{"title":"In Silico Study of Bis(6-Amino-1,3-Dimethylpyrimidine-2,4(1H,3H)-Diones) as EGFR Inhibitors: Synthesis, DFT, Molecular Docking, and MD Simulation Studies","authors":"Zeynab masoumi, Mohammad Bayat, Davood Gheidari","doi":"10.1155/cmi/5585552","DOIUrl":"https://doi.org/10.1155/cmi/5585552","url":null,"abstract":"<p>The epidermal growth factor receptor (EGFR), a protein located on the cell surface, belongs to the tyrosine kinase family and plays a crucial role in cell development and proliferation. Abnormal expression or mutations in the EGFR gene can lead to non–small cell lung cancer. Although established EGFR inhibitors have been effective in the treatment of cancer, they are associated with several side effects. As a result, there is an urgent need to develop novel EGFR inhibitors that can effectively target the receptor while causing no adverse side effects. In this study, a series of bis(6-amino-1,3-dimethylpyrimidine-2,4(1<i>H</i>,3<i>H</i>)-dione derivatives was synthesized in water at room temperature without the use of any catalyst, and pharmaceutical properties are investigated. Computational methods, including density functional theory (DFT), molecular docking, and molecular dynamics (MD), were utilized to investigate the chemical properties, drug-like characteristics, and anticancer potential of the molecule. Quantum chemical calculations indicated that the molecules are relatively stable and exhibit significant electrophilic properties. The analysis of HOMO-LUMO contour maps was conducted to illustrate charge density distributions that may be associated with biological activity. Docking studies with EGFR enzymes indicated that all compounds demonstrated favorable binding affinities, with docking scores ranging from −4.412 to −6.158 kcal/mol. Particularly, Compound 3f, with an energy of −6.158 kcal/mol, showed the best binding affinity, outperforming the native ligand, which had a docking score of −5.076 kcal/mol. The stability of the EGFR-3f complex is significantly enhanced by the formation of five conventional hydrogen bonds and one carbon–hydrogen bond in ligand–protein interactions. MD simulations, which included analyses such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (rGyr), molecular surface area (MolSA), and polar surface area (PSA), were conducted on the EGFR-3f complex. It was found that the EGFR-3f complex is stable, and the results show that Compound 3f has a strong interaction with the target enzyme.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2025 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cmi/5585552","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Svetlana N. Pleskova, Nikolay А. Bezrukov, Ekaterina N. Gorshkova, Eseniya V. Otstavnova, Dmitry V. Novikov
{"title":"Cunning Pathogen Tactics: Neutrophil Movement Influenced by Bacterial Attractants in the Experimental Model","authors":"Svetlana N. Pleskova, Nikolay А. Bezrukov, Ekaterina N. Gorshkova, Eseniya V. Otstavnova, Dmitry V. Novikov","doi":"10.1155/cmi/8859162","DOIUrl":"https://doi.org/10.1155/cmi/8859162","url":null,"abstract":"<p>To explore the peculiarities of neutrophil motility, two models of chemoattraction were created: a horizontal model, where a container with bacterial chemoattractant was attached laterally to the endotheliocyte monolayer, and a vertical model, simulating a pyemic focus in the lower part of the modified Boyden chamber. Low-molecular weight product secretion and/or degradation of <i>Enterococcus faecalis</i> caused “disorientations” of neutrophil migration with hyperproduction reactive oxygen species (ROS) by immune cells, while <i>Proteus mirabilis</i> inhibited both migration of most neutrophils and the production of ROS by them, while the activity of the remaining uninhibited neutrophils increased. Neutrophils generated ROS during migration, especially actively in the case of a large number of mobile cells (under stimulation with low-molecular weight product secretion and/or degradation of <i>Enterococcus faecalis</i> and <i>Escherichia coli</i>). Using high-resolution microscopy, it was shown that low-activity neutrophils cause changes in the morphology of endothelial cells during migration more than high-activity neutrophils. In the vertical migration model, the morphology of endothelial cells significantly changed during neutrophils diapedesis. It was observed that space between endothelial cells was increased (especially in the case of neutrophil swarming).</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2025 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cmi/8859162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144573583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana Karla Cepeda Diaz, Peter S. Back, Sreelakshmi K. Sreenivasamurthy, Jeffrey D. Dvorin
{"title":"Malaria Cytoskeletal Proteins Require Alveolin–Alveolin Interactions for Differential Localization","authors":"Ana Karla Cepeda Diaz, Peter S. Back, Sreelakshmi K. Sreenivasamurthy, Jeffrey D. Dvorin","doi":"10.1155/cmi/4530231","DOIUrl":"https://doi.org/10.1155/cmi/4530231","url":null,"abstract":"<p>The alveolins are a family of intermediate filament-like proteins that form cytoskeletal structures in both free-living and parasitic members of the alveolate kingdom. Despite their important functions, the alveolins’ biochemical properties and organizing principles are still poorly understood. Here, we characterize four alveolins of <i>Plasmodium falciparum</i>, the deadliest malaria parasite, to understand how alveolin domains mediate protein–protein interactions and highly specific recruitment to substructures of the cytoskeleton. Unexpectedly, we uncover variable dependence on alveolin domains for each substructure rather than an overarching mechanism. While <i>Pf</i>IMC1e requires 1f to be sequentially recruited to the basal complex, <i>Pf</i>IMC1c and <i>Pf</i>IMC1g do not require interactions with each other to localize properly to the inner membrane complex. Moreover, alveolin domains are not interchangeable—they contain unique signatures for specialized localization. Finally, we identify a region outside the alveolin domain of <i>Pf</i>IMC1e that is important for basal complex recruitment. These results provide direct evidence that alveolin domains mediate both alveolin–alveolin interactions and compartment-specific localization.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2025 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cmi/4530231","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144536973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andong Zhang, Xin Yan, Ningzhe Li, Shiying Yan, Shu Li, Hua Yang, Yimeng Liu, Jian Zhang, Jia Wang, Jian Zhao, Mei Cao
{"title":"Pseudogene BNIP3P1 Regulates H. pylori–Induced Apoptosis in Gastric Mucosal by Acting on the miR-411-5p/BNIP3 Axis","authors":"Andong Zhang, Xin Yan, Ningzhe Li, Shiying Yan, Shu Li, Hua Yang, Yimeng Liu, Jian Zhang, Jia Wang, Jian Zhao, Mei Cao","doi":"10.1155/cmi/6763794","DOIUrl":"https://doi.org/10.1155/cmi/6763794","url":null,"abstract":"<p><i>Helicobacter pylori</i> (<i>H. pylori</i>) is one of the major causes of gastric mucosal damage, and infection with <i>H. pylori</i> induces an immune response with gastric mucosal cells, which reduces gastric mucosal damage. The pseudogene <i>BNIP3P1</i>, sharing a remarkable 95.92% similarity with its well-characterized counterpart <i>BNIP3</i>, has largely remained unexplored. To elucidate the role of <i>BNIP3P1</i> in gastric mucosal damage induced by <i>H. pylori</i> infection, we meticulously constructed both in vivo and in vitro models. Gene chip sequencing, dual-luciferase assays, and cellular phenotyping were detected. We uncovered a compelling positive correlation between the duration of <i>H. pylori</i> infection and <i>BNIP3</i> overexpression at both the mRNA and protein levels. Intriguingly, overexpression of BNIP3 was found to effectively impede the proliferation and migration of human gastric epithelial cells (GES-1). Furthermore, we identified <i>miR-411-5p</i> as a direct regulator of <i>BNIP3</i>, targeting its 3 <sup>′</sup>UTR region and suppressing its expression during <i>H. pylori</i> infection. Notably, <i>BNIP3P1-</i> 3<sup>′</sup>UTR was observed to competitively bind <i>miR-411-5p</i>, leading to the upregulation of <i>BNIP3</i> expression. Furthermore, overexpression of <i>BNIP3P1</i> was associated with a marked decrease in GES-1 cell proliferation and a concomitant acceleration of apoptosis. Our findings suggest that <i>BNIP3P1</i> functions as a competing endogenous RNA (ceRNA) within the <i>BNIP3/miR-411-5p</i> axis during <i>H. pylori</i> infection, which ultimately hinders cell proliferation and promotes apoptosis in GES-1 cells. This study sheds light on the intricate mechanisms underlying <i>H. pylori</i> infection of GES-1 cells.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2025 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cmi/6763794","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diverse Effects of Fluoro-Phenyl-Styrene-Sulfonamide (FPSS) on Transcription Factor Sigma B Regulons in Gram-Positive Bacillales","authors":"Sirirak Supa-amornkul, Ramita Chalearmchutidath, Nichaporn Nattawut, Phimkanya Liu, Soraya Chaturongakul","doi":"10.1155/cmi/2175797","DOIUrl":"https://doi.org/10.1155/cmi/2175797","url":null,"abstract":"<p><i>Bacillales</i> is an order of Gram-positive bacteria comprising well-known genera such as <i>Staphylococcus</i>, <i>Listeria</i>, and <i>Bacillus. Staphylococcus aureus</i> has been shown to cause various types of tissue and systemic infections in humans and livestock. Some isolates can be highly resistant to antibiotics hence the need to identify better drugs and drug targets. Previous studies have shown that (E)-N-(4-fluorophenyl)-2-phenylethene sulfonamide (FPSS) could inhibit activities of a bacteria-specific transcription factor sigma B. Sigma B regulons in <i>Bacillus subtilis</i> and in <i>Listeria monocytogenes</i>, including virulence factor genes in <i>L. monocytogenes</i>, were decreased. Since sigma B is also presented in <i>S. aureus</i>, we initially postulated the use of FPSS to target <i>S. aureus</i> sigma B activity and to attenuate its virulence gene expression. Surprisingly, qRT-PCR results revealed that FPSS induced the expression of sigma B-dependent gene <i>asp23</i>. RNAseq results showed 39 <i>S. aureus</i> genes were affected by FPSS (37 genes were upregulated and two genes were downregulated). FPSS had no effect on expression of <i>sigB</i> operon in <i>S. aureus</i>. Therefore, we hypothesized that the effects of FPSS on sigma B regulons in <i>L. monocytogenes</i>, <i>B. subtilis</i>, and <i>S. aureus</i> were different. FPSS may target the expression of upstream regulators of sigma B (Rsbs), particularly the stressosome proteins which are lacking in <i>S. aureus.</i> Indeed, in <i>L. monocytogenes</i>, FPSS significantly increased the <i>rsbR</i> expression and could, thereby, dampen the sigma B activity and downregulate the expression of sigma B-dependent virulence genes in <i>L. monocytogenes</i>. This study proposes a narrower spectrum of FPSS application to listerial infections, and not staphylococcal infections.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2025 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cmi/2175797","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ziyu Li, Bo Zeng, Tao Wang, Lizhi Lu, Hang Zhong, Yuan Su, Diyan Li, Wenwu Xu
{"title":"The Chicken Gut Metagenome at Different Egg-Laying Stages and Its Correlation With Egg Production Performance","authors":"Ziyu Li, Bo Zeng, Tao Wang, Lizhi Lu, Hang Zhong, Yuan Su, Diyan Li, Wenwu Xu","doi":"10.1155/cmi/5586545","DOIUrl":"https://doi.org/10.1155/cmi/5586545","url":null,"abstract":"<p>To investigate the investigation of gut microbial communities to chicken egg production performance during different laying stages, we conducted a comparative study of the diversity, composition, and function of microbial communities in the fecal and cecal contents of six hens at the early stage, 25 at the peak stage, and 15 at the late stage. We obtained clean data averaging 13.40 and 13.79 Gb for each of the fecal and cecal content samples. The metagenomic analysis revealed significant differences in fecal and cecal content microbial diversity during different laying stages, especially during the peak stage, and the microbiota structure of fecal contents was more stable compared to that of cecal contents. The dominant microflora in the fecal contents during the peak stage were Firmicutes (74.84%) and <i>Lactobacillus</i> (28.13%). The dominant microflora of cecal contents during different stages were basically the same at the phylum level and genus level. During the peak stage, the dominant bacteria shared by microorganisms in the fecal and cecal contents were <i>Lactobacillus</i>. Functional analyses of the gut microbiome indicate that fecal and cecal content microbes have different functional capacities at different egg-laying stages. We therefore hypothesized that the gut microbiome would vary with laying stage and have a non-negligible effect on egg production performance. These results improved our ability to provide some theoretical basis for feeding management of laying hens during different laying stages and provided insights into the influence of the gut microbiota on the laying performance of chickens.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2025 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cmi/5586545","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Variations in Lorica Morphology and Element Composition in the Euglenoid Trachelomonas hispida var. coronata Under the Influence of Fe and Mn Supply","authors":"Małgorzata Poniewozik, Mateusz Kudlak, Emil Zięba","doi":"10.1155/cmi/6716112","DOIUrl":"https://doi.org/10.1155/cmi/6716112","url":null,"abstract":"<p><i>Trachelomonas hispida</i> var. <i>coronata</i> is one of the most widely reported varieties of <i>T</i>. <i>hispida</i> from water bodies worldwide. The specimens of this variety, apart from their species-specific features, such as an ellipsoidal lorica covered with strong, sharp spines, have a crown consisting of long spines surrounding the apical pore opening. The process of lorica formation is poorly understood, and in the few studies dealing with this topic, results indicate that these taxa and the entire species can produce lorica completely devoid of spines, a diacritic feature of the species. In our study, we observed in detail the formation process of the lorica in this taxon under different chemical conditions in relation to the concentration of the basic elements, Fe and Mn, which are saturated in trachelomonad lorica. The results showed that in the Fe-enriched medium, monads formed delicate, porous, spiny envelopes, whereas in the Mn-enriched medium, the loricae were more solid and less porous and had weaker developed spines; rather, they were in the form of short papillae. Differences were also observed in the structure surrounding the apical pore, which was developed differently in the two sets of media modifications (Fe- or Mn-supplemented media). We also observed different elemental compositions and colouration of loricae of cells growing in different media. This revealed that the features considered during the process of species identification are very unstable making the entire exercise highly complicated. Our research also shows that a broad discussion of the problem should be undertaken, and modern methods must be developed to unravel the complexities not only within the species but also within the entire <i>Trachelomonas</i>.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2025 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cmi/6716112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advantages of Next-Generation Technologies in Comparison to Standard and Commonly Used Methods in the Identification of Colonized Bacteria in the Herniated Lumbar Disc","authors":"Piriyanka Aravinth, Niroshima Withanage, Lohini Athiththan","doi":"10.1155/cmi/8754973","DOIUrl":"https://doi.org/10.1155/cmi/8754973","url":null,"abstract":"<p>The prevalence of low back pain (LBP) due to lumbar disc herniation (LDH) was recorded as 31.9% in the year 2022. Studies carried out around the world have failed to confirm the primary cause of disc herniation. Among the multiple hypothesized contributing factors, a low-grade bacterial infection has been identified as one of the major causes of LDH. Researchers have reported that <i>Propionibacterium acnes (P. acnes</i>) is the predominant bacterial species isolated using culture-derived methods. However, biofilm formation leads to a low bacterial yield in culture methods. Although culture methods remain the gold standard for the identification of bacterial species, there is a growing need for the usage of advanced techniques that are more sensitive, reliable, less time-consuming, and precise. Advancement of high-throughput sequencing tools allows thorough mining of complete bacterial profiles, even for bacteria that are challenging to cultivate in conventional laboratory settings. Currently, both high-throughput sequencing and omics have opened a new avenue, providing clear evidence for addressing queries related to bacterial contamination that have been frequently addressed in culture isolates of herniated discs over the past few decades. This review evaluates how advanced techniques in microbial identification have revolutionized our understanding of bacteria in disc health. Traditional methods confirmed the existence of known bacteria, but advanced techniques revealed a vast, previously unseen diversity, challenging the output of culture-based methods. This new information has even overturned the understanding of the role of <i>P. acnes</i> in evaluating disc health. Advanced techniques have opened a window to the hidden world of microbes and have been attributed to altered views on bacterial communities in healthy and herniated discs.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2025 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cmi/8754973","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Role of Bacterial Proteases From the Microbiome in Human Disease","authors":"Ying-Chiang J. Lee","doi":"10.1155/cmi/8860329","DOIUrl":"https://doi.org/10.1155/cmi/8860329","url":null,"abstract":"<p>Proteases degrade proteins and peptides, recycling materials and preventing unnecessary buildup within the cell. They can also be secreted and act in extracellular space. Bacterial proteases are often secreted and function as virulence factors. In the context of the microbiome, they can contribute to host–microbe interactions to facilitate colonization and disease pathogenesis. Thus, proteolytic activity is often found to be upregulated in patient cohorts. In this minireview, we describe how bacterial proteases in the microbiome can display various bioactivities such as disruption of barrier function, degradation of host defense compounds, modulating inflammatory responses, and allowing for microbial movement. We focus on the gut, skin, vaginal, and urinary microbiomes and describe how specific bacterial organisms have proteolytic activities that can exacerbate or lead to human diseases.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2025 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cmi/8860329","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antitumor Effect of Apilactobacillus kosoi 10H by Inducing Immunostimulatory Macrophages","authors":"Fuka Takahashi, Tai-Ying Chiou, Minako Tsukamoto, Satsuki Moriyama, Tomoya Takahashi, Sachi Tanaka","doi":"10.1155/cmi/4115145","DOIUrl":"https://doi.org/10.1155/cmi/4115145","url":null,"abstract":"<p><i>Apilactobacillus kosoi</i> (<i>A. kosoi</i>) 10H is a fructophilic lactic acid bacterium found in vegetable sugar fermentation liquid. It has been shown to possess high intestinal immunostimulatory activity. In this study, we investigated the potential for <i>A. kosoi</i> 10H heat-killed cells and their components to convert the phenotype of immunosuppressive M2 macrophages to immunostimulatory M1 macrophages. We further investigated the ability of induction of apoptosis of cancer cell lines by macrophage culture medium in the presence of <i>A. kosoi</i> 10H heat-killed cells. After induction of macrophage differentiation by phorbol 12-myristate 13-acetate in a THP-1 human monocyte–derived cell line, immunosuppressive M2 macrophages were induced by interleukin-6 (IL-6). When <i>A. kosoi</i> 10H heat-killed cells were brought into contact with IL-6-induced M2 macrophages, the expression of CD163 and CD209, which are M2 macrophage markers, markedly decreased, and the expression of CD80, human leukocyte antigen-DR isotype (HLA-DR), and tumor necrosis factor-<i>α</i> (TNF-<i>α</i>), markers of M1 macrophages, markedly increased. A similar effect was observed with a water-soluble extract and a hydrophobic liquid extract from <i>A. kosoi</i> 10H heat-killed cells. In addition, when M2 macrophage culture medium that had been conditioned with <i>A. kosoi</i> 10H heat-killed cells was added to the MCF-7 breast cancer cell line, we found that apoptosis was induced. TNF-<i>α</i> in the medium conditioned with macrophages cultured in the presence of <i>A. kosoi</i> 10H heat-killed cells was found to be partially responsible for MCF-7 cell death. This study presents basic data on the potential to use lactic acid bacteria to improve the cancer microenvironment.</p>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"2025 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cmi/4115145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}