The skeletal myosin light chain kinase (skMLCK) was identified in human and chicken embryo myocardium but not in embryo and adult rat heart using western blotting. The content of skMLCK and myosin-activating protein kinases: RhaA-activated protein kinase (ROCK), integrin-linked protein kinase (ILK), and zipper-interacting protein kinase (ZIPK) was compared in normal human myocardium and the hearts of patients with dilated cardiomyopathy (DCM). It was demonstrated that the content of skMLCK, ROCK and ILK increases in DCM whereas the content of ZIPK decreases. The results obtained may reflect compensatory processes in cardiomyocytes in DMC, which are aimed at increasing their viability and contractility.
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Can J Physiol Pharmacol
January 2025
Western University Faculty of Health Sciences, School of Kinesiology, London, Ontario, Canada.
Aerobic exercise (AE) is associated with a significant hypoglycemia risk in individuals with type 1 diabetes mellitus (T1DM). However, the mechanisms in the liver and skeletal muscle governing exercise-induced hypoglycemia in T1DM are poorly understood. This study examined the effects of a 60-minute bout of AE on hepatic and muscle glucose metabolism in T1DM rats.
View Article and Find Full Text PDFN Engl J Med
January 2025
From the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation (C.E.G., E.P.M., N.W., P.R., I.L.W., A.M.B.) and University of Pittsburgh School of Medicine-UPMC Hillman Cancer Center (C.E.G., N.W., P.R., A.M.B.) - both in Pittsburgh; AGO-B and Helios Klinikum Berlin-Buch, Berlin (M.U.), the National Center for Tumor Diseases, Heidelberg University Hospital, and German Cancer Research Center, Heidelberg (A.S.), Evangelische Kliniken Gelsenkirchen, Gelsenkirchen (H.H.F.), Arbeitsgemeinschaft Gynäkologische Onkologie-Breast and Sana Klinikum Offenbach, Offenbach (C.J.), the Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen (P.A.F.), German Breast Group, Neu-Isenburg (P.W., S.L.), and the Center for Hematology and Oncology Bethanien, Goethe University, Frankfurt (S.L.) - all in Germany; National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (C.-S.H.); Instituto do Câncer do Estado de São Paulo, São Paulo (M.S.M.); Orlando Health Cancer Institute, Orlando, FL (E.P.M.); Hospital Universitario La Paz-Instituto de Investigación del Hospital Universitario La Paz, Madrid (A.R.); L'Institut du Cancer de Montpellier-Val d'Aurelle, Montpellier (V.D.), Institut Bergonié, INSERM Unité 1312, and Université de Bordeaux UFR Sciences Médicales, Bordeaux (H.R.B.) - all in France; Providence Cancer Institute, Portland, OR (A.K.C.); the Department of Surgery, Oncology, and Gastroenterology, University of Padua, and Oncology 2, Istituto Oncologico Veneto IRCCS, Padua (V.G.), and the Cancer Center Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo (E.R.C.) - all in Italy; Stanford University School of Medicine, Stanford, CA (I.L.W.); the National Cancer Institute, Mexico City (C.A.-S.); Yale University School of Medicine, Yale Cancer Center, and Smilow Cancer Hospital, New Haven, CT (M.P.D.); the All-Ireland Cooperative Oncology Research Group (J.P.C.), and the Oncology Unit, Cancer Clinical Trials and Research Unit, Beaumont RCSI Cancer Centre, and Cancer Trials Ireland (B.T.H.) - all in Dublin; Fudan University Shanghai Cancer Center, Shanghai, China (Z.S.); Institute for Oncology and Radiology of Serbia, Belgrade (L.S.); Grupo Médico Ángeles, Guatemala City, Guatemala (H.C.-S.); Roche Products, Welwyn Garden City, United Kingdom (A.K., A.S.); and F. Hoffmann-La Roche, Basel, Switzerland (C.L., T.B., B.N., E.R.).
Background: Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer with residual invasive disease after neoadjuvant systemic therapy have a high risk of recurrence and death. The primary analysis of KATHERINE, a phase 3, open-label trial, showed that the risk of invasive breast cancer or death was 50% lower with adjuvant trastuzumab emtansine (T-DM1) than with trastuzumab alone.
Methods: We randomly assigned patients with HER2-positive early breast cancer with residual invasive disease in the breast or axilla after neoadjuvant systemic treatment with taxane-based chemotherapy and trastuzumab to receive T-DM1 or trastuzumab for 14 cycles.
Sci Adv
January 2025
College of Chemistry, Fuzhou University, Fuzhou 350116, China.
The angiopoietin (Ang)-Tie axis, critical for endothelial cell function and vascular development, is a promising therapeutic target for treating vascular disorders and inflammatory conditions like sepsis. This study aimed to enhance the binding affinity of recombinant Ang1 variants to the Tie2 and explore their therapeutic potential. Structural insights from the Ang1-Tie2 complex enabled the identification of key residues within the Ang1 receptor binding domain (RBD) critical for Tie2 interaction.
View Article and Find Full Text PDFSci Transl Med
January 2025
Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada.
In prednisone-dependent severe asthma, uncontrolled sputum eosinophilia is associated with increased numbers of group 2 innate lymphoid cells (ILC2s). These cells represent a relatively steroid-insensitive source of interleukin-5 (IL-5) and IL-13 and are considered critical drivers of asthma pathology. The abundance of ILC subgroups in severe asthma with neutrophilic or mixed granulocytic (both eosinophilic and neutrophilic) airway inflammation, prone to recurrent infective exacerbations, remains unclear.
View Article and Find Full Text PDFPLoS Biol
January 2025
Institute of Biochemistry, ETH Zürich, Zürich, Switzerland.
Noncoding satellite DNA repeats are abundant at the pericentromeric heterochromatin of eukaryotic chromosomes. During interphase, sequence-specific DNA-binding proteins cluster these repeats from multiple chromosomes into nuclear foci known as chromocenters. Despite the pivotal role of chromocenters in cellular processes like genome encapsulation and gene repression, the associated proteins remain incompletely characterized.
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