The Neuroprotective Effect of Erythropoietin on the Optic Nerve and Spinal Cord in Rats with Experimental Autoimmune Encephalomyelitis through the Activation of the Extracellular Signal-Regulated Kinase 1/2 Signaling Pathway.

Experimental autoimmune encephalomyelitis is a demyelinating disease that causes paralysis in laboratory rats. This condition lacks treatment that reverses damage to the myelin sheaths of neuronal cells. Therefore, in this study, treatment with EPO as a neuroprotective effect was established to evaluate the ERK 1/2 signaling pathway and its participation in the EAE model. EPO was administered in 5000 U/Kg Sprague Dawley rats. U0126 was used as an inhibitor of the ERK 1/2 pathway to demonstrate the possible activation of this pathway in the model. Spinal cord and optic nerve tissues were evaluated using staining techniques such as H&E and the Luxol Fast Blue myelin-specific technique, as well as immunohistochemistry of the ERK 1/2 protein. The EPO-treated groups showed a decrease in cellular sampling in the spinal cord tissues but mainly in the optic nerve, as well as an increase in the expression of the ERK 1/2 protein in both tissues. The findings of this study suggest that EPO treatment reduces cellular death in EAE-induced rats by regulating the ERK pathway.

Chronic Administration of Diethylnitrosamine and 2-Acetylaminofluorene Induces Hepatocellular Carcinoma in Wistar Rats.

This study aimed to analyze the biochemical, histological, and gene expression alterations produced in a hepatocarcinogenesis model induced by the chronic administration of diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) in Wistar rats. Thirteen rats weighing 180 to 200 g were divided into two groups: control and treated. Rats in the treated group were administered an intraperitoneal (i.p.) injection of DEN (50 mg/kg/week) and an intragastric (i.g.) dose of 2-AAF (25 mg/kg/week) for 18 weeks. The treated group had significant increases in their total cholesterol, HDL-C, AST, ALT, ALKP, and GGT levels. Furthermore, a histological analysis showed the loss of normal liver architecture with nuclear pleomorphism in the hepatocytes, atypical mitosis, and fibrous septa that were distributed between the portal triads and collagen fibers through the hepatic sinusoids. The gene expressions of 24 genes related to fibrosis, inflammation, apoptosis, cell growth, angiogenesis, lipid metabolism, and alpha-fetoprotein (AFP) were analyzed; only TGFß, COL1α1, CYP2E1, CAT, SOD, IL6, TNF-α, and ALB showed significant differences when both groups were compared. Additionally, lung histopathological alterations were found in the treated group, suggesting metastasis. In this model, the chronic administration of DEN+2-AAF induces characteristic alterations of hepatocellular carcinoma in Wistar rats without AFP gene expression changes, highlighting different signatures in hepatocellular carcinoma heterogeneity.

Transforming growth factor beta isoforms and TGF-ßR1 and TGF-ßR2 expression in systemic sclerosis patients.

Systemic sclerosis (SSc) is characterized by chronic inflammation and fibrosis, two processes associated with transforming growth factor ß (TGF-ß) functions. In the present study, we investigated the expression of TGF-ß isoforms in serum and the skin distribution of TGF-ß and two receptors (TGF-ßR1 and TGF-ßR2) and their relationship with some clinical, inflammatory, autoimmune (autoantibodies), and vascular (platelets) biomarkers in SSc patients. A total of 56 SSc patients and 120 control subjects (CS) were included. The serum levels of TGF-ß isoforms were quantified by immunoassay with magnetic microspheres, and the skin biopsies were processed by immunohistochemistry. The soluble levels of the three active TGF-ß isoforms were lower in SSc patients than in CS (p < 0.0001). However, sTGF-ß1 and sTGF-ß3 levels were positively correlated with C-reactive protein levels in SSc patients. Additionally, sTGF-ß2 and sTGF-ß3 levels were positively correlated with the number of platelets in SSc patients. In skin biopsies, TGF-ß1, TGF-ßR1, and TGF-ßR2 expression levels were higher in SSc patients than CS. In conclusion, this is the first study showing a joint decrease of the 3 active TGF-ß isoforms in SSc patients. However, TGF-ß1, TGF-ßR1, and TGF-ßR2 are possibly increased in clinically involved skin. Therefore, it is likely that a distinct role is played by TGF-ß at the local (skin lesions) and systemic levels in SSc patients.