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Structure-Based Design of "Head-to-Tail" Macrocyclic PROTACs.
JACS Au
December 2024
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, No. 345 Lingling Road, Shanghai 200032, China.
Macrocyclization is a compelling strategy for conventional drug design for improving biological activity, target specificity, and metabolic stability, but it was rarely applied to the design of PROTACs possibly due to the mechanism and structural complexity. Herein, we report the rational design of the first series of "Head-to-Tail" macrocyclic PROTACs. The resulting molecule exhibited pronounced Brd4 protein degradation with low nM DC values while almost totally dismissing the "hook effect", which is a general character and common concern of a PROTAC, in multiple cancer cell lines.
View Article and Find Full Text PDFIncidence, Prediction, and Prevention of Fractures After Kidney Transplantation: A Systematic Review Protocol.
Can J Kidney Health Dis
December 2024
Department of Medicine, Western University, London, ON, Canada.
Background: Kidney transplant recipients are uniquely exposed to the disordered bone metabolism associated with chronic kidney disease beginning before transplantation followed by chronic corticosteroid use after transplantation. Previous efforts to synthesize the rapidly accruing evidence regarding estimation and management of fracture risk in kidney transplant recipients are outdated and incomplete.
Objective: To synthesize the evidence informing the overall incidence, patient-specific risk prediction, and methods of prevention of fractures in patient living with a kidney transplant.
A ceramic microbridge microfluidic chip to study osteogenic differentiation of mesenchymal stem cells in bioactive ceramic immune microenvironment.
Bioact Mater
March 2025
College of Biomedical Engineering, Sichuan University, Chengdu, Sichuan, 610064, China.
Bioactive ceramics have been used in bone tissue repair and regeneration. However, because of the complex in vivo osteogenesis process, long cycle, and difficulty of accurately tracking, the mechanism of interaction between materials and cells has yet to be fully understood, hindering its development. The ceramic microbridge microfluidic chip system may solve the problem and provide an in vitro method to simulate the microenvironment in vivo.
View Article and Find Full Text PDFRobotic-Assisted Minimally Invasive Resection of Multiple Oesophageal Schwannomas: A Case Report.
Cureus
November 2024
Department of Upper Gastrointestinal and Hepatobiliary Surgery, Monash Health, Melbourne, AUS.
Schwannomas are rare, benign tumours arising from Schwann cells, with oesophageal cases representing a small fraction. Their variety of symptoms and nonspecific imaging features often make preoperative diagnosis challenging, frequently requiring immunohistochemical staining for confirmation. We describe the case of a 62-year-old woman with progressive dysphagia, found to have a subepithelial mass at the gastroesophageal junction (GOJ).
View Article and Find Full Text PDFDiaphragmatic Hernia Repair in Adult Patients: A Retrospective Institutional Experience.
Cureus
November 2024
Thoracic Surgery Department, Instituto Nacional de Enfermedades Respiratorias, Mexico City, MEX.
Objectives Diaphragmatic hernias (DHs) in adults are an uncommon condition in which general characteristics and treatment strategies are poorly described. The objective of this study was to describe our institutional experience in the surgical repair of DH in adult patients. Methods A cross-sectional review was conducted on adult patients with DH who were diagnosed and surgically treated between 2012 and 2023 at the Instituto Nacional de Enfermedades Respiratorias in Mexico City.
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