Programmed cell death (PCD), referring to apoptosis, autophagy and programmed necrosis, is proposed to be death of a cell in any pathological format, when mediated by an intracellular program. These three forms of PCD may jointly decide the fate of cells of malignant neoplasms; apoptosis and programmed necrosis invariably contribute to cell death, whereas autophagy can play either pro-survival or pro-death roles. Recent bulk of accumulating evidence has contributed to a wealth of knowledge facilitating better understanding of cancer initiation and progression with the three distinctive types of cell death. To be able to decipher PCD signalling pathways may aid development of new targeted anti-cancer therapeutic strategies. Thus in this review, we present a brief outline of apoptosis, autophagy and programmed necrosis pathways and apoptosis-related microRNA regulation, in cancer. Taken together, understanding PCD and the complex interplay between apoptosis, autophagy and programmed necrosis may ultimately allow scientists and clinicians to harness the three types of PCD for discovery of further novel drug targets, in the future cancer treatment.

The newly emergent Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe pulmonary disease in humans, representing the second example of a highly pathogenic coronavirus, the first being SARS-CoV. CD26 (also known as dipeptidyl peptidase 4, DPP4) was recently identified as the cellular receptor for MERS-CoV. The engagement of the MERS-CoV spike protein with CD26 mediates viral attachment to host cells and virus-cell fusion, thereby initiating infection. Here we delineate the molecular basis of this specific interaction by presenting the first crystal structures of both the free receptor binding domain (RBD) of the MERS-CoV spike protein and its complex with CD26. Furthermore, binding between the RBD and CD26 is measured using real-time surface plasmon resonance with a dissociation constant of 16.7 nM. The viral RBD is composed of a core subdomain homologous to that of the SARS-CoV spike protein, and a unique strand-dominated external receptor binding motif that recognizes blades IV and V of the CD26 β-propeller. The atomic details at the interface between the two binding entities reveal a surprising protein-protein contact mediated mainly by hydrophilic residues. Sequence alignment indicates, among betacoronaviruses, a possible structural conservation for the region homologous to the MERS-CoV RBD core, but a high variation in the external receptor binding motif region for virus-specific pathogenesis such as receptor recognition.

Ferroptosis is a mode of regulated cell death that depends on iron. Cells die from the toxic accumulation of lipid reactive oxygen species. Ferroptosis is tightly linked to a variety of human diseases, such as cancers and degenerative diseases. The ferroptotic process is complicated and consists of a wide range of metabolites and biomolecules. Although great progress has been achieved, the mechanism of ferroptosis remains enigmatic. We have currently entered an era of extensive knowledge advancement, and thus, it is important to find ways to organize and utilize data efficiently. We have observed a high-quality knowledge base of ferroptosis research is lacking. In this study, we downloaded 784 ferroptosis articles from the PubMed database. Ferroptosis regulators and markers and associated diseases were extracted from these articles and annotated. In summary, 253 regulators (including 108 drivers, 69 suppressors, 35 inducers and 41 inhibitors), 111 markers and 95 ferroptosis-disease associations were found. We then developed FerrDb, the first manually curated database for regulators and markers of ferroptosis and ferroptosis-disease associations. The database has a user-friendly interface, and it will be updated every 6 months to offer long-term service. FerrDb is expected to help researchers acquire insights into ferroptosis. Database URL: http://www.zhounan.org/ferrdb

Microautophagy, the non-selective lysosomal degradative process, involves direct engulfment of cytoplasmic cargo at a boundary membrane by autophagic tubes, which mediate both invagination and vesicle scission into the lumen. With its constitutive characteristics, microautophagy of soluble substrates can be induced by nitrogen starvation or rapamycin via regulatory signaling complex pathways. The maintenance of organellar size, membrane homeostasis, and cell survival under nitrogen restriction are the main functions of microautophagy. In addition, microautophagy is coordinated with and complements macroautophagy, chaperone-mediated autophagy, and other self-eating pathways. Three forms of selective microautophagy, including micropexophagy, piecemeal microautophagy of the nucleus, and micromitophagy, share common ground with microautophagy to some degree. As the accumulation of experimental data, the precise mechanisms that govern microautophagy are becoming more appreciated. Here, we review the microautophagic molecular machinery, its physiological functions, and relevance to human diseases, especially in diseases involving multivesicular bodies and multivesicular lysosomes.

Mesenchymal stem cells (MSCs) have been used in cell-based therapy for various diseases, due to their immunomodulatory and inflammatory effects. However, the function of MSCs is known to decline with age, a process that is called senescence. To date, the process of MSC senescence remains unknown as in-depth understanding of the mechanisms involved in cellular senescence is lacking. First, senescent MSCs are so heterogeneous that not all of them express the same phenotypic markers. In addition, the genes and signaling pathways which regulate this process in MSCs are still unknown. Thus, an understanding of the molecular processes controlling MSC senescence is crucial to determining the drivers and effectors of age-associated MSC dysfunction. Moreover, the proper use of MSCs for clinical application requires a general understanding of the MSC aging process. Furthermore, such knowledge is essential for the development of therapeutic interventions that can slow or reverse age-related degenerative changes to enhance repair processes and maintain healthy function in aging tissues. To further clarify the properties of senescent cells, as well as to present significant findings from studies on the mechanisms of cellular aging, we summarize these biological features in the senescence of MSCs in this scenario. This review summarizes recent advances in our understanding of the markers and differentiation potential indicating MSC senescence, as well as factors affecting MSC senescence with particular emphasis on the roles of oxidative stress, intrinsic changes in telomere shortening, histone deacetylase and DNA methyltransferase, genes and signaling pathways and immunological properties.