Abstract Background Psoriatic arthritis (PSA) is a chronic, immune-mediated inflammatory joint disease that is liked to mortality due to cardiovascular disease. Diagnostic markers and effective therapeutic options for PSA remain limited due to the lack of understanding of the pathogenesis. We aimed to identify potential diagnostic markers and screen the therapeutic compounds for PSA based on bioinformatics analysis. Methods Differentially expressed genes (DEGs) of PSA were identified from the GSE61281 dataset. WGCNA was used to identify PSA-related modules and prognostic biomarkers. Clinical samples were collected to validate the expression of the diagnostic gene. These DEGs were subjected to the CMap database for the identification of therapeutic candidates for PSA. Potential pathways and targets for drug candidates to treat PSA were predicted using Network Pharmacology. Molecular docking techniques were used to validate key targets. Results CLEC2B was identified as a diagnostic marker for PSA patients (AUC &gt; 0.8) and was significantly upregulated in blood samples. In addition, celastrol was identified as a candidate drug for PSA. Subsequently, the network pharmacology approach identified four core targets (IL6, TNF, GAPDH, and AKT1) of celastrol and revealed that celastrol could treat PSA by modulating inflammatory-related pathways. Finally, molecular docking demonstrated stable binding of celastrol to four core targets in the treatment of PSA. Animal experiments indicated celastrol alleviated inflammatory response in the mannan-induced PSA. Conclusion CLEC2B was a diagnostic marker for PSA patients. Celastrol was identified as a potential therapeutic drug for PSA via regulating immunity and inflammation. 

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Discovery of CLEC2B as a diagnostic biomarker and screening of celastrol as a candidate drug for psoriatic arthritis through bioinformatics analysis

Neuroblastoma is a pediatric cancer of neural crest cells. It develops most frequently in nerve cells around the adrenal gland, although other locations are possible. Neuroblastomas rely on glycolysis as a source of energy and metabolites, and the enzymes that catalyze glycolysis are potential therapeutic targets for neuroblastoma. Furthermore, glycolysis provides a protective function against DNA damage, and there is evidence that glycolysis inhibitors may improve outcomes from other cancer treatments. This mini-review will focus on glyceraldehyde 3-phosphate dehydrogenase (GAPDH), one of the central enzymes in glycolysis. GAPDH has a key role in metabolism, catalyzing the sixth step in glycolysis and generating NADH. GAPDH also has a surprisingly diverse number of localizations, including the nucleus, where it performs multiple functions, and the plasma membrane. One membrane-associated function of GAPDH is stimulating glucose uptake, consistent with a role for GAPDH in energy and metabolite production. The plasma membrane localization of GAPDH and its role in glucose uptake have been verified in neuroblastoma. Membrane-associated GAPDH also participates in iron uptake, although this has not been tested in neuroblastoma. Finally, GAPDH activates autophagy through a nuclear complex with Sirtuin. This review will discuss these activities and their potential role in cancer metabolism, treatment and drug resistance.

/pdf/gapdh-in-neuroblastoma-functions-in-metabolism-and-survival-3ikaoi1z.pdf

Olivia Back

Papers

GAPDH in neuroblastoma: Functions in metabolism and survival