ABSTRACT Intestinal ischemia–reperfusion injury (IIRI) is a life-threatening vascular emergency with high mortality, commonly occurring as a complication of hemorrhagic shock or acute mesenteric arterial occlusion. When revascularization is performed after this issue, injury will occur. The influence of MSC-MVs and G-CSF on IIRI was detected in this study. Fifty-six male adult albino rats were allocated into five groups: control, ischemia–reperfusion, MSC-MVs, G-CSF, and recovery. Ischemic injury was induced for one hour using micro-vascular clamp across the superior mesenteric artery at its beginning from the aorta. After that, the clamp was withdrawn to allow reperfusion for two hours. At the end of experimental period, rats were sacrificed. Jejunal tissues were processed for assessment of oxidative stress markers (MDA and SOD) as well as for histological and immune histo-chemical analysis. Ischemia-reperfusion group revealed highly statistically significant increase in tissue MDA while SOD showed the reverse, histologically by light microscopic examination; inflammatory cellular infiltration, congested blood vessels, and separated muscle fibers in muscularis mucosa were observed. Ultrastructurally, absorptive columnar cells appeared with heterochromatic nuclei, lost apical microvilli, and widen intercellular space. These findings showed more improvement in MSC-MVs group in comparison with G-CSF group while recovery group exhibited severe affection.

ABSTRACT Lung fibrosis is defined as fibrotic change of the lung architecture within 2.5–3 years of diagnosis, ultimately leading to respiratory failure and death. Prolonged exposure to high concentrations of carbon tetrachloride, especially vapor, can cause lung destruction. Autophagy was crucial for maintaining the organs’ homeostasis. Deficit in autophagy has been commonly associated with fibrosis and pneumonia. Recent research suggests that metformin may provide protection against a variety of lung ailments. To investigate how metformin protects against lung damage caused by carbon tetrachloride via the autophagy pathway, 30 adult male albino rats (10 rats each) were divided into three equal groups. One group served as the control. Group 2: received CCl4 1.5 mg/kg twice weekly S.C. for a duration of 12 weeks. Group 3: Oral metformin and CCl4 were administered for 12 weeks at a dose of 100 mg/kg/day and 1.5 mg/kg twice weekly S.C. After the animal died, its lungs were taken out of each group and studied under an electron and light microscope in addition to being used for immunological research. The histological abnormalities in the lung tissue caused by the administration of CCl4 included areas of tissue destruction, congestion, and fibrosis. Pneumocyte type I, type II, and collagen fiber deposition were found to have changed ultrastructurally. Concurrent metformin and CCl4 treatment resulted in improvements. The histological and biochemical effects of CCl4 on lung tissue can be modulated by administration of metformin.

ABSTRACT Nandrolone decanoate, a synthetic form of the testosterone hormone, is misused by some bodybuilders and adolescents to gain muscle mass. We investigated its effect on the prostate during postpubertal age and evaluated the reversibility of these effects after a period of cessation. Thirty albino rats were utilized and categorized into three distinct groups: Control group, a treated group that received nandrolone decanoate weekly by intramuscular injection with 10 mg/kg for 4 weeks while recovery group received nandrolone, similar to the treated group, followed by an additional recovery period of 4 weeks. In the treated group, there were significant elevation in IL-1β, IL-18, IL-6, TNF-α, COX2, MDA, BAX, PSA, and miRNA-155 expression and decreased in SOD, GST, bcl2, and testosterone hormone compared to the control group. Prostatic acini showed marked epithelial stratification, weak PAS positive reactions, excess collagen depositions, and negative ARs nuclear immunoexpression. Ultrastructrally, cytoplasm contained vacuoles and dilated cisterna of RER. In the recovery group, insignificant differences were observed between the recovery and control groups, and most of the acini appeared normal except for minimal changes. Nandrolone-induced structural and functional impairment of the prostate at cellular and molecular basis and cessation of it in the recovery group ameliorated the impairment.

ABSTRACT Glomangiosarcoma is an extremely rare neoplasm that represents 1% of all glomus tumors, which in turn make up 2% of soft tissue tumors. We discuss the case of a 49-year-old woman who had a slow growing tumor on the left foot dorsum which evolved over a 4-year period. Magnetic resonance imaging (MRI) was performed showing deep, partially infiltrative, heterogeneous soft tissue mass with necrosis. Tru-Cut biopsy was done with a malignant glomus tumor report. Treatment consisted of wide resection and intense rehabilitation program resulting in full-function recovery. The definitive diagnosis based on morphologic, immunohistochemical and ultrastructural studies evidenced a conventional glomus tumor with malignant areas and abrupt transition to dedifferentiated component with myxoinflammatory fibroblastic sarcoma (MIFS) features. To the best of our knowledge, this is the first case showing this kind of dedifferentiation, the ultrastructural characteristics in this study allow us to identify a very rare disease and unique differentiation.

ABSTRACT 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.

ABSTRACT 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.

ABSTRACT 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.

ABSTRACT 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.

ABSTRACT Ischemia/reperfusion (I/R) injury of sciatic nerve is a serious condition that results in nerve fiber degeneration, and reperfusion causes oxidative injury. Peripheral blood mononuclear cells (PBMNCs) have neuroregenerative power. This study was carried out to evaluate the potential ameliorative effect of PBMNCs on changes induced by I/R injury of the sciatic nerve. Fifty adult male albino rats were divided into donor and experimental groups that were subdivided into four groups: group I (control group), group II received 50 µL PBNMCs once intravenously via the tail vein, group III rubber tourniquet was placed around their Rt hind limb root for 2 hours to cause ischemia, group IV was subjected to limb ischemia as group III, then they were injected with 50 ul PBMNCs as group II before reperfusion. I/R injury showed disorganization of nerve fascicles with wide spaces in between nerve fibers. The mean area of collagen fibers, iNOS immunoexpression, and number of GFAP-positive Schwann cells of myelinated fibers showed a highly significant increase, while a highly significant reduction in the G-ratio and neurofilament immunoexpression was observed. Myelin splitting, invagination, evagination, and myelin figures were detected. PBMNC-treated group showed a marked improvement that was confirmed by histological, immunohistochemical, and ultrastructural findings.

ABSTRACT Heavy metals are natural elements characterized by their relatively large atomic mass as well as high density. It can be introduced into the ecosystem by the mining of heavy metals from deep within the earth’s crust, thereby exposing the metals into air and water systems. Cigarette smoke is another source of heavy metal exposure and has been shown to have carcinogenic, toxic and genotoxic properties. Cadmium, lead, and chromium are the most abundant metals found in cigarette smoke. In response to tobacco smoke exposure, endothelial cells release inflammatory and pro-atherogenic cytokines that are linked to endothelial dysfunction. Endothelial dysfunction is directly related to the production of reactive oxygen species, leading to endothelial cell loss through necrosis and/or apoptosis. The current study aimed to investigate the effect of cadmium, lead, and chromium, alone and as part of metal mixtures, on endothelial cells. The EA.hy926 endothelial cell line was exposed to different concentrations of each of these metals and their combinations and analyzed using flow cytometric analyses with Annexin V. A clear trend was seen with the Pb + Cr as well as the triple combination group with the significant increase of early apoptotic cells. Scanning electron microscopy was used to study possible ultrastructural effects. Morphological changes observed with scanning electron microscopy included cell membrane damage and membrane blebbing at certain metal concentrations. In conclusion, the exposure of endothelial cells to cadmium, lead, and chromium, caused a disruption in cellular processes and morphology, possibly diminishing the protective ability of endothelial cells.