Therapeutic Impact of ODN2088 to Block TLR9 Activity in Induced Liver Fibrosis Mice.

BACKGROUND AND OBJECTIVE: Liver fibrosis is the result of an excessive accumulation of extracellular matrix that develops when inflammation and chronic injury form scar tissue in the liver. Toll-like receptor 9 (TLR9) plays a central role in the innate immune response by recognition of pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs). This study aimed to show the therapeutic effects of TLR9 antagonist oligonucleotide (ODN) 2088 on liver fibrogenesis. MATERIALS AND METHODS: Mice were injected intraperitoneally with carbon tetrachloride (CCl4) or corn oil twice weekly for up to 8 weeks. Mice were also injected with CpG ODN 2088 (50 µg/20 g) daily for the last 4 weeks. At sacrifice, the serum level of liver enzyme activity was measured. Expression of pro-inflammatory and pro-fibrotic biomarkers was analyzed in liver tissue. RESULTS: TLR9 antagonist, CpG ODN 2088, remarkably decreased the haptic inflammation and fibrosis during CCl4 administration. Treatment with CpG ODN 2088 resulted in reduced serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST). That was paralleled with inhibition in the production of intrahepatic inflammatory and fibrotic factors including collagen, α-Smooth Muscle Actin (SMA), Transforming Growth Factor-beta (TGF-ß), interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α). Proliferation (Ki-67) and apoptosis (caspase-3) markers were highly suppressed after CpG ODN 2088 administration. CONCLUSION: Our results indicate that TLR9 antagonist, ODN 2088, showed protective effects against hepatics inflammation and fibrosis in the CCl4-induced fibrosis model. These observations suggest that ODN 2088 can be a potential therapeutic target for liver fibrosis treatment.

Impact of Prostate Specific Antigen and Testosterone Hormone Levels in Patients of Benign Prostatic Hyperplasia in Khartoum State-Sudan.

BACKGROUND AND OBJECTIVE: Lower Urinary Tract Symptoms (LUTS) and Benign Prostatic Hyperplasia (BPH) are progressive ailments resulting from androgenic imbalances and aging that can lead to serious long term complications. Objective of this study was to determine the relationship between prostate-specific antigens and testosterone hormone levels in patients with BPH before transurethral surgery. MATERIALS AND METHODS: This case control study was done on 112 serum samples collected from two secondary care centres in Khartoum, Sudan. Collected serum samples were analyzed by ELISA and fluorescence enzymes immunoassay to measure testosterone, total PSA level and free PSA levels, respectively. RESULTS: Out of 112 patients, 56 BPH diagnosed patients were included in the study with mean age 67.10±7.90 years. Total PSA (T. PSA) levels were higher in patients (14.1±10.6 ng mL-1) than the control group (2.21±1.01 ng mL-1). Total 52% of patients had total PSA level in the gray zone (4-10 ng mL-1) and 33% had total PSA more than 10 ng mL-1. Testosterone levels were low in patients 3.97±2.84 ng mL-1 when compared to the control group 4.95±0.59 ng mL-1. CONCLUSION: The present study revealed that, there was a strong association between T. PSA level and testosterone hormone in BPH patients, which suggested that monitoring of testosterone level is useful in patients with prostate enlargement.