Tacedinaline

J-Lat cells are derivatives of the Jurkat CD4⁺ T cell line that contain a non-infectious, inducible HIV provirus with a GFP tag. While these cells have substantially advanced our understanding of HIV latency, their use by many laboratories in low and middle-income countries is restricted by limited access to flow cytometry. To overcome this barrier, we describe a modified J-Lat assay using a standard microplate reader that detects HIV-GFP expression following treatment with latency-reversing agents (LRAs). We show that HIV reactivation by control LRAs like prostratin and romidepsin is readily detected with dose dependence and with significant correlation and sensitivity to standard flow cytometry. For example, 10 μM prostratin induced a 20.1 ± 3.3-fold increase in GFP fluorescence in the microplate reader assay, which corresponded to 64.2 ± 5.0% GFP-positive cells detected by flow cytometery. Similarly, 0.3 μM prostratin induced a 1.7 ± 1.2-fold increase compared to 8.7 ± 5.7% GFP-positive cells detected. Using this method, we screen 79 epigenetic modifiers and identify CUDC-101, molibresib, and quisinostat as novel LRAs. This microplate reader-based method offers accessibility to researchers in resource-limited regions to work with J-Lat cells and more actively participate in global HIV cure research efforts.

Gastric cancer remains a common malignancy with poor prognosis. While lactate metabolism is recognized as a significant factor in tumor progression, its potential as a predictive tool for treatment response remains unexplored. This study introduces a novel Lactate-Related Gene Signature (LRGS) designed to predict both survival outcomes and therapy responses in gastric cancer patients.

We comprehensively analyzed 335 lactate-related genes from 11 metabolic pathways using MSigDB, identifying 278 differentially expressed genes between gastric cancer and normal tissues. Employing the LASSO Cox regression model, we developed an innovative LRGS formula based on the expression of 16 key lactate-related genes. The impact of Solute Carrier Family 5 Member 12 (SLC5A12), a gene of particular interest, on gastric cancer cell functions was evaluated using in vitro assays and an in vivo zebrafish model.

Our newly established LRGS demonstrated robust capability in stratifying gastric cancer patients by survival risk. Notably, the LRGS-low subtype showed significantly improved overall and disease-free survival rates compared to the LRGS-high subtype. A key finding was LRGS's ability to predict patient responses to both adjuvant chemotherapy and immunotherapy. Random forest analysis identified SLC5A12 as the most significant gene differentiating gastric cancer from normal tissues. Functional experiments confirmed SLC5A12's role in promoting gastric cancer cell proliferation, invasion, and migration both in vitro and in vivo.

The LRGS is a dependable and efficient prognostic tool for assessing the survival outcomes in individuals with gastric cancer, as well as a predictor of patient response to adjuvant chemotherapy and immunotherapy.