Samar Ossama El-Ganainy

Objective: Geraniol (GO), a traditional plant-derived medicine, has demonstrated anti-osteoclastogenic properties that preserve bone integrity and inhibit bone resorption. This study aimed to evaluate the effect of GO in the adjuvant arthritis rat model, alone and combined with methotrexate (MX), with emphasis on miR-124 and miR-30a effect on the inflammasome (NLRP3)-related disease progression pathways. Methods: Fourteen days post-adjuvant injection, male Sprague–Dawley rats were treated with methotrexate (MX, 1 mg/kg/week), low-dose GO (100 mg/kg/day), high-dose GO (200 mg/kg/day), or a combination of MX and high-dose GO for 14 days. Arthritis progression was assessed using the arthrogram score and hind paw swelling. Tibiotarsal joint tissue was analyzed for inflammatory and autophagy markers, angiogenic factors, miR-124, and miR-30a. Radiological and histopathological examination of the ankle joint was performed, as well as immunohistochemistry for NLRP3. Results: Increased hind paw swelling and changes in radiological and histopathological characteristics confirmed the development of AA. Biochemical analysis of synovial tissue revealed decreased expression of miR-124 and miR-30a, accompanied by increased NLRP3 expression, as well as enhanced autophagy, angiogenesis, and inflammatory markers. Geraniol, in a dose-dependent manner, could reverse inflammatory parameters without any significant toxicological signs. Conclusion: These findings suggest that GO modulates the NLRP3 pathway through miRNA regulation. The synergistic effect of the GO and MX combination uncovers a novel therapeutic strategy in RA.

Objectives: Breast cancer is the most diagnosed cancer in females worldwide. Phytochemicals are among the recent compelling approaches showing anticancer activity. Geraniol is a monoterpenoid showing anti-tumoral potential in cell lines. However, its exact mechanism in breast cancer has not been elucidated. In addition, the possible chemosenstizing effect of geraniol when combined with chemotherapeutic drugs in breast carcinoma has not been previously addressed. Methods: Therefore, the aim of the current work is to investigate the potential therapeutic as well as chemosensitizing effects of geraniol on breast carcinoma induced in mice through examination of tumour biomarkers and histopathology profile. Key findings: Results showed a prominent suppression of tumour growth following geraniol treatment. This was accompanied with miR-21 downregulation that subsequently upregulated PTEN and suppressed mTOR levels. Geraniol was also able to activate apoptosis and inhibit autophagy. Histopathological examination revealed high necrosis areas separating malignant cells in the geraniol-treated group. Combined geraniol and 5-fluorouracil treatment induced more than 82% inhibition of tumour rate, surpassing the effect of each drug alone. Conclusions: It can be concluded that geraniol could represent a promising avenue for breast cancer treatment as well as a potential sensitizing agent when combined with chemotherapeutic drugs.

Background: Oxcarbazepine (OXC) is a frequently prescribed antiepileptic drug for managing focal and generalized seizures. Its therapeutic benefits are limited by its dose-dependent side effects. Nose-to-brain delivery is a novel route for improving the efficacy of antiepileptics. Drug encapsulation in mucoadhesive nanoparticles offers even more advantages for the nasal route. Objective: The study aimed to develop oxcarbazepine-loaded chitosan nanoparticles (OXC-NP) added to a mucoadhesive thermo-reversible gel for intranasal delivery and enhancement of antiepileptic activity. Methods: The formulation was optimized based on entrapment efficiency, polydispersity index, particle size, zeta potential, and in vitro release analysis. The therapeutic efficacy of OXC-NP was assessed in an epileptic rat model and compared to intranasal OXC and oral OXC. Results: The optimized OXC-NPs with chitosan exhibited particle size, zeta potential, and entrapment efficiency of 189 nm, + 31.4 mV ± 2.5 and 97.6% ± 0.14, respectively. The release of OXC was prolonged, reaching 47.1% after 6 h and 55% after 24 h. Enhanced antiepileptic activity of OXC-NP was manifested as decreased seizure score and prolonged survival. Halting of hippocampal TNF-α and IL-6 together with upregulated IL-10 could explain its anti-inflammatory mechanisms. Conclusions: Intranasal OXC-NP-loaded in situ gel represents a promising formulation for enhanced antiepileptic potential achieved at low drug concentrations.

Oxytocin is a neuropeptide hormone that plays an important role in social bonding and behavior. Recent studies indicate that oxytocin could be involved in the regulation of neurological disorders. However, its role in modulating cognition in Alzheimer’s disease (AD) has never been explored. Hence, the present study aims to investigate the potential of chronic intranasal oxytocin in halting memory impairment & AD pathology in aluminum chloride-induced AD in female rats. Morris water maze was used to assess cognitive dysfunction in two-time points throughout the treatment period. In addition, neuroprotective effects of oxytocin were examined by assessing hippocampal acetylcholinesterase activity, β-amyloid 1–42 protein, and Tau levels. In addition, ERK1/2, GSK3β, and caspase-3 levels were assessed as chief neurobiochemical mediators in AD. Hippocampi histopathological changes were also evaluated. These findings were compared to the standard drug galantamine alone and combined with oxytocin. Results showed that oxytocin restored cognitive functions and improved animals’ behavior in the Morris test. This was accompanied by a significant decline in acetylcholinesterase activity, 1–42 β-amyloid and Tau proteins levels. Hippocampal ERK1/2 and GSK3β were also reduced, exceeding galantamine effects, thus attenuating AD pathological hallmarks formation. Determination of caspase-3 revealed low cytoplasmic positivity, indicating the ceasing of neuronal death. Histopathological examination confirmed these findings, showing restored hippocampal cells structure. Combined galantamine and oxytocin treatment showed even better biochemical and histopathological profiles. It can be thus concluded that oxytocin possesses promising neuroprotective potential in AD mediated via restoring cognition and suppressing β-amyloid, Tau accumulation, and neuronal death.

Aim: Galantamine is an acetylcholinesterase inhibitor frequently used in Alzheimer’s disease management. Its cholinergic adverse effects and rapid elimination limit its therapeutic outcomes. We inv...

Background: The presented meta-analysis was developed in response to the publication of several studies addressing COVID-19 vaccines hesitancy. We aimed to identify the proportion of vaccine acceptance and rejection, and factors affecting vaccine hesitancy worldwide especially with the fast emergency approval of vaccines. Methods: Online database search was performed, and relevant studies were included with no language restriction. A meta-analysis was conducted using R software to obtain the random effect model of the pooled prevalence of vaccine acceptance and rejection. Egger’s regression test was performed to assess publication bias. Quality assessment was assessed using Newcastle-Ottawa Scale quality assessment tool. Results: Thirty-nine out of 12246 articles met the predefined inclusion criteria. All studies were cross-sectional designs. The pooled proportion of COVID-19 vaccine hesitancy was 17% (95% CI: 14-20) while the pooled proportion of COVID-19 vaccine acceptance was 75% (95% CI: 71-79). The vaccine hesitancy and the vaccine acceptance showed high heterogeneity (I ² =100%). Case fatality ratio and the number of reported cases had significant effect on the vaccine acceptance as the pooled proportion of vaccine acceptance increased by 39.95% (95% CI: 20.1-59.8) for each 1% increase in case fatality (P<0.0001) and decreased by 0.1% (95% CI: -0.2-0.01) for each 1000 reported case of COVID-19, P= 0.0183). Conclusion: Transparency in reporting the number of newly diagnosed COVID-19 cases and deaths is mandatory as these factors are the main determinants of COVID-19 vaccine acceptance.