Novel Variants Linked to the Prodromal Stage of Parkinson's Disease (PD) Patients.

BACKGROUND AND OBJECTIVE: The symptoms of most neurodegenerative diseases, including Parkinson's disease (PD), usually do not occur until substantial neuronal loss occurs. This makes the process of early diagnosis very challenging. Hence, this research used variant call format (VCF) analysis to detect variants and novel genes that could be used as prognostic indicators in the early diagnosis of prodromal PD. MATERIALS AND METHODS: Data were obtained from the Parkinson's Progression Markers Initiative (PPMI), and we analyzed prodromal patients with gVCF data collected in the 2021 cohort. A total of 304 participants were included, including 100 healthy controls, 146 prodromal genetic individuals, 21 prodromal hyposmia individuals, and 37 prodromal individuals with RBD. A pipeline was developed to process the samples from gVCF to reach variant annotation and pathway and disease association analysis. RESULTS: Novel variant percentages were detected in the analyzed prodromal subgroups. The prodromal subgroup analysis revealed novel variations of 1.0%, 1.2%, 0.6%, 0.3%, 0.5%, and 0.4% for the genetic male, genetic female, hyposmia male, hyposmia female, RBD male, and RBD female groups, respectively. Interestingly, 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300, and PPP6R2) that were recently detected in PD patients were detected in the prodromal stage of PD. CONCLUSIONS: Genetic biomarkers are crucial for the early detection of Parkinson's disease and its prodromal stage. The novel PD genes detected in prodromal patients could aid in the use of gene biomarkers for early diagnosis of the prodromal stage without relying only on phenotypic traits.

Androstenedione (a Natural Steroid and a Drug Supplement): A Comprehensive Review of Its Consumption, Metabolism, Health Effects, and Toxicity with Sex Differences.

Androstenedione is a steroidal hormone produced in male and female gonads, as well as in the adrenal glands, and it is known for its key role in the production of estrogen and testosterone. Androstenedione is also sold as an oral supplement, that is being utilized to increase testosterone levels. Simply known as "andro" by athletes, it is commonly touted as a natural alternative to anabolic steroids. By boosting testosterone levels, it is thought to be an enhancer for athletic performance, build body muscles, reduce fats, increase energy, maintain healthy RBCs, and increase sexual performance. Nevertheless, several of these effects are not yet scientifically proven. Though commonly used as a supplement for body building, it is listed among performance-enhancing drugs (PEDs) which is banned by the World Anti-Doping Agency, as well as the International Olympic Committee. This review focuses on the action mechanism behind androstenedione's health effects, and further side effects including clinical features, populations at risk, pharmacokinetics, metabolism, and toxicokinetics. A review of androstenedione regulation in drug doping is also presented.

Valorization and extraction optimization of Citrus seeds for food and functional food applications.

Valorization of food byproducts has attracted recently considerable attention. Citrus fruits provide considerable non-edible residues reach 80% in juice production. They are considered agri-wastes to comprise peel, pulp and seeds. Previous investigations have focused on peel and pulp to recover value-added products. The review presents for the first-time phytochemical composition of Citrus seeds' products, i.e., oil and extracts. Fatty acids, phytosterols and tocopherols amounted as the major bioactives in Citrus seeds, in addition to limonoids, dietary fibers and flavonoids. Besides their nutritional values, these chemicals have promising applications including production of biodiesel, food enhancers and antioxidants, especially from mandarin and grapefruit seeds. Optimum conditions of the different Citrus seeds' valorization are discussed to improve extraction yield and lessen environmental hazards of solvent extraction. This review presents the best utilization practices for one of the largest cultivated fruit seeds worldwide and its different applications.

Metabolome-based profiling of African baobab fruit (Adansonia digitata L.) using a multiplex approach of MS and NMR techniques in relation to its biological activity.

Adansonia digitata L. also known as African baobab is one of the most important fruit-producing trees, widely distributed in the African continent. Baobab fruits are known to possess potential health benefits and nutritional value. This study aimed to holistically dissect the metabolome of A. digitata fruits using a novel comparative protocol using three different analytical platforms. Ultra high performance liquid chromatography coupled to high-resolution tandem mass spectrometry (UHPLC-HRMS/MS), and headspace solid-phase microextraction/gas chromatography coupled to mass spectrometry (HS-SPME/GC-MS) were respectively employed for phytonutrients and aroma profiling, whereas GC-MS post silylation provided an overview of nutrients i.e., sugars. UHPLC-HRMS/MS analysis allowed for the assignment of 77 metabolites, among which 50% are reported for the first time in the fruit. While GC-MS of silylated and aroma compounds led to the identification of 74 and 16 compounds, respectively. Finally, NMR-based metabolite fingerprinting permitted the quantification of the major metabolites for future standardization. In parallel, in vivo antidiabetic potential of the baobab fruit using a streptozotocin (STZ) induced diabetic rat model was assessed. Histopathological and immune-histochemical investigations revealed hepatoprotective and renoprotective effects of A. digitata fruit along with mitigation against diabetes complications. Moreover, the administration of A. digitata fruits (150 mg kg-1) twice a week lowered fasting blood glucose levels.

Effects of Turmeric (Curcuma longa) Extract in streptozocin-induced diabetic model.

Herbal remedies have been used for centuries to ameliorate complications of diabetes mellitus (DM). The aim of this study is to compare the effects of the oral curcumin supplement versus parenteral administration of turmeric extract on diabetic complications in a streptozocin (STZ) diabetic model. STZ DM rats received low and high doses turmeric extract intraperitoneally as well as oral curcumin. Curcumin and turmeric extracts significantly reduced blood glucose and creatinine levels, but not urea, and caused an increase in uric acid. Low dose improved liver enzymes, while higher dose and oral administration caused an increase in the ALT and AST. All groups showed an improvement in the serum cholesterol, while the triglycerides were not improved in the high and oral treatment. Histological evaluation showed islet cell protection. High-dose injection showed almost intact renal corpuscles as well as tubular structures with minimal degeneration. Treatment showed limited protection of Liver tissue. PRACTICAL APPLICATION: Curcumin has been heavily marketed as a protective agent. The current study shows some potential risk of curcumin use. Oral and injectable curcumin should be used with caution. Turmeric extract and oral curcumin supplement showed protective effects on pancreatic, and renal structure and function. Although both did show some improvement in liver function, higher doses caused disturbance in liver enzymes and did not show histological evidence of liver tissue protection.