Abstract:With the global elderly population projected to double by 2050, there is an increasing need to address the risk factors associated with neurodegenerative diseases. This article focuses on exploring the potential neuroprotective effects of quercetin mediated through the Nrf2 signaling pathway. Quercetin, a flavonoid pigment known for its antioxidant properties, can directly interact with Keap1, leading to the dissociation of Nrf2 from the Keap1-Nrf2 complex. Consequently, Nrf2 is released and translocates to the nucleus, initiating the transcription of antioxidant enzymes, such as heme oxygenase-1, NAD(P) H: quinone oxidoreductase 1, and glutathione S-transferase. The exploration of quercetin as an Nrf2 activator holds significant therapeutic implications for neurodegenerative disorders. Human studies demonstrate the efficacy of quercetin in neurodegenerative diseases, while animal studies highlight the protective effects of the Nrf2 signaling pathway. Additionally, Nrf2 regulates proinflammatory cytokines. This study aims to investigate the potential neuroprotective effects of quercetin mediated through the Nrf2 signaling pathway. By targeting oxidative stress, neuroinflammation, and improving mitochondrial function, quercetin shows promise as a candidate for preventing or slowing the progression of neurodegenerative diseases.

2024-12-01·Current Molecular Medicine

Evaluation of the Safety and Efficacy of Curcumin-Synthesized Silver Nanoparticles in Rats Exposed to Chlorpyrifos During Puberty Development

Article

作者: Mohaqeq, Alia ; Shakibaie, Mehdi ; Aschner, Michael ; Farkhondeh, Tahereh ; Rezaei, Maryam ; Khoramroudi, Sana ; Samarghandian, Saeed ; Mohaqiq, Zabihullah

Background:Silver nanoparticles (Ag-NPs) have garnered significant attention in recent years due to their therapeutic effects. Curcumin (CUR) has been utilized as a coating agent for synthesizing Ag-NPs, intended to act as a potential drug.Objective::This study was designed to evaluate the safety and efficacy of curcuminsynthesized silver nanoparticles on rats exposed to chlorpyrifos (CPF) during their pubertal development.Methods:Forty-two male Wistar rats, 23 days old, were selected and randomly divided into 7 groups (n=6) as follows: positive control, negative control, CPF (5 mg/kg), silver nanoparticles synthesized using curcumin at 40 μg/kg (CUR-Ag-NPs 40), CUR-Ag-NPs 80, CPF+ CUR-Ag-NPs 40, CPF+ CUR-AgNPs 80. All treatments were administered via gavage for 30 days. At the end of the study, rats were anesthetized using ketamine (50 mg/kg), and xylazine, (10 mg/kg) and blood was collected from the heart for serum analysis of liver enzymes, urea, and creatinine.Results:Liver and kidney tissues were isolated for histopathological analysis. No significant differences were observed in serum levels of AST, ALT, and ALP enzymes as well as urea and creatinine levels among the different groups. Light microscopy observation revealed multifocal inflammatory mononuclear cell subsets in liver tissue associated with mild inflammatory mononuclear cell infiltration in the portal region in CPF, CUR-Ag-NPs 40, CUR-Ag-NPs 80, CPF+CUR-Ag-NPs 40, and CPF+CUR-Ag- NPs 80 groups. Histological examination of kidney tissue showed degenerative changes in the tubular epithelium, congestion, and mild infiltration of mononuclear inflammatory cells in the renal interstitial tissue in the CPF group, CUR-Ag-NPs 40, CUR-Ag-NPs 80, CPF+CUR-Ag-NPs 40 and CPF+CUR-Ag-NPs 80 groups.Conclusion:This study failed to establish the safety and efficacy of CUR-Ag-NP at 40 and 80 μg/kg in prepubertal rats exposed to CPF. However, further studies should be conducted to thoroughly characterize the efficacy of CUR-Ag-NP in developmental animal models.

2024-12-01·Current Molecular Medicine

Aminoglycosides: Single- or Multiple-daily Dosing? An Updated Qualitative Systematic Review of Randomized Trials on Toxicity and Efficacy

Review

作者: Mahi-Birjand, Motahareh ; Abdollahpour-Alitappeh, Meghdad ; Ghaffari, Shokouh ; Barkhordari, Amin ; Karimzadeh, Iman ; Alemzadeh, Effat

Introduction:Aminoglycosides are among the first-choice antibiotics for routine clinical use. However, dose-limiting factors such as ototoxicity and nephrotoxicity are considered as serious complications of aminoglycosides.Objective:In this systematic review, the main goal was to investigate the efficacy and incidence of nephrotoxicity and ototoxicity of once-daily dosing (ODD) and multiple daily dosing (MDD) regimens of aminoglycosides through available randomized controlled trials (RCTs).Methods:We performed a literature-based research in relevant databases, including EMBASE, MEDLINE, and SCOPUS published between 1987 and 2023 using the keywords “aminoglycosides”, “pharmacokinetics”, “ODD”, “MDD”, “once daily”, “multiple daily”, “dosing regimen”, “nephrotoxicity”, “ototoxicity”, “efficacy”, “safety”, and “toxicity”. As so told, the results of this article were limited to papers available in English. Our initial search yielded 1124 results. After a review of the titles and abstracts of the articles, 803 articles were excluded from this study because they did not address the toxicity and effectiveness of ODD versus MDD of aminoglycosides. A total number of 20 studies on gentamicin, tobramycin, netilmicin, and amikacin met the inclusion criteria for the efficacy of aminoglycosides and their role in ototoxicity and nephrotoxicity were included in this review. Studies recruited different age classes, and the age of relevant cohorts varied from only a few days to more than 70 years.Results:The most common clinical condition in the included studies was cystic fibrosis.Conclusion:In most studies, there were no significant differences between the two regimens regarding ototoxicity. In addition, the ODD regimens were safer than MDD concerning nephrotoxicity.

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100 项与 Birjand University of Medical Sciences 相关的转化医学

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