detection-targetable-alterations-non-small-cell-lung-cancer-using

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing

The success of targeted therapy in non-small cell lung cancer (NSCLC) hinges on the precise identification of driver alterations, including mutations, ...

Chinese Academy of Medical Sciences and Peking Union Medical College

Multidrug resistance is the main obstacle in cancer chemotherapy. Emerging evidence demonstrates the important role of autophagy in cancer cell resistance to chemotherapy. Therefore, autophagy inhibition by natural compounds may be a promising strategy for overcoming drug resistance in liver cancer cells. Here, we found that ADCX, a natural cycloartane triterpenoid extracted from the traditional Chinese medicine (TCM) source Cimicifugae rhizoma (Shengma), impaired autophagic degradation by suppressing lysosomal cathepsin B (CTSB) expression in multidrug-resistant liver cancer HepG2/ADM cells, thereby leading to autophagic flux inhibition. Moreover, impairing autophagic flux promoted ADCX-induced apoptotic cell death in HepG2/ADM cells. Interestingly, Akt was overactivated by ADCX treatment, which downregulated CTSB and inhibited autophagic flux. Together, our results provide the first demonstration that an active TCM constituent can overcome multidrug resistance in liver cancer cells via Akt-mediated inhibition of autophagic degradation.

The cycloartane triterpenoid ADCX impairs autophagic degradation through Akt overactivation and promotes apoptotic cell death in multidrug-resistant HepG2/ADM cells.

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are two common subtypes of autoimmune bullous disease (AIBD). The key role of circulating autoreactive immune cells contributing to skin damage of AIBD has been widely recognized. Nevertheless, the immune characteristics in cutaneous lesions remain unclear. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell VDJ sequencing (scRNA-seq) to generate transcriptional profiles for cells and T/B cell clonetype in skin lesions of BP and PV. We found that the proportions of NK&T, macrophages/ dendritic cells, B cells, and mast cells increased in BP and PV lesions. Then, BP and PV cells constituted over 75% of all myeloid cell subtypes, CD4 T cell subtypes and CD8 T cell subtypes. Strikingly, CD8 Trm was identified to be expanded in PV, and located in the intermediate state of the pseudotime trajectory from CD8 Tm to CD8 Tem. Interestingly, CD8 Tem and CD4 Treg highly expressed exhaustion-related genes, especially in BP lesions. Moreover, the enhanced cell communication between stromal cells and immune cells like B cells and macrophages/ dendritic cells was also identified in BP and PV lesions. Finally, clone expansion was observed in T cells of BP and PV compared with HC, while CD8 Trm represented the highest ratio of hyperexpanded TCR clones among all T cell subtypes. Our study generally depicts a large and comprehensive single-cell landscape of cutaneous lesions and highlights immune cell features in BP and PV. This offers potential research targets for further investigation.

Article	Year
The cycloartane triterpenoid ADCX impairs autophagic degradation through Akt overactivation and promotes apoptotic cell death in multidrug-resistant HepG2/ADM cells. Biochemical pharmacology\| PubMed ID: 29074104	2017
Single-cell sequencing reveals distinct immune cell features in cutaneous lesions of pemphigus vulgaris and bullous pemphigoid. Clinical immunology (Orlando, Fla.)\| PubMed ID: 38631594	2024

Nan Yao

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