Harboeheide9221

Parkinsonism is a neurodegenerative disorder that affects elderly people worldwide.

Curcumin, adenosine A2AR antagonist (ZM241385) and Sinemet® (L-dopa) were evaluated against Parkinson's disease (PD) induced by rotenone in rats and comparativelyrelatively compared with our previous study on mice model.

Rats injected with rotenone showed severe alterations in adenosine A2A receptor gene expression, oxidative stress markers, inflammatory mediator, energetic indices, apoptotic marker and DNA fragmentation levels as compare with the control group. Treatments with curcumin, ZM241385, and Sinemet® restored all the selected parameters. The brain histopathological features of cerebellum regions confirmed our results. By comparing our results with the previous results on mice, we noticed that mice respond to rotenone toxicity and treatments more than rats regarding to behavioral observation, A2AR gene expression, neurotransmitter levels, inflammatory mediator and apoptotic markers, while rats showed higher resprevious report on mice explore the response of mice to rotenone toxicity than rats, while rats showed higher response to treatments. Therefore, no animal model can perfectly recapitulate all the pathologies of PD.

The aging process causes physiological changes on its own. The combination of an unhealthy lifestyle with the presence of genetic polymorphisms, such as the Val16Ala of the antioxidant enzyme manganese-dependent superoxide dismutase (MnSOD) may contribute to a greater occurrence of cardiometabolic risk factors.

This study aimed to verify the association of Val16Ala-MnSOD polymorphism with food intake, caloric expenditure, and cardiometabolic risk factors in the elderly.

A cross-sectional study with a sample size of 270 elderly individuals assisted in primary health care in the city of Porto Alegre, RS, Brazil. Val16Ala polymorphism, glucose, lipid profile, insulin, HOMA-IR, blood pressure, waist circumference, PCR-us, IL-6, food consumption, and caloric expenditure were evaluated.

The average age of the elderly was 68.6 ± 7.6 years. There were statistically significant differences regarding the consumption of two or more servings of fruits and vegetables daily between the elderly VV versus AV (P=0.017). There were also statistically significant differences regarding the consumption of two or more daily servings of legumes and eggs between the elderly AA versus VV (P=0.002). The median of insulin was higher in the elderly AA versus AV (P=0.025) and the median of HOMA-IR was higher in the elderly VV versus AV (P=0.029). AA elderly individuals had higher means of high-density lipoprotein (HDL-c) compared to AV (P=0.029).

The results suggest that Val16Ala -MnSOD polymorphism is associated with the consumption of fruits, vegetables, legumes, and eggs, as well as with cardiometabolic risk factors in the elderly.

The results suggest that Val16Ala -MnSOD polymorphism is associated with the consumption of fruits, vegetables, legumes, and eggs, as well as with cardiometabolic risk factors in the elderly.

Methotrexate (MTX) is used potently for a wide range of diseases. However, hepatic intoxication by MTX hinders its clinical use.

The present study was conducted to investigate the diallyl disulfide (DADS) ability to ameliorate MTX-induced hepatotoxicity.

Thirty-two rats were randomly divided into four groups normal control, DADS (50 mg/kg/day, orally), MTX (single i.p. injection of 20 mg/kg) and DADS+MTX. Liver function biomarkers, histopathological examinations, oxidative stress, inflammation, and apoptosis biomarkers were investigated. Besides, an in vitro cytotoxic activity study was conducted to explore the modulatory effects of DADS on MTX cytotoxic activity using Caco-2, MCF-7, and HepG2 cells.

DADS significantly reduced the increased serum activities of ALT, AST, ALP, and LDH. These results were confirmed by the alleviation of liver histopathological changes. P7C3 It restored the decreased GSH content and SOD activity, while significantly decreased MTX-induced elevations in both MDA and NO2- contents. The hepatoprotective effects were mechanistically mediated through the up-regulation of hepatic Nrf-2 and the down-regulation of Keap-1, P38MAPK, and NF-κB expression levels. In addition, an increase in Bcl-2 level with a decrease in the expression of both Bax and caspase-3 was observed. The in vitro study showed that DADS increased MTX anti-tumor efficacy.

DADS potently alleviated MTX-induced hepatotoxicity through the modulation of Keap-1/Nrf-2, P38MAPK/NF-κB and apoptosis signaling pathways and effectively enhanced the MTX cytotoxic effects, which could be promising for further clinical trials.</P>.

.Parkinson's disease is a common neurodegenerative disease affecting the movement and wellbeing of most elderlies. The manifestations of Parkinson's disease often include resting tremor, stiffness, bradykinesia and muscular rigidity. The typical hallmark of Parkinson's disease is the destruction of neurons in the substantia nigra and the presence of Lewy bodies in different compartments of the central nervous system. Due to various limitations to the currently available treatments, immunotherapies have emerged to be the new approach to Parkinson's disease treatment. This approach shows some positive outcomes on the efficacy in removing the aggregated species of alpha-synuclein, which is believed to be one of the causes of Parkinson's disease. In this review, an overview of how alpha-synuclein contributes to Parkinson's disease and the effects of a few new immunotherapeutic treatments, including BIIB054 (cinpanemab), MEDI1341, AFFITOPE and PRX002 (prasinezumab) that are currently under clinical development, will be discussed.AMP-activated protein kinase (AMPK) is a serine/threonine kinase and a driving or deterrent factor in the development of neurodegenerative diseases and dementia. AMPK affects intracellular proteins like the mammalian target of rapamycin (mTOR). Peroxisome proliferator-activated receptor-γ coactivator 1-α (among others) contributes to a wide range of intracellular activities based on its downstream molecules such as energy balancing (ATP synthesis), extracellular inflammation, cell growth, and neuronal cell death (such as apoptosis, necrosis, and necroptosis). Several studies have looked at the dual role of AMPK in neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington disease (HD) but the exact effect of this enzyme on dementia, stroke, and motor neuron dysfunction disorders has not been elucidated yet. In this article, we review current research on the effects of AMPK on the brain to give an overview of the relationship. More specifically, we review the neuroprotective or neurodegenerative effects of AMPK or AMPK activators like metformin, resveratrol, and 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside on neurological diseases and dementia, which exert through the intracellular molecules involved in neuronal survival or death.