic prismatic layer frequently exhibits bioerosion, trapped sedimentary particles, and fan-shaped aragonite aggregates, indicating pronounced environmental influence. In contrast, the middle lamello-fibrillar calcite fabric is highly organized and closely integrated with the innermost organic sheet, indicating strictly biological controls. This study highlights the combined effect of biological controls and environmental influences in serpulid tube calcification, contributing to our understanding of their adaptive evolution in changing oceans. Full article

The relevance of well-structured mitochondria in sustaining the integrity of the retinal pigment epithelium (RPE) is increasingly evident. Conversely, altered mitochondria are a culprit of age-related macular degeneration (AMD), which is influenced by the activity of mechanistic target of rapamycin (mTOR). In the present manuscript, the mitochondrial status of RPE cells was investigated by light and electron microscopy following the administration of various doses of compounds, which modulate mTOR. The study combines MitoTracker dyes and mitochondrial immunohistochemistry with in situ mitochondrial morphometry. Various doses of 3-methyladenine (3-MA), curcumin, and rapamycin were administered alone or in combination. The activity of autophagy and mTOR was quantified following each treatment. Administration of 3-MA led to activation of mTOR, which was associated with severe cell death, altered membrane permeability, and altered ZO-1 expression. In this condition, mitochondrial mass was reduced, despite a dramatic increase in damaged mitochondria being reported. The decrease in healthy mitochondria was concomitant with alterations in key mitochondria-related antigens such as Tomm20, Pink1, and Parkin. Specific mitochondrial alterations were quantified through in situ ultrastructural morphometry. Both curcumin and rapamycin counteract mTOR activation and rescue mitochondrial status, while preventing RPE cell loss and misplacement of decreased ZO-1 expression. Mitigation of mTOR may protect mitochondria in retinal degeneration. Full article

Background and Objectives: Cardiovascular disease remains a leading cause of mortality in Diabetes mellitus (DM), where chronic hyperglycemia induces oxidative stress, mitochondrial dysfunction, and hypoxia in cardiomyocytes. Liraglutide (Lir), a glucagon-like peptide-1 receptor agonist, is widely used for type 2 DM management and has been shown to exert cardioprotective and antioxidant effects. This study aimed to evaluate whether Lir mitigates hyperglycemia-induced oxidative and hypoxic stress in H9c2 cardiomyoblasts while preserving cellular ultrastructure. Materials and Methods: H9c2 cells were cultured under normoglycemic (5.5 mM) or hyperglycemic (30 mM) conditions, with or without Lir. Cell viability was assessed using MTT assay. Ultrastructural changes were examined by transmission electron microscopy (TEM). Hypoxia-inducible factor-1α (HIF-1α), lipid peroxidation markers (LOOH, MDA), advanced oxidation protein products (AOPP), and total antioxidant capacity (TAC) were quantified by spectrophotometric assays. Results: MTT assays revealed that Lir significantly improved cell viability under hyperglycemic conditions and the EC₅₀ was 1.05 ± 0.06 μM after 48 h of treatment. Under HG, HIF-1α, lipid hydroperoxides (LOOH), malondialdehyde (MDA) and advanced oxidation protein products (AOPP) increased and total antioxidant capacity (TAC) decreased (p < 0.001, for all); Lir significantly reversed these changes, restoring values to near-NG levels. Ultrastructural analysis of HG + Lir-treated cells revealed reduced granules, increased vacuolization, and slight rough endoplasmic reticulum dilatation, though mitochondria appeared normal. Conclusions: Lir significantly attenuated oxidative stress and cellular injury in cardiomyocytes under hyperglycemic conditions, improving viability, modulating HIF-1α expression, and restoring antioxidant balance. These findings support a dual role for Lir in diabetic cardiomyopathy: glucose-independent cytoprotection and regulation of mitochondrial and hypoxia pathways, highlighting its therapeutic potential beyond glycemic control. Full article

Background/Objectives: Targeted cancer therapies increasingly rely on modulating specific cell death pathways and kinase signaling. Due to their structural versatility and potential to induce mechanistically distinct cytotoxic responses, benzoxazine–purine hybrids represent a promising scaffold for anticancer drug development. The objective of this study was to design and evaluate novel benzoxazine–purine derivatives for their antiproliferative activity and elucidate their underlying mechanisms of action. Methods: A series of benzoxazine–purine compounds was synthesized via a modular and efficient approach. The synthetic route involved a one-pot cyclization of substituted 2-aminophenols with epichlorohydrin, followed by tosylation and subsequent Mitsunobu coupling with halogenated purines. Their antiproliferative activity was assessed in MCF-7 (breast) and HCT-116 (colon) cancer cell lines using MTT assays. Selected compounds were evaluated further for kinase inhibition, effects on the cell cycle, membrane integrity (Annexin V/PI staining), ultrastructural changes (SEM), and caspase activation (Western blot). In silico ADMET profiling was also performed. Results: Compounds 9 and 12 exhibited the most potent antiproliferative activity, with low micromolar IC₅₀ values. Compound 12 showed dual HER2/JNK1 kinase inhibition and induced caspase-8-dependent pyroptosis-like cell death, characterized by membrane rupture and inflammatory features. In contrast, compound 8 lacked kinase inhibition and promoted S-phase arrest with apoptotic-like morphology. Both compounds demonstrated favorable physicochemical and ADMET profiles, including high intestinal absorption and an absence of mutagenicity. Conclusions: The rational design of benzoxazine–purine hybrids resulted in the discovery of compounds with distinct mechanisms of action. Compound 12 induces inflammatory cell death by modulating kinases, while compound 9 acts through a kinase-independent apoptotic pathway. These results underscore the therapeutic potential of scaffold-based diversification for developing targeted anticancer agents. Full article

A subset of chondrocytes in various human cartilage tissues, including neoplastic, regenerative, and normal cartilage, expresses α-smooth muscle actin (α-SMA), a protein typically found in smooth muscle cells. These α-SMA-containing chondrocytes, termed myochondrocytes and myochondroblasts, may play important roles in cartilage physiology, regeneration, and structural integrity, particularly in auricular and articular cartilage. This review synthesizes current knowledge regarding the terminology, distribution, and biological significance of these cells across normal, osteoarthritic, transplanted, and neoplastic cartilage. We summarize key findings from immunohistochemical studies using markers such as S-100, α-SMA, and SOX9, along with ultrastructural confirmation of myofilament bundles via electron microscopy. Current evidence suggests that myochondrocytes exhibit enhanced regenerative potential and contribute to matrix remodeling. Furthermore, their presence reflects the inherent cellular heterogeneity of cartilage, potentially arising from transdifferentiation processes involving fibroblasts, mesenchymal stem cells, or chondroblasts. Finally, TGF-β1 and PDGF-BB are identified as a critical modulator of α-SMA expression and chondrocyte phenotype. A deeper understanding of nature and function of myochondrocytes and myochondroblasts may improve interpretations of cartilage pathology and inform strategies for tissue engineering and cartilage repair. This review highlights the need for further investigation into the molecular regulation and functional roles of these cells in both physiological and pathological contexts. Full article

Primary ciliary dyskinesia (PCD) is a rare, inherited disease with a complex genetic etiology, leading to ciliary dysfunction and impaired mucociliary clearance. This paper presents the current state of knowledge regarding the clinical presentation, diagnostic approaches, and therapeutic strategies in PCD. The role of genetic testing, ultrastructural analysis of cilia, and modern methods such as high-speed video microscopy (HSVA), nasal nitric oxide (nNO) measurement, and immunofluorescence is discussed. The importance of a multi-step diagnostic process is emphasized, given the absence of a single test with both high sensitivity and specificity. Current treatment options—including respiratory physiotherapy, infection management, and control of ENT symptoms—are reviewed, alongside new experimental approaches such as gene and mRNA therapies. This paper highlights the need for early diagnosis and comprehensive, interdisciplinary care for patients with PCD. Full article

Background: Stannous ions and polyphenols are effective substances in preventive dentistry. The present study’s aim was to investigate whether a combination of these substance groups can achieve increased efficacy. Methods: Initial biofilm formation was performed on bovine enamel slabs, carried by 10 subjects intraorally. The subjects rinsed with tannic acid, SnCl₂, SnF₂, a combination (50:50) of tannic acid and SnCl₂, or a combination of tannic acid and SnF₂, with no rinsing in the negative control. Bacterial adherence, glucan formation (8 h, 48 h oral exposition,) and calcium release kinetics were measured (pH 2; 2.3; 3). Statistics were performed with the Kruskal–Wallis test (p < 0.05), Mann–Whitney U test (p < 0.05), and Bonferroni–Holm correction. Results: All rinsing solutions reduced bacterial adherence by more than 50%. Initial bacterial colonization and glucan formation was significantly reduced by SnF₂ and SnCl₂ as well as their combinations with tannic acid. The most significant reductions in calcium release at pH 2; 2.3; and 3 were obtained by SnF₂ and the combination of SnF₂ and tannic acid. At the acidic pH 2.0, SnF₂, SnCl₂, and tannic acid and SnF₂ showed significant protection compared to the control (p ≤ 0.01). TEM micrographs indicated that rinsing with SnF₂ and tannic acid leads to pronounced electron dense, thick pellicle layers. Conclusions: SnCl₂ and SnF₂, as well as their combinations with tannic acid, led to a reduction in initial bacterial colonization and glucan formation, showing an erosion-protective effect. These findings confirm the clinical applicability hitherto suspected by in vitro findings. Full article