Role of uric acid in neurodegenerative diseases, focusing on Alzheimer and Parkinson disease: A new perspective.

Neurodegenerative diseases (NDs) such as Alzheimer disease (AD) and Parkinson disease (PD) are group of diseases affecting the central nervous system (CNS) characterized by progressive neurodegenerations and cognitive impairment. Findings from different studies highlighted the beneficial and detrimental effects of serum uric acid on the development and progression of NDs. Therefore, this mini-review aims to discuss the beneficial and detrimental effects of uric on NDs. The neuroprotective effect of uric acid is mainly related to the antioxidant effect of uric acid which alleviates oxidative stress-induced neurodegeneration in AD and PD. However, long-term effect of hyperuricemia prompts for the development and progression of cognitive impairment. Hyperuricemia is associated with cognitive impairment and dementia, and gout increases dementia risk. In addition, hyperuricemia can cause cerebral vascular injury which is a risk factor for vascular dementia and cognitive impairment. Taken together, the relationship between uric acid and NDs risk remains conflicting. Hence, preclinical and clinical studies are indicated in this regard.

Cyclin-dependent kinase 5 (CDK5) inhibitors in Parkinson disease.

Cyclin-dependent kinase 5 (Cdk5) is a protein expressed in postmitotic neurons in the central nervous system (CNS). Cdk5 is activated by p35 and p39 which are neuron regulatory subunits. Cdk5/p35 complex is activated by calpain protease to form Cdk5/p35 which has a neuroprotective effect by regulating the synaptic plasticity and memory functions. However, exaggerated Cdk5 is implicated in different types of neurodegenerative diseases including Parkinson disease (PD). Therefore, modulation of Cdk5 signalling may mitigate PD neuropathology. Therefore, the aim of the present review was to discuss the critical role of Cdk5 in the pathogenesis of PD, and how Cdk5 inhibitors are effectual in the management of PD. In conclusion, overactivated Cdk5 is involved the development of neurodegeneration, and Cdk5/calpain inhibitors such as statins, metformin, fenofibrates and rosiglitazone can attenuate the progression of PD neuropathology.

Anti-nociceptive and Anti-inflammatory Activities of Visnagin in Different Nociceptive and Inflammatory Mice Models.

Pain management has been a severe public health issue throughout the world. Acute pain if not treated at the appropriate time can lead to chronic pain that can cause psychological and social distress. Nothing can be more rewarding than treating pain successfully for a physician. However, the use of chemical NSAIDs and opiate drugs has taken a toll on the patients with their unavoidable side effects. This study intends to explore the potential to treat pain by inhibiting nociception and inflammation with a safer, non-addictive, effective, and low-cost alternative agent from a natural source, visnagin. In vivo studies have been conducted using male Swiss albino mice as models for this research. Nociception was induced using different chemical and thermal stimuli such as acetic acid, glutamate, capsaicin, and formalin. To check for the anti-inflammatory properties, carrageenan was used to induce inflammation and the activity was assayed using peritoneal cavity leukocyte infiltration analysis and pro-inflammatory cytokine level comparison with the supplementation of visnagin at three different dosages. The findings of this study revealed that the visnagin treatment effectively attenuated the acetic acid-induced writhing response, glutamate-induced paw licking numbers, capsaicin-induced pain response, and formalin-induced biphasic licking incidences in the experimental mice models. Furthermore, the visnagin treatment remarkably suppressed the carrageenan-induced inflammation in mice, which is evident from the decreased leukocytes, mononuclear, and polymorphonuclear cell numbers in the mice. The levels of cytokines such as TNF-α, IL-1ß, and IL-6 were effectively reduced by the visnagin treatment in the experimental mice. The results of open field test proved that the visnagin showed a better locomotor movement in the experimental mice. These results provided evidence for the potential activity of the visnagin against inflammatory and nociceptive responses in the mice.

Development and validation of a new UPLC-MS/MS method for quantification of ganoderic acid-A loaded nanolipidic carrier in rat plasma and application to pharmacokinetic studies.

A systematic methodology was used to quantify ganoderic acid-A (GA-A) loaded nano-lipid carriers (NLC) in rat plasma using UPLC-MS/MS. Separation of the analyte was achieved using ACQUITY UPLC BEH C18 column (1.7 µm) and mobile phase as water containing 0.1% Acetonitrile (40: 60% v/v) at a flow rate of 0.4 mL·min-1. The analyte was detected using MRM mode to track precursor-to-product ion transitions of 515.37 â†’ 285.31 m/z (time scan of 2 min) for GA-A, and 175.11 â†’ 115.08 m/z (time scan of 4 min) for ascorbic acid as an internal standard (IS), respectively. The developed method was validated for linearity, accuracy, within and between day precisions, limit of quantification and recovery of the analyte. The results indicated intra and inter-day consistency and precision values were found to be within the acceptance limit for the plasma samples. The method applicability for determination of pharmacokinetic parameters of GA-A was assessed after oral administration of free GA-A solution and GA-A-loaded NLC, which indicated significant difference (p < 0.05) in the rate and extent of absorption parameters of GA-A from the NLC formulation vis-à-vis the plain solution. Overall, the studies construed successful development and application of UPLC-MS/MS method for estimation of GA-A in the lipidic formulation.

Nanotherapeutic systems for delivering cancer vaccines: recent advances.

With an increase in the global burden of cancer-related deaths, the quest for developing new therapeutic solutions has taken momentum. In this regard, the idea of using cancer vaccines came to existence approximately 30 years ago, where gene therapy interventions have shown significant improvement in the therapeutic outcomes against several types of cancers. Cancer vaccines usually encounter a number of challenges with limited targeting ability to the tumors. Nanocarriers have been studied as a technological innovation for tumor targeting of gene therapeutics. This article provides a critical insight into the recent progress made in nanotherapeutic strategies for genetic vaccine delivery for treatment against various types of cancers. Moreover, the article intends to provide a summary of the research work being done on this topic.

Epidemiologic Pattern and Types of Oral Smokeless Tobacco Usage in Saudi Arabia.

Aim: Smokeless tobacco (ST) use is a significant health risk and cause of disease. Most studies conducted in the Kingdom of Saudi Arabia (KSA) focused on cigarette smoking. Therefore, the objective was to study the epidemiologic pattern and types of oral ST usage in northern and western Saudi Arabia. Materials and methods: A total of 428 volunteers living in three cities (Hail, Mecca, and Tabuk) were investigated. All of the study subjects were currently ST users of one type or more, including toombak, shammah, pan masala (PM), Afdhal, Nashooq, and others. Results: Most of the study population were found to use toombak representing 127/428 (29.7%), followed by shammah, PM, Afdhal, Nashooq, Adani, Qat, Majun, and others, representing 67/428 (15.7%), 66/428 (15.4%), 44/428 (10.3%), 36/428 (8.4%), 32/428 (7.5%), 23/428 (5.4%), 22/428 (5.1%), 21/428 (4.9%), and 13/428 (3%) respectively. Conclusion: This survey showed a high prevalence of existing ST usage among foreign workers and Saudis, which can establish a prospective public health problem. Clinical significance: Smokeless tobacco cessation is a crucial element of tobacco control policy since it is the most important determinant of many diseases, including oral cancer. Keywords: Kingdom of Saudi Arabia, Oral cancer, Pan masala, Shammah, Smokeless tobacco, Toombak.