Fig 2: Increasing mitochondrial priming enhances NSCLC cell lines sensitivity to conventional chemotherapy.Cell lines (A549, H522, H1975, H3255 and PC9) were exposed to various targeted agents and mitochondrial priming was assessed. In parallel cells were treated to a dose response of chemotherapy ± targeted agent and chemosensitivity was assessed. A Schematic showing the workflow for measuring drug-induced priming using DBP and chemosensitivity using cell viability assay. Created with BioRender.com. B Top heat map shows normalized mitochondrial priming (BIM EC50) for individual targeted agents at indicated concentrations or DMSO-control. Bottom heat map shows normalized chemosensitivity to etoposide or docetaxel plus targeted agent or DMSO-control. C These graphs show the correlation between mitochondrial priming (BIM EC50) Vs. chemosensitivity (etoposide EC50 or docetaxel EC50) for each cell line for various drugs at specific concentrations or DMSO-control (either BIM, etoposide or docetaxel only). Data represents the mean BIM EC50, etoposide EC50 or docetaxel EC50 of three independent experiments ± standard deviation.

Fig 3: miR-19a/19b reduces myocardial infarction-induced inflammation and cell death. a TUNEL staining (red) on transverse sections of adult hearts injected with miR-19a/19b or control mimic 4 days after MI. cTNT marks cardiomyocytes (green) and DAPI marks nuclei (blue). Scale bars = 48 μm. b, c Quantification of TUNEL-positive cardiomyocytes (b) and non-cardiomyocytes (c). n = 4 hearts, 6–14 fields per heart. d qRT-PCR detection of apoptosis gene expression. n = 3–7 hearts. e Western blot analysis of protein levels of PTEN, BIM, cleaved Caspase 3, and BAX in adult hearts. f Quantification of Western blot band density. n = 4 hearts. g Hierarchical clustering of 544 differentially expressed genes between miR-19a/19b and control mimic injected hearts 4 days after MI. Red and blue colors indicate up-regulated or down-regulated genes. h Gene ontology (GO) analysis of 393 down-regulated genes. (i) qRT-PCR analysis of expression of down-regulated genes related to immune response, cell death, and fibrosis. Up-regulated genes were also examined. NPPA serves as a control for cardiomyopathy. n = 3 hearts. j–l Immunohistochemistry analysis of M1 markers, (j) CD80, (k) iNOS, and M2 marker (l) Arg-1 in adult hearts injected with miR-19a/19b or control mimics at 48 and 72 h post MI. n = 4–8 hearts. Scale bars= 50 μm. m qRT-PCR analysis of expression of M1 and M2 marker genes and potential target genes in adult hearts. n = 3–6 hearts. n Western blot analysis of protein levels of SOCS and STAT3 pathways in adult hearts. o Quantification of Western blot band density. n = 3–4 hearts. Statistical significance was calculated using Student’s t-test in b, c, d, f, i, m, and o and data are presented as means ± s.e.m. *p < 0.05, **p < 0.01 vs. control. Source data are provided as a Source Data file

Fig 4: Combination therapy of BTSA1.2 and Navitoclax shows potent efficacy in resistant colorectal tumor xenografts.a Schematic of SW480 xenograft efficacy study. b Body weight measurements of Nu/Nu mice at 0, 7, and last day of treatment with vehicle, 100 mg/kg Navitoclax, 200 mg/kg BTSA1.2 or the combination. c Tumor volume curves of vehicle, Navitoclax, BTSA1.2 or the combination cohorts. d Tumor weight after completing study. Data in b–d, represent from n = 5 mice (Vehicle, BTSA1.2 and Navitoclax) or n = 6 mice (Combination). Statistics were obtained using two-way Anova: *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. e Schematic of SW480 pharmacodynamic xenograft study. f Example of kinetic curve of mitochondria potential in tumors treated with vehicle or combination upon stimuli of BH3-BIM peptide, Puma2A, CCCP or Alamethicin. Data are mean ± SD from n = 3 g, Dynamic BH3-profiling of tumors from mice treated with vehicle or BTSA1.2 and Navitoclax combination. Bar graph represent % of mitochondria depolarization of tumor cells detected by JC-1 upon treatment with BH3-BIM derived peptide or DMSO. Each point corresponds to the mean of n = 3 technical replicates; ± SD from n = 2 independent vehicle mice or n = 3 independent combination mice. Statistics were obtained using two-way Anova: *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. h, i Detection of cleaved Caspase-3 and cleaved PARP apoptotic markers by western blot analysis from SW480 tumors. Relative protein levels were normalized to ß-Actin loading control. Data are mean ± SD from n = 3 mice. Statistics were obtained using two-way Anova: *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. Source data are provided as a Source Data file.

Fig 5: Mst1 is involved in ß-adrenoceptor-mediated YAP phosphorylation and up-regulation of Gal-3 and BIM. Expression of Gal-3 (a, n = 8 per group) and BIM (b, n = 6 per group) in nTG and Mst1-TG hearts. *P < .05, significantly different from nTG. (c) Protein expression of p-YAP, total YAP, and p-YAP/YAP ratio in nTG and Mst1-TG hearts. *P < .05, significantly different from nTG (n = 6 per group). (d) Cardiac expression of Gal-3 in dnMst1-TG and Mst1-TG and respective nTG mice treated with isoprenaline (ISO, 6 mg·kg-1·day-1, 2 days). *P < .05, significantly different from respective CTL; # P < .05, significantly different from nTG + isoprenaline. (e) Absolute changes of Gal-3 content by isoprenaline treatment in nTG, dnMst1-TG, and Mst1-TG mice. *P < .05, significantly different from nTG + isoprenaline (6 mg·kg-1·day-1, 2 days). All data sets in d and e, n = 8 per group. (f) Cardiac expression of BIM in nTG and dnMst1-TG mice treated with isoprenaline (6 mg·kg-1·day-1, 2 days; n = 5 per group). *P < .05, significantly different from respective CTL; # P < .05, significantly different from nTG + isoprenaline. (g) Protein levels of p-YAP and YAP in nTG and dnMst1-TG mice treated with isoprenaline (6 mg·kg-1·day-1, 2 days; n = 5 per group). *P < .05, significantly different from respective CTL; # P < .05, significantly different from nTG + isoprenaline. Data shown are means ± SEM and were compared by two-tailed Student's t test (a–c), one-way (e) or two-way (d, f, g) ANOVA, followed by Bonferroni post hoc test