Assessment of breast cytoarchitecture and its associated axillary lymph node status under normal and pathological conditions in Egyptian women.

OBJECTIVE: Herein, we compare the features of neoplastic cancer cells in invasive ductal carcinoma (IDC) grade II and III patients to their corresponding normal cells both in breast and axillary lymph node (ALN) tissues. METHODS: A retrospective cohort of 70 female breast cancer patients enrolled between 2018 and 2020 at Medical Research Institute, Alexandria University, Egypt, was analyzed for clinicopathological features presentation. Fresh tiny pieces of breast tissue and its associated ALN tissues were then processed to investigate the morphological appearance by scanning electron microscopy. Moreover, the histological architecture of tissue sections stained with hematoxylin and eosin was studied by light microscope, while the characterization of the ultrastructure features of breast and ALN tissues was analyzed by transmission electron microscopy. RESULTS: Clinicopathological presentation of patients revealed that the Egyptian female breast cancer population adhered to the global trends of breast cancer disease with elevated incidence rate among postmenopausal women (61.3%), high frequency of IDC (95.7%), and increased ALN metastasis (65.7%). The percentage of estrogen receptor alpha (ERα) and human epidermal growth factor receptor 2 (HER2) expression, as key indicators for carcinogenesis and disease progression was 87.1% and 55.8%, respectively. The present study points to the observed discrepancies among the investigated variables in the diagnostic separation between IDC grade II and grade III. Ductal epithelial cells organization, nuclei size and irregularity, chromatin amount and uniformity, mitochondrial abundance and dysfunction were differentially manifested in IDC grades. Moreover, aberrations in the cellular organelles like lysosomes, endoplasmic reticulum, and lipid droplets vary according to the grade of IDC and the aggressiveness of the invasive breast cancer. CONCLUSIONS: To sum up, this study emphasizes the importance of accurate specimen evaluation for treatment choice and decision.

Remarkable histopathological improvement of experimental toxoplasmosis after receiving spiramycin-chitosan nanoparticles formulation.

The present study investigated the anti-Toxoplasma effect of chitosan nanoparticles [CS NPs], spiramycin, spiramycin co-administered with metronidazole and spiramycin-CS NPs formulation on the parasite burden and histopathological changes in the liver, spleen and brain in experimentally infected mice. Seventy male Swiss albino mice were classified into seven equal groups: healthy control (I), infected untreated control (II), infected group receiving CS NPs (III), spiramycin administered infected group (IV), infected group receiving spiramycin-metronidazole (V), infected receiving 400 mg/kg spiramycin-CS NPs (VI) and infected treated with spiramycin-loaded CS NPs 100 mg/kg (VII). All groups were inoculated intraperitoneally with 2500 T. gondii tachyzoites RH strain except the healthy control group. All groups were sacrificed on the 8th day after infection. Density of the parasite and histopathological examination of the liver, spleen and brain of all treated mice revealed reduction in the mean tachyzoites count as well as decreased inflammation, congestion and necrosis within tissue sections. Spiramycin-loaded NPs displayed the highest significant reduction in the pathological insult tailed by spiramycin-metronidazole and CS NPs. In conclusion, spiramycin-loaded CS NPs showed a promising synergistic combination in the treatment of the histopathology caused by toxoplasmosis.

Concanavalin-A as a Model for Induction of Murine Autoimmune Hepatitis: Role of TNF-α and NF-κß During The Acute Phase.

Autoimmune hepatitis (AIH) is a heterogeneous immune-mediated chronic liver disease affecting children and adults. It is important to rely on a specific animal model to study the hepatic changes and to evaluate the roles played by pro-inflammatory cytokines such as tumor necrosis factor alpha "TNF-α" and transcription factors such as nuclear factor kappa-light-chain-enhancer of activated B cells "NF-κß" in the pathogenesis and outcome of the disease. This will help to identify specific targets for treatment of AIH. This study aimed at evaluating Concanavalin-A (Con A) as a model for induction of AIH and assessing splenocytes' TNF-α and hepatocytes' NF-κß levels at comparable durations after induction of hepatitis with Con A to evaluate the relationship between both factors. Materials and methods: A total of 130 outbreed CD1 mice were divided into group (1) which included 100 mice with induced AIH and group (2) included 30 normal mice as negative controls. Intra-peritoneal injection of Concanavalin-A was used to induce hepatitis. Hepatic injury was evaluated by the levels of liver enzymes, histopathological evidence for hepatic inflammatory infiltrate and/or apoptosis. Splenocytes and hepatocytes were cultured for assessment of TNF-α and NF-κß levels, respectively. Results: Con A injection caused a significant elevation in ALT and AST levels, portal inflammatory infiltrate, remarkable hepatocytes degeneration and marked increase of TNF-α levels, particularly within 24 hours, but all returned to normal within 1 week. Administration of another dose of Con A resulted in sharp significant elevation of liver enzymes, inflammatory infiltrate and hepatocyte apoptosis after 24 hours and sustained till the end of the study. There was a significant increase in NF-κß throughout most of the study duration following Con A injection as compared to that of normal mice. In conclusions, intra-peritoneal administration of Con A, particularly two doses, represents an efficient approach for induction of immune-mediated hepatitis. T-cells play a major role in AIH through release of TNF-α. Coincidently, hepatitis seems to be associated with elevation of NF-κß to protect hepatocytes. Thus TNF-α and NF-κß can represent targets for treatment of AIH either through inhibition or augmentation, respectively.

The therapeutic effects of bee venom on some metabolic and antioxidant parameters associated with HFD-induced non-alcoholic fatty liver in rats.

The present study was designed to investigate the therapeutic effects of bee venom (BV) on high-fat diet (HFD)-induced non-alcoholic fatty liver (NAFL) in rats at different levels. Histological manifestations, hepatic lipid content, liver function tests, glucose homeostasis, lipid abnormalities, adipocytokines, lipid peroxidation, disturbed glutathione and antioxidant enzymes systems and dysregulation of Nrf2 transcription factor were assessed. In the present study, the NAFL rats were subcutaneously treated with BV with different doses (0.01, 0.05, 0.1 mg/kg). The results indicated that BV treatment completely normalized the lipid profile values of NAFL rats. Fasting blood sugar, insulin level and homeostatic model assessment of insulin resistance significantly decreased. BV treated rats showed a significantly lower level of all liver enzymes and bilirubin. Moreover, BV treatment significantly increased the levels of active nuclear erythroid factor 2 like 2, glutathione (GSH) (total and reduced), GSH/glutathione disulphide ratio and activities of glutathione reductase, glutathione-S-transferase and glutathione peroxidase (total and Se-dependent). The level of tumor necrosis factor-α was reduced. Treatment showed correction of adiponectin level, and significant downregulation of hepatic triglycerides and cholesterol. At the histological level, BV improved the architecture of liver cells showing normal sinusoids. It may be concluded that BV may represent an interesting therapeutic alternative for the treatment of NAFL disease.

Thymoquinone improves the kidney and liver changes induced by chronic cyclosporine A treatment and acute renal ischaemia/reperfusion in rats.

OBJECTIVES: This study was designed to evaluate the effects of chronic cyclosporine A (CsA) treatment and acute renal ischaemia/reperfusion (I/R) on the kidney and liver in thymoquinone (TQ)-treated rats. METHODS: In the CsA study, adult male rats were divided into control, CsA (25 mg/kg per day), TQ (10 mg/kg per day) and CsA + TQ groups, and rat treatment was for 28 days. In the I/R study, adult male rats were divided into sham-operated, I/R (renal ischaemia for 60 min followed by 60 min reperfusion) and TQ + I/R (TQ 10 mg/kg, 24 h and 1 h before ischaemia) groups. KEY FINDINGS: CsA treatment and renal I/R caused kidney and liver dysfunction as evaluated by histopathological changes and biochemical parameters. TQ treatment reduced elevated serum indices back to control levels and ameliorated CsA-induced kidney and liver histopathological changes. In renal and hepatic tissues, CsA and renal I/R induced significant increases in malondialdehyde levels with significant decreases in reduced glutathione levels and superoxide dismutase activities. Such changes in oxidative stress markers were counteracted by TQ treatment. CONCLUSIONS: Kidney and liver injury due to CsA or renal I/R can be significantly reduced by TQ, which resets the oxidant/antioxidant balance of the affected organs through scavenging free radicals and antilipoperoxidative effects.

Improved antitumor activity and reduced cardiotoxicity of epirubicin using hepatocyte-targeted nanoparticles combined with tocotrienols against hepatocellular carcinoma in mice.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide. Epirubicin (EPI), an anthracycline derivative, is one of the main line treatments for HCC. However, serious side effects including cardiomyopathy and congestive heart failure limit its long term administration. Our main goal is to develop a delivery strategy that ensures improved efficacy of the chemotherapeutic agent together with reduced cardiotoxicity. In this context, EPI was loaded in chitosan-PLGA nanoparticles linked with asialofetuin (EPI-NPs) selectively targeting hepatocytes. In an attempt to reduce cardiotoxicity, targeted EPI-NPs were coadministered with tocotrienols. EPI-NPs significantly enhanced the antiproliferative effect compared to free EPI as studied on Hep G2 cell line. Nanoencapsulated EPI injected in HCC mouse model revealed higher p53-mediated apoptosis and reduced angiogenesis in the tumor. Combined therapy of EPI-NPs with tocotrienols further enhanced apoptosis and reduced VEGF level in a dose dependent manner. Assessment of cardiotoxicity indicated that EPI-NPs diminished the high level of proinflammatory cytokine tumor necrosis factor-α (TNF-α) as well as oxidative stress-induced cardiotoxicity as manifested by reduced level of lipid peroxidation products (TBARS) and nitric oxide (NO). EPI-NPs additionally restored the diminished level of superoxide dismutase (SOD) and reduced glutathione (GSH) in the heart. Interestingly, tocotrienols provided both antitumor activity and higher protection against oxidative stress and inflammation induced by EPI in the heart. This hepatocyte-targeted biodegradable nanoparticle/tocotrienol combined therapy represents intriguing therapeutic strategy for EPI providing not only superior efficacy but also higher safety levels.