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Cell Communication and Signaling : CCS Jun 2024Triple-negative breast cancer (TNBC) is recognized as the most aggressive and immunologically infiltrated subtype of breast cancer. A high circulating...
BACKGROUND
Triple-negative breast cancer (TNBC) is recognized as the most aggressive and immunologically infiltrated subtype of breast cancer. A high circulating neutrophil-to-lymphocyte ratio (NLR) is strongly linked to a poor prognosis among patients with breast cancer, emphasizing the critical role of neutrophils. Although the involvement of neutrophils in tumor metastasis is well documented, their interactions with primary tumors and tumor cells are not yet fully understood.
METHODS
Clinical data were analyzed to investigate the role of neutrophils in breast cancer. In vivo mouse model and in vitro co-culture system were used for mechanism researches. Blocking experiments were further performed to identify therapeutic agents against TNBC.
RESULTS
TNBC cells secreted GM-CSF to sustain the survival of mature neutrophils and upregulated CD11b expression. Through CD11b, neutrophils specifically binded to ICAM1 on TNBC cells, facilitating adhesion. Transcriptomic sequencing combined with human and murine functional experiments revealed that neutrophils, through direct CD11b-ICAM1 interactions, activated the MAPK signaling pathway in TNBC cells, thereby enhancing tumor cell invasion and migration. Atorvastatin effectively inhibited ICAM1 expression in tumor cells, and tumor cells with ICAM1 knockout or treated with atorvastatin were unresponsive to neutrophil activation. The MAPK pathway and MMP9 expression were significantly inhibited in the tumor tissues of TNBC patients treated with atorvastatin.
CONCLUSIONS
Targeting CD11b-ICAM1 with atorvastatin represented a potential clinical approach to reduce the malignant characteristics of TNBC.
Topics: Triple Negative Breast Neoplasms; Neutrophils; Humans; Animals; CD11b Antigen; Female; Intercellular Adhesion Molecule-1; Mice; Cell Adhesion; Cell Line, Tumor; Disease Progression; Cell Movement
PubMed: 38907234
DOI: 10.1186/s12964-024-01716-5 -
BMC Infectious Diseases Jun 2024To determine the relationship of Neutrophil Lymphocyte Ratio (NLR), Monocyte Lymphocyte Ratio (MLR), and Neutrophil Monocyte Ratio (NMR) with treatment response in...
Relationship of neutrophil lymphocyte ratio, monocyte lymphocyte ratio and neutrophil monocyte ratio with treatment response in pulmonary tuberculosis patients during intensive phase treatment.
OBJECTIVE
To determine the relationship of Neutrophil Lymphocyte Ratio (NLR), Monocyte Lymphocyte Ratio (MLR), and Neutrophil Monocyte Ratio (NMR) with treatment response in Pulmonary Tuberculosis (PTB) patients during intensive phase treatment (IPT).
METHODS
This analytical cross-sectional study was conducted at Ojha Institute of Chest Diseases (OICD), Dow University of Health Sciences, from February to December 2021. 100 patients were enrolled using purposive sampling technique. Both male and female of age 18 and above, rifampicin sensitive newly diagnosed cases of PTB by Acid Fast Bacilli (AFB) microscopy and Gene Xpert MTB/RIF were included. SPSS version 26 was used to analyze data. Numerical data was expressed in median and interquartile range and categorical data was expressed in frequencies and percentages.
RESULTS
Out of total 100 patients, 81% (n = 81) showed treatment response with negative AFB Sputum Smear Microscopy (SSM) after 2nd month. Out of 81% (n = 81) of the patients who achieved treatment response, 83.9% (n = 68) also had decreased NLR, 85.2% (n = 69) had decreased MLR and 83.9% (n = 68) had decreased NMR from baseline. However 19% (n = 19) did not achieved treatment response with positive AFB SSM after 2nd month of ATT (Anti tuberculosis treatment), among them 10.52% (n = 2) were INH resistant with no decrease in all the ratios after 2nd month.
CONCLUSION
Leukocyte ratios decreased significantly from baseline as PTB was treated in patients who achieved treatment response with negative AFB SSM after two months of ATT and hence these ratios could be used as markers to monitor the treatment response.
Topics: Humans; Male; Female; Tuberculosis, Pulmonary; Adult; Neutrophils; Cross-Sectional Studies; Lymphocytes; Monocytes; Middle Aged; Antitubercular Agents; Treatment Outcome; Young Adult; Sputum; Adolescent; Rifampin
PubMed: 38907220
DOI: 10.1186/s12879-024-09454-2 -
Journal of Nanobiotechnology Jun 2024Periodontitis is a chronic inflammation caused by a bacterial infection and is intimately associated with an overactive immune response. Biomaterials are being utilized... (Review)
Review
Periodontitis is a chronic inflammation caused by a bacterial infection and is intimately associated with an overactive immune response. Biomaterials are being utilized more frequently in periodontal therapy due to their designability and unique drug delivery system. However, local and systemic immune response reactions driven by the implantation of biomaterials could result in inflammation, tissue damage, and fibrosis, which could end up with the failure of the implantation. Therefore, immunological adjustment of biomaterials through precise design can reduce the host reaction while eliminating the periodontal tissue's long-term chronic inflammation response. It is important to note that macrophages are an active immune system component that can participate in the progression of periodontal disease through intricate polarization mechanisms. And modulating macrophage polarization by designing biomaterials has emerged as a new periodontal therapy technique. In this review, we discuss the role of macrophages in periodontitis and typical strategies for polarizing macrophages with biomaterials. Subsequently, we discuss the challenges and potential opportunities of using biomaterials to manipulate periodontal macrophages to facilitate periodontal regeneration.
Topics: Humans; Periodontitis; Biocompatible Materials; Macrophages; Animals; Immunotherapy; Drug Delivery Systems
PubMed: 38907216
DOI: 10.1186/s12951-024-02592-4 -
Scientific Reports Jun 2024Sysmex DI-60 enumerates and classifies leukocytes. Limited research has evaluated the performance of Sysmex DI-60 in abnormal samples, and most focused on leukopenic...
Sysmex DI-60 enumerates and classifies leukocytes. Limited research has evaluated the performance of Sysmex DI-60 in abnormal samples, and most focused on leukopenic samples. We evaluate the efficacy of DI-60 in determining white blood cell (WBC) differentials in normal and abnormal samples in different WBC count. Peripheral blood smears (n = 166) were categorised into normal control and disease groups, and further divided into moderate and severe leucocytosis, mild leucocytosis, normal, mild leukopenia, and moderate and severe leukopenia groups based on WBC count. DI-60 preclassification and verification and manual counting results were assessed using Bland-Altman and Passing-Bablok regression analyses. The Kappa test compared the concordance in the abnormal cell detection between DI-60 and manual counting. DI-60 exhibited notable overall sensitivity and specificity for all cells, except basophils. The correlation between the DI-60 preclassification and manual counting was high for segmented neutrophils, band neutrophils, lymphocytes, and blasts, and improved for all cell classes after verification. The mean difference between DI-60 and manual counting for all cell classes was significantly high in moderate and severe leucocytosis (WBC > 30.0 × 10/L) and moderate and severe leukopenia (WBC < 1.5 × 10/L) groups. For blast cells, immature granulocytes, and atypical lymphocytes, the DI-60 verification results were similar to the manual counting results. Plasma cells showed poor agreement. In conclusion, DI-60 demonstrates consistent and reliable analysis of WBC differentials within the range of 1.5-30.0 × 10. Manual counting was indispensable in examining moderate and severe leucocytosis samples, moderate and severe leukopenia samples, and in enumerating of monocytes and plasma cells.
Topics: Humans; Leukocyte Count; Leukocytes; Leukopenia; Leukocytosis; Sensitivity and Specificity; Female; Male; Neutrophils; Middle Aged
PubMed: 38906933
DOI: 10.1038/s41598-024-65427-0 -
Scientific Reports Jun 2024Non-small cell lung cancer (NSCLC)-originating cancer-associated fibroblasts (CAFs) expressing CD248 regulate interaction with immune cells to accelerate cancer...
Non-small cell lung cancer (NSCLC)-originating cancer-associated fibroblasts (CAFs) expressing CD248 regulate interaction with immune cells to accelerate cancer progression. Epithelial-mesenchymal transition (EMT) is a key feature of metastatic cells. In our pervious study, we found that CD248CAFs activated M2-polarized macrophages, enhancing the progression of NSCLC. However, it is yet unclear how CD248CAFs inducing M2-polarized macrophages induce EMT program in NSCLC cells. Herein, we examined CD248 expression from CAFs derived from NSCLC patient tumour tissues. Furthermore, we determined the influence of CD248 knock down CAFs on macrophages polarization. Next, we explored the influences of CD248-harboring CAFs-mediated M2 macrophage polarization to promote NSCLC cells EMT in vitro. We constructed fibroblasts specific CD248 gene knock out mice to examine the significance of CD248-harboring CAFs-induced M2-polarized macrophages to promote NSCLC cells EMT in vivo. Based on our analysis, CD248 is ubiquitously expressed within NSCLC-originating CAFs. CD248CAFs mediated macrophages polarized to M2 type macrophages. CD248CAFs induced M2 macrophage polarization to enhance NSCLC cells EMT both in vivo and in vitro. Our findings indicate that CD248-harboring CAFs promote NSCLC cells EMT by regulating M2-polarized macrophages.
Topics: Epithelial-Mesenchymal Transition; Carcinoma, Non-Small-Cell Lung; Cancer-Associated Fibroblasts; Humans; Animals; Lung Neoplasms; Macrophages; Mice; Antigens, CD; Mice, Knockout; Cell Line, Tumor; Antigens, Neoplasm
PubMed: 38906929
DOI: 10.1038/s41598-024-65435-0 -
Cell Death & Disease Jun 2024Although adamantinomatous craniopharyngioma (ACP) is a tumour with low histological malignancy, there are very few therapeutic options other than surgery. ACP has high...
Although adamantinomatous craniopharyngioma (ACP) is a tumour with low histological malignancy, there are very few therapeutic options other than surgery. ACP has high histological complexity, and the unique features of the immunological microenvironment within ACP remain elusive. Further elucidation of the tumour microenvironment is particularly important to expand our knowledge of potential therapeutic targets. Here, we performed integrative analysis of 58,081 nuclei through single-nucleus RNA sequencing and spatial transcriptomics on ACP specimens to characterize the features and intercellular network within the microenvironment. The ACP environment is highly immunosuppressive with low levels of T-cell infiltration/cytotoxicity. Moreover, tumour-associated macrophages (TAMs), which originate from distinct sources, highly infiltrate the microenvironment. Using spatial transcriptomic data, we observed one kind of non-microglial derived TAM that highly expressed GPNMB close to the terminally differentiated epithelial cell characterized by RHCG, and this colocalization was verified by asmFISH. We also found the positive correlation of infiltration between these two cell types in datasets with larger cohort. According to intercellular communication analysis, we report a regulatory network that could facilitate the keratinization of RHCG epithelial cells, eventually causing tumour progression. Our findings provide a comprehensive analysis of the ACP immune microenvironment and reveal a potential therapeutic strategy base on interfering with these two types of cells.
Topics: Humans; Craniopharyngioma; Tumor Microenvironment; Pituitary Neoplasms; Tumor-Associated Macrophages; Male; Female; Keratins; Transcriptome; Gene Expression Regulation, Neoplastic; Adult; Middle Aged; Multiomics
PubMed: 38906852
DOI: 10.1038/s41419-024-06840-1 -
Cell Reports Jun 2024Planarian flatworms undergo continuous internal turnover, wherein old cells are replaced by the division progeny of adult pluripotent stem cells (neoblasts). How cell...
Planarian flatworms undergo continuous internal turnover, wherein old cells are replaced by the division progeny of adult pluripotent stem cells (neoblasts). How cell turnover is carried out at the organismal level remains an intriguing question in planarians and other systems. While previous studies have predominantly focused on neoblast proliferation, little is known about the processes that mediate cell loss during tissue homeostasis. Here, we use the planarian epidermis as a model to study the mechanisms of cell removal. We established a covalent dye-labeling assay and image analysis pipeline to quantify the cell turnover rate in the planarian epidermis. Our findings indicate that the ventral epidermis is highly dynamic and epidermal cells undergo internalization via basal extrusion, followed by a relocation toward the intestine and ultimately digestion by intestinal phagocytes. Overall, our study reveals a complex homeostatic process of cell clearance that may generally allow planarians to catabolize their own cells.
PubMed: 38906148
DOI: 10.1016/j.celrep.2024.114305 -
Medicine Jun 2024Preeclampsia (PE) is a serious condition that threatens pregnancy with severe sequelae on both the mother and infant. Early detection of PE will lead to favorable... (Observational Study)
Observational Study
Preeclampsia (PE) is a serious condition that threatens pregnancy with severe sequelae on both the mother and infant. Early detection of PE will lead to favorable outcomes, and using readily available markers like hematological indices is an attractive choice. Examine the diagnostic utility of hematological indices in pregnant women to predict preeclampsia and its severity. In a retrospective case-control study that included 252 women, all had their complete blood picture evaluated during their first and third trimesters as part of their outpatient antenatal care during their pregnancy. They were also divided into 3 groups: healthy pregnant women (control), non-severe PE, and severe PE, each involving 84 women. The changes in platelet to lymphocyte ratio (PLR) between 1st and 3rd trimesters showed an excellent ability to differentiate between severe PE and control (area under the curve = 0.954, cutoff ≤ -5.45%) and a good ability to differentiate between severe PE and non-severe PE (area under the curve = 0.841, cutoff ≤ -7.89%). Neutrophil to lymphocyte ratio showed a good to excellent ability to differentiate between severe PE and non-severe PE compared to control in the first and third trimesters and the percentage change between them. Changes in neutrophil to lymphocyte ratio and PLR strongly predict preeclampsia and its severity since they offer more predictive values than measuring NLP and PLR at different stages of pregnancy individually.
Topics: Humans; Female; Pre-Eclampsia; Pregnancy; Retrospective Studies; Adult; Case-Control Studies; Severity of Illness Index; Lymphocyte Count; Platelet Count; Predictive Value of Tests; Biomarkers; Lymphocytes; Neutrophils
PubMed: 38905404
DOI: 10.1097/MD.0000000000038557 -
Journal of Bacteriology Jun 2024During spore development in bacteria, a polar septum separates two transcriptionally distinct cellular compartments, the mother cell and the forespore. The conserved...
During spore development in bacteria, a polar septum separates two transcriptionally distinct cellular compartments, the mother cell and the forespore. The conserved serine phosphatase SpoIIE is known for its critical role in the formation of this septum and activation of compartment-specific transcription in the forespore. Signaling between the mother cell and forespore then leads to activation of mother cell transcription and a phagocytic-like process called engulfment, which involves dramatic remodeling of the septum and requires a balance between peptidoglycan synthesis and hydrolysis to ensure septal stability and compartmentalization. Using , we identify an additional role for SpoIIE in maintaining septal stability and compartmentalization at the onset of engulfment. This role for SpoIIE is mediated by SpoIIQ, which anchors SpoIIE in the engulfing membrane. A SpoIIQ mutant (SpoIIQ Y28A) that fails to anchor SpoIIE, results in septal instability and miscompartmentalization during septal peptidoglycan hydrolysis, when other septal stabilization factors are absent. Our data support a model whereby SpoIIE and its interactions with the peptidoglycan synthetic machinery contribute to the stabilization of the asymmetric septum early in engulfment, thereby ensuring compartmentalization during spore development.IMPORTANCEBacterial sporulation is a complex process involving a vast array of proteins. Some of these proteins are absolutely critical and regulate key points in the developmental process. Once such protein is SpoIIE, known for its role in the formation of the polar septum, a hallmark of the early stages of sporulation, and activation of the first sporulation-specific sigma factor, σF, in the developing spore. Interestingly, SpoIIE has been shown to interact with SpoIIQ, an important σF-regulated protein that functions during the engulfment stage. However, the significance of this interaction has remained unclear. Here, we unveil the importance of the SpoIIQ-SpoIIE interaction and identify a role for SpoIIE in the stabilization of the polar septum and maintenance of compartmentalization at the onset of engulfment. In this way, we demonstrate that key sporulation proteins, like SpoIIQ and SpoIIE, function in multiple processes during spore development.
PubMed: 38904397
DOI: 10.1128/jb.00220-24 -
MSphere Jun 2024, an emerging multidrug-resistant fungal pathogen, predominately colonizes the human skin long term leading to subsequent life-threatening invasive infections. Fungal...
, an emerging multidrug-resistant fungal pathogen, predominately colonizes the human skin long term leading to subsequent life-threatening invasive infections. Fungal morphology is believed to play a critical role in modulating mucocutaneous antifungal immunity. In this study, we used an intradermal mouse model of infection to examine fungal colonization and the associated innate and adaptive immune response to yeast and filamentous strains. Our results indicate that mice infected with a filamentous had significantly decreased fungal load compared to mice infected with the yeast form. Mice infected with yeast and filamentous forms of stimulated distinct innate immune responses. Phagocytic cells (CD11bLy6G neutrophils, CD11bLy6C inflammatory monocytes, and CD11bMHCIICD64 macrophages) were differentially recruited to mouse skin tissue infected with yeast and filamentous . The percentage and absolute number of interleukin 17 (IL-17) producing innate lymphoid cells, TCRγδ, and CD4 T cells in the skin tissue of mice infected with filamentous were significantly increased compared to the wild-type of yeast strain. Furthermore, complementation of filamentous mutant strain of (Δ) strain exhibited wild-type yeast morphology and induced comparable level of skin immune responses similar to mice infected with yeast strain. Collectively, our findings indicate that yeast and filamentous induce distinct local immune responses in the skin. The decreased fungal load observed in mouse skin infected with filamentous is associated with a potent IL-17 immune response induced by this morphotype.IMPORTANCE is a globally emerging fungal pathogen that transmits among individuals in hospitals and nursing home residents. Unlike other species, predominantly colonizes and persists in skin tissue resulting in outbreaks of systemic infections. Understanding the factors that regulate skin colonization and host immune response is critical to develop novel preventive and therapeutic approaches against this emerging pathogen. We identified that yeast and filamentous forms of induce distinct skin immune responses in the skin. These findings may help explain the differential colonization and persistence of morphotypes in skin tissue. Understanding the skin immune responses induced by yeast and filamentous is important to develop novel vaccine strategies to combat this emerging fungal pathogen.
PubMed: 38904381
DOI: 10.1128/msphere.00055-24