👤 Sameh Saber

Neuroinflammation appears in a variety of neurological disorders, including multiple sclerosis (MS), Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis. The adenosine A₂A receptor (A₂AR), a Gs protein-coupled receptor that affects cAMP signaling and downstream kinases like PKA, CREB, and NF-κB, is one of the primary regulators of this process. Context-dependent effects of A₂AR activation include lowering acute inflammation and promoting neuronal survival when stimulated moderately, but increasing glial activation and cytokine production when overexpressed over an extended period of time. In microglia and astrocytes, A₂AR signaling regulates inflammatory pathways mediated by NF-κB and MAPK, affecting oxidative stress, blood-brain barrier (BBB) stability, and excitotoxicity. Acute or transient (short-term) A₂AR activation, on the other hand, increases the production of anti-inflammatory cytokines like IL-10 and enhances neurotrophic support through BDNF. A₂AR antagonists, including istradefylline and SCH58261, may reduce microglial triggering and have neuroprotective benefits, according to clinical and experimental data. The context-dependent activity of the receptor is shown by the fact that total receptor blockage interferes with adaptive immune control. Therefore, the therapeutic challenge is to carefully modify A₂AR signaling in particular cell populations, specifically targeting astrocytic or microglial receptors while maintaining the peripheral immunoregulatory activities. The dual regulatory role of A₂AR in neuroinflammation is summarized in this review along with its molecular mechanisms, disease-specific actions, and therapeutic significance. Developing next-generation neuroprotective strategies that reduce A₂AR signaling's pro-inflammatory and neurotoxic effects while preserving its beneficial homeostatic effects will require an understanding of the temporal and cell-specific dynamics of this signaling. Show less

Ketosis is one of the most important metabolic disorders occurring in dairy cows after calving, which is caused by a negative energy balance during the peripartum period or around parturition. The current study focused on the diagnostic significance of the clinical scoring system, with serum lipid profiles, mainly lecithin cholesterol acyltransferase (LCAT) and apolipoprotein B-100 (ApoB-100), as recovery indicators in ketotic dairy cattle using the hormonal-steroids-carbohydrate therapeutic protocol. The study also discussed the correlation coefficient between serum apo-B100 and serum non-esterified fatty acids (NEFAs) in pretreated and post-treated ketotic cattle. In this study, 50 ketotic cattle from various dairy farms. The ketotic cows were subjected to a hormonal-steroids-carbohydrate therapeutic regimen extended for a continuous 5 days, including mainly insulin, dexamethasone, and carbohydrate replacement therapy (Glucose solution 50% alternative with dextrose solution 50%) with drenching of propylene glycol. and vitamin B The ketotic dairy cattle needed a maximum 30-day follow-up period post-therapy to restore their physiological status for clinical scoring data (7 days needed) and most serum lipid indices [14 days needed, i.e., apoB-100, β-hydroxy butyric acid, NEFA, glucose, cholesterol, and AST]. A 30-day post-therapy as a follow-up period was urgently required to restore their reference values of serum LCAT. The results of this study indicated that serum LCAT activity and ApoB-100 were the most sensitive indicators of the efficacy of therapy and the restoration of the physiological status. The study revealed a significant negative correlation between serum NEFA and apoB-100 in ketotic cattle. The results of this study indicated that serum LCAT activity and ApoB-100 were the most sensitive indicators of the efficacy of therapy and the restoration of the physiological status. This could be seen by an obvious improvement in serum lipid profiles, mainly LCAT and apoB-100, and clinical findings as well as clinical coring data. The study identified a significant negative correlation between NEFA and apoB-100 in ketotic cattle. Exposure of diseased ketotic dairy cattle to this specific therapeutic strategy had a great impact on their recovery from ketosis and improved their health and productivity status. The current study concluded the diagnostic significance of the clinical scoring system (Appetite score, rumen filling score, manure digestion score, and manure condition score), and serum lipid profiles, mainly LCAT and apoB-100, as recovery indicators in ketotic dairy cattle using hormonal-steroids-carbohydrates therapeutic protocol. Show less

Hereditary multiple osteochondromas (HMO), previously named hereditary multiple exostoses (HME), is an autosomal dominant skeletal disorder characterized by the growth of multiple osteochondromas and is associated with bony deformity, skeletal growth reduction, nerve compression, restriction of joint motion, and premature osteoarthrosis. HMO is genetically heterogeneous, localized on at least three chromosomal loci including 8q24.1 ( This study was performed on an Iranian family with nine affected individuals from three consecutive generations. Here, the proband was an affected woman who received genetic counseling prior to pregnancy. All exons of the three genes were examined in the proband using polymerase chain reaction and sequencing methods (the last member of this family is a male with severe deformities and lesions, especially around his large joints). Exon 4 of The outcome of this study has extended the genotypic spectrum of Iranian patients with HMO, revealing a way for improving detection and genetic counseling in carriers. Show less