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.
CRISPR-activation screen identified potassium channels for protection against mycotoxins through cell cycle progression and mitochondrial function
Tang et al.Zearalenone (ZEA) exposure has carcinogenic effects on human and animal health by exhibiting intestinal, hepatic, and renal toxicity. At present, the underlying mechanisms on how ZEA induces apoptosis and damage to tissues still remain unclear. In this study, we aimed to identify genes that modulate the cellular response to ZEA using clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 screening, and further validate novel gene functions to elucidate molecular mechanisms underlying particular biological processes in vivo and in vitro. Two ZEA-resistant cell lines, designated Ov-KCNJ4 and Ov-KCNJ12, were yielded by CRISPR activation screening which had significant changes in ZEA resistance and growth rates. Results showed that ZEA could interact with the cell membrane proteins (…)
Macrolide antibiotics activate the integrated stress response and promote tumor proliferation
Yu et al.Macrolide antibiotics are widely used antibacterial agents that are associated with autophagy inhibition. This study aimed to investigate the association between macrolide antibiotics and malignant tumors, as well as the effect on autophagy, reactive oxygen species (ROS) accumulation and integrated stress response (ISR). The meta-analysis indicated a modestly higher risk of cancer in macrolide antibiotic ever-users compared to non-users. Further experiments showed that macrolides block autophagic flux by inhibiting lysosomal acidification. Additionally, azithromycin, a representative macrolide antibiotic, induced the accumulation of ROS, and stimulated the ISR and the activation of transcription factor EB (TFEB) and TFE3 in a ROS-dependent manner. Finally, animal experiments confirmed that azithromycin promoted tumor progression in vivo, which (…)
Autophagic degradation of CNS myelin maintains axon integrity
Ktena et al.(Macro)autophagy is a major lysosome-dependent degradation mechanism which engulfs, removes and recycles unwanted cytoplasmic material, including damaged organelles and toxic protein aggregates. Although a few studies implicate autophagy in CNS demyelinating pathologies, its role, particularly in mature oligodendrocytes and CNS myelin, remains poorly studied. Here, using both pharmacological and genetic inhibition of the autophagic machinery, we provide evidence that autophagy is an essential mechanism for oligodendrocyte maturation in vitro. Our study reveals that two core myelin proteins, namely proteolipid protein (PLP) and myelin basic protein (MBP) are incorporated into autophagosomes in oligodendrocytes, resulting in their degradation. Furthermore, we ablated atg5, a core gene of the autophagic machinery, specifically in myelinating (…)
COX4-1 promotes mitochondrial supercomplex assembly and limits reactive oxide species production in radioresistant GBM
Oliva et al.Glioblastoma (GBM) is a fatal disease with recurrences often associated with radioresistance. Although often effective at treating newly diagnosed GBM, increasing evidence suggests that radiotherapy-induced alterations in tumor metabolism promote GBM recurrence and aggressiveness. Using isogenic radiosensitive and radioresistant GBM cell lines and patient-derived xenolines, we found that acquired radioresistance is associated with a shift from a glycolytic metabolism to a more oxidative metabolism marked by a substantial increase in the activity of the mitochondrial respiratory chain complex cytochrome c oxidase (CcO). This elevated CcO activity was associated with a switch in the isoform expression of the CcO regulatory subunit COX4, from COX4-2 to COX4-1, assembly of CcO-containing mitochondrial supercomplexes (SCs), and reduced superoxide (O2●-) production. Overexpression of COX4-1 in the radiosensitive cells was sufficient to promote the switch from glycolytic to (…)
MYCN upregulates the transsulfuration pathway to suppress the ferroptotic vulnerability in MYCN-amplified neuroblastoma
Floros et al.Ferroptosis is an iron-dependent, oxidative form of cell death that is countered mainly by glutathione peroxidase 4 (GPX4) and the production of glutathione (GSH), which is formed from cysteine. The identification of the cancers that may benefit from pharmacological ferroptotic induction is just emerging. We recently demonstrated that inducing ferroptosis genetically or pharmacologically in MYCN-amplified neuroblastoma (NB) is a novel and effective way to kill these cells. MYCN increases iron metabolism and subsequent hydroxyl radicals through increased expression of the transferrin receptor 1 (TfR1) and low levels of the ferroportin receptor. To counter increased hydroxyl radicals, MYCN binds to the promoter of SLC3A2 (solute carrier family 3 member 2). SLC3A2 is a subunit of system Xc-, which is (…)
Evaluation of I-TAC as a potential early plasma marker to differentiate between critical and non-critical COVID-19
Zhang et al.INTRODUCTION The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is not a single entity but a disease with an extraordinary spectrum of phenotypes. The virus can cause asymptomatic
p38 regulates the tumor suppressor PDCD4 via the TSC-mTORC1 pathway
Braun et al.Programmed cell death protein 4 (PDCD4) exerts critical functions as tumor suppressor and in immune cells to regulate inflammatory processes. The phosphoinositide 3-kinase (PI3K) promotes degradation of PDCD4 via mammalian target of rapamycin complex 1 (mTORC1). However, additional pathways that may regulate PDCD4 expression are largely ill-defined. In this study, we have found that activation of the mitogen-activated protein kinase p38 promoted degradation of PDCD4 in macrophages and fibroblasts. Mechanistically, we identified a pathway from p38 and its substrate MAP kinase-activated protein kinase 2 (MK2) to the tuberous sclerosis complex (TSC) to regulate mTORC1-dependent (…)
Targeting the TGFβ pathway in uterine carcinosarcoma
Dwivedi et al.Uterine carcinosarcoma (UCS) is a relatively infrequent, but extremely aggressive endometrial malignancy. Although surgery and chemotherapy have improved outcomes, overall survival (OS) remains dismal due to the lack of targeted therapy and biphasic (epithelial and mesenchymal) nature that renders the tumor aggressive and difficult to manage. Here we report a role of transforming growth factor-β (TGFβ) in maintaining epithelial to mesenchymal transition (EMT) phenotype and aggressiveness in UCS. Using a 3D-culture system, we evaluated the efficacy of the transforming growth factor-β receptor-I (TGFβR1) kinase inhibitor Galunisertib (GLT), alone and in combination with standard chemotherapeutic drugs used for the management of UCS. We demonstrate that GLT by inhibiting canonical and non-canonical signaling emanating from transforming growth factor-β1 (TGFβ1) reduces cellular viability, invasion, clonal growth and differentiation. (…)
HIF1α-dependent mitophagy facilitates cardiomyoblast differentiation
Zhao et al.Mitophagy is thought to play a key role in eliminating damaged mitochondria, with diseases such as cancer and neurodegeneration exhibiting defects in this process. Mitophagy is also involved in cell differentiation and maturation, potentially through modulating mitochondrial metabolic reprogramming. Here we examined mitophagy that is induced upon iron chelation and found that the transcriptional activity of HIF1α, in part through upregulation of BNIP3 and NIX, is an essential mediator of this pathway in SH-SY5Y cells. In contrast, HIF1α is dispensable for mitophagy occurring upon mitochondrial depolarisation. To examine the role of this pathway in a metabolic reprogramming and differentiation context, we utilised the H9c2 cell line model of cardiomyocyte maturation. During differentiation of these cardiomyoblasts, mitophagy increased and required HIF1α-dependent upregulation of NIX. Though HIF1α was essential for expression of key (…)
Unraveling the molecular principles by which ceramides commit cells to death
Dadsena et al.EMERGENCE OF CERAMIDES AS TUMOR SUPPRESSOR LIPIDS Sphingolipids are unusually versatile membrane components that participate in mechanical stability, signaling, and molecular sorting. As the path to their production is paved with toxic intermediates, cells must
Immunosurveillance of cancer cell stress
Lorenzo-Herrero et al.Cancer development is tightly controlled by effector immune responses that recognize and eliminate malignantly transformed cells. Nonetheless, certain immune subsets, such as tumor-associated macrophages, have been described to promote tumor growth, unraveling a double-edge role of the immune system in cancer. Cell stress can modulate the crosstalk between immune cells and tumor cells, reshaping tumor immunogenicity and/or immune function and phenotype. Infiltrating immune cells are exposed to the challenging conditions typically present in the tumor microenvironment. In return, the myriad of signaling pathways activated in response to stress conditions may tip the balance toward stimulation of antitumor responses or immune-mediated tumor progression. Here, we explore how distinct situations of cellular stress influence innate and adaptive immunity and the consequent impact on cancer establishment and progression.
Impact of prophylactic TNF blockade in the dual PD-1 and CTLA-4 immunotherapy efficacy and toxicity
Alvarez et al.Inhibitory checkpoint blockade (ICB) immunotherapy has produced very significant advances in the fight against cancer (Figure 1). The synergistic combination of PD-1 and CTLA-4 blockade therapy has been successfully used against a variety of tumors
The role of epigenetics in hypothalamic energy balance control: implications for obesity
Obri and ClaretINTRODUCTION The prevalence of obesity continues to increase worldwide. This trend is of concern because of its dramatic economic impact, concomitant decreased lifespan and increased comorbidities, such as hypertension, cardiovascular diseases, type 2 diabetes (T2D)
Remodeling of mitochondrial morphology and function: an emerging hallmark of cellular reprogramming
Rastogi et al.Research in the stem cell field has traditionally focused on understanding key transcriptional factors that provide pluripotent cell identity. However, much less is known about other critical non-transcriptional signaling networks that govern stem cell identity. Although we continue to gain critical insights into the mechanisms underlying mitochondrial morphology and function during cellular reprogramming – the process of reverting the fate of a differentiated cell into a stem cell, many uncertainties remain. Recent studies suggest an emerging landscape in which mitochondrial morphology and function have an active role in maintaining and regulating changes in cell identity. In this review, we will focus on these emerging concepts as crucial modulators of cellular reprogramming. Recognition of the widespread applicability of these concepts will increase our understanding of the mitochondrial mechanisms involved in cell identity, cell fate and disease.
The sensing of mitochondrial DAMPs by non-immune cells
Rodríguez-Nuevo and ZorzanoMITOCHONDRIA ARE IMMUNOGENIC ORGANELLES The efficiency of the innate immune system is determined by the capacity of distinct cell types to discriminate self from non-self structures. The dysregulation of this ability results in either immunodeficiency
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.