Triptolide inhibits ovarian cancer growth and metastasis via reprogramming of tumor-associated macrophages
For full text please see pdf.
Cell Stress
Cell Stress (CES) emerges as a peer-reviewed publishing platform for high-impact research. CES publishes articles of extraordinary novelty and significance, including research papers and reviews that cover heterogenous topics in the field of cellular pathophysiology.
MicroRNA as key players in skin regeneration and anti-aging pathways
Azizi et al.For full text please see pdf.
Stress management by benzodiazepines in septic shock and critical illness: mechanistic and clinical evidence supporting alternative sedative strategies
Lambertucci et al.For full text please see pdf.
Triptolide inhibits ovarian cancer growth and metastasis via reprogramming of tumor-associated macrophages
Chen et al.For full text please see pdf.
The IRE1α-XBP1s-NFκB axis controls cell survival and epithelial differentiation under osmotic stress through arachidonic acid metabolism activation
Parra et al.Arachidonic acid (AA) metabolism plays a critical role in renal cell osmoadaptation. We recently demonstrated that hypertonicity induces the expression and activation of cytosolic phospholipase A2 (cPLA2). On one hand, AA released by cPLA2 enhances triacylglyceride (TG) synthesis and accumulation. On the other hand, AA is converted into prostaglandins (PG) through cyclooxygenase 2 (COX2) activity. Both processes are required for renal cell survival under osmotic stress. However, the mechanisms by which hypertonicity induces cPLA2 expression remain poorly understood. Given that we previously shown that hypertonicity regulates TG synthesis through the IRE1α-XBP1s branch of the unfolded protein (…)
Multifaceted role of CNPY2 beyond ER stress: Disease implications and therapeutic potential
Ebadollahibaruq et al.This review meticulously dissects CNPY2’s structural characteristics, expression patterns, and biological functions across various disorders, emphasizing its role on tumor initiation, microenvironmental stress, and chemoresistance, and evaluating its potential as a therapeutic target.
Antifungal peptides: from modes of action to synergistic and immunologic potential
Carmona-Gutierrez et al.Reversal of Cushing syndrome by antibody-mediated neutralization of ACBP/DBI
Shen et al.For full text please see pdf.
RPA and Pif1 cooperate to remove G-rich structures at both leading and lagging strand
Maestroni et al.In Saccharomyces cerevisiae, the absence of Pif1 helicase induces the instability of G4-containing CEB1 minisatellite during leading strand but not lagging strand replication. We report that RPA and Pif1 cooperate to maintain CEB1 stability when the G4 forming strand is either on the leading or lagging strand templates. At the leading strand, RPA acts in the same pathway as Pif1 to maintain CEB1 stability. Consistent with this result, RPA co-precipitates with Pif1. This association between Pif1 and RPA is affected by the rfa1-D228Y mutation that lowers the affinity of RPA in particular for G-rich single-stranded DNA. At the lagging strand, in contrast to pif1∆, the rfa1-D228Y mutation strongly increases the frequency of CEB1 rearrangements. We explain that Pif1 is dispensable at the lagging strand DNA by the ability of RPA by itself to prevent formation of stable G-rich secondary structures during lagging (…)
LTX-315 sequentially promotes lymphocyte-independent and lymphocyte-dependent antitumor effects
Liao et al.LTX-315 is an oncolytic peptide that has antitumor efficacy in mice grafted with various tumor cell lines and is currently being tested in phase II clinical trials. Here we aimed to further evaluate LTX-315 in conditional genetic mouse models of cancer that typically resist current treatment options and to better understand the drug’s mode of action in vivo. We report LTX-315 mediates profound antitumor effects against Braf- and Pten-driven melanoma and delays the progression of Kras- and P53-driven soft tissue sarcoma in mice. Additionally, we show in melanoma that LTX-315 triggers two sequential phases of antitumor response. The first phase of response, which begins within minutes of drug delivery into tumors, is defined by disrupted tumor vasculature and decreased tumor burden and occurs independently of (…)
Inflammation induced PD-L1-specific T cells
Munir et al.PD-L1-specific T cells are a natural part of the T-cell repertoire in humans. Hence, we have previously described spontaneous CD8+ and CD4+ T-cell reactivity against PD-L1 in the peripheral blood of patients with various cancers as well as in healthy donors. It is well described that the expression of the PD-L1 protein is introduced in cells by pro-inflammatory cytokines, e.g. IFN-γ. In the current study, we were able to directly link inflammation with PD-L1-specific T cells by showing that inflammatory mediators such as IFN-γ generate measurable numbers of PD-L1-specific T cells in human PBMCs as well as in in vivo models. These PD-L1-specific T cells can vigorously modulate the cell compartments of the local environment. PD-L1-specific T cells may be important for immune homeostasis by sustaining the ongoing inflammatory response by the suppression of regulatory cell function both (…)
Gold Nanoparticles sensitize pancreatic cancer cells to gemcitabine
Huai et al.INTRODUCTION Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease. The mortality rate closely parallels that of incidence [1][2]. The current standard of care for advanced stage PDAC patients includes combination treatment with Nab-paclitaxel and
The primary cilium protein folliculin is part of the autophagy signaling pathway to regulate epithelial cell size in response to fluid flow
Zemirli et al.Autophagy is a conserved molecular pathway directly involved in the degradation and recycling of intracellular components. Autophagy is associated with a response to stress situations, such as nutrients deficit, chemical toxicity, mechanical stress or microbial host defense. We have recently shown that primary cilium-dependent autophagy is important to control kidney epithelial cell size in response to fluid flow induced shear stress. Here we show that the ciliary protein folliculin (FLCN) actively participates to the signaling cascade leading to the stimulation of fluid flow-dependent autophagy upstream of the cell size regulation in HK2 kidney epithelial cells. The knockdown of FLCN induces a shortening of the primary cilium, inhibits the activation of AMPK and the recruitment of the autophagy protein ATG16L1 at the primary cilium. Altogether, our results suggest that FLCN (…)
Neuronal Lamin regulates motor circuit integrity and controls motor function and lifespan
Oyston et al.Neuronal aging involves a progressive decline in cognitive abilities and loss of motor function. Mutations in human Lamin genes (LMNA, LMNB1, LMNB2) lead to a wide-range of diseases including muscular dystrophy, peripheral neuropathy and progeria. Here we investigate the role of neuronal Lamin in regulating age-related phenotypes. Neuronal targeting of Lamin led to shortened lifespan, progressive impairment of motor function and loss of dopaminergic (DA) neurons within the protocerebral anterior medial (PAM) cluster in the Drosophila melanogaster brain. Loss of neuronal Lamin caused an age-related decline in neural physiology, with slower neurotransmission and increased chance of motor circuit failure with age. Unexpectedly, Lamin-dependent decline in motor function was specific for the chemical synapses of the dorsal longitudinal muscle (DLM). Together (…)
Assay for high-throughput screening of inhibitors of the ASC-PYD inflammasome core filament
Sborgi et al.The protein ASC is a central component of most inflammasome complexes, forming functional oligomeric filaments that activate large amounts of pro-caspase-1 for further IL-1β processing and the induction of Gasdermin D-dependent cell death. The central role of inflammasomes in the innate immune response pose them as new molecular targets for therapy of diverse acute, chronic and inherited autoinflammatory pathologies. In recent years, an increasing number of molecules were proposed to modulate inflammasome signalling by interacting with different components of inflammasome complexes. However, the difficult in vitro reconstitution of the inflammasome has limited the development of specific on-target biochemical assays for compound activity confirmation and for drug discovery in high throughput screening setups. Here we describe a homogeneous, pH (…)
Dram1 regulates DNA damage-induced alternative autophagy
Nagata et al.Autophagy is an evolutionarily conserved process that degrades subcellular constituents. Mammalian cells undergo two types of autophagy; Atg5-dependent conventional autophagy and Atg5-independent alternative autophagy, and the molecules required for the latter type of autophagy are largely unknown. In this study, we analyzed the molecular mechanisms of genotoxic stress-induced alternative autophagy, and identified the essential role of p53 and damage-regulated autophagy modulator (Dram1). Dram1 was sufficient to induce alternative autophagy. In the mechanism of alternative autophagy, Dram1 functions in the closure of isolation membranes downstream of p53. These findings indicate that Dram1 plays a pivotal role in genotoxic stress-induced alternative autophagy.
Mechanisms of YAP/TAZ transcriptional control
Battilana et al.Dysregulated gene expression is intrinsic to cell transformation, tumorigenesis and metastasis. Cancer-specific gene-expression profiles stem from gene regulatory networks fueled by genetic and epigenetic defects, and by abnormal signals of the tumor microenvironment. These oncogenic signals ultimately engage the transcriptional machinery on the cis -regulatory elements of a host of effector genes, through recruitment of transcription factors (TFs), co-activators and chromatin regulators. That said, whether gene -expression in cancer cells is the chaotic product of myriad regulations or rather a relatively ordered process orchestrated by few TFs (master regulators) has long remained enigmatic. Recent work on the YAP/TAZ co-activators has been instrumental to break new ground into this outstanding issue, revealing that tumor cells hijack growth programs that are active during development and regeneration through engagement of a small set of interconnected TFs and their nuclear partners.
GRASPing the unconventional secretory machinery to bridge cellular stress signaling to the extracellular proteome
Demetriades et al.Part of the cellular response to stress is an evolutionarily conserved, poorly-understood process called unconventional protein secretion (UPS). Although cells shut down conventional/bulk secretion to save resources upon stress, UPS is induced by specific stress
Macroautophagy and normal aging of the nervous system: Lessons from animal models
Kallergi and NikoletopoulouAging represents a cumulative form of cellular stress, which is thought to challenge many aspects of proteostasis. The non-dividing, long-lived neurons are particularly vulnerable to stress, and, not surprisingly, even normal aging is highly associated with a decline in brain function in humans, as well as in other animals. Macroautophagy is a fundamental arm of the proteostasis network, safeguarding proper protein turnover during different cellular states and against diverse cellular stressors. An intricate interplay between macroautophagy and aging is beginning to unravel, with the emergence of new tools, including those for monitoring autophagy in cultured neurons and in the nervous system of different organisms in vivo. Here, we review recent findings on the impact of aging on neuronal integrity and on neuronal macroautophagy, as they emerge from studies in invertebrate and mammalian models.
Atg8ylation as a general membrane stress and remodeling response
Kumar et al.The yeast Atg8 protein and its paralogs in mammals, mammalian Atg8s (mAtg8s), have been primarily appreciated for their participation in autophagy. However, lipidated mAtg8s, including the most frequently used autophagosomal membrane marker LC3B, are found on cellular membranes other than autophagosomes. Here we put forward a hypothesis that the lipidation of mAtg8s, termed ‘Atg8ylation’, is a general membrane stress and remodeling response analogous to the role that ubiquitylation plays in tagging proteins. Ubiquitin and mAtg8s are related in sequence and structure, and the lipidation of mAtg8s occurs on its C-terminal glycine, akin to the C-terminal glycine of ubiquitin. Conceptually, we propose that mAtg8s and Atg8ylation are to membranes what ubiquitin and ubiquitylation are to proteins, and that, like ubiquitylation, Atg8ylation has a multitude of downstream effector outputs, one of which is autophagy.
PDLIM1: Structure, function and implication in cancer
Zhou et al.PDLIM1, a member of the PDZ-LIM family, is a cytoskeletal protein and functions as a platform to form distinct protein complexes, thus participating in multiple physiological processes such as cytoskeleton regulation and synapse formation. Emerging evidence demonstrates that PDLIM1 is dysregualted in a variety of tumors and plays essential roles in tumor initiation and progression. In this review, we summarize the structure and function of PDLIM1, as well as its important roles in human cancers.
Towards a better understanding of the neuro-developmental role of autophagy in sickness and in health
Zapata-Muñoz et al.Autophagy is a critical cellular process by which biomolecules and cellular organelles are degraded in an orderly manner inside lysosomes. This process is particularly important in neurons: these post-mitotic cells cannot divide or be easily replaced and are therefore especially sensitive to the accumulation of toxic proteins and damaged organelles. Dysregulation of neuronal autophagy is well documented in a range of neurodegenerative diseases. However, growing evidence indicates that autophagy also critically contributes to neurodevelopmental cellular processes, including neurogenesis, maintenance of neural stem cell homeostasis, differentiation, metabolic reprogramming, and synaptic remodelling. These findings implicate autophagy in neurodevelopmental disorders. In this review we discuss the current understanding of the role of autophagy in neurodevelopment and neurodevelopmental disorders, as well as currently available tools and techniques that (…)
Ribosome traffic jam in neurodegeneration: decoding hurdles in Huntington disease
SubramaniamThe symptoms of HD, a neurodegenerative disorder, are severe disruption of cognitive and motor functions, including changes in posture and gait. HTT, the gene responsible for HD, is CAG (codes for glutamine (Q)) expanded and
The evolution of the concept of stress and the framework of the stress system
Lu et al.Stress is a central concept in biology and has now been widely used in psychological, physiological, social, and even environmental fields. However, the concept of stress was cross-utilized to refer to different elements of the stress system including stressful stimulus, stressor, stress response, and stress effect. Here, we summarized the evolution of the concept of stress and the framework of the stress system. We find although the concept of stress is developed from Selye’s “general adaptation syndrome”, it has now expanded and evolved significantly. Stress is now defined as a state of homeostasis being challenged, including both system stress and local stress. A specific stressor may potentially bring about specific local stress, while the intensity of stress beyond a threshold may commonly activate the hypothalamic-pituitary-adrenal axis and result in a systematic stress response. The framework of the stress system indicates that stress includes three types: (…)
Stress management by benzodiazepines in septic shock and critical illness: mechanistic and clinical evidence supporting alternative sedative strategies
Lambertucci et al.For full text please see pdf.
Burning fat with cysteine depletion
Adams et al.Adams and colleagues comment on two complementary articles by Varghese et al and Lee et al showing that cysteine depletion through combined dietary and genetic means in mice evokes a unique stress response in the liver to amplify these metabolic outcomes and offer a potentially new treatment option for obesity.
Pathogenic hyperactivation of mTORC1 by cytoplasmic EP300 in Hutchinson-Gilford progeria syndrome
Ferret et al.Mechanistic target of rapamycin complex 1 (mTORC1) is a multiprotein complex that serves as a pivotal regulator of cell growth, protein synthesis, metabolism and autophagy [1][2]. This complex compromises mTOR (mechanistic target of rapamycin), RAPTOR
The missing hallmark of health: psychosocial adaptation
López-Otín and KroemerINTRODUCTION The comprehension of health –defined in a positive fashion rather than as the absence of disease–requires a theory. We recently launched the bases of such a health theory by enumerating the fundamental biological characteristics
Gut microbiota turn up the heat after bariatric surgery
Mohammed K. HankirBariatric surgeries like vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) cause well-established shifts in the gut microbiota, but how this contributes to their unique metabolic benefits is poorly understood. Jin et al and Yadav et al now provide two complementary lines of evidence suggesting that gut microbiota-derived metabolites after VSG and RYGB activate thermogenesis in fat through distinct mechanisms, to in turn promote weight loss and/or improvements in glycemic control.
Molecular targets of spermidine: implications for cancer suppression
Zimmermann et al.Spermidine is a ubiquitous, natural polyamine with geroprotective features. Supplementation of spermidine extends the lifespan of yeast, worms, flies, and mice, and dietary spermidine intake correlates with reduced human mortality. However, the crucial role of polyamines in cell proliferation has also implicated polyamine metabolism in neoplastic diseases, such as cancer. While depleting intracellular polyamine biosynthesis halts tumor growth in mouse models, lifelong external spermidine administration in mice does not increase cancer incidence. In contrast, a series of recent findings points to anti-neoplastic properties of spermidine administration in the context of immunotherapy. Various molecular mechanisms for the anti-aging and anti-cancer properties have been proposed, including the promotion of autophagy, enhanced translational control, and augmented mitochondrial function. For instance, spermidine allosterically activates mitochondrial trifunctional protein (MTP), a bipartite protein complex that mediates (…)
Novel insights at the crossroads of antibiotic use and cancer risk
Malanovic and VejzovicThe continuous use of antibiotics is associated with the spread of antimicrobial resistances and the not yet clear link to cancer development. Many conventional antibiotics have already shown different effects on a variety of cancer types raising questions for their rational use in cancer. However, discrepancy in the observed trend for some antibiotics reducing cancer development and being associated with higher risk of cancer underscores the lack of understanding the complex link between antibiotics and cancer. Here, we briefly summarize the possible antibiotic-mediated effects on cancer and conclude that those effects can be direct via i) specific targeting of tumor/cancer, ii) antimicrobial activity and iii) immunomodulatory activity whereby iv) indirectly caused effects primarily affect immune equilibrium between bacteria, cancer and immune cells. Furthermore, we also conclude that there is a great need for bulk profiling, comprehensive screening programs in all countries and in-depth studies to understand the risks and benefits of antibiotic use.
Impact of microbiota on breast cancer hormone therapy
Terrisse et al.Recent observations indicate that the pathogenesis and prognosis of hormone-receptor breast cancer is not only dictated by the properties of the malignant cells but also by immune and microbial parameters. Thus, the immunosurveillance system retards the development of hormone-positive breast cancer and contributes to the therapeutic efficacy of estrogen receptor antagonists and aromatase inhibitors. Moreover, the anticancer immune response is profoundly modulated by the local and intestinal microbiota, which influences cancer cell-intrinsic signaling pathways, affects the composition and function of the immune infiltrate present in the tumor microenvironment and modulates the metabolism of estrogens. Indeed, specific bacteria in the gut produce enzymes that affect the enterohepatic cycle of estrogen metabolites, convert estrogens into androgens or generate estrogen-like molecules. The knowledge of these circuitries is in its infancy, calling for further in-depth analyses.
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Peer-reviewed, open-access research using unicellular organisms (and multicellular microorganisms) to understand cellular responses and human disease.
The journal (founded in 2014) is led by its Editors-in-Chief Frank Madeo, Didac Carmona-Gutierrez, and Guido Kroemer
Microbial Cell has been publishing original scientific literature since 2014, and from the very beginning has been managed by active scientists through an independent Publishing House (Shared science Publishers). The journal was conceived as a platform to acknowledge the importance of unicellular organisms, both as model systems as well as in the biological context of human health and disease.
Ever since, Microbial Cell has very positively developed and strongly grown into a respected journal in the unicellular research community and even beyond. This scientific impact is reflected in the yearly number of citations obtained by articles published in Microbial Cell, as recorded by the Web of Science (Clarivate, formerly Thomson/Reuters):
The scientific impact of Microbial Cell is also mirrored in a series of milestones:
2015: Microbial Cell is included in the Emerging Sources Citation Index (ESCI), a selection of developing journals drafted by Clarivate Analytics based on the candidate’s publishing standards, quality, editorial content, and citation data. Note: As an ESCI-selected journal, Microbial Cell is currently being evaluated in a rigorous and long process to determine an inclusion in the Science Citation Index Expanded (SCIE), which allows the official calculation of Clarivate Analytics’ impact factor.
2016: Microbial Cell is awarded the so-called DOAJ Seal by the selective Directory of Open Access Journals (DOAJ). The DOAJ Seal is an exclusive mark of certification for open access journals granted by DOAJ to journals that adhere to outstanding best practice and achieve an extra high and clear commitment to open access and high publishing standards.
2017: Microbial Cell is included in Pubmed Central (PMC), allowing the archiving of all the journal’s articles in PMC and PubMed.
2019: Microbial Cell is indexed in the prestigious abstract and citation database Scopus after a thorough selection process. This also means that Microbial Cell obtains, for the first time, an official Scopus CiteScore as well as an official journal ranking in the Scimago Journal and Country Ranking.
2022: Microbial Cell’s CiteScore reaches a value of 7.2 for the year 2021, positioning Microbial Cell among the top microbiology journals (previously available CiteScores: 2019: 5.4; 2020: 5.1).
2022: Microbial Cell is indexed in the highly selective Science Citation Index Expanded™, which covers approx. 9,500 of the world’s most impactful journals across 178 scientific disciplines. In their journal selection and curation process, Clarivate´s editors apply 24 ‘quality’ criteria and four ‘impact’ criteria to select the most influential journals in their respective fields. This selection is also a pre-requisite for inclusion in the JCR, which features the impact factor.
2022: Microbial Cell is listed in the Journal Citation Reports™ (JCR), and obtains its first official Journal Impact Factor™ (JIF) for the year 2021: 5.316.Check Article Types and Manuscript Preparation guidelines. Submit online via Scholastica.