Amal Mansour

Effects of pentoxifylline, 7-nitroindazole, and imipramine on tumor necrosis factor-α and indoleamine 2,3-dioxygenase enzyme activity in the hippocampus and frontal cortex of chronic mild-stress-exposed rats

Objectives: This study aimed to investigate the role of tumor necrosis factor (TNF)-α and the neuronal nitric oxide synthase enzyme in dysregulation of indoleamine 2,3-dioxygenase (IDO) enzyme, and hence serotonin availability in chronic mild stress (CMS), an animal model of depression. Methods: Rats were divided into five groups: two control and CMS-exposed for 6 weeks, and another three groups exposed to CMS and administered pentoxifylline 50 mg/kg/day intraperitoneally, 7-nitroindazole 40 mg/kg/day subcutaneously, or imipramine 20 mg/kg/day intraperitoneally for the previous 3 CMS weeks. Rats were assessed for neurochemical and immunohistochemical abnormalities. Results: Pentoxifylline-, 7-nitroindazole-, and imipramine-treated rats showed amelioration of CMS-induced behavioral deficits that was accompanied by significant reduction in kynurenine/serotonin molar ratio and nitrates/nitrites in frontal cortex and hippocampus. In the pentoxifylline and 7-nitroindazole groups, serum TNF-α was reduced relative to the CMS group (18.54 ± 0.85 and 19.16 ± 1.54 vs 26.20 ± 1.83 pg/mL, respectively; P < 0.05). Exposure to CMS increased TNF-α and IDO immunohistochemical staining scores in both hippocampus and midbrain raphe nuclei. 7-Nitroindazole and pentoxifylline significantly (P < 0.05) reduced TNF-α immunostaining in hippocampus and raphe nuclei, with significant (P < 0.01) reduction of IDO immunostaining in raphe nuclei. Likewise, imipramine reduced TNF-α immunostaining (P < 0.05) in hippocampus. Conclusion: Neuronal nitric oxide synthase and TNF-α may play a concerted role in modulating IDO enzyme activity in CMS-exposed rats and provide additional evidence for possible alternative approaches to switch the neurobiological processes in depression.

Behavioural, metabolic, and endothelial effects of the TNF-α suppressor thalidomide on rats subjected to chronic mild stress and fed an atherogenic diet

There is accumulating evidence suggesting that depression is a risk factor for cardiovascular diseases. This study aimed to examine the hypothesis that the proinflammatory cytokine TNF-α would partially explain the link between depression and atherosclerotic endothelial changes. Rats were distributed among 6 groups: (i) control group; (ii) group subjected to chronic mild stress (CMS); (iii) group fed a cholesterol-cholic acid-thiouracil (CCT diet); and (iv) CMS group fed the CCT diet and treated with the vehicle for 8 weeks. The last 2 groups were subjected to CMS-CCT and received thalidomide (THAL) or imipramine (IMIP). Rats were assessed behaviorally (sucrose preference, open field, and forced-swimming tests). TNF-α protein was assessed from the serum, aorta, and liver. Aortic TNF-α gene expression (assessed using RT-PCR), serum lipid profile, and insulin levels were measured. Endothelial function was assessed in isolated aortic rings. The THAL and IMIP groups showed ameliorated CMS-CCT-related behavioral changes. CMS-CCT-induced metabolic and endothelial dysfunctions were improved in the THAL group but were worsened in the IMIP group. RT-PCR showed a significant reduction of aortic TNF-α mRNA expression in the THAL and IMIP treatment groups. These data paralleled the findings for aortic immunohistochemistry. The THAL group, but not the IMIP group, showed improved CMS-CCT-induced changes in the vascular reactivity of the aortic rings. Thus, TNF-α provides a target link between depression, metabolic syndrome, and endothelial dysfunction. This could open a new therapeutic approach to address the comorbidities of depression.

Evaluation of MicroRNA-210 and protein tyrosine phosphatase, non receptor type 2 in pre-eclampsia.

BACKGROUND The precise origin of Pre-eclampsia (PE) remains elusive. Multiple pieces of evidence support the existence of hypoxia in PE. MiRNA-210 (miR-210), which is induced by Hypoxia-Inducible Factor-1α (HIF-1α) during hypoxia, is one of the most hypoxia sensitive miRNAs. MiR-210 mediates these functions by regulating a lot of target mRNAs. Protein tyrosine phosphatase, non-receptor type 2 (PTPN2) was one of miR-210 targets and was found to be down regulated by hypoxia. OBJECTIVE To assess the levels of relative expression of miR-210 and its target PTPN2 in Egyptian women with PE. This is in order to clarify their possible role in the progression of PE and their relation to each other and to different clinicopathological factors. STUDY DESIGN Group1 included 35 normal primigravida and group 2 included 35 primigravida patients with PE. PE group was subdivided into-mild and severe (PE). Total RNA was extracted from placental tissue samples and Real-Time PCR was performed on the extracted RNA. RESULTS There was a highly significant difference between the studied groups as regards fold change of placental miR-210 and PTPN2 (P<0.01). There was a highly significant negative correlation between miR-210 and PTPN2 RQ among the studied groups and among the preeclampsia group (P<0.01). CONCLUSION The results of this study demonstrated that placental expression of miR-210 was up regulated in pregnancies complicated with PE in comparison to normal pregnancies. This increase in miR-210 resulted in down regulation of its target PTPN2 mRNA and this can have a direct role in the pathogenesis of the PE disease. Additionally, both miR-210 & PTPN2 relative expression could differentiate between mild & severe PE.

Retraction Note: Human papillomavirus-16 (HPV-16) infection association with CIAP-2 expression in head and neck cancer

Human papillomavirus (HPV-16) E6 proteins inhibit apoptosis in both p53-dependent and p53-independent manners. So it was relevant to assess the impact of such infection on head and neck cancers and its relation to the inhibitors of apoptosis (IAPs). CIAP2 is one of these IAPs that is postulated to upregulated by E6 proteins of HPV-16 by amplification of the locus bearing it in many tissues. In this study, we aimed to search for the amplification of the locus bearing CIAP-2 and its relation to HPV-16 in head and neck cancer that may have prognostic and therapeutic impacts on these patients. Total 30 patients diagnosed as head and neck cancer (2 tissue samples were taken from each patient: from the tumor and from the safety margin). All samples were subjected to qualitative polymerase chain reaction analysis for HPV-16 and qualitative and semiquantitative reverse transcription polymerase chain reaction of CIAP-2. There was a significant association between HPV-16 and CIAP2 positivity and head and neck tumors (P = 0.01). CIAP-2 expression in malignant tissues was highly associated with HPV-16 infection with 73.9% sensitivity and absolute specificity.

KLK10 exon 3 unmethylated PCR product concentration: a new potential early diagnostic marker in ovarian cancer? - A pilot study

BackgroundKLK10 exon 3 hypermethylation correlated to tumor-specific lack of KLK10 expression in cancer cell lines and primary tumors. In the present study we investigate the possible role of KLK10 exon 3 methylation in ovarian tumor diagnosis and prognosis.ResultsQualitative methylation-specific PCR (MSP) results did not show statistically significant differences in patient group samples (normal and tumor) where all samples were positive only for the unmethylated-specific PCR except for two malignant samples that were either doubly positive (serous carcinoma) or doubly negative (Sertoli-Leydig cell tumor) for the two MSP tests. However, KLK10 exon 3 unmethylated PCR product concentration (ng/μl) showed statistically significant differences in benign and malignant patient group samples; mean ± SD (n): tumor: 0.077 ± 0.035 (14) and 0.047 ± 0.021 (15), respectively, p-value = 0.011; and normal: 0.094 ± 0.039 (7) and 0.046 ± 0.027 (6), respectively, p-value = 0.031. Moreover, ROC curve analysis of KLK10 exon 3 unmethylated PCR product concentration in overall patient group samples showed good diagnostic ability (AUC = 0.778; p-value = 0.002). Patient survival (living and died) showed statistically significant difference according to preoperative serum CA125 concentration (U/ml); median (n): 101.25 (10) and 1252 (5), respectively, p-value = 0.037, but not KLK10 exon 3 unmethylated PCR product concentration (ng/μl) in overall malignant patient samples; mean ± SD (n): 0.042 ± 0.015 (14) and 0.055 ± 0.032 (7), p-value = 0.228.ConclusionTo the best of our knowledge, this is the first report on KLK10 exon 3 unmethylated PCR product concentration as potential early epigenetic diagnostic marker in primary ovarian tumors. Taken into account the limitations in our study (small sample size and semi-quantitative PCR product analysis) further studies are strongly recommended.

B cell non-Hodgkin's lymphoma in chronic hepatitis C virus patients: An interesting relationship.

BackgroundAn association exists between hepatitis C virus (HCV) infection and non-Hodgkin’s lymphoma (NHL), but a causal relationship is not fully established. HCV is a lymphotropic virus that represents a major etiologic agent of mixed cryoglobulinemia (MC) type II which is characterized by a low-grade B cell clonal lymphoproliferative disorder that usually progresses to a more aggressive malignant lymphoma. This study assessed the role of cryoglobulin and B lymphocyte stimulator (BLys) in the pathogenesis of NHL in chronic HCV patients.MethodsSixty HCV patients, 30 free of B cell NHL (group I) and 30 with B cell NHL (group II), and 30 healthy controls (group III) were studied. Qualitative cryoglobulin assessment and a quantitative assay for BLys were done.ResultsIn group II, BLyS positivity rate was 1.5-fold higher than of group I (p ≤ 0.01). A positive association was found between positivity rate of MC and the level of BLyS (p ≤ 0.01).ConclusionHigh BLyS levels were associated with HCV-associated lymphoproliferative disorder coupled with positive MC.