Journal: bioRxiv

Article Title: Lysosomal Ion Homeostasis Drives Delayed Hair Cell Death After Aminoglycoside Uptake

doi: 10.64898/2026.06.10.731244

Figure Lengend Snippet: A) WT larvae were incubated with specific agonists for 1h, then washed, and exposed to 50µM of a mixture of equal parts of G418-Bodipy and G418-pHrodo green for 1h before imaging. Representative images show G418-Bodipy (magenta) localizing to a large extent of vesicles in multiple hair cells, whereas high intensity G418-pHrodo green signal localizes in discrete regions of NM (Merge). Only TPC2-A1-N generates a lower pHrodo green fluorescence intensity. Dotted line delineates all hair cells in the NM. Scale bar: 10μm. B) Using G418-Bodipy fluorescent signal vesicles were segmented. Normalizing mean intensity by the volume of vesicles, integrated density was calculated on both channels, and mean vesicular ratiometric values were calculated. Each dot corresponds to a NM (average vesicle values), 3 NM per larva. 1h Pre-exposure to TPC2-A1-N neutralizes pH in G418-containing vesicles. Non-param. One-way ANOVA. C) Ratiometric values were calculates as previously described. 1h Pre-exposure to TPC2-A1-P doesn’t affect vesicular pH. Stats: Kruskal-Wallis One-way ANOVA, with Dunn’s multiple comparison test.

Article Snippet: To test the TPC2 agonist TPC2-A1-N (Sigma-Aldrich, SML3562) and TPC2-A1-P (MedChemExpress, SML3700) compounds, larvae were preincubated for 1h in 3μM TPC2-A1-N and 10μM TPC2-A1-P, respectively.

Techniques: Incubation, Imaging, Fluorescence, Comparison

Journal: Acta pharmacologica Sinica

Article Title: Tetrandrine augments melanoma cell immunogenicity via dual inhibition of autophagic flux and proteasomal activity enhancing MHC-I presentation.

doi: 10.1038/s41401-025-01507-9

Figure Lengend Snippet: Fig. 8 Mechanistic illustration of tetrandrine-mediated enhance- ment of melanoma cell recognition and killing by CD8+ T cells through the inhibition of autophagy and proteasomal activity. The diagram illustrates how MHC-I molecules in melanoma cells can be degraded through both autophagy and proteasomal pathways, leading to a reduction in surface MHC-I molecules and facilitating immune escape of the melanoma cells. Tetrandrine disrupts this degradation process by concurrently inhibiting late- stage autophagic flux, through lysosomal acidification disrup- tion, and suppressing proteasomal activity. This dual inhibition prevents MHC-I degradation, thereby increasing MHC-I-mediated antigen presentation on the surface of melanoma cells. The elevated antigen presentation enhances CD8+ T cell recognition and cytotoxicity against melanoma cells. Further mechanistic exploration revealed that tetrandrine exerts its effects by blocking the lysosomal calcium efflux channel TPC2, leading to elevated lysosomal calcium levels and reduced cytosolic calcium concentrations. This calcium imbalance inhibits lysosomal acidification and suppresses cytoplasmic proteasomal activity, collectively contributing to reduced MHC-I degradation. The schematic emphasizes tetrandrine’s pivotal role in modulating both autophagic and proteasomal pathways, ultimately enhan- cing the immunogenicity of melanoma cells and increasing their susceptibility to CD8+ T cell-mediated cytotoxicity. Tet tetrandrine.

Article Snippet: The TPC2 agonist TPC2-A1-N (Cat. No. HY-131614) was obtained from MedChemExpress (Monmouth, NJ, USA).

Techniques: Inhibition, Activity Assay, Immunopeptidomics, Blocking Assay