Articles
Journal of Drug Delivery Science and Technology (17732247)112
GABAB receptors are key regulators of neuronal excitability via slow inhibitory mechanisms. Their downregulation in cerebral ischemic stroke impairs excitotoxicity and neuronal death. Quercetin (QC), a well-known flavonoid, has neuroprotective properties but is limited by poor bioavailability and low water solubility. To overcome these restrictions, quercetin was conjugated with superparamagnetic iron oxide nanoparticles (QCSPIONs) and their effectiveness as a treatment was evaluated in an aged rat model of transient middle cerebral artery occlusion (tMCAO). Animals were given QC, QCSPIONs, and vehicle orally for 14 days after reperfusion following exposure to tMCAO. Neurological deficits, infarct volume, brain edema, sensory-motor function, learning, memory, and hippocampal mRNA expression of GABAB receptor subunits, CHOP, Bax, and Bcl-2 were evaluated. Both QC and QCSPIONs significantly enhanced neurological function, reduced infarct volume, alleviated brain edema, and improved cognitive recovery. QCSPIONs showed higher efficacy in comparison to free QC, as evidenced by better performance in behavioral tests, and greater modulation of gene expression. Treatment with QC and QCSPIONs reduced CHOP and the Bax/Bcl-2 ratio while increasing the mRNA expression of GABAB receptor subunits and Bcl-2, suggesting anti-apoptotic and neuroprotective properties. These findings propose that QCSPIONs increase neuroprotection against excitotoxicity by modulating GABAB receptor and CHOP mRNA expression in aged rats following ischemic stroke. Our study highlights the therapeutic potential of QCSPIONs as a novel strategy for moderating brain injury and improving functional recovery after cerebral ischemia/reperfusion. © 2025 Elsevier B.V.
Oncology Reviews (19705557)18
Background: Malignant gliomas are known with poor prognosis and low rate of survival among brain tumors. Resection surgery is followed by chemotherapy and radiotherapy in treatment of gliomas which is known as the conventional treatment. However, this treatment method results in low survival rate. Vaccination has been suggested as a type of immunotherapy to increase survival rate of glioma patients. Different types of vaccines have been developed that are mainly classified in two groups including peptide vaccines and cell-based vaccines. However, there are still conflicts about which type of vaccines is more efficient for malignant glioma treatment. Methods: Phase Ⅰ/Ⅱ clinical trials which compared the efficacy and safety of various vaccines with conventional treatments were searched in databases through November 2022. Overall survival (OS) rate, progression free survival (PFS), and OS duration were used for calculation of pooled risk ratio (RR). In addition, fatigue, headache, nausea, diarrhea, and flu-like syndrome were used for evaluating the safety of vaccines therapy in glioma patients. Results: A total of twelve articles were included in the present meta-analysis. Comparison of OS rate between vaccinated groups and control groups who underwent only conventional treatments showed a significant increase in OS rate in vaccinated patients (I2 = 0%, RR = 11.17, 95% CI: 2.460–50.225). PFS rate was better in vaccinated glioma patients (I2 = 83%, RR = 2.87, 95% CI: 1.63–5.03). Assessment of safety demonstrated that skin reaction (I2 = 0.0%, RR = 3.654; 95% CI: 1.711–7.801, p-value = 0.0058) and flu-like syndrome were significantly more frequent adverse effects win vaccinated groups compared to the control group. Subgroup analysis also showed that vaccination leads to better OS duration in recurrent gliomas than primary gliomas, and in LGG than HGG (p-value = 0). On the other hand, personalized vaccines showed better OS duration than non-personalized vaccines (p-value = 0). Conclusion: Vaccination is a type of immunotherapy which shows promising efficacy in treatment of malignant glioma patients in terms of OS, PFS and duration of survival. In addition, AFTV, peptide, and dendritic cell-based vaccines are among the most efficient vaccines for gliomas. Personalized vaccines also showed considerable efficacy for glioma treatments. Copyright © 2024 Amanzadeh Jajin, Oraee Yazdani, Zali and Esmaeili.
Esmaeili, A.,
Ebrahimpour, S.,
Hefshejani, K.F.,
Esmaeili, A. Archives of Oral Biology (00039969)159
Objective: We investigated the effects of molar tooth shortening on the mRNA expression of the AβPP/BACE1, BDNF/TrkB, and Bax/Bcl-2 signaling pathways in the Wistar male rat hippocampal regions. Design: Four groups (n = 5 per group) of male Wistar rats (control, SRM (shortened right molar), SLM (shortened left molar), and SBM (shortened bilateral molar)) were used. RNA was isolated from the hippocampus and transformed into cDNA. Real-time quantitative PCR was used to evaluate the mRNA expression levels of AβPP, BACE1, Bax, Bcl-2, BDNF, and TrkB. Results: Differential mRNA expression was observed in rat groups. SBM significantly upregulated the AβPP, BACE1, and Bax mRNA expressions, whereas the expression levels of Bcl-2, BDNF, and TrkB were decreased. SRM and SLM approximately had the same effect on the expression enhancement of AβPP, BACE1, and Bax; however, SRM was more effective than SLM in increasing the expression of these genes. Conclusions: Symmetrical molar teeth shortening affected the mRNA expression of AβPP and BACE1, which is related to learning and memory dysfunction. © 2024 Elsevier Ltd
Ageing Research Reviews (15681637)97
Parkinson's disease is predominantly caused by dopaminergic neuron loss in the substantia nigra pars compacta and the accumulation of alpha-synuclein protein. Though the general consensus is that several factors, such as aging, environmental factors, mitochondrial dysfunction, accumulations of neurotoxic alpha-synuclein, malfunctions of the lysosomal and proteasomal protein degradation systems, oxidative stress, and neuroinflammation, are involved in the neurodegeneration process of Parkinson's disease, the precise mechanism by which all of these factors are triggered remains unknown. Typically, neurotoxic compounds such as rotenone, 6-hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl 4-phenyl pyridinium (mpp+), paraquat, and maneb are used to Preclinical models of Parkinson's disease Ferulic acid is often referred to by its scientific name, 4-hydroxy-3-methoxycinnamic acid (C10H10O4), and is found naturally in cereals, fruits, vegetables, and bee products. This substance exhibits neuroprotective effects against Parkinson's disease because of its intriguing potential, which includes anti-inflammatory and antioxidant qualities. This review goes into additional detail about Parkinson's disease and the neuroprotective properties of ferulic acid that may help prevent the condition. © 2024 Elsevier B.V.
