Apoptosis is an important cell death mechanism by which multicellular organisms remove unwanted cells. It culminates in a rapid, controlled removal of cell corpses by neighboring or recruited viable cells. Whilst many of the molecular mechanisms that mediate corpse clearance are components of the innate immune system, clearance of apoptotic cells is an anti-inflammatory process. Control of cell death is dependent on competing pro-apoptotic and anti-apoptotic signals. Evidence now suggests a similar balance of competing signals is central to the effective removal of cells, through so called 'eat me' and 'don't eat me' signals. Competing signals are also important for the controlled recruitment of phagocytes to sites of cell death. Consequently recruitment of phagocytes to and from sites of cell death can underlie the resolution or inappropriate propagation of cell death and inflammation. This article highlights our understanding of mechanisms mediating clearance of dying cells and discusses those mechanisms controlling phagocyte migration and how inappropriate control may promote important pathologies.
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http://dx.doi.org/10.4137/JCD.S11037 | DOI Listing |
J Am Chem Soc
December 2024
School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China.
Oncolytic therapy, inducing cell death via cell membrane lysis, holds considerable promise in cancer treatment. However, achieving precise control over the structure and function of oncolytic materials for highly selective oncolytic therapy is a key challenge in the context of the subtle differences between tumor and normal tissues/cells. Herein, we report the development of pH-ultrasensitive oncolytic polyesters (pOPs) with an alternating sequence of ionizable and hydrophobic groups.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208, United States.
Discovery of cancer immunogenic chemotherapeutics represents an emerging, highly promising direction for cancer treatment that uses a chemical drug to achieve the efficacy of both chemotherapy and immunotherapy. Herein, we report a high-throughput screening platform and the subsequent discovery of a new class of cancer immunogenic chemotherapeutic leads. Our platform integrates informatics-based activity metabolomics for the rapid identification of microbial natural products with both novel structures and potent activities.
View Article and Find Full Text PDFACS 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 PDFAdv Sci (Weinh)
December 2024
New Cornerstone Science Laboratory, MOE Key Laboratory for Analytical Science of Food Safety and Biology, College of Chemistry, Fuzhou University, Fuzhou, 350108, China.
Radiodynamic therapy that employs X-rays to trigger localized reactive oxygen species (ROS) generation can tackle the tissue penetration issue of phototherapy. Although calcium tungstate (CaWO) shows great potential as a radiodynamic agent benefiting from its strong X-ray absorption and the ability to generate electron-hole (e-h) pairs, slow charge carrier transfer and fast e-h recombination greatly limit its ROS-generating performance. Herein, via a one-pot wet-chemical method, oxygen vacancy-rich amorphous/crystalline heterophase CaWO nanoparticles (Ov-a/c-CaWO NPs) with enhanced radiodynamic effect are synthesized for radiodynamic-immunotherapy of cancer.
View Article and Find Full Text PDFClin Transl Med
January 2025
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
Precision medicine in less-defined subtype diffuse large B-cell lymphoma (DLBCL) remains a challenge due to the heterogeneous nature of the disease. Programmed cell death (PCD) pathways are crucial in the advancement of lymphoma and serve as significant prognostic markers for individuals afflicted with lymphoid cancers. To identify robust prognostic biomarkers that can guide personalized management for less-defined subtype DLBCL patients, we integrated multi-omics data derived from 339 standard R-CHOP-treated patients diagnosed with less-defined subtype DLBCL from three independent cohorts.
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