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Fulltext Network pharmacology-based approach to elucidate the pharmacologic mechanisms of natural compounds from Dictyostelium discoideum for Alzheimer's disease treatment

Patil N, Dhariwal R, Mohammed A, Wei LS, Jain M

Heliyon, 2024 Apr 30;10(8):e28852.
PMID: 38644825 DOI: 10.1016/j.heliyon.2024.e28852

Alzheimer's disease (AD) is increasingly becoming a major public health concern in our society. While many studies have explored the use of natural polyketides, alkaloids, and other chemical components in AD treatment, there is an urgent need to clarify the concept of multi-target treatment for AD. This study focuses on using network pharmacology approach to elucidate how secondary metabolites from Dictyostelium discoideum affect AD through multi-target or indirect mechanisms. The secondary metabolites produced by D. discoideum during their development were obtained from literature sources and PubChem. Disease targets were selected using GeneCards, DisGeNET, and CTD databases, while compound-based targets were identified through Swiss target prediction and Venn diagrams were used to find intersections between these targets. A network depicting the interplay among disease, drugs, active ingredients, and key target proteins (PPI network) was formed utilizing the STRING (Protein-Protein Interaction Networks Functional Enrichment Analysis) database. To anticipate the function and mechanism of the screened compounds, GO and KEGG enrichment analyses were conducted and visually presented using graphs and bubble charts. After the screening phase, the top interacting targets in the PPI network and the compound with the most active target were chosen for subsequent molecular docking and molecular dynamic simulation studies. This study identified nearly 50 potential targeting genes for each of the screened compounds and revealed multiple signaling pathways. Among these pathways, the inflammatory pathway stood out. COX-2, a receptor associated with neuroinflammation, showed differential expression in various stages of AD, particularly in pyramidal neurons during the early stages of the disease. This increase in COX-2 expression is likely induce by higher levels of IL-1, which is associated with neuritic plaques and microglial cells in AD. Molecular docking investigations demonstrated a strong binding interaction between the terpene compound PQA-11 and the neuroinflammatory receptor COX2, with a substantial binding affinity of -8.4 kcal/mol. Subsequently, a thorough analysis of the docked complex (COX2-PQA11) through Molecular Dynamics Simulation showed lower RMSD, minimal RMSF fluctuations, and a reduced total energy of -291.35 kJ/mol compared to the standard drug. These findings suggest that the therapeutic effect of PQA-11 operates through the inflammatory pathway, laying the groundwork for further in-depth research into the role of secondary metabolites in AD treatment.
Distal Junctional Failure due to Spondylodiscitis in a Patient with Long Posterior Fixation for Ossified Longitudinal Ligament and Ossified Ligamentum Flavum

Subramaniam KAL, Liang TS, Hao PZ, Senan NAF, Amin MZBHM, Jain M

J Orthop Case Rep, 2024 Mar;14(3):141-145.
PMID: 38560322 DOI: 10.13107/jocr.2024.v14.i03.4320

INTRODUCTION: Distal junctional failure (DJF) is underreported when compared to proximal junctional failure. DJF arising due to spondylodiscitis has never been reported in the literature.
CASE REPORT: A 45-year-old lady with a body mass index of 33 presented with a long-standing inability to walk due to myelopathy secondary to continuous ossified posterior longitudinal ligament and ossified ligamentum flavum. Posterior fusion and laminectomy were done from D2 to L2. She had an initial wound breakdown with a surgical site infection, but after 6 weeks, she developed spondylodiscitis at the distal instrumented vertebra, leading to DJF. She was started on appropriate antibiotics and an extension of fusion.
CONCLUSION: This report demonstrates and discusses the management of a rare case of DJF arising due to spondylodiscitis of the last instrumented vertebra.
Fulltext A systematic review of the prevalence of Morquio A syndrome: challenges for study reporting in rare diseases

Leadley RM, Lang S, Misso K, Bekkering T, Ross J, Akiyama T, et al.

Orphanet J Rare Dis, 2014;9:173.
PMID: 25404155 DOI: 10.1186/s13023-014-0173-x

Morquio A (MPS IVA) is a rare disease characterised by a deficiency of N-acetylgalactosamine-6 sulfatase (GALNS) and presenting with short stature, abnormal gait, cervical spine instability and shortened lifespan.

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