Deletions of SMNI gene exon 7 and NAIP gene exon 5 in spinal muscular atrophy patients in selected population.

OBJECTIVE: Spinal muscular atrophy (SMA) is common among various populations because the genetic makeup is monogamous due to consanguineous marriages. Two genes, i.e., survival motor neuron (SMN1) and neuronal apoptosis inhibitory protein (NAIP) are mapped to the SMA vicinity of chromosome 5q13. The main objective of the study was to develop a solitary advanced genetic tool for the diagnosis of SMA by using SMN1 gene exon 7 and NAIP gene exon 5. PATIENTS AND METHODS: This study involved SMA patients (n=84) belonging to different clinical features and socio-economic status. The identity of the intact NAIP gene is primarily based on the amplification of exon 5 only in those SMA patients that have a deletion of SMN1 gene exon 7. Healthy controls (n=84) were also included in this study. The mutational analysis was observed through the Sanger sequencing method, where chromatograms were observed by using Chromas version 2.6.0. RESULTS: This study showed a higher prevalence of SMA in females than in males. NAIP gene is considered a phenotype modifier as most SMA patients (94.90%) have SMN1 exon 7 deletion along with a deletion in exon 5 of the NAIP gene. Single nucleotide conversion C-T in exon 7 of SMN1 gene leads to its complete deletion. Mutated proteins encoded by SMN1 and NAIP genes also result in degeneration and muscle weakness in SMA patients. CONCLUSIONS: These SMA-associated gene deletions can be used as a molecular evaluation tool for pre- and postnatal diagnosis of SMA. This will be valuable when there is a need for precise and consistent results with a strong focus on quantification.

Ellagic acid prevents streptozotocin-induced hippocampal damage and memory loss in rats by stimulating Nrf2 and nuclear factor-κB, and activating insulin receptor substrate/PI3K/Akt axis.

This study examined the protective effect of ellagic acid (EA) against streptozotocin (STZ)-induced hippocampal damage and memory loss and investigated some mechanisms of action. Adult male rats were divided into 4 groups (n = 12) as control, control + EA (50 mg/kg), STZ-DM, and STZ-DM + EA. Treatments were given orally and daily for 8 weeks. Memory function was assessed by the Morris water maze (MWM) and passive learning avoidance test. In addition, blood samples were used to measure glucose and insulin levels. Also, the hippocampus was used to measure markers of oxidative stress, inflammation, and insulin signaling. Associated with the improved memory, EA preserved the structure of the CA1 area of rats' hippocampus and suppressed the hippocampal expression of Bax and cleaved caspase 3. Concomitantly, EA increased rats' weekly weights gain and fasting plasma insulin levels and reduced the hippocampal levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and plasma glucose levels in diabetic rats. In both the control and STZ-DM rats, EA significantly lowered the hippocampal levels of reactive oxygen species (ROS) and malondialdehyde (MDA) but significantly increased the hippocampal levels of glutathione (GSH) and manganese superoxide dismutase (MnSOD), as well as the nuclear levels of NF-κB and nuclear factor-erythroid 2-related factor (Nrf-2). Besides, and in the hippocampus of both groups, EA increased the phosphorylation of insulin receptor substrate (IRS), PI3K, Akt, GS3Kß, and CREB, and increased levels of BDNF and Bcl-2. In conclusion, these data suggest that the neuroprotective effect of EA on rats' hippocampus and memory function is associated with upregulation of Nrf2 and Bcl-2, suppression of NF-κB, and activation of CREB and IRS/PI3K/Akt/ GS3Kß axis.

Ellagic acid protects against diabetic cardiomyopathy in rats by stimulating cardiac silent information regulator 1 signaling.

This study investigated the protective effect of ellagic acid (EA) against diabetic cardiomyopathy (DC) in streptozotocin (STZ)-treated rats and examined if the mechanism of protection involves modulating silent information regulator 1 (SIRT1). Adult male rats were divided into 5 groups (n = 12/each) as control, control + EA, diabetes mellitus (DM), STZ + EA, and STZ + EA + EX-527 (a SIRT1 inhibitor). With a hypoglycemic and insulin-releasing effect, EA preserved cardiomyocyte structure and suppressed the increase in heart weights and collagen deposition in the left ventricle (LV) of DM rats. Concomitantly, EA improved LV systolic and diastolic functions; reduced serum levels of creatinine kinase-MB (CK-MB), brain natriuretic peptide (BNP), and troponin-I, downregulated transforming growth factor beta 1 (TGF-ß1), smad3, and cleaved caspase-3, and increased Bax/Bcl-2 ratio. Of note, EA increased the expression and activity of SIRT1 and suppressed the acetylation of nuclear factor erythroid-derived 2-like 2 (Nrf2), nuclear factor kappa B (NF-κB), smad2, and forkhead box, class O (FOXO1) in the LVs of both the control and diabetic groups. These effects were associated with a significant reduction in the levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor kappa (TNF-κ), and interleukin 6 (IL-6) levels and activity of NF-κB but with increased activity Nrf2 and levels of glutathione (GSH), superoxide dismutase (SOD), and Bcl-2. All these effects were abolished by EX-527. In conclusion, EA protected against DC by its hypoglycemic, antioxidant, anti-inflammatory, and anti-fibrotic, and anti-apoptotic effects through upregulation and activation of SIRT1.