The purpose of this study is to build a biological age (BA) equation combining telomere length with chronological age (CA) and associated aging biomarkers. In total, 139 healthy volunteers were recruited from a Chinese Han cohort in Beijing. A genetic index, renal function indices, cardiovascular function indices, brain function indices, and oxidative stress and inflammation indices (C-reactive protein [CRP]) were measured and analyzed. A BA equation was proposed based on selected parameters, with terminal telomere restriction fragment (TRF) and CA as the two principal components. The selected aging markers included mitral annulus peak E anterior wall (MVEA), intima-media thickness (IMT), cystatin C (CYSC), D-dimer (DD), and digital symbol test (DST). The BA equation was: BA = −2.281TRF + 26.321CYSC + 0.025DD − 104.419MVEA + 34.863IMT − 0.265DST + 0.305CA + 26.346. To conclude, telomere length and CA as double benchmarks may be a new method to build a BA.
Several genetic and lifestyle indicators were considered as candidate markers of aging. However, ultimately, only markers reflecting the function of the vital organs were included in the BA formula. This study represents a useful attempt to employ multiple indicators to build a comprehensive BA evaluation formula of aging populations.
The cell-surface protein B cell maturation antigen (BCMA, CD269) has emerged as a promising target for CAR-T cell therapy for multiple myeloma. In order to create a novel BCMA CAR, we generated a new BCMA monoclonal antibody, clone 4C8A. This antibody exhibited strong and selective binding to human BCMA. BCMA CAR-T cells containing the 4C8A scFv were readily detected with recombinant BCMA protein by flow cytometry. The cells were cytolytic for RPMI8226, H929, and MM1S multiple myeloma cells and secreted high levels of IFN-γ in vitro. BCMA-dependent cytotoxicity and IFN-γ secretion were also observed in response to CHO (Chinese Hamster Ovary)-BCMA cells but not to parental CHO cells. In a mouse subcutaneous tumor model, BCMA CAR-T cells significantly blocked RPMI8226 tumor formation. When BCMA CAR-T cells were given to mice with established RPMI8226 tumors, the tumors experienced significant shrinkage due to CAR-T cell activity and tumor cell apoptosis. The same effect was observed with 3 humanized BCMA-CAR-T cells in vivo. These data indicate that novel CAR-T cells utilizing the BCMA 4C8A scFv are effective against multiple myeloma and warrant future clinical development.
BackgroundRenal cell carcinoma (RCC) is a common cancer, accounting for about 2–3% of all adult cancers. A novel diagnostic biomarker and therapeutic target is urgently needed. However, the function of miR-451 in RCC remains unknown. Here, we explored the role of miR-451 in RCC.Material/MethodsMiR-451 levels in RCC tissues and cells were tested by qRT-PCR. Cells were transfected miR-451 mimics or miR-451 ASO by Lipofectamine. The cellular proliferation was tested by MTT analysis. The apoptosis rate was revealed by FACS. Bioinformatics algorithms from TargetScanHuman were used to predict the target genes of miR-451. The PSMB8 protein level was tested by Western blot. The interaction between miR-451 and PSMB8 was confirmed by dual luciferase assays.ResultsMiR-451 level of RCC tissues was lower than in normal tissues, which was correlated to the patients’ survival rate. Low levels of miR-451 in RCC cells promoted the growth of cells and inhibited cells apoptosis and vice versa. The targeted gene of miR-451 is PSMB8.ConclusionsMiR-451 acts as an anti-oncogene in RCC. Our data offer a new therapeutic target for further research.
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