Clinical use of the anti-cancer drug doxorubicin (DOX) is largely limited due to its severe cardiotoxicity. Dysregulation of autophagy is implicated in DOX-induced cardiotoxicity (DIC). Prior studies have indicated that Beclin1 and lysosomal-associated membrane proteins-1 (LAMP1) are critical mediators of autophagy. In this work, by assessing autophagic flux in a DOX-stimulated H9C2 model, we observed autolysosome accumulation caused by interruption of autolysosome degradation. Tanshinone IIA (TSA) is a well-known small molecule that exerts impressive cardioprotective effects on heart failure. Here, we investigated the regulation of TSA in DOX-treated zebrafish, mice, and H9C2 models. Results demonstrated that TSA remarkably improved heart function and reversed pathological changes in vivo, while TSA restored autophagic flux by promoting autolysosome degradation and autophagosome formation. Further experiments demonstrated that these effects were mediated through upregulation of Beclin1 and LAMP1. The mTOR agonist MHY1485 was shown to abrogate the effect of TSA via the UNC-51-like kinase 1 (ULK1)-Beclin1/TFEB-LAMP1 signaling pathway in vitro, demonstrating that TSA protects against DIC by promoting autophagy via the Beclin1/LAMP1 signaling pathway. We further employed a U87 model to assess whether TSA would compromise the antitumor activity of DOX. Intriguingly, the co-treatment of TSA was able to synergistically inhibit proliferative activity. Collectively, in this study we uncover the novel insight that TSA is able to reduce the cardiotoxicity of DOX without compromising antitumor activity.
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http://dx.doi.org/10.3390/cancers11070910 | DOI Listing |
Indian J Crit Care Med
December 2024
Department of Critical Care Medicine, Ruby Hall Hospital, Pune, Maharashtra, India.
Objectives: Heart rate control using beta-blockers in sepsis has traditionally been avoided because of concerns with worsening cardiac index and organ perfusion. Recent studies has explored the possible beneficial effects of targeted heart rate control in patients with septic shock who have tachycardia despite initial resuscitation. We performed a systematic review and meta-analysis to explore the effects of heart rate control in septic shock patients.
View Article and Find Full Text PDFJ Shoulder Elbow Surg
January 2025
Division of Shoulder and Elbow Surgery, Department of Orthopedic Surgery, NYU Grossman School of Medicine, NYU Langone Orthopedic Hospital, NYU Langone Health, New York, NY, USA. Electronic address:
Introduction: Patient Reported Outcome Measurement Information Systems (PROMIS) is increasingly being utilized across the United States as a patient reported outcome evaluation tool for a wide variety of musculoskeletal conditions. However, PROMIS Upper Extremity physical function (P-UE) has demonstrated limited responsiveness in the early postoperative period after total shoulder arthroplasty (TSA). The aim of this study is to determine if addition of PROMIS Pain Interference (P-Interference) or Pain Intensity (P-Intensity) scores improve the ability to detect postoperative changes in the one-year postoperative period following TSA.
View Article and Find Full Text PDFJ Shoulder Elbow Surg
January 2025
University of Chicago Department of Orthopaedic Surgery & Rehabilitation Medicine, Chicago, IL, USA.
Background: Radiographs are frequently obtained after total shoulder arthroplasty (TSA) to confirm implant placement and follow the status of the bone and prostheses; however, standardization of their use is lacking. There are concerns regarding frequent use of radiographs due to their cost and patient radiation exposure. The aim of this study is to assess the postoperative radiograph frequency and efficacy in primary anatomic and reverse total shoulder arthroplasty.
View Article and Find Full Text PDFNeurochem Res
January 2025
Huazhong University of Science and Technology, Tongji Medical College, Wuhan, Hubei, 430000, China.
Epilepsy (EP) is a neurological disorder characterized by abnormal, sudden neuronal discharges. Seizures increase extracellular glutamate levels, causing excitotoxic damage. Glutamate transporter type 1 (GLT-1) and its human homologue excitatory amino acid transporter-2 (EAAT2) clear 95% of extracellular glutamate.
View Article and Find Full Text PDFJ Adv Nurs
January 2025
School of Nursing, The Hong Kong Polytechnic University, Hong Kong, SAR, China.
Background: Sense of coherence (SoC) is a core concept of 'salutogenesis' in positive psychology, correlated with emotional distress and disease development in adults with chronic disease and older adults. A diversity of non-pharmacological interventions (NPIs) has been developed to enhance SoC, but research findings are conflicting and the adequacy of sample sizes is uncertainty.
Objective: This paper aimed to explore appropriate interventions, evaluate the effectiveness of these SoC interventions and verify the statistical robustness and reliability of pooled results.
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