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Kidney Targeting Smart Antibiotic Discovery: Multimechanism Pleuromutilins for Pyelonephritis Therapy.

J Med Chem

January 2025

Xi'an Key Laboratory for Antiviral and Antimicrobial-Resistant Bacteria Therapeutics Research, Xi'an 710021, China.

Multidrug-resistant (MDR) bacteria pose a global health threat, underscoring the need for new antibiotics. Lefamulin, the first novel-mechanism antibiotic approved by the FDA in decades, showcases pleuromutilins' promise due to low mutation frequency. However, their clinical use is limited by poor pharmacokinetics and organ toxicity.

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Introduction: Systemic lupus erythematosus (SLE) causes widespread inflammation and damage in affected organs. Severity is determined by the type of organ systems affected and the extent of involvement. SLE occurs in childhood or adulthood and disease severity varies according to age of onset.

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The cardiovascular implications of thyroid disease have been recognized as one of the most characteristic signs that result from the effect of thyroid hormone (TH). Both hyperthyroidism and hypothyroidism produce changes in cardiac contractility, myocardial oxygen consumption, cardiac output, blood pressure, and systemic vascular resistance. The bradyarrhythmias, including atrioventricular block and sick sinus syndrome, are exceedingly rare in hyperthyroidism.

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Background: Internal mammary node irradiation (IMNI) improves overall survival (OS) in node-positive breast cancer patients. However, the effect is not documented in breast cancer patients treated with newer systemic therapies and 3D-based radiotherapy (RT). Therefore, the Danish Breast Cancer Group (DBCG) IMN2 study aimed to investigate the effect of IMNI in node-positive breast cancer patients treated with newer systemic therapies and 3D-based RT.

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Introduction: Primary sclerosing cholangitis (PSC) is an uncommon, chronic liver disease characterised by fibrosis and strictures of a bile ducts, causing cholestasis. In the long term it can lead to complete stenosis leading in turn to liver cirrhosis. In patients with severe form of the disease, the recommended treatment is liver transplantation.

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