Acute kidney injury (AKI) is primarily caused by renal ischemia/reperfusion (I/R) injury, which is clinically linked to significant morbidity and death in both developed and developing countries. Therefore, the aim of this work is to compare the possible ameliorative effect of dapagliflozin (DAPA) versus human umbilical cord mesenchymal stem cells derived microvesicles (HUC-MSC-MVs) through biochemical, light, and electron microscope studies. Fifty-six adult male albino rats were divided into four groups: control, I/R, I/R+DAPA, and I/R+MVs groups. Both serum and tissue samples were collected for biochemical analysis. Renal specimens were processed to evaluate the histological structure, collagen content, desmin, and β-catenin immune expression. Morphometric and statistical analyses were performed. I/R group revealed prominent histoarchitectural alterations and a significant rise in the serum urea, creatinine, oxidative stress markers, and inflammatory mediators. Alterations were partially attenuated by DAPA therapy, whereas HUC-MSC-MVs significantly improved all parameters. We concluded that MSC-MVs administration exert a more significant ameliorative effect comparing to DAPA therapy via attenuating the oxidative stress and inflammation in addition to, restoring angiogenesis and cell proliferation. However, these findings remain preclinical and further researches are acclaimed for dose optimization, safety evaluation, and clinical validation before application in human AKI.

High-quality brain fixation is essential in experimental neuropathology, as it determines tissue preservation for ultrastructural investigations and preclinical drug evaluation. This study examined the effects of two fixation methods - immersion and transcardial perfusion - on neural preservation of adult male Wistar rats. Ultrastructural analysis was performed on the pyramidal cortex and hippocampal CA1 layer under six experimental conditions: (1) brain immersion in fixative immediately after euthanasia; (2) brain immersion in fixative 6 h post-euthanasia; (3) transcardial perfusion fixation using peristaltic pump at physiological flow rate; (4) transcardial perfusion fixation using peristaltic pump at supraphysiological flow rate; (5) transcardial perfusion fixation using gravity-fed hydrostatic system at physiological pressure; and (6) transcardial perfusion fixation using gravity-fed hydrostatic system at supraphysiological pressure. Light microscopy revealed no major differences among groups fixed through transcardial perfusion, whereas immersion fixation was associated with artifactual dark neurons and spongiform-like appearance of the neuropil. Electron microscopy demonstrated that immersion fixation caused poor morphological preservation and prominent artifacts. In contrast, perfusion fixation achieved superior preservation with physiological volumes. However, deviations from appropriate volume or pressure resulted in autolytic changes and artifacts. These findings highlight the critical need for optimal fixation protocols in experimental neuropathological research to prevent fixation-induced artifacts and ensure ultrastructural integrity, especially in pre-clinical drug evaluation in animal models for neurological diseases.

Head and neck cancer treatments, such as radiation therapy (RT), often cause acute tissue changes, but still little is known about the long-term effects. This study aimed to identify pathological changes and the role of transmembrane MUC1 (tMUC1) in the oral mucosa and its correlation to RT. A total of 87 patients were recruited for the study: 34 irradiated patients and 53 healthy controls (HC). The data of irradiation dose, hyperbaric oxygen therapy (HBOT), and radiation-to-biopsy interval (RTBI) were collected. Samples of the patient's oral mucosa were prepared for histological, immunohistological, electron microscopical, and immunoelectron microscopical studies. Staining intensity of tMUC1 was significantly stronger in the irradiated patients than in the controls. Only patients with RTBI of 17 months or less presented cell hyperchromatism and low intensity of tMUC1 staining. Long-term changes were not affected by the local dose. HBOT redirected tMUC1 staining toward values of the control group. The irradiated oral mucosa appears to improve over time, and HBOT could also be a contributing factor in long-term positive changes. tMUC1 can be used as a biomarker when examining the oral mucosal health after cancer treatment.

Gallstone disease affects individuals of different ages, yet age-related variations in stone morphology, histology, and chemical composition remain insufficiently defined. Understanding these patterns may clarify pathogenic mechanisms and their potential links to clinical or metabolic profiles. This study investigated age-related differences in gallstone characteristics. Thirty-seven gallstones were analyzed and grouped into three age categories (<20, 21-30, and 31-40 years), with additional stratification by sex. Morphological classification was performed macroscopically and by scanning electron microscopy, while composition was assessed using energy-dispersive spectroscopy. Histological evaluation of the gallbladder wall focused on chronic inflammation, Rokitansky-Aschoff sinuses, fibrosis, and metaplasia. Female predominance was observed in all groups, reaching 100% in the 31-40-year category. Patients under 20 years presented heterogeneous stones, including pigmented and amorphous patterns, early structural changes, and chemically diverse profiles containing Calcium (Ca), Sodium (Na), Phosphorus (P), and Magnesium (Mg). Individuals aged 21-30 years showed mostly cholesterol stones, moderate histological alterations, and frequent Ca and Na incorporation with reduced elemental variability. In contrast, the 31-40-year group exhibited exclusively cholesterol stones with milder but consistent chronic changes and a homogeneous chemical composition mainly comprising Carbon (C) and Oxygen (O). These results demonstrate age-related transitions in gallstone morphology, chemistry, and associated gallbladder alterations.

Gestational diabetes mellitus (GDM) is a pregnancy-associated metabolic disorder characterized by hyperglycemia and chronic low-grade inflammation, both contributing to placental dysfunction. This study investigated placental pathology in a South African cohort. GDM placentas demonstrated increased fibrin deposition and altered villous stromal architecture, consistent with a stressed placental microenvironment. Polarized light microscopy revealed heterogeneous collagen birefringence patterns, indicating disrupted extracellular matrix organization with a shift in type I and type III collagen balance, consistent with progressive fibrotic remodeling and impaired microvascular integrity. Ultrastructural examination revealed thickened basement membranes and mitochondrial degeneration, indicative of microangiopathic injury and oxidative stress-related cellular damage. These findings demonstrate coordinated histopathological and ultrastructural placental remodeling in GDM involving inflammation, fibrosis, and microvascular dysfunction.

Podocyte infolding glomerulopathy (PIG) is a rare pathological diagnosis based on characteristic electron microscopic findings of microspheres and/or microtubular structures associated with podocyte infoldings into the glomerular basement membrane (GBM) and was proposed as a new entity from Japan in 2008. PIG has been increasingly reported not only in Japan but also worldwide; however, the precise cause and mechanisms of PIG are unknown. PIG cases investigated by repeated renal biopsies are even rarer. We herein report a patient with systemic lupus erythematosus (SLE) who showed progressive podocyte infoldings into GBM by serial renal biopsies and review previous reports of PIG comparing the findings of serial renal biopsies. PIG may progress in association with the activity of the underlying disease, particularly in patients with autoimmune diseases. In the present case, proteinuria persisted, and PIG progressed independently of the activity of SLE. Although PIG appears to follow a progressive course accompanied by proteinuria, further accumulation of data on PIG cases with serial renal biopsies will contribute to elucidating its pathophysiology.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that typically appears in early childhood, and there is a link between ASD and zinc deficiency. Neither the potential protective effects of the trace element zinc on the cerebellum against ultrastructural damage in animal models of ASD, nor its ability to protect against the modulation of the oxidative stress/gliosis/neuronal loss axis implicated in autism, have been previously investigated. Young rats were injected with the short-chain fatty acid produced by gut bacteria that is known to induce ASD, propionic acid (PPA) (500 mg/kg) for 5 days (model group) and the protection group was treated with 2 mg/kg zinc sulfate for two weeks following PPA injections. Cerebellum damage and behavioral impairment developed in the model group of rats as demonstrated by profound cerebellar ultrastructural alterations such as degeneration of Purkinje neurons and fragmented endoplasmic reticulum, as well as anxiety-like behavior and social interaction deficits. PPA also significantly (p < .05) modulated the cerebellar protein levels of the gliosis biomarker GFAP and the neuronal loss biomarker calbindin D28K, as well as the cerebellar tissue levels of zinc, glutathione, and the oxidative stress biomarker malondialdehyde (MDA). All these parameters were significantly (p < .05) protected by zinc treatment. Additionally, we observed a significant (p < .001) correlation between the degree of Purkinje cell damage and these parameters associated with autism. In conclusion, PPA-induced autistic behaviors in rats are associated with alteration to the cerebellar ultrastructure, modulation of the oxidative stress/gliosis/neuronal loss axis of ASD, and a decline in zinc and glutathione, which were protected by zinc treatment.

Adult neural stem cells (NSCs) are located in the sub-granular zone (SGZ) of the dentate gyrus (DG) of the hippocampus, one of the prominent regions of neurogenesis in the adult brain. Activation of endogenous stem cells may provide a therapeutic approach in demyelinating diseases. Due to their minuscule size, nanoparticles (AuNPs) can cross the blood-brain barrier. To evaluate the effect of AuNPs on adult NSCs and the progression of demyelination in the hippocampus in a model of demyelination, thirty-two adult mice were divided into: control group I, AuNPs group II (10 mg/kg BW/day), cuprizone (CPZ) group III (0.2% orally for 8 weeks to induce demyelination), and CPZ & AuNPs group IV. Hippocampus was prepared for light microscopy, nestin immunohistochemical staining (NSCs' immune marker), and electron microscopy. In groups I and II, spindle-shaped adult NSCs in the SGZ of DG showed a positive nestin immunoreaction. In group III, most of the nerves were demyelinated. Pyramidal and granular neurons showed degenerative changes. Nestin-immune-positive cells were significantly decreased. In group IV, preservation of the myelin, less degenerative changes, and a significant increase in nestin-positive cells were detected. In conclusion, AuNPs activated adult NSCs in the mouse hippocampus, partially ameliorated degenerative changes, and enhanced partial remyelination in the CPZ demyelination model.

Autism is a neurodevelopmental condition with challenges in establishing and sustaining social relationships and communication. Apigenin (AP) is a natural flavonoid with numerous valuable effects on brain disorders. The current study emerged to study the cerebellar histopathological changes in valproic acid (VPA)-induced autism in male albino rat pups and assess the possible neuroprotective role of AP in minimizing these alterations. Forty male albino rat pups were categorized randomly into four equal groups: control group, AP group administered AP (250 mg/kg/day orally) from postnatal days (PND)14 to PND 40, VPA group received single subcutaneous injection of VPA (400 mg/kg) on PND14 and VPA+AP group were injected with VPA, then received AP at the identical dosage and approach as the preceding groups. Shrunken Purkinje cells with dark heterochromatic nuclei, neuropil vacuolation, and myelin sheath deformities were reported on VPA administration. A significant rise in cerebellar immune expression of GFAP, p-Tau and nestin. Also, a significant reduction in the duration of sniffing, line crossing, and rearing was recorded. Additionally, a decline of glutathione peroxidase, serotonin and the rise of malondialdehyde and IL-1β levels were recorded in cerebellar homogenate. The co-treatment of AP with VPA significantly rescued these histological alterations and reinstated antioxidant equilibrium.

Lung fibrosis is an irreversible life-threatening condition. So, this study directed to investigate the structure of lung tissue following bleomycin-induced pulmonary injury and to evaluate the potential protective effects of pirfenidone, granulocyte colony-stimulating factor (GCSF), and their combined administration. Fifty-six adult rats were allocated into control, bleomycin-treated, pirfenidone-treated, GCSF-treated, and combination groups. Lung specimens were processed and examined using light & transmission electron microscopes beside biochemical examination for MDA and GSH. Bleomycin administration caused marked structural alterations. Both Pirfenidone and GCSF alone resulted in partial improvement of pneumocyte ultrastructure and reduced fibrotic features. Notably, the combined therapy group demonstrated the most evident protection, with near-normal pneumocyte morphology and reduced degenerative changes. These findings suggest that combined pirfenidone and GCSF therapy exerts a synergistic effect in ameliorating bleomycin-induced lung injury at the ultrastructural level.

Differentiated human SH-SY5Y neuroblastoma cells used to model neurodegenerative defects, cholinergic neuron differentiation, neurotropic virus infection, and neurotoxicity have not been comprehensively studied with fine structure. Our goal is thus to further disclose their cytology. Differentiated in vitro with retinoic acid (RA), SH-SY5Y cells were processed for fine structure analyses with transmission, scanning electron microscopy, and X-ray spectroscopy microanalysis. The neoplastic cells showed typical high nucleus: cytoplasm ratio with neuron-like profiles extending to one long neurite that can carry dense core vesicles and associated cytoskeletons. Among the organelles, one-fifth of mitochondria profiles were noted to bear prominent anomalies of both outer and internal membranes. These organelles formed bursts, long or folded lamellae, with the matrix either replaced by accumulated contrasted compound or striated content created through random sectioning sorts of appendages constituting views of so-called "lamellar bodies," and other dense bodies accompanied by mitophagy. Most lining membranes joined the endoplasmic reticulum network with lipid storage droplets. RA differentiation of neuroblastoma cells involved cell genome and mitochondria metabolism to favor an increased lipid and phospholipids precursors to store associated endoplasm and mitochondria membrane and matrix changes resulting in defective fine structures and content. Some of them bore analogy with those noted when one or more mitochondria regulatory proteins (e.g. OPA1 and mitofusin) occurred in other neurodegenerative pathologies, including Parkinson's disease. Our observations should incite further molecular investigations about this neuroblastoma cell proteome and lipidome organelles because of this cell line usage in numerous biomedical investigations.

Renal tubular casts are cylindrical structures formed primarily in the distal convoluted tubule or collecting tubule. They are composed of materials filling the tubular lumen and molding along its contour. The clinicopathologic attributes of tubular cast including light microscopic features are well described. In contrast, knowledge on the ultrastructural changes of these casts is limited. This communication focuses on the electron microscopic studies of renal tubular casts. It fully abstracts the current literature and, together with a meticulous review of institutional renal biopsy archive, confirms the current knowledge, expands it, and further reports novel observations. Distinctive and rarely pathognomonic ultrastructural features are expressed by most types of tubular casts, which are well correlated with light microscopic changes. This review further demonstrates that beyond the often elegant and artful images under the electron microscope, the ultrastructural morphology of the tubular casts not only offers diagnostic clue or initiate molecular/chemical studies, but can also provide definite diagnosis or pathogenetic insight unaffordable by other traditional studies.

Lutein provides a promising approach to protect the testes against damage induced by deltamethrin. The current study was applied to investigate the protective effect of lutein on the testis of adult male albino rats against testicular toxicity induced by deltamethrin. Sixty adult male albino rats were randomly allocated into six experimental groups. Group I served as control, group II received lutein (40 mg/kg/day orally), group III received deltamethrin (5 mg/kg/day orally), group IV received deltamethrin (5 mg/kg/day orally) concomitant with lutein (40 mg/kg/day orally), all for 4 weeks. Group V received lutein (40 mg/kg/day) throughout 8 weeks, whereas deltamethrin was given at week 5 till the end of week 8. Group VI served as a withdrawal group in which animals received deltamethrin for four weeks, followed by a four-week treatment-free period to assess the reversibility of its toxic effects. Biochemical, histological, and ultrastructural techniques were used to evaluate the testicular changes. Deltamethrin-treated rats showed decreased serum testosterone. Testicular tissue exhibited pronounced histopathological changes. Histopathological examination of testicular tissue showed that apoptosis was observed in the basal germ cells, primary and secondary spermatocytes. The testes exhibited distorted Sertoli cells accompanied by depletion of spermatogenic cells, along with significant reductions in seminiferous tubular diameter and serum testosterone levels relative to control. While the percentage of apoptotic cells was significantly increased. Group V showed improvement in histological structure, the testosterone levels, and other morphometrical parameters. Pretreatment of lutein to deltamethrin-treated rats prevents the histopathological alterations by deltamethrin in testis.