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PURPOSE: To evaluate the effects of 1800 MHz continuous wave (CW) and global system for mobile communications (GSM) modulated radiofrequency electromagnetic field (RFEMF) exposures on signal transduction (ST) protein and cytokine expression in differentiated human-derived monocytic THP-1 cells. MATERIALS AND METHODS: THP-1 cells were differentiated into adherent macrophage-like cells using phorbol 12-myristate 13-acetate (PMA). Following differentiation, cells were exposed to 1800 MHz CW or GSM modulated RFEMF for 0.5, 4, or 24 h at a specific absorption rate (SAR) of 0 (sham) or 2.0 W/kg. Concurrent positive controls (lipopolysaccharide for cytokines; anisomycin for ST proteins) and negative controls were included in each experiment. The expression levels of cytokines (GM-CSF, IFN-γ, IL-1ß, IL-6, IL-10, TNF-α) from culture media and phosphorylated and total ST proteins (CREB, JNK, NF-κB, p38, ERK1/2, Akt, p70S6k, STAT3, STAT5) from cell lysates were assessed using Milliplex magnetic bead array panels. RESULTS: No consistent effect of RFEMF exposure was observed in differentiated THP-1 cells. A statistically significant effect of overall exposure condition was observed for IL-6 with GSM modulation (P = 0.042), but no difference between RFEMF and sham for any exposure condition remained following adjustment for multiple comparisons (P ≥ 0.128). No statistically significant effect of exposure condition was detected for any other cytokine evaluated with either of the RFEMF modulations (P ≥ 0.078). There were no statistically significant changes in expression levels for any of the ST proteins under any studied exposure condition (P ≥ 0.320). CONCLUSIONS: In this study, no evidence of changes were observed in differentiated human derived THP-1 cells following exposure of up to 24 h to 1800 MHz RFEMF at SARs of 0 and 2.0 W/kg on the expression of ST proteins or cytokines.

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Background: Heart failure (HF) and inflammation have a bidirectional relation leading to activation and adaptation of multiple cellular lines, including leucocyte subtypes and platelets. We aimed to assess and compare the predictive value of the neutrophil-lymphocyte (NLR), monocyte-lymphocyte (MLR) and platelet-lymphocyte (PLR) ratios for all-cause long-term mortality in HF. Methods: This is an observational retrospective cohort study that included patients from the HI-HF cohort that survived the initial hospitalization. Vital status and survival time were assessed in June 2020. Results: We analyzed 1018 HF patients with a mean age of 72.32 ± 10.29 years and 53.54 % women. All-cause long-term mortality was 38.21 % after a median follow-up time of 68 [38 - 82] months. NLR (AUC 0.667, 95 %CI 0.637 - 0.697), MLR (AUC 0.670, 95 %CI 0.640 - 0.700) and PLR (AUC 0.606, 95 %CI 0.574 - 0.636) were predictors of all-cause mortality. In multivariable Cox proportional hazards analysis, NLR≥3.56 was the only hematological index independent predictor of fatality (HR 1.36, 95 %CI 1.05 - 1.76). Conclusions: Of the three hematological indices, NLR was the only independent predictor of all-cause long-term mortality of HF patients. We suggest NLR≥3.56 as an auxiliary prognostic biomarker for the evaluation of HF patients.

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Purpose: Kawasaki disease (KD) is an acute systemic vasculitis that is associated with dysregulated immune responses. Monocytes play a central role in innate immunity. Our previous single-cell RNA sequencing of peripheral blood mononuclear cells (PBMC) revealed a new subset of monocytes in children with KD called L-Selectin+ classical monocytes (SELL+ CM). Therefore, we aimed to investigate the correlation between KD and SELL+ CM. Patients and Methods: Peripheral blood samples were collected from 81 KD patients, 18 febrile patients and 36 healthy children before treatment. Among them, ten KD patients were followed up, and samples were obtained before and after intravenous immunoglobulin (IVIG) treatment. Analysis of SELL+ CM was performed using flow cytometry. Additionally, ROC curve analysis was conducted to assess the diagnostic value of SELL+ CM for KD. Results: Classical monocytes (CM) expressed the highest levels of L-selectin in children with KD. The ratio of SELL+ CM in CM was significantly higher in KD patients than in febrile and healthy children. Following IVIG treatment, the ratio of SELL+ CM in CM showed a downward trend. The receiver operating characteristic (ROC) curve analysis (the area under the curve, AUC = 0.71) indicated the potential diagnostic value of SELL+ CM in KD. The correlation analysis suggested that SELL+ CM may serve as a new clinical index for patients with KD. Conclusion: In KD, the ratio of SELL+ CM in CM significantly increases during the acute phase, which may become a potential biomarker and help facilitate KD diagnosis based on clinical features.

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Background: Systemic immune-inflammatory markers combine various individual inflammatory cell parameters to comprehensively explore their relationship with the development and long-term outcomes of cardiovascular, cerebrovascular, and oncological disorders. The systemic immune-inflammatory marker index has not been extensively studied in terms of its impact on the long-term prognosis following cerebral revascularization in MMD patients. Our research aims to address this gap and improve the prediction of long-term outcomes for these patients. Methods: We included 851 patients with Moyamoya disease who underwent cerebral revascularization at our medical center from 2009 to 2021. Systemic immune-inflammatory markers were calculated based on routine blood test results at admission, and follow-up was conducted for over 6 months after surgery. During monitoring and upon release, we evaluated patient neurological condition by utilizing the modified Rankin Scale (mRS). We examined the correlation between alterations in mRS ratings and systemic immune-inflammatory markers. Results: Comparing the unfavorable long-term prognosis group to the favorable long-term prognosis group, it was found that the NLR level was markedly higher (p = 0.037), while the LMR was lower in the unfavorable long-term prognosis group (p = 0.004). Results from logistic regression analysis revealed that the high-level LMR group had a lower risk of unfavorable long-term prognosis compared to the low-level group (T3: OR = 0.433, 95% CI [0.204-0.859], p = 0.026). The AUC of the model was 0.750 (95% CI [0.693-0.806]). Conclusion: Lymphocyte-to-monocyte ratio levels are independently linked to an increased risk of unfavorable long-term prognosis, highlighting LMR as a new and effective predictor for postoperative Moyamoya patients.

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OBJECTIVE: Cardiovascular diseases (CVDs) are the leading cause of death worldwide, with atherosclerosis serving as a primary factor in their development. Platelets, leukocytes, and their interactions play a crucial role in initiating and amplifying atherosclerosis. This study aims to evaluate the levels of platelet-monocyte aggregates (PMA) and specific integrins involved in leukocyte recruitment, including macrophage-1 antigen (Mac-1) and lymphocyte functionassociated antigen-1 (Lfa-1), in patients with acute coronary syndrome (ACS). MATERIALS AND METHODS: In this case-control study, thirty-two subjects with ACS and 30 healthy individuals participated. It aimed to evaluate PMA expression and the median fluorescence intensity (MFI) of Mac-1 and Lfa-1 using flow cytometry. Dot plots and Pearson correlation coefficient were employed to examine the relationship between PMA, Mac-1, and Lfa-1. Multilevel model analysis was used to explore the effects and relationships of various parameters, including Mac-1 and Lfa-1, on PMA. Finally, receiver operating characteristic (ROC) curves were utilized to assess the diagnostic accuracy of PMA, Mac-1, and Lfa-1 markers. RESULTS: It was observed that patients had higher PMA levels compared to the control group (58.99 ± 16.27 vs. 29.99 ± 4.19 in controls, P<0.001), which correlated with PLT (ρ=0.512, P=0.035). Additionally, CD18 and CD11b expression on monocytes were significantly elevated in patients (P<0.001) and were positively associated with PMA (ß=19.09, P<0.001; ß=6.90, P=0.022), but no significant relationship between CD11a and PMA was observed (ß=5.06, P=0.315). PMA and Mac-1 were identified as better markers for differentiating patients from healthy individuals. (respectively, AUC=0.94, Sensitivity= 0.84, specificity=0.98; AUC=0.84, Sensitivity= 0.93, specificity=0.70). CONCLUSION: The study results indicated an increase in both Mac-1 and PMA levels in patients with ACS. Additionally, the significant association observed between Mac-1 and PMA in the patient group suggests a potential relationship between these markers and ACS.

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Obesity is characterized by the chronic low-grade activation of the innate immune system. In this respect, macrophage-elicited metabolic inflammation and adipocyte-macrophage interaction have primary importance in obesity. Large quantity of macrophages is accumulated by different mechanisms in obese adipose tissue. Hypertrophic adipocyte-derived chemotactic monocyte chemoattractant protein-1 (MCP-1)/C-C chemokine receptor 2 (CCR2) pathway promotes more macrophage accumulation into the obese adipose tissue. However, obesity-induced changes in adipose tissue macrophage density are mainly dependent on increases in the triple-positive cluster of differentiation (CD)11b+ F4/80+ CD11c+ adipose tissue macrophage subpopulation. As epigenetic regulators, microRNAs (miRNAs) are one of the most important mediators of obesity. miRNAs are expressed by adipocytes as well as macrophages and regulate inflammation with the expression of target genes. A paracrine loop involving free fatty acids and tumor necrosis factor-alpha (TNF-α) between adipocytes and macrophages establishes a vicious cycle that aggravates inflammatory changes in the adipose tissue. Adipocyte-specific caspase-1 and production of interleukin-1beta (IL-1ß) by macrophages; both adipocyte and macrophage induction by toll-like receptor-4 (TLR4) through nuclear factor-kappaB (NF-κB) activation; free fatty acid-induced and TLR-mediated activation of c-Jun N-terminal kinase (JNK)-related pro-inflammatory pathways in CD11c+ immune cells; are effective in mutual message transmission between adipocyte and macrophage and in the development of adipose tissue inflammation. Thus, the metabolic status of adipocytes and their released exosomes are important determinants of macrophage inflammatory output. However, old adipocytes are removed by macrophages through trogocytosis or sending an "eat me" signal. As a single miRNA can be able to regulate a variety of target genes and signaling pathways, reciprocal transfer of miRNAs between adipocytes and macrophages via miRNA-loaded exosomes reorganizes the different stages of obesity. Changes in the expression of circulating miRNAs because of obesity progression or anti-obesity treatment indicate that miRNAs could be used as potential biomarkers. Therefore, it is believed that targeting macrophage-associated miRNAs with anti-obesity miRNA-loaded nano-carriers may be successful in the attenuation of both obesity and adipose tissue inflammation in clinical practice. Moreover, miRNA-containing exosomes and transferable mitochondria between the adipocyte and macrophage are investigated as new therapeutic targets for obesity-related metabolic disorders.

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Chronic low-grade inflammation is a central component in the pathogenesis of obesity-related expansion of adipose tissue and complications in other metabolic tissues. Five different signaling pathways are defined as dominant determinants of adipose tissue inflammation: These are increased circulating endotoxin due to dysregulation in the microbiota-gut-brain axis, systemic oxidative stress, macrophage accumulation, and adipocyte death. Finally, the nucleotide-binding and oligomerization domain (NOD) leucine-rich repeat family pyrin domain-containing 3 (NLRP3) inflammasome pathway is noted to be a key regulator of metabolic inflammation. The NLRP3 inflammasome and associated metabolic inflammation play an important role in the relationships among fatty acids and obesity. Several highly active molecules, including primarily leptin, resistin, adiponectin, visfatin, and classical cytokines, are abundantly released from adipocytes. The most important cytokines that are released by inflammatory cells infiltrating obese adipose tissue are tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), monocyte chemoattractant protein 1 (MCP-1) (CCL-2), and IL-1. All these molecules mentioned above act on immune cells, causing local and then general inflammation. Three metabolic pathways are noteworthy in the development of adipose tissue inflammation: toll-like receptor 4 (TLR4)/phosphatidylinositol-3'-kinase (PI3K)/Protein kinase B (Akt) signaling pathway, endoplasmic reticulum (ER) stress-derived unfolded protein response (UPR), and inhibitor of nuclear factor kappa-B kinase beta (IKKß)-nuclear factor kappa B (NF-κB) pathway. In fact, adipose tissue inflammation is an adaptive response that contributes to a visceral depot barrier that effectively filters gut-derived endotoxin. Excessive fatty acid release worsens adipose tissue inflammation and contributes to insulin resistance. However, suppression of adipose inflammation in obesity with anti-inflammatory drugs is not a rational solution and paradoxically promotes insulin resistance, despite beneficial effects on weight gain. Inflammatory pathways in adipocytes are indeed indispensable for maintaining systemic insulin sensitivity. Cannabinoid type 1 receptor (CB1R) is important in obesity-induced pro-inflammatory response; however, blockade of CB1R, contrary to anti-inflammatory drugs, breaks the links between insulin resistance and adipose tissue inflammation. Obesity, however, could be decreased by improving leptin signaling, white adipose tissue browning, gut microbiota interactions, and alleviating inflammation. Furthermore, capsaicin synthesized by chilies is thought to be a new and promising therapeutic option in obesity, as it prevents metabolic endotoxemia and systemic chronic low-grade inflammation caused by high-fat diet.

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Understanding the pig immune function is crucial for disease-resistant breeding and potentially for human health research due to shared immune system features. Immune cell ratios, like monocyte/lymphocyte ratio (MLR) and neutrophil/lymphocyte ratio (NLR), offer a more comprehensive view of immune status compared to individual cell counts. However, research on pig immune cell ratios remains limited. This study investigated MLR and NLR in a Duroc × Erhualian F2 resource population. Heritability analysis revealed high values (0.649 and 0.688 for MLR and NLR, respectively), suggesting a strong genetic component. Furthermore, we employed an ensemble-like GWAS (E-GWAS) strategy and functional annotation analysis to identify 11 MLR-associated and 6 NLR-associated candidate genes. These genes were significantly enriched in immune-related biological processes. These findings provide novel genetic markers and candidate genes associated with porcine immunity, thereby providing valuable insights for addressing biosecurity and animal welfare concerns in the pig industry.

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OBJECTIVE: In this study, we investigated 25-hydroxyvitamin D (25(OH)D, vitamin D), inflammatory hematologic ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), monocyte/HDL-C ratio (MHR) and plasma atherogenic index (PAI) and possible relationships with insulin resistance (IR) in children. METHODS: A total of 210 individuals, including 96 children with IR and 114 children without IR, aged 6-18 years, who were admitted to the Pediatric Endocrinology Outpatient Clinic at Medicine Hospital, Istanbul Atlas University were included in our study. RESULT: Compared to patients without IR, NLR, PLR, SII, and MHR were significantly higher in patients with IR. Fasting insulin, PAI, homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA-ß were significantly higher and quantitative insulin sensitivity check index (QUICKI) was considerably lower in patients with IR compared to those without IR. NLR, SII, and MHR were lower in normal vitamin D groups than the others (p < 0.001). PLR was lower in the group with normal vitamin D levels than the groups with insufficient or deficient levels of vitamin D (D < 21). CONCLUSIONS: We found that vitamin D deficiency in childhood is related to increased levels of circulating inflammatory markers (NLR, PLR, MHR, PAI), IR, and decreased insulin sensitivity. According to our results, supplementation of vitamin D may be beneficial in averting IR and enhanced systemic inflammation.

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INTRODUCTION: In sarcoidosis granulomas, monocyte-derived macrophages are activated by pro-inflammatory cytokines including TNF and IL-6. Current drug treatment for sarcoidosis aims to suppress inflammation but disabling side effects can ensue. The macrolide azithromycin may be anti-inflammatory. We aimed to determine whether treatment with azithromycin affects blood inflammatory gene expression and monocyte functions in sarcoidosis. METHODS: Blood samples were collected from patients with chronic pulmonary sarcoidosis enrolled in a single arm, open label clinical trial who received oral azithromycin 250 mg once daily for 3 months. Whole blood inflammatory gene expression with or without LPS stimulation was measured using a 770-mRNA panel. Phenotypic analysis and cytokine production were conducted by flow cytometry and ELISA after 24h stimulation with growth factors and TLR ligands. mTOR activity was assessed by measuring phosphorylated S6RP. RESULTS: Differential gene expression analysis indicated a state of heightened myeloid cell activation in sarcoidosis. Compared with controls, sarcoidosis patients showed increased LPS responses for several cytokines and chemokines. Treatment with azithromycin had minimal effect on blood gene expression overall, but supervised clustering analysis identified several chemokine genes that were upregulated. At the protein level, azithromycin treatment increased LPS-stimulated TNF and unstimulated IL-8 production. No other cytokines showed significant changes following azithromycin. Blood neutrophil counts fell during azithromycin treatment whereas mononuclear cells remained stable. Azithromycin had no detectable effects on mTOR activity or activation markers. CONCLUSION: Blood myeloid cells are activated in sarcoidosis, but azithromycin therapy did not suppress inflammatory gene expression or cytokine production in blood. TRIAL REGISTRATION: EudraCT 2019-000580-24 (17 May 2019).

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Background: Mesenchymal stem/stromal cells (MSCs) maintain tissue homeostasis in response to microenvironmental perturbations. Toll-like receptors (TLRs) are key sensors for exogenous and endogenous signals produced during injury. In this study, we aimed to investigate whether TLRs affect the homeostatic functions of MSCs after injury. Methods: We examined the expression of TLR2, TLR3 and TLR4 in MSCs, and analyzed the functional significance of TLR2 activation using single-cell RNA sequencing. Additionally, we investigated the effects and mechanisms of TLR2 and its downstream activation in MSCs on the MSCs themselves, on monocytes/macrophages, and in a mouse model of sterile injury-induced inflammatory corneal angiogenesis. Results: MSCs expressed TLR2, which was upregulated by monocytes/macrophages. Activation of TLR2 in MSCs promoted their immunoregulatory and angiostatic functions in monocytes/macrophages and in mice with inflammatory corneal angiogenesis, whereas TLR2 inhibition attenuated these functions. Single-cell RNA sequencing revealed AKR1C1, a gene encoding aldo-keto reductase family 1 member C1, as the most significantly inducible gene in MSCs upon TLR2 stimulation, though its stimulation did not affect cell compositions. AKR1C1 protected MSCs against ferroptosis, increased secretion of anti-inflammatory cytokines, and enhanced their ability to drive monocytes/macrophages towards immunoregulatory phenotypes, leading to the amelioration of inflammatory corneal neovascularization in mice. Conclusion: Our findings suggest that activation of TLR2-AKR1C1 signaling in MSCs serves as an important pathway for the survival and homeostatic activities of MSCs during injury.

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BACKGROUND: Bipolar disorder (BPD) is a kind of manic and depressive phase alternate episodes of serious mental illness, and it is correlated with well-documented cortical brain abnormalities. Emerging evidence supports that autophagy dysfunction in neuronal system contributes to pathophysiological changes in neurological disease. However, the role of autophagy in bipolar disorder has rarely been elucidated. This study aimed to identify the autophagy-related gene as a potential biomarker Correlated to immune infiltration in BPD. METHODS: The microarray dataset GSE23848 and autophagy-related genes (ARGs) were downloaded. Differentially expressed genes (DEGs) between normal and BPD samples were screened using the R software. Machine learning algorithms were performed to screen the significant candidate biomarker from autophagy-related differentially expressed genes (ARDEGs). The correlation between the screened ARDEGs and infiltrating immune cells was explored through correlation analysis. RESULTS: In this study, the autophagy pathway was abundantly enriched and activated in BPD, as indicated by Pathway enrichment analysis. We identified 16 ARDEGs in BPD compared to the normal group. A signature of 4 ARDEGs (ERN1, ATG3, CTSB, and EIF2AK3) was screened. ROC analysis showed that the above genes have good diagnostic performance. In addition, immune correlation analysis considered that the above four genes significantly correlated with immune cells in BPD. CONCLUSIONS: Autophagy - immune cell axis mediates pathophysiological changes in BPD. Four important ARDEGs are prospective to be potential biomarkers associated with immune infiltration in BPD and helpful for the prediction or diagnosis of BPD.

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Arteriogenesis is an inflammatory driven mechanism, describing the growth of a natural bypass from pre-existing collateral arteries to compensate for an occluded artery. The complement system component C3 is a potent natural inflammatory activator. Here, we investigated its impact on the process of collateral artery growth using C3-deficient (C3 -/-) and wildtype control mice in a murine hindlimb model of arteriogenesis. Induction of arteriogenesis by unilateral femoral artery ligation resulted in decreased perfusion recovery in C3 -/- mice on day 7 as shown by Laser Doppler imaging. Immunofluorescence staining revealed a reduced vascular cell proliferation in C3 -/- mice. Gene expression analysis displayed a significant reduction in monocyte chemoattractant protein-1 (MCP-1) expression in C3 -/- mice. Interestingly, 3 days after induction of arteriogenesis, the number of macrophages (CD68+) recruited to growing collaterals was not affected by C3 deficiency. However, a significant reduction in inflammatory M1-like polarized macrophages (CD68+/MRC1-) was noted. Forced mast cell activation by Compound 48/80 as well as exogenous MCP-1 application rescued the number of M1-like polarized macrophages along with perfusion recovery in C3 -/- mice. In summary, this study demonstrates that complement C3 influences arteriogenesis by mediating MCP-1 expression, which is essential for the induction and enhancement of sterile inflammation.

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Epithelial injury calls for a regenerative response from a coordinated network of epithelial stem cells and immune cells. Defining this network is key to preserving the repair process for acute resolution, but also for preventing a remodeling process with chronic dysfunction. We recently identified an immune niche for basal-epithelial stem cells using mouse models of injury after respiratory viral infection. Niche function depended on an early sentinel population of monocyte-derived dendritic cells (moDCs) that provided ligand GPNMB to basal-ESC receptor CD44 for reprogramming towards chronic lung disease. These same cell and molecular control points worked directly in mouse and human basal-ESC organoids, but the findings were not yet validated in vivo in human disease. Further, persistence of GPNMB expression in moDCs and M2-macrophages in mouse models suggested utility as a long-term disease biomarker in humans. Here we show increased expression of GPNMB localized to moDC-macrophage populations in lung tissue samples from long-term Covid, asthma, and COPD. The findings thereby provide initial evidence of a persistent and correctable pathway from acute injury to chronic disease with implications for cellular reprogramming and inflammatory memory.

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Inflammation is one biological pathway thought to impact the brain to contribute to major depressive disorder (MDD) and is reliably associated with resistance to standard antidepressant treatments. While peripheral immune cells, particularly monocytes, have been associated with aspects of increased inflammation in MDD and symptom severity, significant gaps in knowledge exist regarding the mechanisms by which these cells are activated to contribute to behavioral symptoms in MDD. One concept that has gained recent appreciation is that metabolic rewiring to glycolysis in activated myeloid cells plays a crucial role in facilitating these cells' pro-inflammatory functions, which may underlie myeloid contribution to systemic inflammation and its effects on the brain. Given emerging evidence from translational studies of depression that peripheral monocytes exhibit signs of glycolytic activation, better understanding the immunometabolic phenotypes of monocytes which are known to be elevated in MDD with high inflammation is a critical step toward comprehending and treating the impact of inflammation on the brain. This narrative review examines the extant literature on glycolytic metabolism of circulating monocytes in depression and discusses the functional implications of immunometabolic shifts at both cellular and systemic levels. Additionally, it proposes potential therapeutic applications of existing immunomodulators that target glycolysis and related metabolic pathways in order to reverse the impact of elevated inflammation on the brain and depressive symptoms.

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Background: Recent evidence indicates that inflammation plays a major role in the pathogenesis and progression of CCA. This meta-analysis seeks to evaluate the prognostic implications of preoperative inflammatory markers, specifically NLR, PLR, and LMR, in patients with eCCA. By focusing on these preoperative biomarkers, this study aims to provide valuable insights into their prognostic value and potential utility in clinical practice. Methods: For this analysis, comprehensive searches were conducted in PubMed, Embase, and Web of Science databases from inception to May 2024. The primary outcomes of interest focused on the association between the levels of NLR, PLR, and LMR and the prognosis of eCCA patients. Statistical analyses were conducted using STATA 17.0 software. Results: The meta-analysis, involving 20 retrospective studies with 5553 participants, revealed significant correlations between preoperative biomarkers and the prognosis of eCCA patients. Elevated NLR, PLR, and decreased LMR levels were extensively studied regarding overall survival (OS) in eCCA patients. Elevated NLR was an independent predictor of poor OS (HR 1.86, p < 0.001), similar to elevated PLR (HR 1.76, p < 0.001), while decreased LMR predicted poor OS (HR 2.16, p < 0.001). Subgroup analyses based on eCCA subtypes and curative surgery status showed consistent results. Conclusions: In conclusion, our study emphasizes the clinical significance of assessing NLR, PLR, and LMR preoperatively to predict patient prognosis. Elevated NLR and PLR values, along with decreased LMR values, were linked to poorer overall survival (OS). Large-scale prospective cohort studies are required to confirm their independent prognostic value in eCCA. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024551031.

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Background: Preoperative immune-inflammatory condition influencing the metabolism of malignancies. We sought to investigate the prognostic value of a novel immune-inflammatory metabolic marker, the monocyte-to-high-density lipoprotein ratio (MHR), in patients with locally advanced pancreatic cancer. Methods: A retrospective analysis was conducted on the clinical data of 118 patients with locally advanced pancreatic cancer and obstructive jaundice who underwent allogeneic vascular replacement pancreaticoduodenectomy in our hospital from Apr. 2011 to Dec. 2023. To assess the predictive capacity of immune-inflammatory metabolic marker, we utilized the area under the receiver operating characteristic curve (AUC-ROC) and assessed the predictive potential of MHR in forecasting outcomes through both univariate and multivariate Cox proportional hazard analyses. Results: The area under AUC for MHR in predicting 1-year postoperative survival was 0.714, with an optimal cutoff value of 1.184, yielding a sensitivity of 78.9% and specificity of 66.2%. Based on this cutoff value, patients were divided into a low MHR group (MHR ≤1.184, n = 61) and a high MHR group (MHR >1.184, n = 57). The median survival times for the low and high MHR groups were 27.0 months and 12.0 months, respectively (χ2 = 30.575, p < 0.001), and the median DFS were 18.0 months and 8.0 months, respectively (χ2 = 26.330, p < 0.001). Univariate and multivariate analyses indicated that preoperative MHR, preoperative creatinine, operation duration, and TNM stage were independent predictors of postoperative mortality, while preoperative MHR, preoperative creatinine, and TNM stage were independent predictors of postoperative recurrence risk. Conclusion: MHR, as an independent immune-inflammatory metabolic predictor of OS and DFS in patients with advanced PC after pancreaticoduodenectomy. Early monitoring and reduction of MHR may be of great significance in improving prognosis.

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BACKGROUND: Locoregional surgical pathology, with surgical margins at the primary site and lymph node (LN) metastasis, particularly extranodal extension (ENE), plays an important role in the prognosis of oral squamous cell carcinoma (OSCC). In addition, systemic inflammatory response and nutritional status are associated with poor prognosis. PURPOSE: This study aimed to comprehensively assess the effect of inflammatory markers and locoregional factors on the prognosis of patients with OSCC who underwent neck dissection (ND). METHODS: This retrospective cohort study included patients who had undergone ND for OSCC between 2013 and 2021. The primary predictive variables were the weighted lymph node ratio (WLNR) and inflammatory markers. Primary outcome variables were overall survival (OS) and disease-free survival (DFS). RESULTS: Among 153 patients (99 males, 54 females), 55 (35.9 %) had LN metastasis and 11 (7.2 %) exhibited ENE. The inflammatory markers lymphocyte/monocyte ratio (LMR), monocyte/albumin ratio (MAR), C-reactive protein/albumin ratio (CAR), and WLNR demonstrated significant cut-off values for survival, with values of 4.805, 104.72, 0.041, and 0.0235, respectively. The Cox proportional hazards model revealed significant differences in age, WLNR, LMR, MAR, CAR, and vascular, lymphatic, and perineural invasion (Pn). Multivariate analysis indicated that the hazard ratios (95 % confidence intervals) for WLNR (3.416; 1.542-7.566), MAR (2.404; 1.254-4.607), and Pn (2.516; 1.291-4.905) were independent variables for OS. CONCLUSIONS: In patients with OSCC who underwent ND, the inflammatory marker MAR and locoregional factors WLNR and Pn were simultaneously identified as prognostic factors.

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BACKGROUND: Chronic inflammation initiated by inflammatory monocytes underlies the pathogenesis of atherosclerosis. However, approaches that can effectively resolve chronic low-grade inflammation targeting monocytes are not readily available. The small chemical compound 4-phenylbutyric acid (4-PBA) exhibits broad anti-inflammatory effects in reducing atherosclerosis. Selective delivery of 4-PBA reprogrammed monocytes may hold novel potential in providing targeted and precision therapeutics for the treatment of atherosclerosis. METHODS: Systems analyses integrating single-cell RNA sequencing and complementary immunologic approaches characterized key resolving characteristics as well as defining markers of reprogrammed monocytes trained by 4-PBA. Molecular mechanisms responsible for monocyte reprogramming were assessed by integrated biochemical and genetic approaches. The intercellular propagation of homeostasis resolution was evaluated by coculture assays with donor monocytes trained by 4-PBA and recipient naive monocytes. The in vivo effects of monocyte resolution and atherosclerosis prevention by 4-PBA were assessed with the high-fat diet-fed ApoE-/- mouse model with IP 4-PBA administration. Furthermore, the selective efficacy of 4-PBA-trained monocytes was examined by IV transfusion of ex vivo trained monocytes by 4-PBA into recipient high-fat diet-fed ApoE-/- mice. RESULTS: In this study, we found that monocytes can be potently reprogrammed by 4-PBA into an immune-resolving state characterized by reduced adhesion and enhanced expression of anti-inflammatory mediator CD24. Mechanistically, 4-PBA reduced the expression of ICAM-1 (intercellular adhesion molecule 1) via reducing peroxisome stress and attenuating SYK (spleen tyrosine kinase)-mTOR (mammalian target of rapamycin) signaling. Concurrently, 4-PBA enhanced the expression of resolving mediator CD24 through promoting PPARγ (peroxisome proliferator-activated receptor γ) neddylation mediated by TOLLIP (toll-interacting protein). 4-PBA-trained monocytes can effectively propagate anti-inflammation activity to neighboring monocytes through CD24. Our data further demonstrated that 4-PBA-trained monocytes effectively reduce atherosclerosis pathogenesis when administered in vivo. CONCLUSIONS: Our study describes a robust and effective approach to generate resolving monocytes, characterizes novel mechanisms for targeted monocyte reprogramming, and offers a precision therapeutics for atherosclerosis based on delivering reprogrammed resolving monocytes.

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Macrophage infiltration and accumulation in the atherosclerotic lesion are associated with plaque progression and instability. Depletion of macrophages from the lesion might provide valuable insights into plaque stabilization processes. Therefore, we assessed the effects of systemic and local macrophage depletion on atherogenesis. To deplete monocytes/macrophages we used atherosclerosis-susceptible Apoe- /- mice, bearing a MaFIA (macrophage-Fas-induced-apoptosis) suicide construct under control of the Csf1r (CD115) promotor, where selective apoptosis of Csf1r-expressing cells was induced in a controlled manner, by administration of a drug, AP20187. Systemic induction of apoptosis resulted in a decrease in lesion macrophages and smooth-muscle cells. Plaque size and necrotic core size remained unaffected. Two weeks after the systemic depletion of macrophages, we observed a replenishment of the myeloid compartment. Myelopoiesis was modulated resulting in an expansion of CSF1Rlo myeloid cells in the circulation and a shift from Ly6chi monocytes toward Ly6cint and Ly6clo populations in the spleen. Local apoptosis induction led to a decrease in plaque burden and macrophage content with marginal effects on the circulating myeloid cells. Local, but not systemic depletion of Csf1r+ myeloid cells resulted in decreased plaque burden. Systemic depletion led to CSF1Rlo-monocyte expansion in blood, possibly explaining the lack of effects on plaque development.