Publications

To report an autoimmune paraneoplastic encephalitis characterized by immunoglobulin G (IgG) antibody targeting synaptic protein calmodulin kinase-like vesicle-associated (CAMKV).

• Link: https://onlinelibrary.wiley.com/doi/10.1002/ana.26943

Autoantibodies are a common mark of autoimmune reaction and their identification in the patients’ serum, cerebrospinal fluid, or tissues is generally believed to represent diagnostic or prognostic biomarkers of autoimmune diseases or autoinflammatory conditions. Traditionally, autoantibody testing is an important part of the clinical examination of suspected patients, and in the absence of reliable T cell tests, characterization of autoantibody responses might be suitable in finding causes of specific autoimmune responses, their strength, and sometimes commencement of autoimmune disease.

• Link: https://www.dovepress.com/clinical-significance-of-uncommon-non-clinical-and-novel-autoantibodie-peer-reviewed-fulltext-article-ITT

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become an increasingly important health challenge, with a substantial rise linked to changing lifestyles and global obesity. Ursolic acid, a natural pentacyclic triterpenoid, has been explored for its potential therapeutic effects. Given its multifunctional bioactive properties, this research further revealed the pharmacological mechanisms of ursolic acid on MASLD.

• Link: https://www.e-cmh.org/journal/view.php?doi=10.3350/cmh.2024.0047

Endothelial dysfunction induced by oxidative stress is an early predictor of atherosclerosis, which can cause various cardiovascular diseases. The glycocalyx layer on the endothelial cell surface acts as a barrier to maintain endothelial biological function, and it can be impaired by oxidative stress. However, the mechanism of glycocalyx damage during the development of atherosclerosis remains largely unclear. Herein, we established a novel strategy to address these issues from the glycomic perspective that has long been neglected. Using countercharged fluorescence protein staining and quantitative mass spectrometry, we found that heparan sulfate, a major component of the glycocalyx, was structurally altered by oxidative stress.

• Link: https://www.sciencedirect.com/science/article/abs/pii/S0144861724000602?via%3Dihub

P21 activated kinase 6 (PAK6) is a serine-threonine kinase with physiological expression enriched in the brain and overexpressed in a number of human tumors. While the role of PAK6 in cancer cells has been extensively investigated, the physiological function of the kinase in the context of brain cells is poorly understood. Our previous work uncovered a link between PAK6 and the Parkinson’s disease (PD)-associated kinase LRRK2, with PAK6 controlling LRRK2 activity and subcellular localization via phosphorylation of 14-3-3 proteins.

• Link: https://www.biorxiv.org/content/10.1101/2024.04.11.589075v1

Double cortin-like kinase 1 (DCLK1) exhibits high expression levels across various cancers, notably in human colorectal cancer (CRC). Diacerein, a clinically approved interleukin (IL)-1β inhibitor for osteoarthritis treatment, was evaluated for its impact on CRC proliferation and migration, alongside its underlying mechanisms, through both in vitro and in vivo analyses. The study employed MTT assay, colony formation, wound healing, transwell assays, flow cytometry, and Hoechst 33342 staining to assess cell proliferation, migration, and apoptosis.

• Link: https://www.sciencedirect.com/science/article/abs/pii/S1875536424606217?via%3Dihub

Weakly virulent environmental mycobacteria (EM) can cause severe disease in HLA-DRB1*15:02 or 16:02 adults harboring neutralizing anti-IFN-γ autoantibodies (nAIGAs). The overall prevalence of nAIGAs in the general population is unknown, as are the penetrance of nAIGAs in HLA-DRB1*15:02 or 16:02 individuals and the proportion of patients with unexplained, adult-onset EM infections carrying nAIGAs.

• Link: https://www.jci.org/articles/view/178263

Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers in urgent need of effective drugs. Echinatin, a natural compound extracted from Glycyrrhiza plants, exhibited promising anti-tumor effects. However, the efficacy and direct target of Echinatin in cSCC remain unclear.

• Link: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4745961

Immune-checkpoint inhibitors (ICIs) are increasingly used in the treatment of cancer, but they cause immune-related adverse events (irAEs) in around 40% of patients treated. Identifying biomarkers predictive of irAEs has become a priority for the optimal management of patients on ICIs. Herein, we review the state of the art regarding the most relevant biomarkers for predicting irAEs, distinguishing between biomarkers already clinically available and those under investigation. Although none of these biomarkers has been validated in prospective studies, there is growing evidence supporting their use for irAE prediction and clinical characterization, which depend on cancer type, ICI agent and organ affected by the toxicity. A better understanding of the pathogenic mechanisms underlying irAEs and the combination of different emerging biomarkers would allow us to improve the risk-benefit balance for patients who are candidates for ICI therapy.

• Link: https://www.mdpi.com/2072-6694/15/5/1629

We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre–α T cell receptor (pre-TCRα) expression. Low circulating naive αβ T cell counts at birth persisted over time, with normal memory αβ and high γδ T cell counts. Their TCRα repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue αβ T cell development. Only a minority of these individuals were sick, with infection, lymphoproliferation, and/or autoimmunity. We also report that 1 in 4000 individuals from the Middle East and South Asia are homozygous for a common hypomorphic PTCRA variant. They had normal circulating naive αβ T cell counts but high γδ T cell counts. Although residual pre-TCRα expression drove the differentiation of more αβ T cells, autoimmune conditions were more frequent in these patients compared with the general population.

• Link: https://www.science.org/doi/10.1126/science.adh4059#core-collateral-purchase-access