Seyed Esmaeil Khoshnam

Background The use of natural compounds with potent antioxidant and anti-inflammatory properties is a key strategy against age-related neurobehavioral deficits. This study investigated the protective effects of Zingerone (ZIN) and its underlying mechanisms against D-galactose (D-gal)-induced brain aging, with a focus on oxidative stress, inflammatory markers, and neurobehavioral deficits. Material and Methods Male Wistar rats were divided into five groups: a control group (normal saline), a D-gal group (100 mg/kg), and three ZIN treatment groups (5, 10, and 20 mg/kg). An aging model was induced by daily subcutaneous injection of D-gal for eight weeks. Concurrently, the ZIN treatment groups received their respective doses by daily gavage over the same eight-week period. We evaluated the cognitive and locomotor functions of the animals using standard behavioral tests including Morris water maze (MWM), passive avoidance task (PAT), open field test (OFT) and rotarod test. In addition, we assessed the oxidative-antioxidative status and inflammatory conditions in the hippocampus, and conducted a qualitative histopathological evaluation of the hippocampal tissue and cortex of the experimental rats. Results Our findings indicate that ZIN treatment significantly enhanced cognitive and motor function and reduced oxidative stress and neuroinflammation in the hippocampus, as well as attenuate histopathological changes in the cortex and hippocampal areas of D-gal-induced brain aging rats. These effects were dose-dependent, and the most protective effects were demonstrated at the 20 mg/kg dosage. A significant association between oxidative stress markers, inflammatory cytokines, and cognitive functions was confirmed by correlation analyses. Conclusion This study demonstrates that ZIN protects against D-gal-induced cognitive and motor deficits by enhancing antioxidant and anti-inflammatory activity in the hippocampus. These findings support the potential of ZIN as a natural compound with therapeutic and health benefits for improving age-related neurobehavioral decline.

Sleep deprivation (SD) is known to impair memory and cognitive functions often linked to heightened oxidative stress and neuroinflammation. While caffeine and exercise individually offer neuroprotective effects, the combined influence of these interventions on preserving cognitive function and reducing hippocampal damage during REM-SD has yet to be fully explored. This study investigates the synergistic potential of caffeine and exercise in mitigating these neurological damages induced by REM-SD. Male Wistar rats were divided into five groups: control, SD, caffeine + SD, exercise + SD, and caffeine + exercise + SD. The rats received caffeine (30 mg/kg, p.o) and underwent a treadmill exercise regimen, running 5 days a week for 4 weeks. Following this, they were placed in a REM-SD apparatus for 72 h. We evaluated the cognitive functions of the animals using standard behavioral tests. In addition, we assessed BBB permeability, brain water content (BWC), oxidative-antioxidative status, inflammatory/anti-inflammatory conditions, and apoptotic and neurotrophic indices in the hippocampus of REM-SD rats. Our findings indicate that the combination of caffeine and exercise significantly enhanced cognitive functions in REM-SD rats. This combination also reduced BBB permeability and BWC, alleviated oxidative stress, lowered inflammatory and apoptotic indices, and increased neurotrophic gene expression in the hippocampus of REM-SD rats. This study highlights the protective effects of caffeine and exercise on cognitive function and BBB integrity, likely through the enhancement of antioxidant and anti-inflammatory indices in the hippocampus, as well as their anti-apoptotic and neurotrophic effects in REM-SD rats.

Gliomas are a group of brain cancers with various clinical and biological features, and they are mostly malignant. Progressions in therapy approaches, comprising radiotherapy, chemotherapy, and surgery, have not been so considerable in the prognosis of glioma cases. Recently, long non-coding RNAs (lncRNAs) have been found with putative regulatory roles in gene expression, epigenetic regulation, neurogenesis, cell cycle, and cellular transportation. The lncRNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) is frequently reported to be associated with multiple disorders, such as various types of cancers. Upregulation of MALAT1 is detected in different tumours, including glioma, and functional analyses reveal it affects malignant features of cancer cells like proliferation, migration, invasion and apoptosis. MALAT1 impacts those features by modulating various epigenetic histones, hormones, growth factors, and transcription factors. Therefore, this lncRNA can be regarded as a potent therapeutic target for glioma. In this review, we summarized the functional roles of MALAT1 in glioma.

Ischemic stroke (IS) stands as a prominent cause of mortality and long-term disability around the world. It arises primarily from a disruption in cerebral blood flow, inflicting severe neural injuries. Hence, there is a pressing need to comprehensively understand the intricate mechanisms underlying IS and identify novel therapeutic targets. Recently, long noncoding RNAs (lncRNAs) have emerged as a novel class of regulatory molecules with the potential to attenuate pathogenic mechanisms following IS. Among these lncRNAs, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) has been extensively studied due to its involvement in the pathophysiological processes of IS. In this review, we provide an in-depth analysis of the essential role of MALAT1 in the development and progression of both pathogenic and protective mechanisms following IS. These mechanisms include oxidative stress, neuroinflammation, cell death signaling, blood brain barrier dysfunction, and angiogenesis. Furthermore, we summarize the impact of MALAT1 on the susceptibility and severity of IS. This review highlights the potential risks associated with the therapeutic use of MALAT1 for IS, which are attributable to the stimulatory action of MALAT1 on ischemia/reperfusion injury. Ultimately, this review sheds light on the potential molecular mechanisms and associated signaling pathways underlying MALAT1 expression post-IS, with the aim of uncovering potential therapeutic targets.

Parkinson's disease (PD) is a complex neurological disorder characterized by a combination of motor and non-motor symptoms (NMS). Antioxidant and anti-inflammatory compounds are considered a potential therapeutic strategy against PD. The present study examined the neuroprotective effects of anethole as a potent antioxidant and anti-inflammatory agent against motor and non-motor deficits induced by rotenone toxicity. Rats were treated with anethole (62.5, 125, and 250 mg/kg, i.g) concomitantly with rotenone (2 mg/kg, s.c) for 5 weeks. After the treatment, behavioral tests were performed to evaluate motor function and depression-/anxiety-like behaviors. After the behavioral tests, rats were decapitated and brains were removed for histological analysis. Striatum samples were also isolated for neurochemical, and molecular analysis. Our data showed that rotenone-induced motor deficit, anxiety-and depression-like behaviors were significantly improved in rats treated with anethole. Furthermore, anethole treatment reduced inflammatory cytokines tumor necrosis factor α (TNFα) and Interleukin 6 (IL-6), and increased anti-inflammatory cytokine IL-4 in the striatum of rotenone-induced PD rats. Western blot analysis showed that treatment with anethole markedly suppressed caspase-3 activation induced by rotenone. Moreover, histological examination of striatum showed an increase in the number of surviving neurons after treatment with anethole. Anethole also significantly enhanced the striatal levels of dopamine in rotenone-induced PD rats. In addition, treatment with L-Dopa as a positive control group had effects similar to those of anethole on histological, neurochemical, and molecular parameters in rotenone-induced parkinsonian rats. Our results suggested the neuroprotective effects of anethole through anti-inflammatory, anti-apoptotic, and antioxidant mechanisms against rotenone-induced toxicity in rats.

Parkinson's disease (PD) is a common age-related neurodegenerative disorder whose pathogenesis is not completely understood. Mitochondrial dysfunction and increased oxidative stress have been considered as major causes and central events responsible for the progressive degeneration of dopaminergic (DA) neurons in PD. Therefore, investigating mitochondrial disorders plays a role in understanding the pathogenesis of PD and can be an important therapeutic target for this disease. This study discusses the effect of environmental, genetic and biological factors on mitochondrial dysfunction and also focuses on the mitochondrial molecular mechanisms underlying neurodegeneration, and its possible therapeutic targets in PD, including reactive oxygen species generation, calcium overload, inflammasome activation, apoptosis, mitophagy, mitochondrial biogenesis, and mitochondrial dynamics. Other potential therapeutic strategies such as mitochondrial transfer/transplantation, targeting microRNAs, using stem cells, photobiomodulation, diet, and exercise were also discussed in this review, which may provide valuable insights into clinical aspects. A better understanding of the roles of mitochondria in the pathophysiology of PD may provide a rationale for designing novel therapeutic interventions in our fight against PD.

Long non-coding RNAs (lncRNAs) are non-coding RNAs that contain more than 200 nucleotides but do not code for proteins. In tumorigenesis, lncRNAs can have both oncogenic and tumor-suppressive properties. X inactive-specific transcript (XIST) is a known lncRNA that has been implicated in X chromosome silencing in female cells. Dysregulation of XIST is associated with an increased risk of various cancers. Therefore, XIST can be a beneficial prognostic biomarker for human malignancies. In this review, we attempt to summarize the emerging roles of XIST in human cancers.