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.
CircRNA regulates the liquid-liquid phase separation of ATG4B, a novel strategy to inhibit cancer metastasis?
© 2024 Guo et al.
Metastasis is the leading cause of death in cancer patients. Currently, there are no effective treatments to prevent cancer metastases. Therefore, it is imperative to provide more effective biomarkers and targets for the diagnosis and
STING-driven activation of T cells: relevance for the adoptive cell therapy of cancer
Richter et al.Adoptive cell therapy (ACT) can successfully treat hematopoietic cancers but lacks efficacy against solid tumors. This is due to insufficient T cell infiltration, high tumor heterogeneity, frequent antigen loss with subsequent tumor escape, and the immunosuppressive tumor microenvironment (TME). Alternative methods to boost the anticancer efficacy of adoptively transferred cells are actively pursued. Among adjuvants that are utilized to stimulate anticancer immune responses, ligands of the stimulator of interferon genes (STING) pathway have received increasing attention. STING activation can trigger dendritic cell (DC) activation and endogenous immune responses, thereby preventing tumor escape. Activation of the STING pathway in the context of ACT was accordingly associated with improved T cell trafficking and persistence in the TME combined with the reduced presence of immunosuppressive cells. Recent findings (…)
Chronic heart failure following hemorrhagic myocardial infarction: mechanism, treatment and outlook
Chan et al.Myocardial infarction (MI), the blockage of arterial blood supply of the heart, is among the most common causes of death worldwide. Even when patients receive immediate treatment by re-opening blocked arteries, they often develop chronic heart failure (CHF) in the aftermath of MI events. Yet, the factors that contribute to the development of MI-associated CHF are poorly understood. In our recent study (Nat Commun 13:6394), we link intramyocardial hemorrhage, an injury which can occur during reperfusion of areas affected by MI, to an increased risk of CHF. Mechanistically, our data suggest that an iron-induced adverse cascade of events after hemorrhagic MI drives fatty degeneration of infarcted tissue, which ultimately contributes to negative cardiac remodeling. In this Microreview, we discuss the implications of our findings regarding the molecular mechanism, more targeted treatment options as well as perspectives in the clinical (…)
Unraveling the surface proteomic profile of multiple myeloma to reveal new immunotherapeutic targets and markers of drug resistance
Patiño-Escobar et al.The cell surface proteome (“surfaceome”) serves as the interface between diseased cells and their local microenvironment. In cancer, this compartment is critical not only for defining tumor biology but also serves as a rich source of potential therapeutic targets and diagnostic markers. Recently, we profiled the surfaceome of the blood cancer multiple myeloma, an incurable plasma cell malignancy. While available small molecule agents can drive initial remissions in myeloma, resistance inevitably occurs. Several new classes of immunotherapies targeting myeloma surface antigens, including antibody therapeutics and chimeric antigen receptor (CAR) T-cells, can further prolong survival. However, new approaches are still needed for those who relapse. We thus applied the glycoprotein cell surface capture (CSC) methodology to panel of multiple myeloma cell lines, identifying key surface protein features of malignant plasma cells. We characterized the most (…)
Pyroptosis in NLRP3 inflammasome-related atherosclerosis
Zeng et al.Pyroptosis is a proinflammatory form of programmed cell death in response to inflammation. It involves in the pathogenesis and outcomes of atherosclerosis characterized by NLRP3 inflammasome assembly, membrane pore formation, cell swelling, pro-inflammatory mediator and cytokine release. There are known pyroptosis molecular pathways including the caspase-1 depended canonical signaling pathway and the caspase-4/5/11 determined non-canonical signaling pathway. It is essential to explore the connection among NLRP3 inflammasome, pyroptosis and atherosclerosis, which may shed light on the potential therapeutic strategies that target pyroptosis in atherosclerotic treatment.
COX-2 upregulation by tumour cells post-chemotherapy fuels the immune evasive dark side of cancer inflammation
Charlotte R. Bell and Santiago ZelenayCytotoxic therapies, such as chemotherapy and radiotherapy, are mainstays of cancer treatment for both early and unresectable, advanced disease. In addition to debulking the tumour mass through direct killing of proliferating tumour cells, these treatments can promote tumour control via immune-stimulating effects. Nonetheless, chemoresistance and tumour relapse remain huge clinical problems, suggesting that induction of anti-cancer immunity post-cytotoxic therapy is often weak, not durable and/or overcome by immune evasive mechanisms. In our recent study (Nat Commun 13:2063), we demonstrate that cancer cell-intrinsic activation of the cyclooxygenase (COX)-2/prostaglandin E2 (PGE2) pathway post-chemotherapy treatment is a prevalent phenomenon which profoundly alters the inflammatory properties of the treated cancer cells. Of particular translational relevance, our findings support a model whereby upregulation of COX-2 expression (…)
Could TNF-antagonists be a novel treatment strategy for BPH patients?
Vickman et alTumor necrosis factor (TNF) is widely recognized as a pivotal player in both systemic and local inflammatory processes. Due to the critical role this molecule has in driving both chronic and acute inflammation, it was among the earliest therapeutic targets utilized for pa-tients with autoimmune (AI) diseases. While inflamma-tion in the prostate is commonly observed, the organ has not previously been considered a target of systemic inflammation associated with some AI diseases. In pa-tients with benign prostatic hyperplasia (BPH), chronic inflammation is common, and immune cells represent a significant proportion of cells in the organ. Accumulation of inflammatory cells may be a response to an initial in-sult and/or a factor in driving BPH pathogenesis. Cer-tainly, inflammation can limit the efficacy of existing medical therapies in these patients. We previously showed that a pattern of gene expression in BPH tissues from patients who had progressed to indication-specific surgery was consistent with the changes seen in AI dis-eases. Recently, we demonstrated that patients with AI disease have an approximately 50% increase in (…)
A pathological role of the Hsp40 protein Ydj1/DnaJA1 in models of Alzheimer’s disease
Tadic et al.Alzheimer’s disease (AD) is the most common form of dementia with millions of people affected worldwide. Pathophysiological manifestations of AD include the extracellular accumulation of amyloid beta (Abeta) peptides, products of the proteolytic cleavage of the amyloid precursor protein APP. Increasing evidence suggests that Abeta peptides also accumulate intracellularly, triggering neurotoxic events such as mitochondrial dysfunction. However, the molecular factors driving formation and toxicity of intracellular Abeta are poorly understood. In our recent study [EMBO Mol Med 2022 – e13952], we used different eukaryotic model systems to identify such factors. Based on a genetic screen in yeast and subsequent molecular analyses, we found that both the yeast chaperone Ydj1 and its human ortholog DnaJA1 physically interact with Abeta, facilitate the aggregation of Abeta (…)
Genotoxic stress signalling as a driver of macrophage diversity
Kasapi and TriantafyllopoulouTissue macrophages arise from yolk sac, fetal liver and hematopoietic progenitors and adopt diverse transcriptional programs and phenotypes, instructed by their microenvironment. In chronic inflammation, such as in chronic infections, autoimmunity, or cancer, tissue microenvironments change dramatically thus imprinting new programs on tissue macrophages. While stress is a known driver of carcinogenesis in epithelial cells, emerging evidence suggests that macrophage responses to genotoxic stress are embedded in their ‘physiologic’ immune and tissue healing programs and in most cases do not lead to myeloid malignancies. The role of genotoxic stress as an instructor of macrophage-mediated immune defense and tissue remodeling is only beginning to be understood. Here, we review the evidence showing that genotoxic stress, which macrophages and their precursors face (…)
HIF1α or mitophagy: which drives cardiomyocyte differentiation?
Villarejo-Zori et al.Cardiomyocytes (CMs) are the main cellular component of the heart's atria and ventricles, and their contractile capacity is the engine that drives blood flow throughout the body. The differentiation of cardiac myoblasts into CMs during
Copper – a novel stimulator of autophagy
Zischka and KroemerIn biomedicine, the transition metal copper has a Janus-faced dual role, as an essential but static cofactor of vital enzymes but also as a highly detrimental poison, if in excess. This vision is best exemplified
Coronavirus infections: Epidemiological, clinical and immunological features and hypotheses
INTRODUCTION Infections have been limiting quality of life and longevity throughout human history. Endemic infections have been associated to a significant number of avoidable deaths and a significant increase of morbidity all around the word.
ACBP is an appetite stimulator across phylogenetic barriers
Madeo et al.Human civilization is unique with respect to the organization of our natural environment, allowing constant supply of nutrients to most individuals in developed countries, contrasting with the natural fluctuation in food sources found in wildlife.
LTX-315 – a promising novel antitumor peptide and immunotherapeutic agent
ZweytickHost defense in mammals, as provided by the innate immune system, comprises proteins such as lactoferrin (LF), a multifunctional iron-binding glycoprotein originally discovered in bovine milk. LF is further pepsin-cleaved to a cationic amphipathic peptide,
Anti-regulatory T cells are natural regulatory effector T cells
ØdumIt is well established that the immune system uses regulatory immune-suppressive cells to inhibit and terminate immune reactions and maintain immune balance. In the last decade, Andersen and colleagues have discovered that regulatory cells also
The targeting of tumor-associated macrophages by vaccination
AndersenImmune suppressive myeloid cells include a heterogenous population of cells that include tumor-associated macrophages (TAMs). TAMs are major players in inducing the immunosuppressive microenvironment associated with many tumors. These lesions were recently defined as tumors
Mitochondrial stress delays tumorigenesis in a Li-Fraumeni syndrome mouse model
Donnelly et al.As a prominent hub of metabolic activity, the mitochondrion can initiate retrograde signaling in response to bioenergetic stress that is important for various adaptive changes including cell cycle regulation [1][2]. There is abundant evidence that
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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.