Ultrastructural Pathology最新文献

Objectives: Intramural hematoma (IMH) is a serious aortic condition characterized by the presence of a contained hematoma within the aortic media. However, the animal model with a high incidence of IMH was lacking, and the specific pathological characteristics of IMH have not been thoroughly characterized.

Methods and results: We conducted an experimental study using 4-week-old male, 4-week-old female, and 8-week-old male C57BL/6J mice. These mice were subjected to angiotensin II infusion at a rate of 1000 ng/kg/min for a period of 4 days. In situ imaging was performed, and aorta was harvested and serially sectioned. Histological staining and immunostaining techniques were employed, and the subcellular structure was examined using transmission electron microscopy. Our findings revealed that 4-week-old male mice exhibited a higher susceptibility to angiotensin II-induced IMH, characterized by more circumferential appearances and larger affected areas. Furthermore, IMH was more likely to occur in the upper segment of the descending aorta rather than the lower segment. Within the IMH, older fibrinous thrombus was predominantly observed near the adventitia, while younger red thrombus was more prevalent near the lumen. Additionally, platelet activation and degranulation were observed, along with fibrin cross-linking and thrombus organization, indicating a potential relationship between platelet activation and the progression of IMH.

Conclusion: Our study demonstrated that angiotensin II infusion promoted the development of IMH during the early stages, especially in juvenile mice. Furthermore, the presence of platelet activation and thrombus organization suggested their potential involvement in the progression of IMH.

Introduction: A murine model mimicking the human osmotic demyelination syndrome (ODS) revealed with histology demyelinated alterations in the relay posterolateral (VPL) and ventral posteromedial (VPM) thalamic nuclei 12 h and 48 h after chronic hyponatremia due to a fast reinstatement of osmolality. Abnormal expression astrocyte markers ALDHL1 and GFAP with immunohistochemistry in these ODS altered zones, prompted aims to verify in both protoplasmic and fibrillar astrocytes with ultrastructure those changes and other associated subcellular modifications.

Method: This ODS investigation included four groups of mice: Sham (NN; n = 13), hyponatremic (HN; n = 11), those sacrificed 12 h after a fast restoration of normal natremia (ODS12h; n = 6), and mice sacrificed 48 h afterward, or ODS48 h (n = 9). Out of those four groups of mice, with LM and ultrastructure microscopy, the thalamic zones included NN (n = 2), HN (n = 2), ODS12h (n = 3) and ODS48h (n = 3) samples. There, comparisons between astrocytes included organelles, GFAP, and glycogen content changes.

Results: Thalamic ODS epicenter damages comprised both protoplasmic (PA) and fibrillar (FA) astrocyte necroses along with those of neuropil destructions and neuron Wallerian demyelinated injuries surrounded by a centrifugal region gradient revealing worse to mild destructions. Ultrastructure aspects of resilient HN and ODS12h PAs disclosed altered mitochondria and accumulations of beta- to alpha-glycogen granules that became eventually captured into phagophores as glycophagosomes in ODS48h. HN and ODS12h time lapse FAs accumulated ribonucleoproteins, cytoskeletal aggresomes, and proteasomes but distant and resilient ODS48h FAs maintained GFAP fibrils along with typical mitochondria and dispersed β-glycogen, including in their neuropil surroundings. Thus, ODS triggered astrocyte injuries that involved both post-transcriptional and post-translational modifications such that astrocytes were unable to use glycogen and metabolites due to their own mitochondria defects while accumulated stalled ribonucleoproteins, cytoskeletal aggresomes were associated with proteasomes and GFAP ablation. Resilient but distant astrocytes revealed restitution of amphibolism where typical carbohydrate storages were revealed along with GFAP, as tripartite extensions supply for restored nerve axon initial segments, neural Ranvier's junctions, and oligodendrocyte -neuron junctional contacts.

Conclusion: ODS caused astrocyte damage associated with adjacent neuropil destruction that included a regional demyelination caused by a loss of dispatched energetic and metabolic exchanges within the injured region, bearing proportional and collateral centrifugal injuries, which involved reactive repairs time after rebalanced osmolarity.

Hepatic fibrinogen storage disease is an uncommon autosomal dominant hereditary illness marked by hypofibrinogenemia and the accumulation of variant fibrinogen in the hepatic endoplasmic reticulum. We present an asymptomatic 15-month-old male with elevated liver enzymes. Test results indicate hypofibrinogenemia. The liver biopsy revealed circular eosinophilic inclusion bodies within the hepatocyte cytoplasm. After diastase pretreatment, the inclusion bodies did not stain using the periodic acid - Schiff procedure. Ultrastructural examination revealed the characteristic fibrinogen storage curvilinear inclusions. Sequence analysis using the Blueprint Genetics (BpG) FLEX Bleeding Disorder/Coagulopathy Panel identified a heterozygous missense variant FGG c.1075 G>C, p. (Gly359Arg). Thus, the patient was diagnosed with hepatic fibrinogen storage disease. Our findings suggest that in patients with asymptomatic elevated liver enzymes presenting with unanticipated hypofibrinogenemia, hepatic fibrinogen storage disorder must be included in the differential diagnosis. Furthermore, our results underscore the significance of molecular diagnosis in patients diagnosed with cryptogenic liver disease.

There is an important concern about the potential health and environmental risks that may develop due to exposure to copper oxide nanoparticles (CuO-NPs). Selenium is an essential trace element. It supports the expression of a variety of selenoproteins. The present study was designed to study the ultrastructural and biochemical changes in the adult rat ovary after oral administration of CuO-NPs and to assess the possible ameliorative influence of Selenium. Sixty adult female albino rats were divided in two major groups: Group I and Group II. Group I was further subdivided into three groups: Group IA (control), Group IB: received a single high dose of 2000 mg/kg CuO-NPs, Group IC: received selenium (0.5 mg/kg), five days before giving a single high dose of CuO-NPs (2000 mg/kg). Thereafter, given selenium for 14 days. Group II was subdivided into three groups: Group IIA (control), Group IIB: received a small dose of 300 mg/kg of CuO-NPs for 28 days, Group IIC: received selenium (0.5 mg/kg), five days before starting concomitant administration of CuO-NPs (300 mg/kg) and Selenium (0.5 mg/kg) for 28 days. Damage of the ovarian ultrastructural features, increased MDA levels, and decreased serum estrogen and progesterone hormones levels were detected in group IB and group IIB. Group IC and group IIC showed improvement of ovarian ultrastructural, decreased MDA levels, and increased serum estrogen and progesterone hormones levels as compared to group IB and group IIB indicating that Selenium could decrease the damage induced by CuO-NPs in the adult rat ovaries.

We have assessed the effects of copper oxide nanoparticles on the testis of adult male albino rats, and evaluated the protective potential of EVOO, which has antioxidant properties. The study involved treatment of seventy adult male rats followed by examination of their testis. The rats were divided into four groups (I-V), each contained 20 rats except group II which contained 10 rats. Each of groups (I, III, IV) was subdivided equally into two subgroups (A and B). Rats in group I did not receive any treatment (IA) or injected intraperitoneal (IP) with 0.5 ml of distilled water daily for two weeks (IB). Rats in group II were gavaged 0.4 ml EVOO daily for 2 weeks. Rats in group III injected IP daily for 2 weeks with 0.5 ml distilled water containing 1 mg CuO NPs (subgroup IIIA) and 4 mg CuO NPs (IIIB). Rats in group IV were gavaged 0.4 ml EVOO before IP injected daily for 2 weeks with 0.5 ml distilled water containing either 1 mg CuO NPs (subgroup IVA) or 4 mg CuO NPs (IVB). After treatment, morphological, histological and biochemical studies on the testes were conducted. Examination of CuO NPs treated groups revealed dose dependant increase in pathological changes. These changes were reduced body weight, distorted basement membranes of seminiferous tubules and degeneration of seminiferous cells. Co-administration of EVOO ameliorated most pathological changes. We concluded that CuO NPs induced deteriorating changes in rats' testes which were improved after co-administration of EVOO.

The prognosis of myeloma is based on controlling the plasma cell burden and thus, management of the production of monoclonal light chains has improved considerably, expanding survival and quality of life. However, the effects of the monoclonal light chains in the various organs result in alterations that may lead to renal failure. There is a crucial need to ameliorate or abolish renal damage. Organ-based therapies must be developed. Glomerulopathic light chains interact with mesangial cells using the SORL1 receptor and downstream effects lead to divergent mesangial alterations. While the multi-step process occurring when amyloidogenic light chains interact with mesangial cells has been elucidated in the laboratory, gene expression profiles and activated cellular pathways in human glomeruli have not been probed. Mesangial cells from five renal biopsies at different stages of glomerular amyloidosis were interrogated using spatial transcriptomics and compared with those from normal biopsy controls to identify cellular pathways and gene expression changes. The two most significant statistically overexpressed genes (FDR <0.05) when comparing control, early vs late cases were heat shock protein 90AB1 and HSPB1, known to be involved in protein misfolding and aggregation. The overexpressed genes exercise function and regulation over cellular pathways promoting apoptosis, vesicular transport, metalloproteinase activation, collagen degradation, gap junction degradation, GTPase cycle activation, and organelle biogenesis. This data confirmed the results previously reached in the research laboratory. Spatial transcriptomics demonstrated uniquely activated genes and cellular pathways in mesangial cells involved in the initiation and progression of glomerular amyloidosis, uncovering novel genes and new therapeutic targets.

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.

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.

Over half million individuals suffer from chronic kidney disease (CKD) worldwide. In addition to raising the possibility of cardiovascular diseases, skeletal myopathy remains a challenging complication that is highly correlated with mortality and a lower quality of life. Granulocyte-colony stimulating factor (G-CSF) is an active cytokine for mobilization of immunological and hematopoietic stem cells that can replace exogenous stem cell infusions. So, it is seen as a less expensive and noninvasive tool for regenerative medicine. Sixty three rats were divided into 4 groups: I control, II CKD induced, IIIa, IIIb treated and IV recovery groups. After induction of CKD in all rats, group II were sacrificed after 4 weeks. Rats of group IIIa received NaHCO₃. Group IIIb rats were injected subcutaneously by G-CSF as 100 µg/kg/day for 5 successive days in addition to NaHCO₃ as group IIIa. Group IV rats were housed for 4 weeks without treatment. Serum urea, creatinine, tissue MDA& TNF-α were assessed. Renal and gastrocnemius muscle sections were evaluated for histological structure, CD34 and myogenin immune expression, morphometric and statistical analyses. The CKD group revealed a significant increase in MDA and TNF-α. Furthermore, features of renal injury, muscle degenerative changes, increased collagen and decreased CD34 and myogenin expression were observed. Alterations were partially attenuated by NaHCO₃, while GCSF remarkably improved most parameters. The current results indicated that co-administration of GCSF and NaHCO₃ could ameliorate CKD myopathy via attenuating oxidative stress, immunomodulation, pro-angiogenic ability, myocyte regeneration. In addition to the reduction of mitochondrial stress and maintenance of cellular homeostasis.