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Single-cell RNA-sequencing identifies unique cell-specific gene expression profiles in high-grade cardiac allograft vasculopathy.
J Heart Lung Transplant
November 2024
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN; Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN.
Article Synopsis
- - The study investigates cardiac allograft vasculopathy (CAV), a major cause of failure and death post-heart transplant, using single-cell RNA-sequencing to identify potential new biomarkers and pathways for early diagnosis and treatment.
- - Researchers collected blood from 22 heart transplant recipients with CAV and 18 without, analyzing over 134,000 cells and finding notable increases in specific immune cells associated with high-grade CAV, alongside 745 differentially expressed genes linked to inflammation and blood vessel growth.
- - The findings suggest that measuring specific gene expression in the blood could help diagnose CAV, and that targeting identified pathways might lead to new treatments to prevent its progression.
Targeting P-selectin and interleukin-1β in mice with sickle cell disease: effects on vaso-occlusion, liver injury and organ iron deposition.
Haematologica
November 2024
Hematology Center, University of Campinas - UNICAMP, Campinas - São Paulo.
Continuous vaso-occlusive and inflammatory processes cause extensive end-organ damage in adults with sickle cell disease (SCD), and there is little evidence that longterm hydroxyurea therapy prevents this. In initial trials, P-selectin blockade with crizanlizumab reduced SCD vaso-occlusive crisis frequency, and interleukin (IL)-1β inhibition in SCD patients, using canakinumab, lowered inflammatory markers. We used murine SCD models to examine the effects of acute and chronic blockade of Pselectin and of IL-1β on vaso-occlusive events, their inflammatory profile and organ health.
View Article and Find Full Text PDFSpartalizumab in combination with platinum-doublet chemotherapy with or without canakinumab in patients with PD-L1-unselected, metastatic NSCLC.
BMC Cancer
October 2024
Department of Medical Oncology, Highlands Oncology Group, Fayetteville, AZ, USA.
Article Synopsis
- A multicenter phase 1b study explored the effectiveness and tolerability of combining spartalizumab with various platinum-doublet chemotherapy regimens in treatment-naïve patients with non-small cell lung cancer (NSCLC) that were not selected based on PD-L1 expression.
- The study found that the maximum tolerated dose for spartalizumab was 300 mg every 3 weeks, and overall response rates to the treatment generally ranged from 51.5% to 57.6%, indicating a good level of efficacy across different chemotherapy combinations.
- Notably, patients receiving pemetrexed/cisplatin showed the longest median progression-free survival and overall survival compared to other treatment groups, highlighting the potential of this regimen in
Targeting Inflammatory Pathways in Atherosclerosis: Exploring New Opportunities for Treatment.
Curr Atheroscler Rep
December 2024
Department of Cardiovascular Sciences- CUORE, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Largo A. Gemelli 8, 00168, Rome, Italy.
Purpose Of The Review: This review discusses the molecular mechanisms involved in the immuno-pathogenesis of atherosclerosis, the pleiotropic anti-inflammatory effects of approved cardiovascular therapies and the available evidence on immunomodulatory therapies for atherosclerotic cardiovascular disease (ACVD). We highlight the importance of clinical and translational research in identifying molecular mechanisms and discovering new therapeutic targets.
Recent Findings: The CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) trial was the first to demonstrate a reduction in cardiovascular (CV) risk with anti-inflammatory therapy, irrespective of serum lipid levels.
Addressing residual risk beyond statin therapy: New targets in the management of dyslipidaemias-A report from the European Society of Cardiology Cardiovascular Round Table.
J Clin Lipidol
November 2024
Cardiovascular Medicine Division, Brigham and Women's Hospital, Boston, MA, USA (Dr Libby).
Cardiovascular (CV) disease is the most common cause of death in Europe. Despite proven benefits, use of lipid-lowering therapy remains suboptimal. Treatment goals are often not achieved, even in patients at high risk with atherosclerotic CV disease (ASCVD).
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