Dysregulation in the expression of (lncRNA-TSIX, TP53INP2 mRNA, miRNA-1283) in spinal cord injury.

AIM: The objective of this study is to examine the alterations in the levels of expression of serum lncRNA-TSIX, TP53INP2 mRNA, miRNA-1283 in spinal cord injured (SCI) patients versus healthy control. METHOD: The expression of the selected RNAs in the sera was determined in 23 patients suffering from acute spinal cord injury, 41 individuals with chronic spinal cord injury, and 36 healthy control using real-time reverse-transcription polymerase chain reaction method. RESULTS: The results showed that lncRNA-TSIX and the TP53INP2 mRNA expression levels in SCI patients was overexpressed in comparison to the control group alongside with a significant downregulation of miR-1283. Statistically,there was a highly significant positive correlation between lnc-RNA-TRIX and TP53INP2 mRNA with inverse correlation between miRNA-1283 and lnc-RNA-TRIX based on fold changes. CONCLUSION: Up-regulation of lncRNA-TSIX, TP53INP2 mRNA with downregulation of miRNA-1283 might be closely associated with progression of SCI.

Effects of losartan, HO-1 inducers or HO-1 inhibitors on erectile signaling in diabetic rats.

INTRODUCTION: Activation of the renin-angiotensin system which is common in diabetes mellitus might affect heme oxygenase (HO-1) gene expression. AIM: Assessment of the effects of administration of angiotensin II (Ang II) receptor antagonist (losartan) with HO-1 inducer or inhibitor on erectile signaling in diabetic rats. MATERIALS AND METHODS: Seventy male rats were divided equally into seven groups; healthy controls, streptozotocin-induced diabetic rats, rats on citrate buffer, diabetic rats on losartan, diabetic rats on HO-1 inducer (cobalt protoporphyrin [CoPP]), diabetic rats on losartan and CoPP, and diabetic rats on losartan and HO-1 inhibitor (stannus mesoporphyrin [SnMP]). MAIN OUTCOME MEASURE: HO enzyme activity, HO-1 gene expression, cyclic guanosine monophosphate (cGMP) assay, intracavernosal pressure (ICP), and cavernous tissue sinusoids surface area. RESULTS: HO-1 gene expression, HO enzymatic activity, and cGMP were significantly decreased in the cavernous tissue of diabetic rats. These parameters were significantly elevated with the use of CoPP that restored the normal control levels of HO enzyme activity. Administration of losartan exhibited a significant enhancing effect on these parameters compared with the diabetic group, but not restored to the control levels, whereas administration of CoPP combined with losartan led to the restoration of their normal levels. ICP demonstrated significant decline in diabetic rats. The use of CoPP and/or losartan led to its significant improvement compared with diabetic rats. Administration of either losartan and/or CoPP led to a significant increase in the cavernous sinusoids surface area of diabetic rats. Administration of losartan with SnMP significantly decreased the enhancing effect of losartan on the studied parameters. CONCLUSION: The decline in erectile function in diabetes mellitus could be attributed to the downregulation of HO-1 gene expression. HO-1 induction added to Ang II receptor antagonist could improve erectile function.

Heme oxygenase vs. nitric oxide synthase in signaling mediating sildenafil citrate action.

INTRODUCTION: Heme oxygenase (HO) enzyme catalyzes the rate limiting step in oxidative degradation of heme to biliverdin and carbon monoxide (CO). CO has been shown to share many properties with nitric oxide (NO), including activation of guanyl cyclase, signal transduction, and gene regulation. AIM: To assess the signaling pathways mediating cavernous tissues response to sildenafil citrate intake experimentally. MAIN OUTCOME MEASURES: In dissected cavernous tissues; detection of HO-1, HO-2 and nueronal nitric oxide synthase (nNOS) gene expressions by reverse transcriptase polymerase chain reaction (RT-PCR), HO enzyme activity assay, HO-1, HO-2 protein detection by Western blot, cyclic guanosine monophosphate (cGMP) tissue levels by enzyme linked immunosorbent assay (ELISA) and histopathology. METHODS: Two hundred forty Sprague-Dawley rats divided into five equal groups were investigated: group (Gr) 1, controls received regular diet; Gr 2, received sildenafil citrate 4 mg/kg orally; Gr 3, received the same dose of sildenafil added to HO inducer, diferuloylmethane; Gr 4, received sildenafil added to HO inhibitor, zinc protoporphyrin, and Gr 5, received sildenafil kg orally by gastric tube. Gr 3 received the same dose of sildenafil added to HO inducer, added to nitric oxide synthase inhibitor, L-Nitroarginine methylester. Twelve rats from each group were sacrificed by cervical dislocation successively after 1/2, 1, 2, and 3 hours from the intake. RESULTS: HO-2 gene expression was demonstrated in all groups. HO-1 was not expressed in controls, expressed in Gr 2, accentuated in Gr 3, and attenuated in Gr 4 and 5. These results were confirmed by Western blot. The nNOS was expressed in controls, increased in Gr 2 and 3, and decreased in Gr 4 and 5. HO enzyme activity and cGMP levels were significantly elevated in Gr 2, accentuated in Gr 3, and significantly decreased in Gr 4 and 5 compared to controls. Vasodilatations were observed in cavernous tissues of histopathologic sections of Gr 2 and increased in those of Gr 3. CONCLUSION: Sildenafil citrate actions may be mediated by up-regulation of HO-1 gene expression.