In this study, a projection of effective blood concentration (EBC) readings of digoxin is made using the inverse problem algorithm based on clinical data for patients with heart failure diseases. Seven factors, including body surface area (BSA), blood urine nitrogen (BUN), creatinine, sodium (Na), potassium (K), magnesium (Mg) ion readings, and mean arterial pressure (MAP) were compiled with nonlinear regression fit to develop a projection function having 29 terms obtained from an inverse problem algorithm via the default function run in STATISTICA. Accordingly, data collected from the clinical 168 heart failure patients were normalized to be included in same domain range ([Formula: see text]1 to +1), and then calculated by the specific algorithm to optimize the numerical solution to evaluate EBC readings of digoxin. The evaluated first-order regression fit owned an optimal loss function ([Formula: see text]) coupled with correlation coefficient [Formula: see text] = 0.892 and variance of 89.20%. Furthermore, 45 patients having similar clinical syndromes were also adopted to verify the projection and implied with high agreement. The BUN factor dominated the projection and defined as the most significant coefficient in the analysis, and K ion, MAP, BSA, and Mg ion factors exhibited minor contributions to the projection. The repeated trials to lower number of factors from seven to a smaller number (namely 6, 5, 4, 3, 2, and 1) for simplifying method but resulting with unaccepted outcomes, with high loss function values and low linearity. However, the algorithm held its accuracy to handle the verified data that were out of the original bounds. The proposed algorithm demonstrated a useful analysis to handle the drug administration in pharmaceutical field.

Context Protocatechuic aldehyde (PCA) is a natural product that has various benefits for fibrosis. Objective This study evaluated the effects of PCA on renal fibrosis. Materials and methods Epithelial–mesenchymal transition (EMT) was induced by 20 ng/mL transforming growth factor-β1 (TGF-β1), followed by treatment with 1 and 5 μM PCA, in the rat renal proximal tubular cell line NRK-52E. Cell viability, protein expression, and scratch wound-healing assays were conducted. Sprague–Dawley (SD) rats underwent unilateral ureteral obstruction (UUO) surgery for renal fibrosis indication and were treated with 50 and 100 mg/kg PCA for 14 days. Results The IC 50 of PCA was appropriately 13.75 ± 1.91 μM in NRK-52E cells, and no significant difference at concentrations less than 5 μM. PCA ameliorated TGF-β1-induced EMT, such as enhanced E-cadherin and decreased vimentin. Fibrotic markers collagen IV and α-smooth muscle actin (α-SMA) increased in TGF-β1-induced NRK-52E. Moreover, PCA reduced TGF-β1-induced migration in the wound-healing assay. Analysis of rat kidneys indicated that PCA reduced UUO-induced hydronephrosis (control: 15.11 ± 1.00%; UUO: 39.89 ± 1.91%; UUO + PCA50: 18.37 ± 1.61%; UUO + PCA100: 17.67 ± 1.39%). Protein level demonstrated that PCA not only decreased vimentin expression and enhanced E-cadherin expression, but inhibited UUO-induced collagen IV and α-SMA upregulation, indicating that it could mitigate EMT in a rat model of UUO-induced renal fibrosis. Discussion and conclusions This study suggested that PCA decreases TGF-β1-induced fibrosis and EMT in vitro and in vivo . These findings demonstrate pharmacological effects of PCA and might be a potential strategy for the prevention of organ fibrosis in clinics.

Diabetic nephropathy (DN) is one of the most severe chronic kidney diseases in diabetes and is the main cause of end-stage renal disease (ESRD). Protocatechuic aldehyde (PCA) is a natural product with a variety of effects on pulmonary fibrosis. In this study, we examined the effects of PCA in C57BL/KS db/db male mice. Kidney morphology, renal function indicators, and Western blot, immunohistochemistry, and hematoxylin and eosin (H&E) staining data were analyzed. The results revealed that treatment with PCA could reduce diabetic-induced renal dysfunction, as indicated by the urine albumin-to-creatinine ratio (db/m: 120.1 ± 46.1μg/mg, db/db: 453.8 ± 78.7 µg/mg, db/db + 30 mg/kg PCA: 196.6 ± 52.9 µg/mg, db/db + 60 mg/kg PCA: 163.3 ± 24.6 μg/mg, p < 0.001). However, PCA did not decrease body weight, fasting plasma glucose, or food and water intake in db/db mice. H&E staining data revealed that PCA reduced glomerular size in db/db mice (db/m: 3506.3 ± 789.3 μm2, db/db: 6538.5 ± 1818.6 μm2, db/db + 30 mg/kg PCA: 4916.9 ± 1149.6 μm2, db/db + 60 mg/kg PCA: 4160.4 ± 1186.5 μm2p < 0.001). Western blot and immunohistochemistry staining indicated that PCA restored the normal levels of diabetes-induced fibrosis markers, such as transforming growth factor-beta (TGF-β) and type IV collagen. Similar results were observed for epithelial–mesenchymal transition-related markers, including fibronectin, E-cadherin, and α-smooth muscle actin (α-SMA). PCA also decreased oxidative stress and inflammation in the kidney of db/db mice. This research provides a foundation for using PCA as an alternative therapy for DN in the future.

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