Promoting M2 Macrophage Research Articles

PURPL Promotes M2 Macrophage Polarization in Lung Cancer by Regulating RBM4/xCT Signaling.

Lung cancer is the most common malignancy worldwide. Long non-coding RNA (lncRNA) p53 upregulated regulator of P53 levels (PURPL) is abnormally in various cancers. However, the reports on its roles in lung cancer are limited. The purpose of present study is to investigate the potentials of lncRNA PURPL in lung cancer. PURPL and mRNA expression was determined using real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). The location of PURPL was detected using RNA fluorescence in situ hybridization (FISH) assay. Protein expression was detected using western blot. Cellular functions were determined using flow cytometry. The interaction between PURPL and RNA-binding motif 4 (RBM4) was confirmed using RNA immunoprecipitation (RIP) assay. PURPL was overexpressed in lung cancer cells and patients. Overexpressed PURPL promoted M2 macrophage polarization and suppressed ferroptosis. Additionally, PURPL maintained the mRNA stability of cystine glutamate reverse transporter (xCT) via regulating RBM4. xCT knockdown antagonized the effects of overexpressed PURPL and inhibited M2 macrophage polarization via inducing macrophage ferroptosis. PURPL/RBM4/xCT axis promoted M2 macrophage polarization in lung cancer. Therefore, PURPL may be a potential target of lung cancer.

Melatonin and calcium phosphate crystal-loaded poly(L-lactic acid) porous microspheres reprogram macrophages to improve bone repair.

The bone immune microenvironment can influence the occurrence and progression of bone defects. To date, research on promoting macrophage M2 polarization to improve bone injury repair has been insufficient. In this study, we designed an injectable poly(L-lactic acid) (PLLA) porous microsphere that forms calcium phosphate crystals on its surface by binding to melatonin, followed by bionanomimetic mineralization in vitro. The microsphere is injectable and degradable, and its release of melatonin (MT) and calcium phosphate (CaP) crystals promotes macrophage M2 polarization, reprogramming of macrophages, and enhanced osteogenesis. After LPS stimulation, the proportion of M2-polarized macrophages in the MS@CaP@MT group was 39.2 ± 2.7%, significantly higher than that in other groups (P < 0.05). Further, in the MS@CaP@MT group, rats exhibited bone mineral densities of 129.4 ± 12.8 mg cc-1 at 2 weeks and 171.6 ± 13.6 mg cc-1 at 4 weeks in the defect area, which were significantly higher than those in other groups (P < 0.05). Using an animal model of femoral condylar defects, we demonstrated that MT PLLA porous microspheres loaded with calcium phosphate crystals can improve the immune microenvironment and form a microsphere-centered osteogenesis model. This significantly accelerates bone defect repair and provides a potential strategy for bone defect treatment.

FOXM1 derived from Triple negative breast cancer exosomes promotes cancer progression by activating IDO1 transcription in macrophages to suppress ferroptosis and induce M2 polarization of Tumor-associated macrophages.

To explore the oncogenic mechanism of FOXM1 in the tumor microenvironment (TME) regarding triple negative breast cancer (TNBC) promotion. The mRNA and protein levels of target genes in TNBC cells and their exosomes were detected by RT-qPCR and western blot. Co-culture models of TNBC cells and THP-1/M0 macrophages was established to detect the impact of co-culture on FOXM1 expression and macrophage polarization direction. The bioinformatics website was used to predict the binding sites between the FOXM1 and IDO1 promoter, which were further validated using dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay. Finally, after erastin-induced ferroptosis, Cell Counting Kit-8 (CCK-8), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and other experiments were conducted to investigate whether the FOXM1/IDO1 axis regulates M2 macrophage polarization through ferroptosis. It was found that FOXM1 was highly expressed in exosomes derived from TNBC cells, and TNBC cells upregulated FOXM1 expression in THP-1 cells through exosomes to promote M2 macrophage polarization. Furthermore, FOXM1 upregulated IDO1 in M2-type TAMs by regulating transcription. Lastly, FOXM1/IDO1 inhibited ferroptosis, promoting M2 macrophage polarization, thereby advancing TNBC progression. In conclusions, FOXM1 derived from TNBC cell-derived exosomes activated IDO1 transcription in TAMs to inhibit ferroptosis, promoting TAMs' M2 polarization and exerting carcinogenic effects.

Branched-chain amino acid catabolism promotes M2 macrophage polarization.

During an immune response, macrophages undergo systematic metabolic rewiring tailored to support their functions. Branched-chain amino acid (BCAA) metabolism has been reported to modulate macrophage function; however, its role in macrophage alternative activation remain unclear. We aimed to investigate the role of BCAA metabolism in macrophage alternative activation. The metabolomics of BMDM-derived M0 and M2 macrophages were analyzed using LC-MS. BCAAs were supplemented and genes involved in BCAA catabolism were inhibited during M2 macrophage polarization. The expression of M2 marker genes was assessed through RT-qPCR, immunofluorescence, and flow cytometry. Metabolomic analysis identified increased BCAA metabolism as one of the most significantly rewired pathways upon alternative activation. M2 macrophages had significantly lower BCAA levels compared to controls. BCAA supplementation promoted M2 macrophage polarization both in vitro and in vivo and increased oxidative phosphorylation in M2 macrophages. Blocking BCAA entry into mitochondria by knockdown of SLC25A44 inhibited M2 macrophage polarization. Furthermore, M2 macrophages polarization was suppressed by knockdown of Branched-chain amino-acid transaminase 2 (BCAT2) and branched chain keto acid dehydrogenase E1 subunit alpha (BCKDHA), both of which are key enzymes involved in BCAA oxidation. Overall, our findings suggest that BCAA catabolism plays an important role in polarization toward M2 macrophages.

Retraction: Strontium-doped gelatin scaffolds promote M2 macrophage switch and angiogenesis through modulating the polarization of neutrophils.

Retraction of 'Strontium-doped gelatin scaffolds promote M2 macrophage switch and angiogenesis through modulating the polarization of neutrophils' by Tao Li et al., Biomater. Sci., 2021, 9, 2931-2946, https://doi.org/10.1039/D0BM02126A.

Mesenchymal stem cells overexpressing XIST induce macrophage M2 polarization and improve neural stem cell homeostatic microenvironment, alleviating spinal cord injury

Spinal cord injury (SCI) is a significant cause of disability worldwide, with limited treatment options. This study investigated the potential of bone marrow-derived mesenchymal stem cells (BMSCs) modified with XIST lentiviral vector to modulate macrophage polarization and affect neural stem cell (NSC) microenvironment reconstruction following SCI. Bioinformatics analysis revealed that MID1 might be crucial for BMSCs’ treatment of SCI. XIST overexpression enriched Zmynd8 to the promoter region of MID1 and inhibited MID1 transcription, which promoted macrophage M2 polarization. In vitro experiments showed that BMSCs-XIST promoted NSC proliferation, migration, differentiation, and axonal growth by inducing macrophage M2 polarization, suppressing inflammation, and accelerating the re-establishment of the homeostatic microenvironment of NSCs. In vivo, animal experiments confirmed that BMSCs-XIST significantly alleviated SCI by promoting NSC differentiation and axon formation in the injured area. The study demonstrated the potential of XIST-overexpressing BMSCs for treating SCI by regulating macrophage polarization and homeostasis of the NSC microenvironment. These findings provide new insights into the development of stem cell-based therapies for SCI.

Chiral hydrogels facilitate rapid diabetic wound healing by promoting macrophage M2 polarization and cellular proliferation

The left-handed helical nanofibers of L-Fmoc-NV can significantly affect the polarization of macrophages towards the M2 phenotype, which facilitates diabetic wound healing.

Identification of Transcriptomic Signatures of Pancreatic Ductal Adenocarcinoma-Derived Exosomes That Promote Macrophage M2 Polarization and Predict Prognosis: S100A9 Reveals Tumor Progression.

Exosomes play a role in intercellular communication and participate in the interaction between pancreatic ductal adenocarcinoma (PDAC) cells and immune cells. Macrophages can receive tumor cell-derived exosomes to polarize into M2-type macrophages, which can enhance the invasion and metastasis of pancreatic cancer, leading to poor prognosis. However, the mechanism by which pancreatic cancer cell-derived exosomes promote M2-type macrophages is still unclear. M2 macrophage-associated exosome-derived key module genes were identified by differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) analysis using exoRbase 2.0, The Cancer Genome Atlas (TCGA), and The International Cancer Genome Consortium (ICGC) databases. Multivariate Cox regression analysis was used to identify key prognostic genes and obtain regression coefficients to establish prognostic signature. Immune infiltration, tumor mutations, and GSEA among different risk groups were compared. exoRbase 2.0, Gene Expression Profiling Interactive Analysis 2 (GEPIA2), HPA, and TISCH2 databases were used to further analyze the expression pattern of S100A9 in pancreatic cancer. In vitro experiments, cell-derived exosome isolation, quantitative polymerase chain reaction (qPCR), western blot, flow cytometry analysis, cell transfection, transwell assay, and CCK-8 assay were applied to investigate the roles of S100A9 in macrophage M2 polarization and tumor progression. The key genes of PDAC-derived exosomes promoting M2-type macrophage polarization were identified, and a risk score model was established. The risk score is related to the expression of common immune checkpoints, immune score, and stromal score, and the tumor mutational burden and biological function of high- and low-risk groups were also different. S100A9 was positively correlated with M2-type macrophage marker. In addition, scRNA-seq data from the TISCH2 database revealed that S100A9 is predominantly expressed in pancreatic cancer cells and mono/macrophage cells, suggesting that S100A9 in pancreatic cancer cells could be received by macrophages, thereby inducing macrophage polarization. In vitro, we used exosomes from BxPC-3 cell lines to coculture macrophages and found that macrophages were mainly polarized toward M2 type, which further promoted the proliferation and metastasis of PDAC. Our study established a reliable risk score model for PDAC-derived exosomes and M2 macrophages, identified the important role of S100A9 in macrophage M2 polarization, which provides a new strategy for the diagnosis and treatment of PDAC, and strengthened the understanding of the mechanism of tumor development and metastasis.

GelMA/tannic acid hydrogel decorated polypropylene mesh facilitating regeneration of abdominal wall defects.

Polypropylene (PP) mesh is a widely used prosthetic material in hernia repair due to its excellent mechanical properties and appropriate biocompatibility. However, its application is limited due to severe adhesion between the mesh and the abdominal viscera, leading to complications such as chronic pain, intestinal obstruction, and hernia recurrence. Currently, building anti-adhesive PP mesh remains a formidable challenge. In this work, a novel anti-adhesive PP mesh (PPM/GelMA/TA) was designed with a simple and efficient in situ gel of GelMA solution on the surface of PP mesh and further crosslinking of tannic acid (TA). It was demonstrated that PPM/GelMA/TA has good biocompatibility and excellent antioxidant property and effectively activates the polarization of macrophages toward the M2 phenotype in vitro. In addition, PPM/GelMA/TA could inhibit the growth of bacteria, which is of great significance for preventing postoperative infections. Furthermore, in the repair of full-thickness abdominal wall defects in rats, PPM/GelMA/TA reduced inflammation, promoted macrophage M2 polarization, and collagen deposition and angiogenesis so that does not cause any abdominal adhesion compared with PP mesh. As a result, our PPM/GelMA/TA shows an attractive prospect in the treatment of abdominal wall defect without adhesions.

IL-34 attenuates acute T cell-mediated rejection following renal transplantation by upregulating M2 macrophages polarization

ObjectiveTo investigate the role of Interleukin-34 (IL-34) in acute T cell-mediated rejection (TCMR) following renal transplantation. MethodsThe mice acute TCMR model of renal transplantation was established and identified by hematoxylin and eosin (HE) and immunohistochemistry (IHC) staining. Then, IHC staining of IL-34 was also performed to determine the expression of IL-34 in allografts. Recipients were infected with IL-34 overexpression adeno-associated virus, infection efficiency of which was estimated by enzyme linked immunosorbent assay (ELISA), Western blot, and immunofluorescence. HE and IHC staining were used to estimate the grades of TCMR. Flow cytometry was performed on lymphocytes in spleens of recipients including regulatory T cells (Tregs) and M2 macrophages. The expression of cytokines in vivo was analyzed by Mouse Cytokine Grp I Panel. Finally, Tregs and M2 macrophages were cultured in vitro and treated with IL-34 to observe the effects of IL-34 on the differentiation of the cells. ResultsThe mouse TCMR model was successfully established by HE, periodic acid shiff (PAS), CD4 and CD8 IHC staining. The expression of IL-34 was significantly decreased in allografts with TCMR. BALB/c mice were successfully infected with IL-34 overexpression adeno-associated virus. Subsequently, the grade of rejection in mice TCMR model was evaluated by HE and IHC staining according to Banff criteria. It is suggested that the grade of TCMR in IL-34 overexpressed mice was significantly decreased. IHC staining and Flow cytometry showed that the proportion of Tregs and M2 macrophages in the spleens and allografts were significantly increased in IL-34 overexpressed mice. Serum levels of interferon-gamma (IFN-γ), IL-17 and tumor necrosis factor-alpha (TNF-α) were downregulated in IL-34 overexpressed mice. Moreover, IL-34 could promote macrophage M2 polarization, while failed to promote differentiation of naïve T cells into Tregs in vitro. ConclusionOverexpression of IL-34 may attenuate the progression of TCMR episodes in allografts by increasing the polarization of M2 macrophages in the spleens and allografts, which may become a potential therapeutic strategy for TCMR.

Magnesium Ion-Doped Mesoporous Bioactive Glasses Loaded with Gallic Acid Against Myocardial Ischemia/Reperfusion Injury by Affecting the Biological Functions of Multiple Cells.

Excessive generation of reactive oxygen species (ROS) following myocardial ischemia-reperfusion (I/R) can result in additional death of myocardial cells. The rapid clearance of ROS after reperfusion injury and intervention during subsequent cardiac repair stages are crucial for the ultimate recovery of cardiac function. Magnesium-doped mesoporous bioactive glasses were prepared and loaded with the antioxidant drug gallic acid into MgNPs by sol-gel method. The antioxidant effects of MgNPs/GA were tested for their pro-angiogenic and anti-inflammatory effects based on the release characteristics of GA and Mg2+ from MgNPs/GA. Later, we confirmed in our in vivo tests through immunofluorescence staining of tissue sections at various time points that MgNPs/GA exhibited initial antioxidant effects and had both pro-angiogenic and anti-inflammatory effects during the cardiac repair phase. Finally, we evaluated the cardiac function in mice treated with MgNPs/GA. We provide evidence that GA released by MgNPs/GA can effectively eliminate ROS in the early stage, decreasing myocardial cell apoptosis. During the subsequent cardiac repair phase, the gradual release of Mg2+ from MgNPs/GA stimulated angiogenesis and promoted M2 macrophage polarization, thereby reducing the release of inflammatory factors. MgNPs/GA acting on multiple cell types is an integrated solution for comprehensive attenuation of myocardial ischaemia-reperfusion injury and cardiac function protection.

D-Mannose promotes recovery from experimental colitis by inducing AMPK phosphorylation to stimulate epithelial repair.

Delayed mucosal healing and impaired intestinal epithelial barrier function have been implicated in the pathogenesis of ulcerative colitis (UC). Accordingly, restoration of epithelial barrier function as a means to reshape mucosal homeostasis represents an important strategy for use in the treatment of UC. In this study, we examined the role and mechanisms of D-mannose in the recovery of colitis as assessed in both animal and cell models. We found that D-mannose ameliorated inflammation, promoted mucosal healing in the colon and therefore was able to induce the recovery of UC. Furthermore, D-mannose increased the expression of tight junction (TJ) proteins and reduced the intestinal permeability during the recovery of colitis. Moreover, D-mannose inhibited M1 macrophage polarization and promoted M2 macrophage polarization via inducing AMPK phosphorylation while reducing mTOR phosphorylation in both models. In addition, increased TJ protein expression and decreased paracellular permeability were observed in NCM460 cells when incubated with the supernatants of D-mannose-treated RAW264.7 cells, suggesting that M1/M2 polarization induced by D-mannose modulates the expression of TJ proteins. Further study showed that D-mannose significantly upregulated the expression of TJ proteins in DSS-treated NCM460 cells by inducing AMPK phosphorylation, indicating a direct protective effect on epithelial cells. Finally, the protective effects of D-mannose were significantly abrogated by the presence of compound C, an AMPK inhibitor. Taken together, our data indicate that D-mannose can alleviate inflammation and foster epithelial restitution in UC recovery by inducing the TJ protein expression, which are achieved by inducing AMPK phosphorylation in the epithelium and/or macrophages.

Myeloid cell-expressed MNDA enhances M2 polarization to facilitate the metastasis of hepatocellular carcinoma.

Stable infiltration of myeloid cells, especially tumor-associated M2 macrophages, acts as one of the essential features of the tumor immune microenvironment by promoting the malignant progression of hepatocellular carcinoma (HCC). However, the factors affecting the infiltration of M2 macrophages are not fully understood. In this study, we found the molecular subtypes of HCC with the worst prognosis are characterized by immune disorders dominated by myeloid cell infiltration. Myeloid cell nuclear differentiation antigen (MNDA) was significantly elevated in the most aggressive subtype and exhibited a positively correlation with M2 infiltration and HCC metastasis. Moreover, MNDA functioned as an independent prognostic predictor and has a good synergistic effect with some existing prognostic clinical indicators. We further confirmed that MNDA was primarily expressed in tumor M2 macrophages and contributed to the enhancement of its polarization by upregulating the expression of the M2 polarization enhancers. Furthermore, MNDA could drive the secretion of M2 macrophage-derived pro-metastasis proteins to accelerate HCC cells metastasis both in vivo and in vitro. In summary, MNDA exerts a protumor role by promoting M2 macrophages polarization and HCC metastasis, and can serve as a potential biomarker and therapeutic target for HCC.

Baicalein exerts beneficial effects in lipopolysaccharide-induced pulmonary inflammation by modulating macrophage polarization and inhibiting pyroptosis.

The disruption of the immune system by viral attack is a major influencing factor in the lethality of COVID-19. Baicalein is one of the key effective compounds against COVID-19. The molecular mechanisms regarding the anti-inflammatory properties of Baicalein are still unclear. In this study, we established LPS-induced mice to elucidate the role of Baicalein in the treatment of acute lung injury (ALI) and its potential molecular mechanisms. In vivo experiments showed that Baicalein could significantly ameliorate LPS-induced acute lung injury and reduce proteinous edema in lung tissue. In addition, Baicalein inhibited M1 macrophage polarization, promote M2 macrophage polarization, and regulate inflammatory responses. Furthermore, Baicalein could inhibit the expression of protein molecules associated with pyroptosis and mitigate the lung tissue injury. In summary, we revealed the therapeutic effects of Baicalein in acute lung injury, providing the theoretical basis for its clinical application.

Exercise Attenuates Doxorubicin‐Induced Myocardial Injury by Inhibiting TSHR and Regulating Macrophage Polarization Through miR‐30d‐5p/GALNT7

Objective: Doxorubicin (DOX) is an extensively used chemotherapeutic agent that induces cardiotoxicity. Studies have reported that exercise (EXE) can alleviate DOX‐induced cardiotoxicity. Therefore, this study aimed to explore the mechanism by which EXE attenuates DOX‐induced myocardial injury.Methods: In this study, cell and animal models of DOX‐induced myocardial injury were constructed. The animal model was subjected to EXE intervention.Results: In this study, in vitro experiments revealed that miR‐30d‐5p negatively regulated polypeptide N‐acetylgalactosaminyltransferase 7 (GALNT7) and that GALNT7 negatively regulated the expression of thyroid stimulating hormone receptor (TSHR). miR‐30d‐5p downregulated the expression of GALNT7, promoted the expression of TSHR, and promoted macrophage M1 polarization, thus aggravating cardiomyocyte injury. In vivo experiments revealed that EXE intervention significantly downregulated miR‐30d‐5p and TSHR expression, upregulated GALNT7, reduced inflammation, and promoted M2 macrophage polarization, thereby alleviating DOX‐induced myocardial injury. In addition, overexpression of miR‐30d‐5p or knockdown of GALNT7 weakened the intervention effect of EXE, whereas overexpression of GALNT7 or knockdown of TSHR promoted the effect of EXE.Conclusion: EXE can modulate the miR‐30d‐5p/GALNT7 axis to inhibit the expression of TSHR, thereby regulating the polarization of macrophages to the M2 phenotype and ultimately alleviating DOX‐induced myocardial injury, which provides new targets and strategies for the clinical treatment of myocardial injury.

Endoplasmic Reticulum Membrane Protein Complex Regulates Cancer Stem Cells and is Associated with Sorafenib Resistance in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, underscoring the need for novel therapeutic targets. This study aimed to elucidate the role of endoplasmic reticulum membrane protein complex subunit 1 (EMC1) in HCC progression and its therapeutic potential. Publicly available sequencing data and biopsy specimens were analyzed to assess EMC's clinical value and functions in HCC. In vitro experiments validated EMC functions, and multiplex immunofluorescence analysis examined EMC-associated sorafenib resistance mechanisms. EMC1 expression was knocked down in HCC cell lines, followed by cell viability, wound healing, and transwell migration assays. Tumor growth and response to sorafenib treatment were evaluated in mouse models. Metabolomic analysis assessed changes in the TCA cycle. EMC genes were aberrantly expressed in HCC, and high EMC1 expression correlated with poorer survival rates. EMC1 disruption enhanced HCC cells' sensitivity to sorafenib, reducing cell viability, increasing apoptosis, and decreasing tumor size and weight. EMC1 maintained cancer cell stemness and promoted M2 macrophage infiltration. Metabolomic analysis revealed significant changes in the TCA cycle, indicating EMC1's role in HCC metabolic reprogramming. Importantly, EMC1 is highly associated with sorafenib resistance, potentially linked to CTNNB1 mutation or activation. EMC1 plays a critical role in regulating the sorafenib resistance in HCC. Targeting EMC1 may improve HCC treatment efficacy.

AFM41a: A Novel PAD2 Inhibitor for Sepsis Treatment-Efficacy and Mechanism.

Pseudomonas aeruginosa (PA) infection can cause pneumonia and sepsis by activating peptidyl-arginine deiminase (PAD) and triggering the formation of neutrophil extracellular traps (NETs). Our previous research has elucidated the crucial role of PAD2 in regulating CitH3 production and NETosis signaling following bacterial infection. Therefore, targeting PAD2 with selective inhibitors holds promise for treating PA-induced sepsis. Here, we compare the structure and function of two PAD2 inhibitors, AFM32a and AFM41a, and investigate their biological effects in mice subjected with PA. We analyze their impact on PAD2 inhibition, macrophage polarization, and other host defense mechanisms against PA-induced sepsis utilizing both in vivo and in vitro approaches. Our findings demonstrate that both PAD2 inhibitors (AFM32a and AFM41a) and Pad2 deficiency substantially enhance protection against PA-induced sepsis, with AFM41a showing superior efficacy over AFM32a. This protective effect is marked by improved survival rates, reduced bacterial growth in mice subjected to PA infection, and the promotion of M2 macrophage polarization coupled with enhanced autophagic activity. Our results advocate for targeting PAD2 as an effective strategy to bolster host defenses against PA infection. Utilizing AFM41a to promote M2 macrophage polarization and autophagy offers promising avenues for the treatment of PA infection and the improvement of sepsis outcomes.

A novel pterostilbene compound DCZ0825 induces macrophage M1 differentiation and Th1 polarization to exert anti-myeloma and immunomodulatory.

Multiple myeloma (MM) is an incurable and recurrent malignancy characterized by abnormal plasma cell proliferation. There is an urgent need to develop effective drugs in MM. DCZ0825 is a small molecule compound derived from pterostilbene with direct anti-myeloma activity and indirect immune-killing effects though reversal of the immunosuppression. DCZ0825 inhibits the activity and proliferation of MM cells causing no significant toxicity to normal cells. Using flow cytometry, this study found that DCZ0825 induced caspase-dependent apoptosis in MM cells and arrested the cell cycle in the G2/M phase by down-regulating CyclinB1, CDK1 and CDC25. Moreover, DCZ0825 up-regulated IRF3 and IRF7 to increase IFN-γ, promoting M2 macrophages to transform into M1 macrophages, releasing the immunosuppression of CD4T cells and stimulated M1 macrophages and Th1 cells to secrete more INF-γ to form immune killing effect on MM cells. Treatment with DCZ0825 resulted in an increased proportion of positive regulatory cells such as CD4T, memory T cells, CD8T, and NK cells, with downregulation of the proportion of negative regulatory cells such as Treg cells and MDSCs. In conclusion, DCZ0825 is a novel compound with both antitumor and immunomodulatory activity.

Extracellular vesicles from a novel Lactiplantibacillus plantarum strain suppress inflammation and promote M2 macrophage polarization.

Lactiplantibacillus plantarum (L. plantarum) is known for its probiotic properties, including antioxidant and anti-inflammatory effects. Recent studies have highlighted the role of extracellular vesicles (EVs) from prokaryotic cells in anti-inflammatory effects. This study aims to investigate the anti-inflammatory effects of extracellular vesicles derived from a newly isolated strain of L. plantarum (LP25 strain) and their role in macrophage polarization. The LP25 strain and its extracellular vesicles were isolated and identified through genomic sequencing, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). RAW 264.7 cells were treated with lipopolysaccharide (LPS) and/or LP25-derived extracellular vesicles (LEV). Morphological changes in the cells were observed, and the expression levels of pro-inflammatory cytokines (TNF-α, IL-6)、iNOS and anti-inflammatory cytokines (IL-10) 、Arg-1 were measured using quantitative real-time PCR (qPCR). Flow cytometry was used to detect the expression of Arg-1 in the treated cells. Treatment with LP25 EVs led to significant morphological changes in RAW 264.7 cells exposed to LPS. LP25 EVs treatment resulted in increased expression of Arg-1 and anti-inflammatory cytokines IL-10, and decreased expression of iNOS and surface markers protein CD86. Flow cytometry confirmed the increased expression of the M2 macrophage marker Arg-1 in the LP25 EVs-treated group. Extracellular vesicles from Lactiplantibacillus plantarum LP25 can suppress inflammatory responses and promote the polarization of macrophages toward the anti-inflammatory M2 phenotype. These findings provide new evidence supporting the anti-inflammatory activity of L. plantarum-derived EVs.

Extracellular Vesicles Obtained From Lung Adenocarcinoma Cells Cultured Under Intermittent Hypoxia Induce M2 Macrophage Polarization via miR-20a-5p Delivery.

Conclusion: These findings indicate that EVs obtained from lung adenocarcinoma cells cultured under IH deliver miR-20a-5p to promote M2 macrophage polarization by targeting PTEN.