Nancy Shahin

OBJECTIVES: The use of stem cells is a promising strategy for seizure treatment owing to their unique characteristics. We investigated the role of endothelial progenitor cells (EPCs) in a pentylenetetrazole (PTZ)‍-induced rat seizure model. A selected panel of long noncoding RNAs (lncRNAs), which maintain an elaborate balance in brain neural regulatory networks as well as the autophagy pathway, was also targeted.

METHODS: The impact of intravenously administered EPCs on PTZ-induced kindling in rats was evaluated by measuring the expression of neuronal damage markers, neurotrophic factors, and relevant lncRNA genes. Rat behavior was assessed using Y-maze test and open field test (OFT).

RESULTS: EPCs mitigated seizure-associated neurological damage and reversed PTZ-induced working memory and locomotor activity deficits, as evidenced by improved performance in the Y-maze test and OFT. EPC treatment reversed the downregulation of the expression of the lncRNAs , , , , , and . EPCs also boosted vascular endothelial growth factor (VEGF) expression. The ameliorative effect achieved by EPCs was comparable to that produced by valproate.

CONCLUSIONS: These findings indicate that EPCs ameliorate kindling epileptic seizures and their associated abnormalities and that the effect of EPCs may be mediated via the upregulation of certain regulatory lncRNAs.

Fibromyalgia (FM) patients are highly susceptible to depression. Wnt/β-catenin signaling has shown a crucial role against depression in several studies. The FDA-approved FM drug, milnacipran (Miln), has shown antinociceptive potential against FM. Yet, no study has investigated its antidepressant potential in FM. Vanillin (Van), a well-known phytochemical often employed as flavoring agent, has been previously reported for its antidepressant and antinociceptive effects in several animal models, but has not been tested so far in FM. This study explored the antidepressant effect of Van and Miln in FM through investigating Wnt/β-catenin signaling. FM was induced in female Wistar rats by injecting reserpine (1 mg/kg/day s.c) for 3 days. Thereafter, animals received either Miln (30 mg/kg/day p.o) or Van (100 mg/kg/day p.o) for the subsequent 14 days. Results showed that both drugs demonstrated antidepressant effect in forced swimming test besides analgesic, and antiallodynic influences observed in Randall-Selitto, hot plate, cold allodynia, Von-Frey, and tail immersion tests. Biochemically, Miln and Van significantly enhanced serotonergic transmission in the hippocampus and upregulated the protein expression of the Wnt/GSK-3β/β-catenin signaling axis, including the downstream proteins, T cell factor, and dicer. This is followed by subsequent upregulation of the resilience micro ribonucleic acids (miRNAs) 124 and 135. Histopathological examinations corroborated the biochemical and molecular findings. Interestingly, these effects of Miln and Van were overturned via administration of the β-catenin inhibitor, XAV939 (0.1 mg/kg, i.p., daily). In conclusion, this study outlined the antidepressant aptitude of Miln and Van through activating Wnt/β-catenin signaling in the hippocampus in reserpine-induced FM.

BACKGROUND: Huntington's disease (HD) is a progressive neurodegenerative disease that causes motor, cognitive, and psychiatric abnormalities, with no satisfying disease-modifying therapy so far. 3-nitropropionic acid (3NP) induces behavioural deficits, together with biochemical and histological alterations in animals' striata that mimic HD. The role of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome in HD pathogenesis remains largely uncharacterized. Parthenolide (PTL), a naturally occurring nuclear factor kappa B (NF-κB) inhibitor, is also known to inhibit NLRP3 inflammasome. Whether PTL is beneficial in HD has not been established yet.

AIM: This study evaluated the possible neuroprotective effects of PTL against 3NP-induced behavioural abnormalities, striatal biochemical derangements, and histological aberrations.

METHODS: Male Wistar rats received PTL (0.5 mg/kg/day, i.p) for 3 weeks and 3NP (10 mg/kg/day, i.p) was administered alongside for the latter 2 weeks to induce HD. Finally, animals were subjected to open-field, Morris water maze and rotarod tests. Rat striata were examined histologically, striatal protein expression levels of glial fibrillary acidic protein (GFAP), cluster of differentiation 45 (CD45) and neuron-specific enolase (NSE) were evaluated immunohistochemically, while those of interleukin (IL)-1β, IL-18, ionized calcium-binding adapter molecule-1 (Iba1) and glutamate were determined by ELISA. Striatal nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein (Keap1), NF-κB, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, S100 calcium-binding protein A10 (S100A10) and complement-3 (C3) were assessed by gene expression analysis.

RESULTS: PTL improved motor, locomotor, cognitive and anxiety-like behaviours, restored neuronal integrity, upregulated Nrf2, and inhibited NLRP3 inflammasome, NF-κB and microglial activation. Additionally, PTL induced astrocyte shifting towards the neuroprotective A2 phenotype.

CONCLUSION: PTL exhibits neuroprotection against 3NP-induced HD, that might be ascribed, at least in part, to its modulatory effects on Keap1/Nrf2 and NF-κB/NLRP3 inflammasome signaling.

Diabetes mellitus (DM) is a chronic disorder that affects nearly half a billion people around the world and causes millions of deaths annually. Treatment of diabetes or related complications represents an economic burden not only for developing countries but also for the developed ones. Hence, new efficient therapeutic and preventive strategies and screening tools are necessary. The current work aimed to assess the potential association of single nucleotide polymorphisms (SNPs) in ghrelin O-acyltransferase (GOAT) rs10096097, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) rs6740584, and v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) rs62521874 genes with type 2 DM susceptibility in Egyptians. A total of 96 patients with type 2 DM along with 72 healthy individuals participated in this study. Genotyping was executed via real-time polymerase chain reaction (PCR), and the serum protein levels of GOAT, CREB, and MafA were measured by enzyme-linked immunosorbent assay (ELISA). Genotyping revealed a significant association of GOAT rs10096097 and CREB1 rs6740584 SNPs with type 2 diabetes risk, with significantly higher GOAT rs10096097 G allele and CREB1 rs6740584 T allele frequencies in diabetic patients than in controls. However, insignificant association was identified between the MafA rs62521874 SNP and diabetes in the examined sample of the Egyptian residents. Serum GOAT, CREB1, and MafA protein levels did not vary significantly between diabetic and control individuals. Yet, significant variation in serum GOAT and CREB1 levels was detected between CREB1 rs6740584 genotypes within the diabetic group, with CT and TT genotype carriers showing higher levels than AA genotype patients. GOAT rs10096097 and CREB1 rs6740584, but not MafA rs62521874, SNPs are associated with type 2 diabetes risk in the studied Egyptians.