The possible protective effect of ginger extract on toxic changes induced by bisphenol A on the thyroid gland of adult male albino rats: light and electron microscopic study
Bisphenol A (BPA) is a chemical substance used in the plastic industry and considered as an endocrine disruptor. Ginger is a herbal material used in the food industry and has antioxidant activity. The present study was performed to evaluate the histological changes in the thyroid gland of adult male albino rats after intake of BPA and if there is any protective role for ginger extract (GE). Eighty adult male rats were divided equally into four groups. Group I as a control group, group II included rats that received 250 mg/kg/day GE orally for eight weeks, group III included rats that received 200 mg/kg/day BPA orally for the same period and group IV included rats that received BPA in the same dose for the same duration concomitantly with GE. At the end of the experiment, blood samples were taken for hormonal essay and tissue samples were processed. Light and electron microscopic studies were done. Morphometric and statistical studies were carried out. Group III showed degenerative changes in the thyroid gland, decreased serum levels of T3 and T4 and a strong positive inducible nitric oxide synthase (iNOS) immune response. Group IV showed restoration of thyroid gland architecture and function. In conclusion, GE protected the thyroid structure from the damaging effect of BPA oxidative stress through its anti-oxidant effect, thus preserving thyroid activity.
Efficacy of ozone versus mesenchymal stem cell-derived microvesicles in ameliorating testicular changes after hypothyroidism in adult albino rats: a histological and immunohistochemical study
This study was performed to: detect the histological, immunohistochemical, and biochemical alterations that may occur in the testes of adult rats in induced hypothyroidism. And to investigate which one, ozone or MSCs-MVs have better therapeutic effect on testicular changes after hypothyroidism. Eighty-four male adult rats were separated into: control group, hypothyroidism group: rats will be given carbimazole for 30 days, ozone group: rats treated as hypothyroidism group then will be injected with ozone intraperitoneal for 7 days. MSC-MVs group: rats treated as hypothyroidism group then will be injected with a single intravenous dose MSC-MVs. Specimens of testes were handled for light, electron microscope, and immunohistochemical of vimentin and S100. Biochemical analysis for; MDA and TNFα; serum testosterone, TSH, T3, and T4 was done, also, sperm count and morphology assay. Morphometric and statistical analysis were performed. Hypothyroidism group showed disorganized seminiferous tubules. A noticeable gap was between the basement membrane and the germinal epithelium. Wide interstitium had congested vessels and acidophilic homogenous material. Vacuolated germinal epithelium and few germ cells had dark nuclei with noticeable separation of between the basement membrane and the germinal epithelium. Ozone and MSCs-MVs induced improvement in all the previous parameters and restoration of spermatogenesis. MSCs-MVs has better ameliorative effect than ozone on hypothyroidism-exposed testes.
Immunohistochemical and ultrastructural identification of telocytes in the infantile hemangioma
Telocytes (TCs) are a distinctive cell entity of the stromal microenvironment of multiple tumors; to date, their existence in infantile hemangioma (IH) remains almost unexplored. This study was therefore undertaken to characterize the immunophenotype, location, morphology, and ultrastructure of telocytes in the IH by means of immunohistochemistry, immunofluorescence confocal microscopy, and transmission electron microscopy. Telocytes were initially identified by CD34, PDGFR-α, Vimentin, and AQP-1 immunostaining. Analyzing the spatial relationship among telocytes, stem cells, endothelial cells, pericytes in the IH with AQP-1/CD31, AQP-1/Glut-1, AQP-1/α-SMA, AQP-1/CD146 and AQP-1/CD133 double immunofluorescence. TCs were immunonegative for CD31, Glut-1, CD146, α-SMA, CD133, and C-kit in the IH. The ultrastructural examination confirmed the presence of TCs, namely stromal cells with characteristic cytoplasmic processes (i.e. telopodes) forming labyrinthine networks around microvessels and releasing extracellular vesicles. Our study provides evidence that telocytes are present and PDGFR-α and AQP-1 are specific antigenic markers in the IH.
The possible effects of chronic administration of amiodarone hydrochloride on the seminiferous tubules of adult male albino rats: histological and biochemical study
Amiodarone hydrochloride is an antiarrhythmic agent that is widely prescribed. However, it has serious side effects that approximately affect the whole body organs. In our study, we aimed to assess the possible effects of chronic administration of two different doses of amiodarone hydrochloride on the oxidative and inflammatory parameters as well as the histological morphology and ultrastructure of the seminiferous tubules of adult male albino rats. Forty rats were divided into four groups; : each rat did not receive any drugs at all. : each rat received 3 ml of 0.16% methylcellulose, orally and daily for 4 weeks. : each rat received 3 ml of 0.16% methylcellulose contained 3.6 mg amiodarone, orally and daily for 4 weeks. : each rat received 3 ml of 0.16% methylcellulose contained 7.2 mg amiodarone, orally and daily for 4 weeks. Blood samples were collected for measuring serum levels of malondialdehyde, superoxide dismutase, interleukin-6 and tumor necrosis factor-alpha. Testes specimens were examined to assess the morphological changes and the level of expression of caspase-3 apoptotic marker. The results indicated that; amiodarone hydrochloride could induce a dose-dependent toxicity, causing oxidative stress, inflammation, cellular degeneration, deposition of collagen and enhanced apoptosis in the seminiferous tubules.
Value of electron microscopy as perceived by nephrologists in Flanders, Belgium
Electron microscopy (EM) is an important complementary tool in biopsy diagnosis of kidney disease. However, EM is a costly technique and not universally available. In order to understand nephrologists' perspectives on EM, a survey among Flemish nephrologists was conducted. The survey explores nephrologists' knowledge and satisfaction with EM, the barriers in its use, and its role in decision-making.A questionnaire was sent out to Dutch-speaking nephrologists in Belgium (Flanders) via the professional organization NBVN .The average satisfaction of EM accessibility in nephrologists, was 4.0 on a scale from 1 (very unsatisfied) to 5 (very satisfied). The main barrier in ordering EM appeared to be the long turnaround time, indicated by 32.5% of nephrologists. The reports were found mostly understandable by 61.0% of the nephrologists. The impact of EM on diagnosis of kidney disease was estimated higher than its impact on the treatment: 24.4% of respondents estimated diagnosis changes in less than 5% of cases, versus 68.3% estimated treatment changes in less than 5% of cases.This study provides key insights into nephrologists' perception on EM services, revealing high overall satisfaction. However, there is potential for improvement, especially regarding turnaround times.
Streptozotocin-induced morphological changes in rat lungs
Streptozotocin (STZ) is a commonly used compound for the induction of type 2 diabetes (T2D) in animal models, but its effects on non-pancreatic tissues like the lungs are not well understood. This study aimed to examine the histopathological impact of STZ on the lungs using male Sprague-Dawley rats. The rats were divided into two groups: a control group on a normal diet and an STZ-treated group receiving a high-fat diet and 10% sucrose water for 8 weeks, followed by an STZ injection (30 mg/kg body weight). All rats were terminated 9 days after STZ administration, and lung samples were collected for light microscopy, transmission electron microscopy (TEM), and confocal laser scanning microscopy. Light microscopy revealed thickening of alveolar septa, narrowing of alveoli, and inflammatory infiltrates in the STZ group. TEM showed mitochondrial damage in type 2 pneumocytes, including membrane fragmentation, cristae loss, and formation of mitochondrial-derived vesicles. Confocal microscopy revealed significantly higher expression of myeloperoxidase, neutrophil elastase, and citrullinated histone 3 in the STZ group compared to controls. These findings suggest that STZ induces considerable lung damage, emphasizing the need to consider lung toxicity in studies involving STZ.
The therapeutic efficacy of adipose mesenchymal stem cell-derived microvesicles versus infliximab in a dextran sodium sulfate induced ulcerative colitis rat model
Ulcerative colitis (UC) is a chronic relapsing intestinal inflammation that is becoming of increasing incidence worldwide and has insufficient treatment. Therefore, finding effective therapies remains a priority. A dextran sodium sulfate colitis model was established to elucidate colonic layers alterations and compare adipose mesenchymal stem cell-derived microvesicles (MSC-MVs) versus infliximab (IFX) efficacy through biochemical, light, and electron microscope studies. Fifty-four rats were allocated to 4 groups: Control (Con), UC, UC+IFX, and UC+MSC-MVs groups. End body weights (BW) and serum malondialdehyde (MDA) levels were recorded. Colitis severity was estimated by disease activity index (DAI). Colonic specimens were processed to evaluate the histological structure, collagen content, surface mucous and goblet cells, CD44, TNF-α, and GFAP immune expression. Morphometric and statistical analyses were performed. The UC group revealed congested, stenosed colons, a significant decline in end BW, and a significant increase in serum MDA and DAI. Furthermore, disturbed histoarchitecture, inflammatory infiltration, depletion of surface mucous and goblet cells, increased collagen, and TNF-α expression and decreased GFAP expression were observed. Alterations were partially attenuated by IFX therapy, whereas MSC-MVs significantly improved all parameters. In conclusion, MSC-MVs were a superior therapeutic option, via attenuating oxidative stress and inflammatory infiltration, in addition to restoring intestinal epithelial integrity and mucosal barrier.
Live and let die: analyzing ultrastructural features in cell death
Cell death is an important process that supports morphogenesis during development and tissue homeostasis during adult life by removing damaged or unwanted cells and its dysregulation is associated with numerous disease states. There are different pathways through which a cell can undergo cell death, each relying on peculiar molecular mechanisms and morpho-ultrastructural features. To date, however, while molecular and genetic approaches have been successfully integrated into the field, cell death studies rarely incorporate ultrastructural data from electron microscopy. This review article reports a gallery of original transmission electron microscopy images to describe the ultrastructural features of cells undergoing different types of cell death programs, including necrosis, apoptosis, autophagy, mitotic catastrophe, ferroptosis, methuosis, and paraptosis. TEM has been an important technology in cell biology for well over 50 years and still continues to offer significant advantages in the area of cell death research. TEM allows detailed characterization of the ultrastructural changes within the cell, such as the alteration of organelles and subcellular structures, the nuclear reorganization, and the loss of membrane integrity that enable a distinction between the different forms of cell death based on morphological criteria. Possible pitfalls are also described.
The potential protective effect of propolis on diabetic nephropathy induced by streptozotocin in adult albino rats
Diabetes mellitus is a common metabolic disorder. It is associated with serious life-threatening complications if not properly managed. The current study aimed at investigating the possible protective role of propolis on streptozotocin-induced diabetic nephropathy. A diabetic rat model was induced by a single intraperitoneal injection of 55 mg/kg streptozotocin. After 4 days, the diabetic rats received oral propolis (300 mg/kg/day) via gastric gavage for 28 days. Biochemical, histopathological and ultrastructural evaluations were performed. The results showed that: streptozotocin-induced diabetes was associated with a marked decrease in the serum high-density lipoproteins and antioxidant enzymes. However, a significant elevation in the levels of serum creatinine, blood urea nitrogen, uric acid, cholesterol, triglycerides and low-density lipoproteins was detected. Furthermore, streptozotocin treatment induced histopathological alterations of the renal cortex; in the form of distorted glomerular capillaries, widened Bowman's space and signs of epithelial tubular degeneration. Ultra-structurally, thickening and irregularity of the glomerular basement membrane and podocytes foot processes effacement were observed. The tubular epithelial cells showed swollen vacuolated mitochondria, scarce basal infoldings and loss of microvilli. Conversely, propolis partially restored the normal lipid profile, antioxidant biomarkers and renal cortical morphology. Propolis exhibited a sort of renoprotection through hypoglycemic, anti-hyperlipidemic and antioxidant effects.
Ameliorative effects of gallic acid on tebuconazole-induced adverse effects in the cerebellum of adult albino rats: histopathological and immunohistochemical evidence
Tebuconazole (TEB) is a common triazole sterol demethylation inhibitor fungicide utilized to manage a variety of diseases in crops like cereals, fruits, and vegetables. The aim of this work was to assess the effects of TEB on the structure of the cerebellum in adult albino rats and possible protective impact of co-administration of Gallic acid (GA). Four groups of forty adult male albino rats were randomly selected, and the rats in group I received corn oil through daily gavage for 4 weeks. Group II received GA dissolved in the normal saline at a dose of 100 mg/kg through daily gavage for 4 weeks, group III administered with TEB dissolved in corn oil at its acceptable daily intake dose (0.02 mg/kg body weight) through daily gavage for 4 weeks, group IV rats received both TEB and GA. For light microscopic, ultrastructural, and immunohistochemical investigations, cerebellar specimens were prepared. TEB exposure led to neuronal damage in the form of degenerated Purkinje cells with vacuolated cytoplasm, areas of lost Purkinje cells, the basket cells appeared vacuolated with degenerated neuropil, the granule cells clumped with congested areas between them, dilated cerebellar islands, weak positive bcl2 immunoreactions in the Purkinje cells, and numerous GFAP-positive astrocytes. GA mitigated TEB-mediated histological changes in the cerebellar cortex. We concluded that TEB caused Purkinje neurons in the rat cerebellar cortex to degenerate and undergo apoptosis. GA had a neuroprotective benefit against TEB toxicity in the rat cerebellar cortex.
Excessive lipid production shapes glioma tumor microenvironment
Disrupted lipid metabolism is a characteristic of gliomas. This study utilizes an ultrastructural approach to characterize the prevalence and distribution of lipids within gliomas. This study made use of tissue from IDH1 wild type (IDH1-wt) glioblastoma ( = 18) and IDH1 mutant (IDH1-mt) astrocytoma ( = 12) tumors. We uncover a prevalent and intriguing surplus of lipids. The bulk of the lipids manifested as sizable cytoplasmic inclusions and extracellular deposits in the tumor microenvironment (TME); in some tumors the lipids were stored in the classical membraneless spheroidal lipid droplets (LDs). Frequently, lipids accumulated inside mitochondria, suggesting possible dysfunction of the beta-oxidation pathway. Additionally, the tumor vasculature have lipid deposits in their lumen and vessel walls; this lipid could have shifted in from the tumor microenvironment or have been produced by the vessel-invading tumor cells. Lipid excess in gliomas stems from disrupted beta-oxidation and dysfunctional oxidative phosphorylation pathways. The implications of this lipid-driven environment include structural support for the tumor cells and protection against immune responses, non-lipophilic drugs, and free radicals.
Features that characterize monoclonal light chain ("myeloma") cast nephropathy with immunofluorescence challenges and emphasis on electron microscopy
Renal disease is a common cause of morbidity and mortality in patients with plasma cell dyscrasias. The serum-free light chain assay is used in patients, mostly older, with unexplained acute kidney injury to screen for potential myeloma cast nephropathy. This study consists of a systematic review of diagnostic features in myeloma cast nephropathy. The morphological features of tubular casts in patients with multiple myeloma have not been systematically analyzed. This study focuses on the morphology of these casts, emphasizing ultrastructural features, in a series of 23 patients with light chain ("myeloma") cast nephropathy and compared them with casts in 10 patients with various diseases. The immunofluorescence data were correlated with morphological findings to provide diagnostic assessments and practice guidelines. The ultrastructural features identified as diagnostic of casts associated with myeloma included: amyloid and crystals in the casts, multiple well-defined fracture planes forming a complex jigsaw puzzle arrangement of cast contents, indicative of the fragility of the immunoglobulin light chains involved, and reactive tubular cells lining the tubules with the casts. These features were seen in 95.2% of MCN cases and none of the casts in other renal conditions. Myeloma casts exhibited light chain monoclonality in a significant percentage of the MCN cases and often no staining for IgA or IgM. In contrast, the majority of non-myeloma casts stained for both kappa and lambda light chains, lgA, and lgM, and showed ultrastructurally a rather uniform finely to coarsely granular electron density occasionally admixed with cellular debris.
. A phenomenon not associated with Rosai-Dorfman disease, report of a case
Emperipolesis is a cell-within-cell phenomenon distinct from phagocytosis more often described in Rosai-Dorfman disease, where usually lymphocytes or other bone marrow cells (plasma cells, erythroblasts or neutrophils) are entirely surrounded but not engulfed by macrophages as the host cell, but occasionally megakaryocytes and neoplastic could be. Mesothelial cell has been described in a couple of cases of lymphomas affecting serous membranes, but never described in pleuritis. In the present work, the first case of emperipolesis by mesothelial cells in a patient with self-limited pleural effusion was demonstrated by immunohistochemistry and Electron Microscopy studies.
Reactivation of nucleases with peroxidation damages induced by a menadione: ascorbate combination devastates human prostate carcinomas: ultrastructural aspects
Xenografts of androgen-independent human DU145 prostate metastatic carcinomas implanted in male mice have revealed a significant survival after a prooxidant anticancer treatment consisting of a combination of menadione bisulfite and sodium ascorbate (VK3:VC).
The effects of the combination of temozolomide and Eribulin on T98G human glioblastoma cell line: an ultrastructural study
Glioblastoma tumors are the most aggressive primary brain tumors that develop resistance to temozolomide (TMZ). Eribulin (ERB) exhibits a unique mechanism of action by inhibiting microtubule dynamics during the G2/M cell cycle phase. We utilized the T98G human glioma cell line to investigate the effects of ERB and TMZ, both individually and in combination. The experimental groups were established as follows: control, E5 (5 nM ERB), T0.75 (0.75 mM TMZ), T1 (1.0 mM TMZ), and combination groups (E5+T0.75 and E5+T1). All groups showed a significant decrease in cell proliferation. Apoptotic markers revealed a time-dependent increase in annexin-V expression, across all treatment groups at the 48-hour time point. Caspase-3, exhibited an increase in the combination treatment groups at the 48-hour mark. Transmission electron microscopy (TEM) revealed normal ultrastructural features in the glioma cells of the control group. However, treatments induced ultrastructural changes within the spheroid glioblastoma model, particularly in the combination groups. These changes included a dose-dependent increase in autophagic vacuoles and apoptotic morphology of the cells. In conclusion, the similarity in the mechanism of action between ERB and TMZ suggests the potential for synergistic effects when combined. Our results highlight that this combination induced severe damage and autophagy in glioma spheroids after 48 hours.
Infection as a trigger of acute, transient glomerular deposition of clonal immunoglobulins
Glomerular deposition of monoclonal IgM, frequently in the form of intracapillary pseudothrombi, can be seen in Waldenström macroglobulinemia (WM) and type I cryoglobulinemia (CG). They are typically associated with plasma cell or B-lymphoid neoplasms, particularly lymphoplasmacytic lymphoma (LPL). While infection is a frequent trigger of mixed (type II and III) CG, its association with type I CG is uncommon. We report two cases in which striking lambda-chain-restricted IgM deposits and acute kidney injury (AKI) occurred in the setting of known or suspected systemic infections, with prompt resolution on treatment of the infection.
Unveiling renal pathology's potential: exploring a rare subtype of amyloid - apolipoprotein CII amyloidosis in the youngest patient: a case report and literature review
In this clinical case report, we present a rare subtype of amyloidosis, apolipoprotein CII (apo CII), which was diagnosed through a renal biopsy and subsequently confirmed by identifying the p.K41T mutation via germline DNA sequencing. Upon reviewing the literature, five patients exhibiting identical mutation were identified via renal biopsy, while an additional patient was diagnosed through biopsies of the fat pad and bone marrow. Notably, our patient is the youngest recorded case. We pioneered the application of immunofluorescence and immunogold electron microscopy techniques for apo CII evaluation. Our report provides a detailed description of this case, supplemented by an extensive review encompassing apo CII, documented instances of apo CII amyloidosis with renal or systemic involvement, and potential underlying mechanisms.
Can the analysis of chromatin texture and nuclear fractal dimensions serve as effective means to distinguish non-invasive follicular thyroid neoplasm with papillary-like nuclear features from other malignancies with follicular pattern in the thyroid?: a study
Thyroid carcinoma ranks as the 9th most prevalent global cancer, accounting for 586,202 cases and 43,636 deaths in 2020. Computerized image analysis, utilizing artificial intelligence algorithms, emerges as a potential tool for tumor evaluation.
Chronic liver fibrosis induction in aging causes significant ultra-structural deterioration in liver and alteration on immune response gene expressions in liver-spleen axis
The relationship between damage to the liver and spleen by aging and the immune response status in these two organs, which are anatomically and immunologically interconnected, is unknown. The authors investigated the histopathological, ultrastructural, and immunological effects of aging in young and aged fibrotic mice by using an experimental model. Four groups were planned, with 10 mice in each experimental group. The levels of fibrosis and ultrastructural destruction in the liver were determined by α-SMA staining and TEM analysis. Expression levels of immunity genes (, , ) were carried out by qRT-PCR. While structural disorders were detected in the mitochondria of aged healthy group, cellular destruction in the fibrosis-induced elderly group was at a dramatic level. Fibrosis induction in aged mice caused an elevation in the expression of chemokines (CCl2, CXCL10, CCR2) and cytokine (IL-17a) genes that induce autoinflammatory response in the liver. Unlike the cellular pathology and genes activated in fibrosis in youth and the natural occurrence of fibrosis with aging, induction of fibrosis during aging causes deterioration in the liver and expression of genes responsible for autoimmunity in both the liver and spleen.
Morphological and histopathological changes of maternal levetiracetam on the cerebellar cortex of the offspring of albino rat
Levetiracetam (LEV) is being used by women with reproductive-age epilepsy at a significantly higher rate. The purpose of the study was to assess how levetiracetam treatment during pregnancy affected the offspring's weight and cerebellum. Forty pregnant rats were divided into two groups (I, II). Two smaller groups (A, B) were created from each group. The rats in group I were gavaged with approximately 1.5 mL/day of distilled water either continuously during pregnancy (for subgroup IA) or continuously during pregnancy and 14 days postpartum (for subgroup IB). The rats in group II were gavaged with about 1.5 mL/day of distilled water (containing 36 mg levetiracetam) either continuously during pregnancy (for subgroup IA) or continuously during pregnancy and 14 days postpartum (for subgroup IB). After the work was completed, the body weight of the pups in each group was recorded, and their cerebella were analyzed histologically and morphometrically. Following levetiracetam treatment, the offspring showed decreased body weight and their cerebella displayed delayed development and pathological alterations. These alterations manifested as, differences in the thicknesses of the layers of cerebellar cortex as compared to the control groups; additionally, their cells displayed cytoplasmic vacuolation, nuclear alterations, fragmented rough endoplasmic reticulum and lost mitochondrial cristae. Giving levetiracetam to pregnant and lactating female rats had a negative impact on the body weight and cerebella of the offspring. Levetiracetam should be given with caution during pregnancy and lactation.
The potential therapeutic effects of exosomes derived from bone marrow mesenchymal stem cells on ileum injury of a rat sepsis model (histological and immunohistochemical study)
Sepsis denotes a serious high mortality concern. The study was designed to evaluate the effect of mesenchymal stem cell exosomes (MSC-exosomes) on the evolution of the animal model of sepsis. In this study, 36 rats were distributed into three groups, (I) controls, (II) LPS-treated, and (III) LPS+MSC-EVs. Sepsis was simulated by administering E. coli-LPS to the laboratory animals. Group III was given MSC-exosomes four hours after the LPS injection. Forty-eight hours later rats were sacrificed. Ileum samples were excised, and processed for the histological assessment, immunohistochemical identification of CD44, and inducible nitric oxide synthase (iNOS). Ileum homogenate was used to estimate tumor necrosis factor α (TNF α) besides Cyclooxygenase-2 (COX 2). PCR was used for the detection of interleukin 1α (IL‑1α), and interleukin 17 (IL‑17). Statistical and morphometrical analysis was done. The LPS-treated group showed increased TNF-α, IL‑1α, IL‑17, and decreased COX 2. LPS administration led to cytoplasmic vacuolization of enterocytes, an increase in the vasculature, and cellular infiltrations invaded the lamina propria. There was a significant rise in goblet cells and the proportion of collagen fibers. Ultrastructurally, the enterocytes displayed nuclear irregularity, rough endoplasmic reticulum (rER) dilatation, and increased mitochondria number. Sepsis induces a significant increase in iNOS and a decrease in CD44 immune expressions. LPS+MSC-EVs group restored normal ileum structure and revealed a significant elevation in CD44 and a reduction in iNOS immunoreactions. LPS-sepsis induced an obvious ileum inflammatory deterioration ameliorated by MSC-exosomes, mostly through their antioxidant, anti-inflammatory, and anti-apoptotic properties.