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Emerging Research in Cell Death and Differentiation

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (10 April 2023) | Viewed by 11077

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Special Issue Editors

Prof. Dr. Roberta Di Pietro

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Guest Editor

1. Department of Medicine and Aging Sciences, Section of Biomorphology, “G. d’Annunzio” University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy
2. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
Interests: pancreas adenocarcinoma; hematological malignancies; lymphoma; CREB; TRAIL; apoptosis; caspase enzymes; extracellular vesicles; transmission electron microscopy
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Sandra Marmiroli

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Guest Editor

Department of Biomedical, Metabolic and Neuronal Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy
Interests: cellular signaling; lipid-activated protein kinases; identification of isoform-specific substrates of the AKT protein kinase; modulation of glycolytic vs. oxidative cellular phenotypes by signaling pathways in acute leukemia models; definition of the phosphorylome of primary blast cells from leukemia patients, and its modulation by the PI3K pathway; kinase-inhibitor therapy in hematological malignancies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are delighted to announce a call for submissions to this Special Issue of the International Journal of Molecular Sciences on the topic of Emerging Research in Cell Death and Differentiation. Despite its late onset as a biomedical research area, cell death is now a field in continuous development. The latest recommendations of the Nomenclature Committee on Cell Death (NCCD) are dated 2018 (Galluzzi et al., 2018). More recently, other authors have proposed a simple classification system, where the cell death entities are primarily categorized into programmed cell death (PCD) or non‑PCD (necrosis) based on their signal dependency (Yan et al., 2020). Dissecting the molecular mechanisms of both positive and negative regulation of PCD is the mainstay to develop treatments for several diseases, including cancer and neurodegeneration.

A more irregular form of death is typically described as differentiation (as in the case of keratinocytes) and exemplifies how cell death is not only essential for the renewal of tissues, but also for direct protection from the outside world and pathogens.

We encourage the submission of both original research articles and topical reviews tackling all aspects of cell death and differentiation, as well as addressing what lies ahead regarding technologies and methods.

Prof. Dr. Roberta Di Pietro
Prof. Dr. Sandra Marmiroli
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

regulated cell death pathways
cell differentiation
cell ageing and senescence
apoptosis
necrosis
autophagy
aponecrosis
pyroptosis
caspase pathway
cancer

Published Papers (5 papers)

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Research

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17 pages, 4471 KiB

Open AccessArticle

Mitochondrial Trafficking of MLKL, Bak/Bax, and Drp1 Is Mediated by RIP1 and ROS which Leads to Decreased Mitochondrial Membrane Integrity during the Hyperglycemic Shift to Necroptosis

by Matthew A. Deragon, William D. McCaig, Phillip V. Truong, Kevin R. Metz, Katherine A. Carron, Keven J. Hughes, Angeleigh R. Knapp, Molly J. Dougherty and Timothy J. LaRocca

Int. J. Mol. Sci. 2023, 24(10), 8609; https://doi.org/10.3390/ijms24108609 - 11 May 2023

Cited by 3 | Viewed by 1659

Abstract

Apoptosis and necroptosis overlap in their initial signaling but diverge to produce non-inflammatory and pro-inflammatory outcomes, respectively. High glucose pushes signaling in favor of necroptosis producing a hyperglycemic shift from apoptosis to necroptosis. This shift depends on receptor-interacting protein 1 (RIP1) and mitochondrial reactive oxygen species (ROS). Here, we show that RIP1, mixed lineage kinase domain-like (MLKL) protein, Bcl-2 agonist/killer (Bak), Bcl-2 associated x (Bax) protein, and dynamin-related protein 1 (Drp1) traffic to the mitochondria in high glucose. RIP1 and MLKL appear in the mitochondria in their activated, phosphorylated states while Drp1 appears in its activated, dephosphorylated state in high glucose. Mitochondrial trafficking is prevented in rip1 KO cells and upon treatment with N-acetylcysteine. Induction of ROS replicated the mitochondrial trafficking seen in high glucose. MLKL forms high MW oligomers in the outer and inner mitochondrial membranes while Bak and Bax form high MW oligomers in the outer mitochondrial membrane in high glucose, suggesting pore formation. MLKL, Bax, and Drp1 promoted cytochrome c release from the mitochondria as well as a decrease in mitochondrial membrane potential in high glucose. These results indicate that mitochondrial trafficking of RIP1, MLKL, Bak, Bax, and Drp1 are key events in the hyperglycemic shift from apoptosis to necroptosis. This is also the first report to show oligomerization of MLKL in the inner and outer mitochondrial membranes and dependence of mitochondrial permeability on MLKL. Full article

(This article belongs to the Special Issue Emerging Research in Cell Death and Differentiation)

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16 pages, 3470 KiB

Open AccessArticle

Gluten Exorphins Promote Cell Proliferation through the Activation of Mitogenic and Pro-Survival Pathways

by Federico Manai, Lisa Zanoletti, Giulia Morra, Samman Mansoor, Francesca Carriero, Elena Bozzola, Stella Muscianisi and Sergio Comincini

Int. J. Mol. Sci. 2023, 24(4), 3912; https://doi.org/10.3390/ijms24043912 - 15 Feb 2023

Viewed by 2688

Abstract

Celiac disease (CD) is a chronic and systemic autoimmune disorder that affects preferentially the small intestine of individuals with a genetic predisposition. CD is promoted by the ingestion of gluten, a storage protein contained in the endosperm of the seeds of wheat, barley, rye, and related cereals. Once in the gastrointestinal (GI) tract, gluten is enzymatically digested with the consequent release of immunomodulatory and cytotoxic peptides, i.e., 33mer and p31-43. In the late 1970s a new group of biologically active peptides, called gluten exorphins (GEs), was discovered and characterized. In particular, these short peptides showed a morphine-like activity and high affinity for the δ-opioid receptor (DOR). The relevance of GEs in the pathogenesis of CD is still unknown. Recently, it has been proposed that GEs could contribute to asymptomatic CD, which is characterized by the absence of symptoms that are typical of this disorder. In the present work, GEs cellular and molecular effects were in vitro investigated in SUP-T1 and Caco-2 cells, also comparing viability effects with human normal primary lymphocytes. As a result, GEs treatments increased tumor cell proliferation by cell cycle and Cyclins activation as well as by induction of mitogenic and pro-survival pathways. Finally, a computational model of GEs interaction with DOR is provided. Altogether, the results might suggest a possible role of GEs in CD pathogenesis and on its associated cancer comorbidities. Full article

(This article belongs to the Special Issue Emerging Research in Cell Death and Differentiation)

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18 pages, 6906 KiB

Open AccessArticle

Effects of Focused Vibrations on Human Satellite Cells

by Silvia Sancilio, Sara Nobilio, Antonio Giulio Ruggiero, Ester Sara Di Filippo, Gianmarco Stati, Stefania Fulle, Rosa Grazia Bellomo, Raoul Saggini and Roberta Di Pietro

Int. J. Mol. Sci. 2022, 23(11), 6026; https://doi.org/10.3390/ijms23116026 - 27 May 2022

Cited by 2 | Viewed by 2150

Abstract

Skeletal muscle consists of long plurinucleate and contractile structures, able to regenerate and repair tissue damage by their resident stem cells: satellite cells (SCs). Reduced skeletal muscle regeneration and progressive atrophy are typical features of sarcopenia, which has important health care implications for humans. Sarcopenia treatment is usually based on physical exercise and nutritional plans, possibly associated with rehabilitation programs, such as vibratory stimulation. Vibrations stimulate muscles and can increase postural stability, balance, and walking in aged and sarcopenic patients. However, the possible direct effect of vibration on SCs is still unclear. Here, we show the effects of focused vibrations administered at increasing time intervals on SCs, isolated from young and aged subjects and cultured in vitro. After stimulations, we found in both young and aged subjects a reduced percentage of apoptotic cells, increased cell size and percentage of aligned cells, mitotic events, and activated cells. We also found an increased number of cells only in young samples. Our results highlight for the first time the presence of direct effects of mechanical vibrations on human SCs. These effects seem to be age-dependent, consisting of a proliferative response of cells derived from young subjects vs. a differentiative response of cells from aged subjects. Full article

(This article belongs to the Special Issue Emerging Research in Cell Death and Differentiation)

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Review

Jump to: Research

16 pages, 1654 KiB

Open AccessReview

The Dual Role of Necroptosis in Pancreatic Ductal Adenocarcinoma

by Valentina Giansante, Gianmarco Stati, Silvia Sancilio, Emanuela Guerra, Saverio Alberti and Roberta Di Pietro

Int. J. Mol. Sci. 2023, 24(16), 12633; https://doi.org/10.3390/ijms241612633 - 10 Aug 2023

Cited by 1 | Viewed by 1200

Abstract

Pancreatic cancer (PC) is the seventh leading cause of cancer-related death. PC incidence has continued to increase by about 1% each year in both men and women. Although the 5-year relative survival rate of PC has increased from 3% to 12%, it is still the lowest among cancers. Hence, novel therapeutic strategies are urgently needed. Challenges in PC-targeted therapeutic strategies stem from the high PC heterogeneity and from the poorly understood interplay between cancer cells and the surrounding microenvironment. Signaling pathways that drive PC cell growth have been the subject of intense scrutiny and interest has been attracted by necroptosis, a distinct type of programmed cell death. In this review, we provide a historical background on necroptosis and a detailed analysis of the ongoing debate on the role of necroptosis in PC malignant progression. Full article

(This article belongs to the Special Issue Emerging Research in Cell Death and Differentiation)

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19 pages, 2174 KiB

Open AccessReview

Role of YAP as a Mechanosensing Molecule in Stem Cells and Stem Cell-Derived Hematopoietic Cells

by Nattaya Damkham, Surapol Issaragrisil and Chanchao Lorthongpanich

Int. J. Mol. Sci. 2022, 23(23), 14634; https://doi.org/10.3390/ijms232314634 - 23 Nov 2022

Cited by 5 | Viewed by 2130

Abstract

Yes-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1, also known as TAZ) are transcriptional coactivators in the Hippo signaling pathway. Both are well-known regulators of cell proliferation and organ size control, and they have significant roles in promoting cell proliferation and differentiation. The roles of YAP and TAZ in stem cell pluripotency and differentiation have been extensively studied. However, the upstream mediators of YAP and TAZ are not well understood. Recently, a novel role of YAP in mechanosensing and mechanotransduction has been reported. The present review updates information on the regulation of YAP by mechanical cues such as extracellular matrix stiffness, fluid shear stress, and actin cytoskeleton tension in stem cell behaviors and differentiation. The review explores mesenchymal stem cell fate decisions, pluripotent stem cells (PSCs), self-renewal, pluripotency, and differentiation to blood products. Understanding how cells sense their microenvironment or niche and mimic those microenvironments in vitro could improve the efficiency of producing stem cell products and the efficacy of the products. Full article

(This article belongs to the Special Issue Emerging Research in Cell Death and Differentiation)

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