Ultrastructural Pathology最新文献

Background: Nonalcoholic fatty liver disease (NAFLD) is the extremely usual reason of chronic liver disease, extending from simple hepatic steatosis (HS), nonalcoholic steatohepatitis (NASH) to advanced hepatic fibrosis and cirrhosis. Though orlistat is a Food and Drug Administration (FDA) approved drug for long-duration management of obesity, few cases of severe hepatic insult were declared. Melatonin is an efficient antioxidant; it also regulates metabolic processes that lead to fat accumulation and obesity.

Aim of the work: The current research aimed to compare the impact of orlistat, melatonin, and their combination on the structural changes of the hepatic tissue of adult male albino rats supplied with high fat diet (HFD).

Material and methods: Thirty adult male albino rats divided into five groups. Liver specimens were divided into two parts. One-half was processed to obtain paraffin blocks, and the other half was processed to obtain semithin sections. Morphometric study and statistical analysis were done.

Results: Hepatic tissue from the HFD group showed steatosis, ballooning, and inflammation and all these parameters were moderately improved - except for inflammation which worsened with therapy. Combined orlistat and melatonin-treated groups showed marked improvement of all parameters as well as marked improvement in the hepatic fibrosis.Orlistat/Melatonin combination therapy is both safe and effective in comparison to orlistat and melatonin monotherapy.

Protein deficiency in the diet during pregnancy and lactation has a serious impact on the offspring by programming a predisposition to such serious diseases as hypertension and type 2 diabetes mellitus. In our study, we examined liver ultrastructure of rat pups at ages 2, 21, and 40 days with maternal protein deficiency. Body weight of the pups progressively lagged behind the control throughout the experiment, and the timing of eye opening indicated a slowdown of development. In the liver of 2-day-old animals, the proportion of hematopoietic cells at early stages of differentiation was higher as compared to the control. At the ultrastructural level, no obvious pathological changes were revealed, but a decrease in the amount of organelles was observed simultaneously with accumulation of lipids and glycogen. In the course of the experiment, a progressive decrease in the amount of the rough endoplasmic reticulum and ribosomes and increasing accumulation of glycogen in the cytoplasm of hepatocytes were noted. The most pronounced difference in ultrastructure between periportal and pericentral hepatocytes of control rat pups was detected on the 40th day of development, whereas in the low-protein diet group, the difference was weakly pronounced throughout the experiment. Thus, we showed that with prenatal and early postnatal protein deficiency, the growth and development of rat pups slows down, and glycogen accumulates excessively in the liver concurrently with a decrease in the amount of organelles.

Diabetes is a known inducer of hepatic ultrastructural alterations, and the expression of the immune biomarker that involves in T-cell immunity, cluster of differentiation 86 (CD86) is increased in diabetic patients with liver cirrhosis. The antidiabetic drug metformin has not previously been used to protect against type 2 diabetes mellitus (T2DM)-induced alternations in hepatic ultrastructure and the induction of the hepatic CD86/inflammation axis in diabetic animal models induced by streptozotocin and a high fat diet. To test our hypotheses, T2DM was induced in rats (model group) and the protective animals were treated with the antidiabetic drug metformin (200 mg/kg) until being sacrificed at week 12. A profound ultrastructural damage to the hepatocytes and liver tissue injury was induced by T2DM as demonstrated by hepatocytes with dark shrunken irregular nuclei, rarefied cytoplasm with lipid droplets, mitochondria with disrupted cristae, as well as depletion of glycogen granules and damaged of liver architecture, which were effectively (p < .0001) protected with metformin. Metformin also suppressed diabetes-induced hepatic gene expression of CD86 and inflammation as well as glycemia and liver injury markers. Furthermore, a significant correlation between hepatocyte damage and CD86, inflammation, glycemia, and biomarkers of liver injury was observed. These findings demonstrate that diabetes is associated with the induction of the hepatic CD86/inflammation axis and hepatocyte ultrastructural alterations while being protected by metformin.

Methods: Twelve pregnant female rats were divided into a control group and a valproic acid (VPA) treated group (injected intraperitoneally on embryonic day 12 with 600 mg/kg body weight of VPA). Neurobehavioral tests were conducted on the offspring of both groups. The cerebellum was studied by light and electron microscopy as well as GFAP and caspase-3 immunohistochemical staining.

Results: The VPA-treated group showed signs of neuronal degeneration, such as congested blood vessels, vacuolations, irregularly shrunken with dark small heterochromatic nuclei and numerous apoptotic blebs in the Purkinje and granule cells with vacuolated cerebellar glomeruli. The myelinated nerve fibers showed rarefaction and loss of their neurofilaments. GFAP and caspase-3 immune expression were significantly altered in the VPA-treated group.

Conclusion: The VPA rat model can serve as an excellent model of autism at the structural level, which may be used as a validated model in preclinical studies to evaluate novel drugs.

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.

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.

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; Control group 1: each rat did not receive any drugs at all. Control group 2: each rat received 3 ml of 0.16% methylcellulose, orally and daily for 4 weeks. Low dose amiodarone group: each rat received 3 ml of 0.16% methylcellulose contained 3.6 mg amiodarone, orally and daily for 4 weeks. High dose amiodarone group: 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.

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.

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.

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. In Conclusion MSCs-MVs has better ameliorative effect than ozone on hypothyroidism-exposed testes.