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Keywords = microenvironnement

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21 pages, 908 KiB  
Review
The Critical Role of Adipocytes in Leukemia
by Romane Higos, Kevin Saitoski, Mathieu Hautefeuille, Geneviève Marcelin, Karine Clément, Nadine Varin-Blank, Christophe Breton, Simon Lecoutre and Mélanie Lambert
Biology 2025, 14(6), 624; https://doi.org/10.3390/biology14060624 - 28 May 2025
Viewed by 729
Abstract
The bone marrow microenvironment is a dynamic and complex niche that plays a central role in the development, progression, and therapeutic resistance of leukemia. Among the various stromal and immune cells that compose this microenvironment, adipocytes are increasingly recognized as active participants rather [...] Read more.
The bone marrow microenvironment is a dynamic and complex niche that plays a central role in the development, progression, and therapeutic resistance of leukemia. Among the various stromal and immune cells that compose this microenvironment, adipocytes are increasingly recognized as active participants rather than passive bystanders. These cells contribute to leukemia pathophysiology by supplying leukemic cells with vital metabolic fuels such as free fatty acids and glutamine, which support cellular bioenergetics and biosynthesis. Furthermore, adipocytes secrete adipokines—including leptin, adiponectin, and others—that influence leukemic cell proliferation, apoptosis, and chemoresistance. Leukemic cells, in turn, are not merely recipients of these signals, but actively remodel the marrow niche to their advantage. They can suppress adipogenesis, inhibit the differentiation of mesenchymal stem cells into adipocytes, or reprogram existing adipocytes to adopt a tumor-supportive phenotype. These transformed adipocytes may enhance leukemic cell survival, dampen immune responses, and create a metabolic sanctuary that enables resistance to standard chemotherapies. This reciprocal and dynamic interaction between leukemic cells and adipocytes contributes significantly to minimal residual disease and relapse, posing a major challenge for durable remission. Recent advances in tissue engineering—such as organ-on-chip and 3D co-culture systems—offer promising platforms to recapitulate and study these leukemia–adipocyte interactions with high fidelity. These models facilitate mechanistic insights and provide a foundation for developing novel therapeutic strategies aimed at disrupting the metabolic and paracrine crosstalk within the leukemic niche. Targeting the adipocyte–leukemia axis represents a compelling and underexplored avenue for improving leukemia treatment by sensitizing malignant cells to existing therapies and overcoming the protective influence of the bone marrow microenvironment. Full article
(This article belongs to the Section Physiology)
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32 pages, 2322 KiB  
Review
Exposure to Air Pollution in Transport Microenvironments
by Samuele Marinello, Francesco Lolli, Antonio Maria Coruzzolo and Rita Gamberini
Sustainability 2023, 15(15), 11958; https://doi.org/10.3390/su151511958 - 3 Aug 2023
Cited by 9 | Viewed by 3490
Abstract
People spend approximately 90% of their day in confined spaces (at home, work, school or in transit). During these periods, exposure to high concentrations of atmospheric pollutants can pose serious health risks, particularly to the respiratory system. The objective of this paper is [...] Read more.
People spend approximately 90% of their day in confined spaces (at home, work, school or in transit). During these periods, exposure to high concentrations of atmospheric pollutants can pose serious health risks, particularly to the respiratory system. The objective of this paper is to define a framework of the existing literature on the assessment of air quality in various transport microenvironments. A total of 297 papers, published from 2002 to 2021, were analyzed with respect to the type of transport microenvironments, the pollutants monitored, the concentrations measured and the sampling methods adopted. The analysis emphasizes the increasing interest in this topic, particularly regarding the evaluation of exposure in moving cars and buses. It specifically focuses on the exposure of occupants to atmospheric particulate matter (PM) and total volatile organic compounds (TVOCs). Concentrations of these pollutants can reach several hundreds of µg/m3 in some cases, significantly exceeding the recommended levels. The findings presented in this paper serve as a valuable resource for urban planners and decision-makers in formulating effective urban policies. Full article
(This article belongs to the Special Issue Microenvironmental Air Pollution Control, Comfort and Health Risk)
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18 pages, 3014 KiB  
Article
The Stress-Responsive microRNA-34a Alters Insulin Signaling and Actions in Adipocytes through Induction of the Tyrosine Phosphatase PTP1B
by Pierre-Jean Cornejo, Bastien Vergoni, Mickaël Ohanna, Brice Angot, Teresa Gonzalez, Jennifer Jager, Jean-François Tanti and Mireille Cormont
Cells 2022, 11(16), 2581; https://doi.org/10.3390/cells11162581 - 19 Aug 2022
Cited by 10 | Viewed by 3016
Abstract
Metabolic stresses alter the signaling and actions of insulin in adipocytes during obesity, but the molecular links remain incompletely understood. Members of the microRNA-34 (miR-34 family play a pivotal role in stress response, and previous studies showed an upregulation of miR-34a in adipose [...] Read more.
Metabolic stresses alter the signaling and actions of insulin in adipocytes during obesity, but the molecular links remain incompletely understood. Members of the microRNA-34 (miR-34 family play a pivotal role in stress response, and previous studies showed an upregulation of miR-34a in adipose tissue during obesity. Here, we identified miR-34a as a new mediator of adipocyte insulin resistance. We confirmed the upregulation of miR-34a in adipose tissues of obese mice, which was observed in the adipocyte fraction exclusively. Overexpression of miR-34a in 3T3-L1 adipocytes or in fat pads of lean mice markedly reduced Akt activation by insulin and the insulin-induced glucose transport. This was accompanied by a decreased expression of VAMP2, a target of miR-34a, and an increased expression of the tyrosine phosphatase PTP1B. Importantly, PTP1B silencing prevented the inhibitory effect of miR-34a on insulin signaling. Mechanistically, miR-34a decreased the NAD+ level through inhibition of Naprt and Nampt, resulting in an inhibition of Sirtuin-1, which promoted an upregulation of PTP1B. Furthermore, the mRNA expression of Nampt and Naprt was decreased in adipose tissue of obese mice. Collectively, our results identify miR-34a as a new inhibitor of insulin signaling in adipocytes, providing a potential pathway to target to fight insulin resistance. Full article
(This article belongs to the Special Issue The Role of Adipose Tissue in Metabolic Diseases and Beyond)
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13 pages, 1237 KiB  
Article
Non-Classical HLA Determinants of the Clinical Response after Autologous Stem Cell Transplantation for Systemic Sclerosis
by Wahid Boukouaci, Pauline Lansiaux, Nathalie C. Lambert, Christophe Picard, Emmanuel Clave, Audrey Cras, Zora Marjanovic, Dominique Farge and Ryad Tamouza
Int. J. Mol. Sci. 2022, 23(13), 7223; https://doi.org/10.3390/ijms23137223 - 29 Jun 2022
Cited by 4 | Viewed by 2323
Abstract
Systemic Sclerosis (SSc) is a chronic autoimmune disease with high morbidity and mortality. Autologous Hematopoietic Stem Cell Transplantation (AHSCT) is the best therapeutic option for rapidly progressive SSc, allowing increased survival with regression of skin and lung fibrosis. The immune determinants of the [...] Read more.
Systemic Sclerosis (SSc) is a chronic autoimmune disease with high morbidity and mortality. Autologous Hematopoietic Stem Cell Transplantation (AHSCT) is the best therapeutic option for rapidly progressive SSc, allowing increased survival with regression of skin and lung fibrosis. The immune determinants of the clinical response after AHSCT have yet to be well characterized. In particular, the pivotal role of the Human Leukocyte Antigen (HLA) system is not well understood, including the role of non-classical immuno-modulatory HLA-E and HLA-G molecules in developing tolerance and the role of Natural Killer cells (NK) in the immunomodulation processes. We retrospectively tested whether the genetic and/or circulating expression of the non-classical HLA-E and HLA-G loci, as well as the imputed classical HLA determinants of HLA-E expression, influence the observed clinical response to AHSCT at 12- and 24-month follow-up. In a phenotypically well-defined sample of 46 SSc patients classified as clinical responders or non-responders, we performed HLA genotyping using next-generation sequencing and circulating levels of HLA-G and quantified HLA-E soluble isoforms by ELISA. The -21HLA-B leader peptide dimorphism and the differential expression level of HLA-A and HLA-C alleles were imputed. We observed a strong trend towards better clinical response in HLA-E*01:03 or HLA-G 14bp Del allele carriers, which are known to be associated with high expression of the corresponding molecules. At 12-month post-AHSCT follow-up, higher circulating levels of soluble HLA-E were associated with higher values of modified Rodnan Skin Score (mRSS) (p = 0.0275), a proxy of disease severity. In the non-responder group, the majority of patients carried a double dose of the HLA-B Threonine leader peptide, suggesting a non-efficient inhibitory effect of the HLA-E molecules. We did not find any correlation between the soluble HLA-G levels and the observed clinical response after AHSCT. High imputed expression levels of HLA-C alleles, reflecting more efficient NK cell inhibition, correlated with low values of the mRSS 3 months after AHSCT (p = 0.0087). This first pilot analysis of HLA-E and HLA-G immuno-modulatory molecules suggests that efficient inhibition of NK cells contributes to clinical response after AHSCT for SSc. Further studies are warranted in larger patient cohorts to confirm our results. Full article
(This article belongs to the Special Issue The Immune Checkpoint HLA-G)
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16 pages, 3531 KiB  
Article
The Expression Quantitative Trait Loci in Immune Response Genes Impact the Characteristics and Survival of Colorectal Cancer
by Ren-Hao Chan, Po-Chuan Chen, Yu-Min Yeh, Bo-Wen Lin, Kai-Di Yang, Meng-Ru Shen and Peng-Chan Lin
Diagnostics 2022, 12(2), 315; https://doi.org/10.3390/diagnostics12020315 - 26 Jan 2022
Cited by 5 | Viewed by 3303
Abstract
The impact of germline variants on the regulation of the expression of tumor microenvironment (TME)-based immune response genes remains unclear. Expression quantitative trait loci (eQTL) provide insight into the effect of downstream target genes (eGenes) regulated by germline-associated variants (eVariants). Through eQTL analyses, [...] Read more.
The impact of germline variants on the regulation of the expression of tumor microenvironment (TME)-based immune response genes remains unclear. Expression quantitative trait loci (eQTL) provide insight into the effect of downstream target genes (eGenes) regulated by germline-associated variants (eVariants). Through eQTL analyses, we illustrated the relationships between germline eVariants, TME-based immune response eGenes, and clinical outcomes. In this study, both RNA sequencing data from primary tumor and germline whole-genome sequencing data were collected from patients with stage III colorectal cancer (CRC). Ninety-nine high-risk subjects were subjected to immune response gene expression analyses. Seventy-seven subjects remained for further analysis after quality control, of which twenty-two patients (28.5%) experienced tumor recurrence. We found that 65 eQTL, including 60 germline eVariants and 22 TME-based eGenes, impacted the survival of cancer patients. For the recurrence prediction model, 41 differentially expressed genes (DEGs) achieved the best area under the receiver operating characteristic curve of 0.93. In total, 19 survival-associated eGenes were identified among the DEGs. Most of these genes were related to the regulation of lymphocytes and cytokines. A high expression of HGF, CCR5, IL18, FCER1G, TDO2, IFITM2, and LAPTM5 was significantly associated with a poor prognosis. In addition, the FCER1G eGene was associated with tumor invasion, tumor nodal stage, and tumor site. The eVariants that regulate the TME-based expression of FCER1G, including rs2118867 and rs12124509, were determined to influence survival and chromatin binding preferences. We also demonstrated that FCER1G and co-expressed genes in TME were related to the aggregation of leukocytes via pathway analysis. By analyzing the eQTL from the cancer genome using germline variants and TME-based RNA sequencing, we identified the eQTL in immune response genes that impact colorectal cancer characteristics and survival. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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33 pages, 521 KiB  
Review
Enterococcus spp.: Is It a Bad Choice for a Good Use—A Conundrum to Solve?
by Mounir Ferchichi, Khaled Sebei, Amine Mohamed Boukerb, Najoua Karray-Bouraoui, Sylvie Chevalier, Marc G. J. Feuilloley, Nathalie Connil and Mohamed Zommiti
Microorganisms 2021, 9(11), 2222; https://doi.org/10.3390/microorganisms9112222 - 26 Oct 2021
Cited by 37 | Viewed by 5878
Abstract
Since antiquity, the ubiquitous lactic acid bacteria (LAB) Enterococci, which are just as predominant in both human and animal intestinal commensal flora, have been used (and still are) as probiotics in food and feed production. Their qualities encounter several hurdles, particularly in terms [...] Read more.
Since antiquity, the ubiquitous lactic acid bacteria (LAB) Enterococci, which are just as predominant in both human and animal intestinal commensal flora, have been used (and still are) as probiotics in food and feed production. Their qualities encounter several hurdles, particularly in terms of the array of virulence determinants, reflecting a notorious reputation that nearly prevents their use as probiotics. Additionally, representatives of the Enterococcus spp. genus showed intrinsic resistance to several antimicrobial agents, and flexibility to acquire resistance determinants encoded on a broad array of conjugative plasmids, transposons, and bacteriophages. The presence of such pathogenic aspects among some species represents a critical barrier compromising their use as probiotics in food. Thus, the genus neither has Generally Recognized as Safe (GRAS) status nor has it been included in the Qualified Presumption of Safety (QPS) list implying drastic legislation towards these microorganisms. To date, the knowledge of the virulence factors and the genetic structure of foodborne enterococcal strains is rather limited. Although enterococcal infections originating from food have never been reported, the consumption of food carrying virulence enterococci seems to be a risky path of transfer, and hence, it renders them poor choices as probiotics. Auspiciously, enterococcal virulence factors seem to be strain specific suggesting that clinical isolates carry much more determinants that food isolates. The latter remain widely susceptible to clinically relevant antibiotics and subsequently, have a lower potential for pathogenicity. In terms of the ideal enterococcal candidate, selected strains deemed for use in foods should not possess any virulence genes and should be susceptible to clinically relevant antibiotics. Overall, implementation of an appropriate risk/benefit analysis, in addition to the case-by-case assessment, the establishment of a strain’s innocuity, and consideration for relevant guidelines, legislation, and regulatory aspects surrounding functional food development seem to be the crucial elements for industries, health-staff and consumers to accept enterococci, like other LAB, as important candidates for useful and beneficial applications in food industry and food biotechnology. The present review aims at shedding light on the world of hurdles and limitations that hampers the Enterococcus spp. genus and its representatives from being used or proposed for use as probiotics. The future of enterococci use as probiotics and legislation in this field are also discussed. Full article
(This article belongs to the Special Issue Enterococci for Probiotic Use: Safety and Risk)
20 pages, 3861 KiB  
Article
Effects of Ulva sp. Extracts on the Growth, Biofilm Production, and Virulence of Skin Bacteria Microbiota: Staphylococcus aureus, Staphylococcus epidermidis, and Cutibacterium acnes Strains
by Mathilde Fournière, Gilles Bedoux, Djouhar Souak, Nathalie Bourgougnon, Marc G. J. Feuilloley and Thomas Latire
Molecules 2021, 26(16), 4763; https://doi.org/10.3390/molecules26164763 - 6 Aug 2021
Cited by 6 | Viewed by 3978
Abstract
Ulva sp. is known to be a source of bioactive compounds such as ulvans, but to date, their biological activity on skin commensal and/or opportunistic pathogen bacteria has not been reported. In this study, the effects of poly- and oligosaccharide fractions produced by [...] Read more.
Ulva sp. is known to be a source of bioactive compounds such as ulvans, but to date, their biological activity on skin commensal and/or opportunistic pathogen bacteria has not been reported. In this study, the effects of poly- and oligosaccharide fractions produced by enzyme-assisted extraction and depolymerization were investigated, for the first time in vitro, on cutaneous bacteria: Staphylococcus aureus, Staphylococcus epidermidis, and Cutibacterium acnes. At 1000 μg/mL, poly- and oligosaccharide fractions did not affect the growth of the bacteria regarding their generation time. Polysaccharide Ulva sp. fractions at 1000 μg/mL did not alter the bacterial biofilm formation, while oligosaccharide fractions modified S. epidermidis and C. acnes biofilm structures. None of the fractions at 1000 μg/mL significantly modified the cytotoxic potential of S. epidermidis and S. aureus towards keratinocytes. However, poly- and oligosaccharide fractions at 1000 μg/mL induced a decrease in the inflammatory potential of both acneic and non-acneic C. acnes strains on keratinocytes of up to 39.8%; the strongest and most significant effect occurred when the bacteria were grown in the presence of polysaccharide fractions. Our research shows that poly- and oligosaccharide Ulva sp. fractions present notable biological activities on cutaneous bacteria, especially towards C. acnes acneic and non-acneic strains, which supports their potential use for dermo-cosmetic applications. Full article
(This article belongs to the Special Issue Marine Polysaccharides 2022)
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11 pages, 1201 KiB  
Review
Challenging Cosmetic Innovation: The Skin Microbiota and Probiotics Protect the Skin from UV-Induced Damage
by Djouhar Souak, Magalie Barreau, Aurélie Courtois, Valérie André, Cécile Duclairoir Poc, Marc G. J. Feuilloley and Manon Gault
Microorganisms 2021, 9(5), 936; https://doi.org/10.3390/microorganisms9050936 - 27 Apr 2021
Cited by 42 | Viewed by 10860
Abstract
Many studies performed in the last decade have focused on the cutaneous microbiota. It has been shown that this microbiota plays a key role in skin homeostasis. Considered as “a second barrier” to the environment, it is very important to know how it [...] Read more.
Many studies performed in the last decade have focused on the cutaneous microbiota. It has been shown that this microbiota plays a key role in skin homeostasis. Considered as “a second barrier” to the environment, it is very important to know how it reacts to exogenous aggressions. The cosmetics industry has a started to use this microbiota as a source of natural ingredients, particularly ones that confer photoprotection against ultraviolet (UV) rays. Interestingly, it has been demonstrated that bacterial molecules can block UV rays or reverse their harmful effects. Oral probiotics containing living microorganisms have also shown promising results in restoring skin homeostasis and reversing the negative effects of UV rays. Microbial-based active sunscreen compounds have huge potential for use as next-generation photoprotection products. Full article
(This article belongs to the Special Issue Human Skin Microbiota)
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20 pages, 9475 KiB  
Article
Inhibiting FAK–Paxillin Interaction Reduces Migration and Invadopodia-Mediated Matrix Degradation in Metastatic Melanoma Cells
by Antoine Mousson, Marlène Legrand, Tania Steffan, Romain Vauchelles, Philippe Carl, Jean-Pierre Gies, Maxime Lehmann, Guy Zuber, Jan De Mey, Denis Dujardin, Emilie Sick and Philippe Rondé
Cancers 2021, 13(8), 1871; https://doi.org/10.3390/cancers13081871 - 14 Apr 2021
Cited by 26 | Viewed by 4953
Abstract
The nonreceptor tyrosine kinase FAK is a promising target for solid tumor treatment because it promotes invasion, tumor progression, and drug resistance when overexpressed. Investigating the role of FAK in human melanoma cells, we found that both in situ and metastatic melanoma cells [...] Read more.
The nonreceptor tyrosine kinase FAK is a promising target for solid tumor treatment because it promotes invasion, tumor progression, and drug resistance when overexpressed. Investigating the role of FAK in human melanoma cells, we found that both in situ and metastatic melanoma cells strongly express FAK, where it controls tumor cells’ invasiveness by regulating focal adhesion-mediated cell motility. Inhibiting FAK in human metastatic melanoma cells with either siRNA or a small inhibitor targeting the kinase domain impaired migration but led to increased invadopodia formation and extracellular matrix degradation. Using FAK mutated at Y397, we found that this unexpected increase in invadopodia activity is due to the lack of phosphorylation at this residue. To preserve FAK–Src interaction while inhibiting pro-migratory functions of FAK, we found that altering FAK–paxillin interaction, with either FAK mutation in the focal adhesion targeting (FAT) domain or a competitive inhibitor peptide mimicking paxillin LD domains drastically reduces cell migration and matrix degradation by preserving FAK activity in the cytoplasm. In conclusion, our data show that targeting FAK–paxillin interactions could be a potential therapeutic strategy to prevent metastasis formation, and molecules targeting this interface could be alternative to inhibitors of FAK kinase activity which display unexpected effects. Full article
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28 pages, 3385 KiB  
Review
Pseudomonas Flagella: Generalities and Specificities
by Mathilde Bouteiller, Charly Dupont, Yvann Bourigault, Xavier Latour, Corinne Barbey, Yoan Konto-Ghiorghi and Annabelle Merieau
Int. J. Mol. Sci. 2021, 22(7), 3337; https://doi.org/10.3390/ijms22073337 - 24 Mar 2021
Cited by 64 | Viewed by 8143
Abstract
Flagella-driven motility is an important trait for bacterial colonization and virulence. Flagella rotate and propel bacteria in liquid or semi-liquid media to ensure such bacterial fitness. Bacterial flagella are composed of three parts: a membrane complex, a flexible-hook, and a flagellin filament. The [...] Read more.
Flagella-driven motility is an important trait for bacterial colonization and virulence. Flagella rotate and propel bacteria in liquid or semi-liquid media to ensure such bacterial fitness. Bacterial flagella are composed of three parts: a membrane complex, a flexible-hook, and a flagellin filament. The most widely studied models in terms of the flagellar apparatus are E. coli and Salmonella. However, there are many differences between these enteric bacteria and the bacteria of the Pseudomonas genus. Enteric bacteria possess peritrichous flagella, in contrast to Pseudomonads, which possess polar flagella. In addition, flagellar gene expression in Pseudomonas is under a four-tiered regulatory circuit, whereas enteric bacteria express flagellar genes in a three-step manner. Here, we use knowledge of E. coli and Salmonella flagella to describe the general properties of flagella and then focus on the specificities of Pseudomonas flagella. After a description of flagellar structure, which is highly conserved among Gram-negative bacteria, we focus on the steps of flagellar assembly that differ between enteric and polar-flagellated bacteria. In addition, we summarize generalities concerning the fuel used for the production and rotation of the flagellar macromolecular complex. The last part summarizes known regulatory pathways and potential links with the type-six secretion system (T6SS). Full article
(This article belongs to the Section Molecular Microbiology)
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19 pages, 3936 KiB  
Article
Comparison of SYK Signaling Networks Reveals the Potential Molecular Determinants of Its Tumor-Promoting and Suppressing Functions
by Marion Buffard, Aurélien Naldi, Gilles Freiss, Marcel Deckert, Ovidiu Radulescu, Peter J. Coopman and Romain M. Larive
Biomolecules 2021, 11(2), 308; https://doi.org/10.3390/biom11020308 - 18 Feb 2021
Cited by 5 | Viewed by 3667
Abstract
Spleen tyrosine kinase (SYK) can behave as an oncogene or a tumor suppressor, depending on the cell and tissue type. As pharmacological SYK inhibitors are currently evaluated in clinical trials, it is important to gain more information on the molecular mechanisms underpinning these [...] Read more.
Spleen tyrosine kinase (SYK) can behave as an oncogene or a tumor suppressor, depending on the cell and tissue type. As pharmacological SYK inhibitors are currently evaluated in clinical trials, it is important to gain more information on the molecular mechanisms underpinning these opposite roles. To this aim, we reconstructed and compared its signaling networks using phosphoproteomic data from breast cancer and Burkitt lymphoma cell lines where SYK behaves as a tumor suppressor and promoter. Bioinformatic analyses allowed for unveiling the main differences in signaling pathways, network topology and signal propagation from SYK to its potential effectors. In breast cancer cells, the SYK target-enriched signaling pathways included intercellular adhesion and Hippo signaling components that are often linked to tumor suppression. In Burkitt lymphoma cells, the SYK target-enriched signaling pathways included molecules that could play a role in SYK pro-oncogenic function in B-cell lymphomas. Several protein interactions were profoundly rewired in the breast cancer network compared with the Burkitt lymphoma network. These data demonstrate that proteomic profiling combined with mathematical network modeling allows untangling complex pathway interplays and revealing difficult to discern interactions among the SYK pathways that positively and negatively affect tumor formation and progression. Full article
(This article belongs to the Special Issue Protein Phosphorylation in Cancer: Unraveling the Signaling Pathways)
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25 pages, 4289 KiB  
Article
Tackling Pseudomonas aeruginosa Virulence by Mulinane-Like Diterpenoids from Azorella atacamensis
by Onyedikachi Cecil Azuama, Sergio Ortiz, Luis Quirós-Guerrero, Emeline Bouffartigues, Damien Tortuel, Olivier Maillot, Marc Feuilloley, Pierre Cornelis, Olivier Lesouhaitier, Raphaël Grougnet, Sabrina Boutefnouchet, Jean-Luc Wolfender, Sylvie Chevalier and Ali Tahrioui
Biomolecules 2020, 10(12), 1626; https://doi.org/10.3390/biom10121626 - 2 Dec 2020
Cited by 19 | Viewed by 4363
Abstract
Pseudomonas aeruginosa is an important multidrug-resistant human pathogen by dint of its high intrinsic, acquired, and adaptive resistance mechanisms, causing great concern for immune-compromised individuals and public health. Additionally, P. aeruginosa resilience lies in the production of a myriad of virulence factors, which [...] Read more.
Pseudomonas aeruginosa is an important multidrug-resistant human pathogen by dint of its high intrinsic, acquired, and adaptive resistance mechanisms, causing great concern for immune-compromised individuals and public health. Additionally, P. aeruginosa resilience lies in the production of a myriad of virulence factors, which are known to be tightly regulated by the quorum sensing (QS) system. Anti-virulence therapy has been adopted as an innovative alternative approach to circumvent bacterial antibiotic resistance. Since plants are known repositories of natural phytochemicals, herein, we explored the anti-virulence potential of Azorella atacamensis, a medicinal plant from the Taira Atacama community (Calama, Chile), against P. aeruginosa. Interestingly, A. atacamensis extract (AaE) conferred a significant protection for human lung cells and Caenorhabditis elegans nematodes towards P. aeruginosa pathogenicity. The production of key virulence factors was decreased upon AaE exposure without affecting P. aeruginosa growth. In addition, AaE was able to decrease QS-molecules production. Furthermore, metabolite profiling of AaE and its derived fractions achieved by combination of a molecular network and in silico annotation allowed the putative identification of fourteen diterpenoids bearing a mulinane-like skeleton. Remarkably, this unique interesting group of diterpenoids seems to be responsible for the interference with virulence factors as well as on the perturbation of membrane homeostasis of P. aeruginosa. Hence, there was a significant increase in membrane stiffness, which appears to be modulated by the cell wall stress response ECFσ SigX, an extracytoplasmic function sigma factor involved in membrane homeostasis as well as P. aeruginosa virulence. Full article
(This article belongs to the Collection Pharmacology of Medicinal Plants)
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33 pages, 491 KiB  
Review
Update of Probiotics in Human World: A Nonstop Source of Benefactions till the End of Time
by Mohamed Zommiti, Marc G. J. Feuilloley and Nathalie Connil
Microorganisms 2020, 8(12), 1907; https://doi.org/10.3390/microorganisms8121907 - 30 Nov 2020
Cited by 172 | Viewed by 11282
Abstract
Lactic acid bacteria (LAB) are known for their biotechnological potential. Moreover, LAB are distinguished by amazing criteria: Adjusting the intestinal environment, inhibiting pathogenic microbes in the gastrointestinal tract, ability to reduce pathogen adhesion activity, improving the balance of the microbiota inside the intestine, [...] Read more.
Lactic acid bacteria (LAB) are known for their biotechnological potential. Moreover, LAB are distinguished by amazing criteria: Adjusting the intestinal environment, inhibiting pathogenic microbes in the gastrointestinal tract, ability to reduce pathogen adhesion activity, improving the balance of the microbiota inside the intestine, capabilities of regulating intestinal mucosal immunity, and maintaining intestinal barrier function. The escalating number of research and studies about beneficial microorganisms and their impact on promoting health has attracted a big interest in the last decades. Since antiquity, various based fermented products of different kinds have been utilized as potential probiotic products. Nevertheless, the current upsurge in consumers’ interest in bioalternatives has opened new horizons for the probiotic field in terms of research and development. The present review aims at shedding light on the world of probiotics, a continuous story of astonishing success in various fields, in particular, the biomedical sector and pharmaceutical industry, as well as to display the importance of probiotics and their therapeutic potential in purpose to compete for sturdy pathogens and to struggle against diseases and acute infections. Shadows and future trends of probiotics use are also discussed. Full article
(This article belongs to the Special Issue Physiology of Lactic Acid Bacteria and Applications to Biotechnology)
20 pages, 3375 KiB  
Article
Activation of the Cell Wall Stress Response in Pseudomonas aeruginosa Infected by a Pf4 Phage Variant
by Damien Tortuel, Ali Tahrioui, Sophie Rodrigues, Mélyssa Cambronel, Amine M. Boukerb, Olivier Maillot, Julien Verdon, Emile Bere, Michael Nusser, Gerald Brenner-Weiss, Audrey David, Onyedikachi Cecil Azuama, Marc G. J. Feuilloley, Nicole Orange, Olivier Lesouhaitier, Pierre Cornelis, Sylvie Chevalier and Emeline Bouffartigues
Microorganisms 2020, 8(11), 1700; https://doi.org/10.3390/microorganisms8111700 - 30 Oct 2020
Cited by 15 | Viewed by 4695
Abstract
Pseudomonas aeruginosa PAO1 has an integrated Pf4 prophage in its genome, encoding a relatively well-characterized filamentous phage, which contributes to the bacterial biofilm organization and maturation. Pf4 variants are considered as superinfectives when they can re-infect and kill the prophage-carrying host. Herein, the [...] Read more.
Pseudomonas aeruginosa PAO1 has an integrated Pf4 prophage in its genome, encoding a relatively well-characterized filamentous phage, which contributes to the bacterial biofilm organization and maturation. Pf4 variants are considered as superinfectives when they can re-infect and kill the prophage-carrying host. Herein, the response of P. aeruginosa H103 to Pf4 variant infection was investigated. This phage variant caused partial lysis of the bacterial population and modulated H103 physiology. We show by confocal laser scanning microscopy that a Pf4 variant-infection altered P. aeruginosa H103 biofilm architecture either in static or dynamic conditions. Interestingly, in the latter condition, numerous cells displayed a filamentous morphology, suggesting a link between this phenotype and flow-related forces. In addition, Pf4 variant-infection resulted in cell envelope stress response, mostly mediated by the AlgU and SigX extracytoplasmic function sigma factors (ECFσ). AlgU and SigX involvement may account, at least partly, for the enhanced expression level of genes involved in the biosynthesis pathways of two matrix exopolysaccharides (Pel and alginates) and bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) metabolism. Full article
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20 pages, 1827 KiB  
Article
MeJA Elicitation of Chicory Hairy Roots Promotes Efficient Increase of 3,5-diCQA Accumulation, a Potent Antioxidant and Antibacterial Molecule
by Guillaume Bernard, Harmony Alves Dos Santos, Audrey Etienne, Jennifer Samaillie, Christel Neut, Sevser Sahpaz, Jean-Louis Hilbert, David Gagneul, Nathalie Jullian, Ali Tahrioui, Sylvie Chevalier, Céline Rivière and Caroline Rambaud
Antibiotics 2020, 9(10), 659; https://doi.org/10.3390/antibiotics9100659 - 30 Sep 2020
Cited by 14 | Viewed by 4231
Abstract
Cichorium intybus L. (Asteraceae) is an important industrial crop, as well as a medicinal plant which produces some bioactive compounds implicated in various biological effects with potential applications in human health. Particularly, roots produce hydroxycinnamic acids like 5-caffeoyquinic acid and 3,5-dicaffeoylquinic [...] Read more.
Cichorium intybus L. (Asteraceae) is an important industrial crop, as well as a medicinal plant which produces some bioactive compounds implicated in various biological effects with potential applications in human health. Particularly, roots produce hydroxycinnamic acids like 5-caffeoyquinic acid and 3,5-dicaffeoylquinic acid (di-CQA). The present investigation relates to the use of methyl jasmonate for enhancing phenolic compounds accumulation and production in hairy root cultures of C. intybus. Elicitated hairy root growth rate increased 13.3 times compared with the initial inoculum in a period of 14 days and di-CQA production represented about 12% of DW. The elicitation has also promoted the production of tricaffeoylquinic acid never described in the chicory roots and identified as 3,4,5-tricaffeoyquinic acid by means of nuclear magnetic resonance. Our study confirmed the strong anti-oxidant effect of di-CQA. Our results also confirmed globally a selectivity of action of di-CQA against Gram-positive bacteria, in particular against some strains of Staphylococcus and Streptococcus. However, a non-negligible antibacterial activity of di-CQA against Pseudomonas aeruginosa was also underlined (MIC = 0.156 mg.mL−1 against some P. aeruginosa strains). The influence of di-CQA has been explored to evaluate its impact on the physiology of P. aeruginosa. Di-CQA showed no effect on the biofilm formation and the production of extracellular pyocyanin. However, it demonstrated an effect on virulence through the production of pyoverdine with a dose-dependent manner by more than 7-fold when treated at a concentration of 128 µg·mL−1, thus suggesting a link between di-CQA and iron sequestration. This study shows that elicitated hairy root cultures of chicory can be developed for the production of di-CQA, a secondary metabolite with high antibacterial potential. Full article
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