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The spatiotemporal proteome of the intervertebral disc (IVD) underpins its integrity and function. We present DIPPER, a deep and comprehensive IVD proteomic resource comprising 94 genome-wide profiles from 17 individuals. To begin with, protein modules defining key directional trends spanning the lateral and anteroposterior axes were derived from high-resolution spatial proteomes of intact young cadaveric lumbar IVDs. They revealed novel region-specific profiles of regulatory activities and displayed potential paths of deconstruction in the level- and location-matched aged cadaveric discs. Machine learning methods predicted a 'hydration matrisome' that connects extracellular matrix with MRI intensity. Importantly, the static proteome used as point-references can be integrated with dynamic proteome (SILAC/degradome) and transcriptome data from multiple clinical samples, enhancing robustness and clinical relevance. The data, findings, and methodology, available on a web interface (http://www.sbms.hku.hk/dclab/ DIPPER/), will be valuable references in the field of IVD biology and proteomic analytics. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to determine if adding spironolactone to an angiotensin II receptor blocker improves left ventricular (LV) function, mass, and volumes in chronic heart failure. Background: Add-on spironolactone therapy substantially improves clinical outcomes among patients with severe heart failure (HF) on standard therapy. However, the value of combining spironolactone with an angiotensin II receptor blocker on LV reverse remodeling in mild-to-moderate systolic HF is unclear. Methods: Fifty-one systolic HF patients with left ventricular ejection fraction (LVEF) <40% were randomly assigned to receive 1-year treatment of candesartan and spironolactone (combination group) or candesartan and placebo (control group). Reverse remodeling was assessed by serial cardiac magnetic resonance imaging and echocardiographic tissue Doppler imaging (TDI). Results: There were significant improvements in LVEF (35 ± 3% vs. 26 ± 2%, p < 0.01) and reduction of LV end-diastolic volume index (121 ± 16 ml/m2 vs. 155 ± 14 ml/m2, p = 0.001), end-systolic volume index (88 ± 17 ml/m2 vs. 120 ± 15 ml/m2, p < 0.0005), and LV mass index (81 ± 6 g/m2 vs. 93 ± 6 g/m2, p = 0.002) in the combination group at 1 year. In addition, there was significant increase in peak basal systolic velocity and strain by TDI, decrease in index of filling pressure, and increase in cyclic variation integrated backscatter. In the control group, there were no significant changes in all these parameters after 1 year. Conclusions: The addition of spironolactone to candesartan has significant beneficial effects on LV reverse remodeling in patients with mild-to-moderate chronic systolic HF. [Copyright &y& Elsevier]