Ultrastructural Pathology最新文献

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.

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.

Breast cancer patients experience more severe emotional distress and depression compared to those with other cancers. Selective serotonin reuptake inhibitors (SSRIs), like citalopram, are commonly used to treat depression. However, the link between SSRI use and breast cancer progression is debated. This study examined the cytotoxic effects of citalopram on triple-negative (MDA-MB231) and ER-positive (MCF-7) breast cancer cells. Results showed a significant decrease in cell viability in both cell lines following citalopram treatment. Interestingly, flow cytometry analysis revealed increased apoptotic cells and induction of cell cycle arrest upon treatment of the cells with citalopram. MCF-7 cells were arrested in the sub-G0-G1 phase, while MDA-MB231 cells accumulated in the S phase. Gene expression analysis demonstrated increased Bax expression and decreased Bcl2 levels. Moreover, cytochrome c and NF-κB were upregulated upon treatment with citalopram. Furthermore, transmission electron microscopy (TEM) analysis of treated cells showed apoptotic morphological changes including shrunken nuclei, membrane blebbing, and chromatin condensation with prominent appearance of autophagosomes and autolysosomes. Additionally, GADD45a and p21, involved in growth arrest and DNA damage, were significantly upregulated. In conclusion, citalopram's ability to induce apoptosis and alter cell cycle suggests its potential in breast cancer treatment.

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.

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.

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.