Septic acute kidney injury (AKI) and myocardial dysfunction are leading causes of mortality with no accepted method of therapy. In this study we demonstrate the role of growth differentiating factor 15 (GDF15) in septic AKI and myocardial dysfunction using a murine lipopolysaccharide (LPS)-induced sepsis model and an in vitro cell culture system. Data show that GDF15 deficiency augments inflammatory response and exacerbates renal and cardiac injury induced by LPS, while over-expression of GDF15 protects the kidney and heart from LPS-induced organ dysfunction. Therefore, this study highlights the therapeutic potential of GDF15 in the treatment of endotoxin-induced sepsis.
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http://dx.doi.org/10.1038/s41598-017-00902-5 | DOI Listing |
ACS Nano
December 2024
The Fifth Affiliated Hospital, Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, the School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China.
Tumor-specific cytotoxic T cell immunity is critically dependent on effective antigen presentation and sustained signal transduction. However, this immune response is frequently compromised by the inherently low immunogenicity of breast cancer and the deficiency in major histocompatibility complex class I (MHC-I) expression. Herein, a chimeric peptide-engineered stoichiometric polyprodrug (PDPP) is fabricated to potentiate the cytotoxic T cell response, characterized by a high drug loading capacity and precise stoichiometric drug ratio, of which the immunogenic cell death (ICD) inducer of protoporphyrin IX (PpIX) and the epigenetic drug of decitabine (DAC) are condensed into a polyprodrug called PpIX-DAC.
View Article and Find Full Text PDFActa Biochim Biophys Sin (Shanghai)
December 2024
Fibrosis is the main pathological feature of aortic stiffness, which is a common extracardiac comorbidity of heart failure with preserved ejection fraction (HFpEF) and a contributor to left ventricular (LV) diastolic dysfunction. Systemic low-grade inflammation plays a crucial role in the pathogenesis of HFpEF and the development of vascular fibrosis. In this study, we investigate the inflammatory mechanism of aortic fibrosis in HFpEF using a novel mouse model.
View Article and Find Full Text PDFEur J Pharmacol
December 2024
Keio University, Tokyo, Japan.
Klotho deficiency is prevalent in various chronic kidney diseases. Although klotho is known to bind transforming growth factor β (TGFβ) receptor 1 to antagonize renal fibrosis, TGFβ also maintains regulatory T cells with inducing forkhead box protein P3 (FOXP3). Female New Zealand Black/White F (NZBWF1) mice were divided into two groups (n=10 for each): one group was treated with daily subcutaneous injection of klotho protein (30 μg/kg/day) for 8 weeks, and the other only received vehicle.
View Article and Find Full Text PDFCureus
November 2024
Department of Dentistry, Tawq Alseha Medical Center, Najran, SAU.
Dental implants have revolutionized tooth replacement, offering a functional and aesthetically pleasing alternative to traditional dentures and bridges. While conventional implants, typically titanium screws placed into the jawbone, have become the gold standard, many studies explore non-conventional implant designs and materials to address specific challenges and patient needs. This series of literature reviews aimed to delve into non-conventional dental implants, examining their unique features and applications and the current state of evidence supporting their use.
View Article and Find Full Text PDFCell Mol Life Sci
December 2024
Center for Mitochondrial Research and Medicine, College of Medicine Chang Gung University, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Imbalances in gut microbiota and their metabolites have been implicated in osteoporotic disorders. Trimethylamine-n-oxide (TMAO), a metabolite of L-carnitine produced by gut microorganisms and flavin-containing monooxygenase-3, is known to accelerate tissue metabolism and remodeling; however, its role in bone loss remained unexplored. This study investigates the relationship between gut microbiota dysbiosis, TMAO production, and osteoporosis development.
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