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Medicine Jun 2024The neutrophil lymphocyte ratio (NLR) and red blood cell distribution width (RDW) have been repeatedly demonstrated to be associated with risk of severity, progression,... (Observational Study)
Observational Study
The neutrophil lymphocyte ratio (NLR) and red blood cell distribution width (RDW) have been repeatedly demonstrated to be associated with risk of severity, progression, and prognosis of chronic obstructive pulmonary disease (COPD), but data on respiratory failure (RF) in patients with COPD are very limited. This study aimed to examine the relationship between NLR and RDW and the incident RF in patients with COPD. This is a retrospective study that reviewed data by examining the hospitalization medical records to identify those who were admitted with a diagnosis of COPD. Based on whether RF occurred during index hospitalization, patients were classified as COPD group and COPD combined with RF group. Also, healthy controls of the same age and sex were enrolled in a 1:1 ratio as the COPD group. Univariate comparisons were performed between three groups to examine differences. With the COPD group as reference, multivariable logistic regression was formed to identify the relationship between NLR and RDW and RF, with adjustment for multiple covariates. There were 136 healthy controls, 136 COPD patients and 62 patients with COPD combined with RF included for analysis. There was a significant difference for eight variables, including age, WBC, neutrophil, NLR, RDW, platelet, PLR, and CRP. The Spearman test showed the significant correlation between NLR and WBC (correlation coefficient, 0.38; P = .008), NLR and RDW (correlation coefficient, 0.32; P = .013), and NLR and CRP level (correlation coefficient, 0.54; P < .001). The multivariable logistic regression showed that age (every additional 10 years) (OR, 1.785), NLR (OR, 1.716), RDW (OR, 2.266), and CRP (OR, 1.163) were independently associated with an increased risk of RF. This study demonstrated the independent associative effect of NLR and RDW with RF in patients with COPD, exhibiting the potential clinical role in evaluating the progress of COPD to RF.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Male; Female; Retrospective Studies; Erythrocyte Indices; Neutrophils; Middle Aged; Aged; Lymphocytes; Respiratory Insufficiency; Lymphocyte Count; Prognosis
PubMed: 38875435
DOI: 10.1097/MD.0000000000038512 -
Medicine Jun 2024Preoperative laboratory data indicators significantly affect the prognosis of a variety of tumors. Nevertheless, the combined effect of systemic immune-inflammation... (Observational Study)
Observational Study
Preoperative laboratory data indicators significantly affect the prognosis of a variety of tumors. Nevertheless, the combined effect of systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) on overall survival (OS) in patients with esophageal carcinoma remains unclear. Thus, we examined these associations among patients with postoperative staged T3N0M0 esophageal carcinoma. The data of 246 patients with postoperative staged T3N0M0 esophageal carcinoma from January 1, 2010, to December 31, 2022, were retrospectively analyzed. OS was measured from the date of pathological diagnosis until either death or the last follow-up. The Kaplan-Meier method and multivariate Cox regression model were used to analyze the relationship between neutrophil-to-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR), Platelet-to-lymphocyte ratio (LMR), SII, PNI, and OS. The predictive value of SII and PNI as a combined index was analyzed by the receiver operating characteristic curve (ROC). A total of 246 patients aged 65.5 ± 7.4 years were included in this study and 181 (73.6%) were male. The univariate analysis revealed that differentiation, vessel involvement, postoperative treatment, NLR, SII, PLR, LMR, PNI were predictors of OS (P < .05). After adjusted for potential confounds, multivariate Cox regression analysis showed that the differentiation, SII, PNI, and postoperative treatment were independent prognostic factors correlated with OS in patients with postoperative staged T3N0M0 esophageal carcinoma (P < .05). SII and PNI, as a combined indicator, have a higher predictive value for OS. The NLR, SII, PLR, LMR, and PNI could all be used as independent predictors of OS in patients with postoperative staged T3N0M0 esophageal carcinoma. The combination of SII and PNI can significantly improve the accuracy of prediction.
Topics: Humans; Esophageal Neoplasms; Male; Female; Aged; Retrospective Studies; Prognosis; Middle Aged; Neutrophils; Nutrition Assessment; Lymphocyte Count; Kaplan-Meier Estimate; Preoperative Period; Platelet Count; ROC Curve; Lymphocytes; Proportional Hazards Models; Neoplasm Staging
PubMed: 38875403
DOI: 10.1097/MD.0000000000038477 -
Medicine Jun 2024Blood cell ratios are a standard clinical index for the assessment of inflammation. Although a large number of epidemiological investigations have shown that...
Blood cell ratios are a standard clinical index for the assessment of inflammation. Although a large number of epidemiological investigations have shown that inflammation is a potential risk factor for the development of coronary heart disease (CHD), there is not sufficient and direct evidence to confirm the relationship between blood cell ratios and CHD. Therefore, this study aimed to elucidate the effect of blood cell ratios on the incidence of coronary heart disease. This 10-year national study included data from 24,924 participants. The independent variable was blood cell ratios, and the dependent variable was coronary heart diseases (yes or no). The relationship between blood cell ratios and coronary heart disease was verified using baseline characteristic analysis, multivariate logistic regression analysis, smoothed fitted curves, and subgroup analysis. This study found that in multiple logistic regression analysis showed significant positive correlation between monocyte counts × meutrophil counts/lymphocyte counts (SIRI) (OR = 1.495; 95% CI = 1.154-1.938), monocyte-lymphocyte ratio (MLR) (OR = 3.081; 95% CI = 1.476-6.433) and the incidence of CHD; lymphocyte-monocyte ratio (LMR) (OR = 0.928;95% CI = 0.873-0.987), monocyte-lymphocyte ratio (PLR) (OR = 0.997;95% CI = 0.994-1.000) showed negative correlation with CHD. The smoothed curve fitting shows a nonlinear relationship between SIRI, LMR, PLR, and CHD, with an inverted U-shaped curve between SIRI and CHD, an L-shaped angle between LMR and CHD, and a U-shaped curve between PLR and CHD, respectively. Their inflection points are 1.462, 3.75, and 185.714, respectively. SIRI has an inverted U-shaped curve with coronary heart disease, suggesting that low levels of SIRI increase the risk of CHD; LMR with an L-shaped curve with CHD, and PLR with a U-shaped curve with CHD, suggesting that the risk of CHD can be prevented when LMR and PLR are reduced to a certain level. This has positive implications for the prevention and treatment of CHD.
Topics: Humans; Male; Female; Coronary Disease; Middle Aged; Incidence; Adult; Aged; Monocytes; Risk Factors; Lymphocyte Count; Leukocyte Count
PubMed: 38875383
DOI: 10.1097/MD.0000000000038506 -
PloS One 2024Electrical signaling plays a crucial role in the cellular response to tissue injury in wound healing and an external electric field (EF) may expedite the healing...
Electrical signaling plays a crucial role in the cellular response to tissue injury in wound healing and an external electric field (EF) may expedite the healing process. Here, we have developed a standalone, wearable, and programmable electronic device to administer a well-controlled exogenous EF, aiming to accelerate wound healing in an in vivo mouse model to provide pre-clinical evidence. We monitored the healing process by assessing the re-epithelization rate and the ratio of M1/M2 macrophage phenotypes through histology staining. Following three days of treatment, the M1/M2 macrophage ratio decreased by 30.6% and the re-epithelization in the EF-treated wounds trended towards a non-statically significant 24.2% increase compared to the control. These findings provide point towards the effectiveness of the device in shortening the inflammatory phase by promoting reparative macrophages over inflammatory macrophages, and in speeding up re-epithelialization. Our wearable device supports the rationale for the application of programmed EFs for wound management in vivo and provides an exciting basis for further development of our technology based on the modulation of macrophages and inflammation to better wound healing.
Topics: Animals; Mice; Wound Healing; Inflammation; Macrophages; Disease Models, Animal; Male; Wearable Electronic Devices
PubMed: 38875291
DOI: 10.1371/journal.pone.0303692 -
PloS One 2024Diabetes often results in chronic ulcers that fail to heal. Effective treatment for diabetic wounds has not been achieved, although stem-cell-treatment has shown...
Diabetes often results in chronic ulcers that fail to heal. Effective treatment for diabetic wounds has not been achieved, although stem-cell-treatment has shown promise. Hair-follicle-associated-pluripotent (HAP)-stem-cells from bulge area of mouse hair follicle have been shown to differentiate into keratinocytes, vascular endothelial cells, smooth muscle cells, and some other types of cells. In the present study, we developed HAP-cell-sheets to determine their effects on wound healing in type-2 diabetes mellitus (db/db) C57BL/6 mouse model. Flow cytometry analysis showed cytokeratin 15 expression in 64% of cells and macrophage expression in 3.6% of cells in HAP-cell-sheets. A scratch cell migration assay in vitro showed the ability of fibroblasts to migrate and proliferate was enhanced when co-cultured with HAP-cell-sheets. To investigate in vivo effects of the HAP-cell-sheets, they were implanted into 10 mm circular full-thickness resection wounds made on the back of db/db mice. Wound closure was facilitated in the implanted group until day 16. The thickness of epithelium and granulation tissue volume at day 7 were significantly increased by the implantation. CD68 positive area and TGF-β1 positive area were significantly increased; meanwhile, iNOS positive area was reduced at day 7 in the HAP-cell-sheets implanted group. After 21 days, CD68 positive areas in the implanted group were reduced to under the control group level, and TGF-β1 positive area had no difference between the two groups. These observations strongly suggest that the HAP-cell-sheets implantation is efficient to facilitate early macrophage activity and to suppress inflammation level. Using immuno-double-staining against CD34 and α-SMA, we found more vigorous angiogenesis in the implanted wound tissue. The present results suggest autologous HAP-cell-sheets can be used to heal refractory diabetic ulcers and have clinical promise.
Topics: Animals; Wound Healing; Hair Follicle; Mice; Mice, Inbred C57BL; Cell Movement; Pluripotent Stem Cells; Diabetes Mellitus, Type 2; Male; Cell Proliferation; Transforming Growth Factor beta1; Fibroblasts; Granulation Tissue; Macrophages; Diabetes Mellitus, Experimental
PubMed: 38875234
DOI: 10.1371/journal.pone.0304676 -
PloS One 2024The relationship between the levels of Systemic Immune-inflammation Index (SII) and chronic obstructive pulmonary disease (COPD), lung function, and COPD severity were...
PURPOSE
The relationship between the levels of Systemic Immune-inflammation Index (SII) and chronic obstructive pulmonary disease (COPD), lung function, and COPD severity were not fully understood. We conducted this cross-sectional, population-based study to investigate the complex association between SII and COPD, lung function, and COPD severity among the US adults.
METHODS
Overall, 18,349 participants were included in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018. The exposure variable was SII, calculated from platelet counts, neutrophil counts, and lymphocyte counts. Weighted univariable and multivariable logistic regression, subgroup analysis, and restricted cubic spline (RCS) regression were performed to assess the relationship between COPD, lung function, COPD severity and SII. Last, we used a propensity score matching (PSM) analysis to reduce selective bias and validate these relationships.
RESULTS
Approximately 1,094 (5.96%) of the participants were diagnosed as COPD. The multivariable-adjusted odds ratio (OR) (95% confidence interval, CI) for the Q2 group (Log-SII > 2.740) was 1.39 (1.16 to 1.68). Before and after matching, multivariable logistic regression models revealed that increased Log-SII levels (SII Logarithmic transformation) associated positively with the risk of COPD. The subgroup analysis showed no interaction between Log-SII and a variety of variables (P for interaction > 0.05). RCS showed a reversed L-shaped relationship between Log-SII with COPD (P for nonlinear = 0.001) in individuals. In addition, we observed negative significant correlations between forced expiratory volume in one second (FEV1) / forced vital capacity (FVC) %, FEV1/FVC% predicted and SII, and reversed U-shaped curve relationships between FEV1, FEV1% predicted and SII. High SII level is associated with severity of COPD, especially at Global Initiative on Obstructive Lung Disease (GOLD) 1 and GOLD 3.
CONCLUSIONS
In summary, the Log-SII level is associated with COPD risk, lung function, and COPD severity.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Male; Female; Middle Aged; Cross-Sectional Studies; Severity of Illness Index; Inflammation; Nutrition Surveys; Aged; Lung; Adult; Risk Factors; Forced Expiratory Volume; Neutrophils; Respiratory Function Tests; Platelet Count
PubMed: 38875233
DOI: 10.1371/journal.pone.0303286 -
Frontiers in Immunology 2024Chronic obstructive pulmonary disease (COPD) is one of the most prevalent chronic respiratory diseases and the fourth cause of mortality globally. Neutrophilic...
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is one of the most prevalent chronic respiratory diseases and the fourth cause of mortality globally. Neutrophilic inflammation has a vital role in the occurrence and progression of COPD. This study aimed to identify the novel hub genes involved in neutrophilic inflammation in COPD through bioinformatic prediction and experimental validation.
METHODS
Both the single-cell RNA sequencing (scRNA-seq) dataset (GSE173896) and the RNA sequencing (RNA-seq) dataset (GSE57148) were downloaded from the Gene Expression Omnibus (GEO) database. The Seurat package was used for quality control, dimensions reduction, and cell identification of scRNA-seq. The irGSEA package was used for scoring individual cells. The Monocle2 package was used for the trajectory analysis of neutrophils. The CIBERSORT algorithm was used for analysis of immune cell infiltration in the lungs of COPD patients and controls in RNA-seq dataset, and weighted gene co-expression network analysis (WGCNA) correlated gene modules with neutrophil infiltration. The Mendelian randomization (MR) analysis explored the causal relationship between feature DEGs and COPD. The protein-protein interaction (PPI) network of novel hub genes was constructed, and real-time quantitative polymerase chain reaction (qRT-PCR) was used to validate novel hub genes in clinical specimens.
RESULTS
In scRNA-seq, the gene sets upregulated in COPD samples were related to the neutrophilic inflammatory response and TNF-α activation of the NF-κB signaling pathway. In RNA-seq, immune infiltration analysis showed neutrophils were upregulated in COPD lung tissue. We combined data from differential and modular genes and identified 51 differential genes associated with neutrophilic inflammation. Using MR analysis, 6 genes were explored to be causally associated with COPD. Meanwhile, 11 hub genes were identified by PPI network analysis, and all of them were upregulated. qRT-PCR experiments validated 9 out of 11 genes in peripheral blood leukocytes of COPD patients. Furthermore, 5 genes negatively correlated with lung function in COPD patients. Finally, a network of transcription factors for NAMPT and PTGS2 was constructed.
CONCLUSION
This study identified nine novel hub genes related to the neutrophilic inflammation in COPD, and two genes were risk factors of COPD, which may serve as potential biomarkers for the clinical severity of COPD.
Topics: Pulmonary Disease, Chronic Obstructive; Humans; Neutrophils; Biomarkers; Gene Regulatory Networks; Protein Interaction Maps; Inflammation; Gene Expression Profiling; Computational Biology; Male; Transcriptome; Databases, Genetic
PubMed: 38873611
DOI: 10.3389/fimmu.2024.1410158 -
Frontiers in Immunology 2024Mycobacterium tuberculosis (Mtb) is an intracellular pathogen capable of adapting and surviving within macrophages, utilizing host nutrients for its growth and... (Review)
Review
Mycobacterium tuberculosis (Mtb) is an intracellular pathogen capable of adapting and surviving within macrophages, utilizing host nutrients for its growth and replication. Cholesterol is the main carbon source during the infection process of Mtb. Cholesterol metabolism in macrophages is tightly associated with cell functions such as phagocytosis of pathogens, antigen presentation, inflammatory responses, and tissue repair. Research has shown that Mtb infection increases the uptake of low-density lipoprotein (LDL) and cholesterol by macrophages, and enhances cholesterol synthesis in macrophages. Excessive cholesterol is converted into cholesterol esters, while the degradation of cholesterol esters in macrophages is inhibited by Mtb. Furthermore, Mtb infection suppresses the expression of ATP-binding cassette (ABC) transporters in macrophages, impeding cholesterol efflux. These alterations result in the massive accumulation of cholesterol in macrophages, promoting the formation of lipid droplets and foam cells, which ultimately facilitates the persistent survival of Mtb and the progression of tuberculosis (TB), including granuloma formation, tissue cavitation, and systemic dissemination. Mtb infection may also promote the conversion of cholesterol into oxidized cholesterol within macrophages, with the oxidized cholesterol exhibiting anti-Mtb activity. Recent drug development has discovered that reducing cholesterol levels in macrophages can inhibit the invasion of Mtb into macrophages and increase the permeability of anti-tuberculosis drugs. The development of drugs targeting cholesterol metabolic pathways in macrophages, as well as the modification of existing drugs, holds promise for the development of more efficient anti-tuberculosis medications.
Topics: Mycobacterium tuberculosis; Cholesterol; Humans; Macrophages; Tuberculosis; Animals; Host-Pathogen Interactions; Antitubercular Agents; Lipid Metabolism
PubMed: 38873598
DOI: 10.3389/fimmu.2024.1402024 -
Frontiers in Molecular Neuroscience 2024Phagocytes maintain homeostasis in a healthy brain. Upon injury, they are essential for repairing damaged tissue, recruiting other immune cells, and releasing cytokines... (Review)
Review
Phagocytes maintain homeostasis in a healthy brain. Upon injury, they are essential for repairing damaged tissue, recruiting other immune cells, and releasing cytokines as the first line of defense. However, there seems to be a delicate balance between the beneficial and detrimental effects of their activation in a seizing brain. Blocking the infiltration of peripheral phagocytes (macrophages) or their depletion can partially alleviate epileptic seizures and prevent the death of neurons in experimental models of epilepsy. However, the depletion of resident phagocytes in the brain (microglia) can aggravate disease outcomes. This review describes the role of resident microglia and peripheral infiltrating monocytes in animal models of acutely triggered seizures and epilepsy. Understanding the roles of phagocytes in ictogenesis and the time course of their activation and involvement in epileptogenesis and disease progression can offer us new biomarkers to identify patients at risk of developing epilepsy after a brain insult, as well as provide novel therapeutic targets for treating epilepsy.
PubMed: 38873242
DOI: 10.3389/fnmol.2024.1404022 -
Frontiers in Cellular and Infection... 2024Bacterial extracellular vesicles (EVs) are crucial mediators of information transfer between bacteria and host cells. Macrophages, as key effector cells in the innate... (Review)
Review
Bacterial extracellular vesicles (EVs) are crucial mediators of information transfer between bacteria and host cells. Macrophages, as key effector cells in the innate immune system, have garnered widespread attention for their interactions with bacterial EVs. Increasing evidence indicates that bacterial EVs can be internalized by macrophages through multiple pathways, thereby influencing their immune functions. These functions include inflammatory responses, antimicrobial activity, antigen presentation, and programmed cell death. Therefore, this review summarizes current research on the interactions between bacterial EVs and macrophages. This will aid in the deeper understanding of immune modulation mediated by pathogenic microorganisms and provide a basis for developing novel antibacterial therapeutic strategies.
Topics: Extracellular Vesicles; Macrophages; Humans; Animals; Bacteria; Immunity, Innate; Host-Pathogen Interactions
PubMed: 38873097
DOI: 10.3389/fcimb.2024.1411196