Combination of Coevolutionary Information and Supervised Learning Enables Generation of Cyclic Peptide Inhibitors with Enhanced Potency from a Small Data Set.

Computational generation of cyclic peptide inhibitors using machine learning models requires large size training data sets often difficult to generate experimentally. Here we demonstrated that sequential combination of Random Forest Regression with the pseudolikelihood maximization Direct Coupling Analysis method and Monte Carlo simulation can effectively enhance the design pipeline of cyclic peptide inhibitors of a tumor-associated protease even for small experimental data sets. Further studies showed that such -evolved cyclic peptides are more potent than the best peptide inhibitors previously developed to this target.

Tandem upregulation of ion transporters in thick ascending limb of Henle's loop of young Milan hypertensive strain of rats.

Introduction: Milan hypertensive strain (MHS) of rat represents as one of the ideal rat models to study the genetic form of hypertension associated with aberrant renal salt reabsorption. In contrast to Milan normotensive strain (MNS), MHS rats possess missense mutations in three adducin genes and develop hypertension at 3 months old due to upregulation of sodium-chloride cotransporter (NCC). At pre-hypertensive stage (23-25 days old), MHS rats show enhanced protein abundance of Na+-K+-2Cl- cotransporter (NKCC2) but retain blood pressure comparable to MNS probably through enhanced GFR and reduced NCC and α-subunit of epithelial sodium channel (α-ENaC) expressed in distal convoluted tubule (DCT) and collecting duct (CD).

Changes in 24-hour blood pressure profile after 12 weeks of dapagliflozin treatment in patients with diabetic kidney disease: an Italian multicenter prospective study.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) lower ambulatory blood pressure (ABP) in patients with type 2 diabetes mellitus; whether the same holds true in diabetic kidney disease (DKD) is unknown. This information is critical to the knowledge of mechanisms of nephroprotection and safety of this therapy.

Methods: This multicenter prospective study evaluates the changes in ABP after 12 weeks of dapagliflozin 10 mg/day in a cohort of patients with type 2 DKD and glomerular filtration rate (GFR) >25 mL/min/1.

Acute Kidney Disease in Oncology: A New Concept to Enhance the Understanding of the Impact of Kidney Injury in Patients with Cancer.

Background: Cancer patients are prone to developing acute kidney disease (AKD), yet this phenomenon remains understudied compared to acute kidney injury (AKI). AKD, which often develops insidiously, can cause treatment interruptions, extended hospital stays, and increased mortality.

Summary: This perspective article explores the intricate relationship between AKD and cancer, focusing on prevalence, risk factors, implications for anticancer therapy, and long-term outcomes, including chronic kidney disease progression.