Total Neutrophil Research Articles

Complete blood count parameters and inflammation-related biomarkers in patients with colorectal carcinoma.

The aim of this study was to determine whether there are differences in complete blood count parameters (CBC) and inflammation-related biomarkers, MPV/PC, PLR, NLR, LWR, LMR, NMR, and LCR, among patients with colorectal carcinoma (CRC) and patients with colorectal adenomas. The study included 155 patients who were divided into two groups according to histopathological analysis - 74 adenomas patients and 81 CRC patients. A routine examination of CBC was conducted on Sysmex XN1000 whereas CRP was measured on Alinity ci-series. Statistical analysis was performed by ROC curve analysis using MedCalc Statistical Software. In CRC patients, hemoglobin concentration, hematocrit, MCV, MCH, and MCHC were lower, while RDW was higher (p < 0.001), compared to patients with adenomas. Total leukocyte count (p = 0 .006), absolute neutrophils (p = 0.005), and absolute monocytes (p = 0.007) were lower while relative eosinophils (p = 0.001) and relative basophils (p = 0.001) were higher in CRC patients. Platelet count (p < 0.001) was significantly higher and MPV (p = 0.003) was significantly lower in CRC patients. Furthermore, MPV/PC (p < 0.001) was significantly lower and PLR (p < 0.001) was significantly higher in CRC. Moreover, Receiver Operating Characteristic (ROC) analysis revealed poor diagnostic accuracy, for all tested parameters (AUC was 0.7 or less). PC, MPV, MPV/PC, and PLR were significantly different between study groups, but ROC analysis revealed poor diagnostic accuracy. Lower hemo globin levels in CRC patients are possibly due to more frequent and excessive bleeding. Higher levels of basophils and eosinophils in CRC patients are indicators of inflammatory reaction, which is linked to CRC.

Predictive biomarkers for severity of respiratory syndrome: the role of eGFR and hematological parameters in ICU patients

Introduction: Studying respiratory syndromes like COVID-19 is crucial for understanding viral-induced inflammatory responses and their impact on organ function. Insights from these studies are essential for managing current and future pandemics and improving patient outcomes in respiratory health crises. This study investigates the behavior of the estimated glomerular filtration rate (eGFR) and its correlation with hematological parameters in ICU patients with COVID-19. Objective: To assess eGFR behavior and its correlation with hematological parameters in respiratory syndromes ICU patients. Materials and Methods: 217 patient records were analyzed, with 144 discharged and 73 deaths. Patients were divided into discharge and death groups and laboratory parameters such as glomerular filtration rate and blood count were.evaluated at admission and outcome. Results and Discussion: There was a significant reduction in eGFR among patients in the death group at both admission and outcome. Significant correlations were observed between eGFR and hemoglobin (Hb), total neutrophils (N), and platelets (PLT) at the outcome. These findings suggest that the reduction in eGFR is a predictor of poor prognosis in COVID-19 ICU patients. Additionally, the significant correlations between eGFR and hematological parameters highlight their role in the inflammatory process and clinical deterioration. Conclusion: The reduction of eGFR is a significant predictor of poor prognosis in ICU patients with COVID-19. Significant correlations between eGFR and hematological parameters underscore their importance in the inflammatory process and disease progression. Studying respiratory syndromes like COVID-19 is crucial for understanding viral-induced inflammatory responses and improving critical care strategies for future respiratory health crises.

Cardioimmunology in Health and Diseases: Impairment of the Cardio-Spleno-Bone Marrow Axis Following Myocardial Infarction in Diabetes Mellitus.

A comprehensive understanding of the cardio-spleen-bone marrow immune cell axis is essential for elucidating the alterations occurring during the pathogenesis of diabetes mellitus (DM). This study investigates the dynamics of immune cell kinetics in DM after myocardial infarction (MI) over time. MI was induced in diabetic and healthy control groups using C57BL/N6 mice, with sacrifices occurring at days 1, 3, 7, and 28 post-MI to collect heart, peripheral blood (PB), spleen, and bone marrow (BM) samples. Cell suspensions from each organ were isolated and analyzed via flow cytometry. Additionally, the endothelial progenitor cell-colony-forming assay (EPC-CFA) was performed using mononuclear cells derived from BM, PB, and the spleen. The results indicated that, despite normal production in BM and the spleen, CD45+ cells were lower in the PB of DM mice at days 1 to 3. Further analysis revealed a reduction in total and pro-inflammatory neutrophils (N1s) in PB at days 1 to 3 and in the spleen at days 3 to 7 in DM mice, suggesting that DM-induced alterations in splenic neutrophils fail to meet the demand in PB and ischemic tissues. Infiltrating macrophages (total, M1, M2) were reduced at day 3 in the DM-ischemic heart, with total and M1 (days 1-3) and M2 (days 3-7) macrophages being significantly decreased in DM-PB compared to controls, indicating impaired macrophage recruitment and polarization in DM. Myeloid dendritic cells (mDCs) in the heart were higher from days 1 to 7, which corresponded with the enhanced recruitment of CD8+ cells from days 1 to 28 in the DM-infarcted myocardium. Total CD4+ cells decreased in DM-PB at days 1 to 3, suggesting a delayed adaptive immune response to MI. B cells were reduced in PB at days 1 to 3, in myocardium at day 3, and in the spleen at day 7, indicating compromised mobilization from BM. EPC-CFA results showed a marked decrease in definitive EPC colonies in the spleen and BM from days 1 to 28 in DM mice compared to controls in vitro, highlighting that DM severely impairs EPC colony-forming activity by limiting the differentiation of EPCs from primitive to definitive forms. Taking together, this study underscores significant disruptions in the cardio-spleen-bone marrow immune cell axis following MI in DM, revealing delayed innate and adaptive immune responses along with impaired EPC differentiation.

Diagnostic value of biochemical markers in prediction of perforation in acute appendicitis: a cross-sectional study.

Acute appendicitis, despite being the most common surgery, can result in increased morbidity and mortality in the case of perforated appendicitis. Identifying a perforation early can reduce the impact on the patient. Bilirubin, C-reactive protein (CRP), and white blood cell (WBC) count have been shown to indicate perforation in appendicitis. A cross-sectional analytical study was conducted to observe the association between preoperative bilirubin, CRP, and white cell count with the histological findings of either the presence or absence of perforation of the appendix. The eligibility criteria included all patients above 18 years with appendicitis who were managed surgically in the study hospital, Shree Birendra Hosptial, between 1 December 2021 to 30 May 2022. The study was conducted after the approval from the ethics committee. Out of 150 patients, 112 had open surgery and 38 underwent laparoscopic appendectomy. One hundred thirty-four had non-perforated appendix and 16 cases had perforated appendix. The older age group was associated with appendiceal perforation more than the younger age group. Patients with a duration of symptoms less than 24 h and more than 72 h developed perforated appendicitis less frequently. The odds of encountering perforated appendicitis increased by 2.644 times per 0.972 rise in total bilirubin (P= 0.004) and the odds of encountering perforated appendicitis increased by 6.474 times per 1.868 rise in conjugated bilirubin (P= 0.003). There was no significant difference in total leucocyte count and neutrophil percentage among perforated and non-perforated groups. The diagnostic value of the CRP, total bilirubin, and conjugated bilirubin levels was strong and significant when used in combination rather than their individual performance in the diagnosis of perforated acute appendicitis.

Sex-Specific Associations Between Leucocyte Measures and Obstructive Sleep Apnea in Han Chinese.

White blood cell (WBC) and its subset counts are standard, inexpensive, direct markers of inflammation. Obstructive sleep apnea (OSA) is implicated in changes in inflammation markers, and sex differences are evident in both OSA and inflammation. It is unknown whether sex modulates the relationship between OSA severity and leukocyte measures. 1222 patients (914 males, 308 females) underwent overnight laboratorial polysomnography and measurement of WBC and its subset (lymphocyte, neutrophil, monocyte) counts. Patients were divided into primary snoring and mild, moderate, and severe OSA groups, and differences in leukocyte parameters were analyzed separately by sex in multivariable analyses. In multiple regression models, higher apnea-hypopnea index (AHI) was independently associated with neutrophil counts only in men, and with higher total WBC, lymphocyte and monocyte counts both in women and men. Further ordinal logistic regression analysis revealed a significant association between AHI and total WBC (OR 1.87, 95% CI 1.09-3.23) and neutrophil (OR 1.77, 95% CI 1.02-3.07) counts in men only. Correlation analysis also revealed more robust relationships between leukocyte measures and cardiometabolic risk markers in men than in women. This study provides novel data suggesting a significant association between neutrophil count and OSA severity only in men but not women. Similarly, the relationship between leukocyte parameters and cardiometabolic risk markers were more pronounced in men than women. Our findings suggest a sex-specific impact of OSA on leukocyte measures and on their relationship with indices of cardiometabolic risk.

Cholestatic insult triggers alcohol-associated hepatitis in mice.

Alcohol-associated hepatitis (AH) is a severe, potentially life-threatening form of alcohol-associated liver disease with limited therapeutic options. Existing evidence shows that biliary dysfunction and cholestasis are common in patients with AH and are associated with poorer prognosis. However, the role of cholestasis in the development of AH is largely unknown. We aimed to examine the hypothesis that cholestasis can be an important etiology factor for AH. To study the interaction of cholestasis and alcohol, chronically ethanol (EtOH)-fed mice were challenged with a subtoxic dose of α-naphthylisothiocyanate (ANIT), a well-studied intrahepatic cholestasis inducer. Liver injury was measured by biochemical and histological methods. RNAseq was performed to determine hepatic transcriptomic changes. The impact of inflammation was assessed using an anti-LY6G antibody to deplete the neutrophils and DNase I to degrade neutrophil extracellular traps. ANIT synergistically enhanced liver injury following a 4-week EtOH feeding with typical features of AH, including increased serum levels of ALT, AST, and total bile acids, cholestasis, necrosis, neutrophil infiltration, and accumulation of neutrophil extracellular traps. RNAseq revealed multiple genes uniquely altered in the livers of EtOH/ANIT-treated mice. Analysis of differentially expressed genes suggested an enrichment of genes related to inflammatory response. Anti-LY6G antibody or DNase I treatment significantly inhibited liver damage in EtOH/ANIT-treated mice. Our results support the hypothesis that cholestasis can be a critical contributor to the pathogenesis of AH. A combined treatment of EtOH and ANIT in mice presents biochemical, histological, and molecular features similar to those found in patients with AH, suggesting that this treatment scheme can be a useful model for studying Alcohol-associated Cholestasis and Hepatitis (AlChoHep).

Opposite effects of systemic and local conditional CD11c+ myeloid cell depletion during bleomycin-induced inflammation and fibrosis in mice.

Elevated levels of CD11c+ myeloid cells are observed in various pulmonary disorders, including Idiopathic Pulmonary Fibrosis (IPF). Dendritic cells (DCs) and macrophages (MΦ) are critical antigen-presenting cells (APCs) that direct adaptive immunity. However, the role of CD11c+ myeloid cells in lung extracellular matrix (ECM) accumulation and pulmonary fibrosis is poorly understood. We aimed to investigate the impact of depleting CD11c+ myeloid cells, including DCs and macrophages, during bleomycin-induced pulmonary fibrosis in mice. We used a diphtheria toxin (DTx) receptor (DTR) transgenic mouse model (CD11c-DTR-Tg) to deplete CD11c+ myeloid cells through two methods: Systemic Depletion (SD) via intraperitoneal injection (i.p.) and local depletion (LD) via intranasal instillation (i.n.). We then assessed the effects of CD11c+ cell depletion during bleomycin-induced lung inflammation and fibrosis. Fourteen days after bleomycin instillation, there was a progressive accumulation of myeloid cells, specifically F4/80-MHCII+CD11c+ DCs and F4/80 + MHCII+CD11c+ MΦ, preceding mortality and pulmonary fibrosis. Systemic depletion of CD11c+ DCs and MΦ via i.p. DTx administration in CD11c-DTR-Tg mice protected against bleomycin-induced mortality and pulmonary fibrosis compared to wild-type (WT) mice. Systemic depletion reduced myeloid cells, airway inflammation (total leukocytes, neutrophils, and CD4+ lymphocytes in bronchoalveolar lavage (BAL), inflammatory and fibrogenic mediators, and fibrosis-related mRNAs (Collagen-1α1 and α-SMA). Increased anti-inflammatory cytokine IL-10 and CXCL9 levels were observed, resulting in lower lung hydroxyproline content and Ashcroft fibrosis score. Conversely, local depletion of CD11c+ cells increased mortality by acute leukocyte influx (predominantly neutrophils, DCs, and MΦ in BAL) correlated to IL-1β, with lung hyper-inflammation and early fibrosis development. Systemic depletion of CD11c+ cells confers protection against inflammation and fibrosis induced by Bleomycin, underscoring the significance of myeloid cells expressing F4/80-MHCII+CD11c+ DCs and F4/80 + MHCII+CD11c+ MΦ orchestrating the inflammatory milieu within the lungs, potentially as a source of cytokines sustaining pulmonary chronic inflammation leading to progressive fibrosis and mortality.

MiR-144/451 attenuates lipopolysaccharide-induced lung inflammation by downregulating Rac1 and STAT-3 in macrophages.

MicroRNAs have been shown to play a critical role in lung inflammatory diseases. Here, we report that knocking out miR-144/451 in mice exacerbates lipopolysaccharide (LPS)-induced lung inflammation. The lung inflammation in mice was induced by intratracheal instillation of LPS. Loss-of-function experiments demonstrated that miR-144/451 gene knockout (KO) increased LPS-induced lung inflammation and oxidant stress compared with wild-type (WT) mice, as manifested by increased total bronchoalveolar lavage fluid cells and neutrophil counts, elevated TNF-α and IL-6 levels in bronchoalveolar lavage fluid, enhanced myeloperoxidase activity, and reduced catalase and glutathione peroxidase activity in lung tissues. We also found that LPS significantly decreased miR-451 expression in lung tissues and macrophages; while miR-451 overexpression in LPS-induced RAW264.7 cells remarkably reduced TNF-α and IL-6 levels as well as reactive oxygen species (ROS) production, suggesting a feedback loop might exist in inflammatory cells. Rac1 mRNA and protein levels were downregulated in miR-451-overexpressed RAW264.7 cells. Ex vivo stimulation experiments, performed using alveolar macrophages isolated from miR-144/451 KO mice, confirmed that Rac1 inhibitor alleviated levels of TNF-α and ROS in response to LPS stimulation compared with WT controls. Luciferase reporter assay demonstrated that STAT-3 is a direct target of miR-451. STAT-3 protein levels were elevated in miR-144/451 KO macrophages. LPS treatment also resulted in higher phosphorylation levels of STAT-3 in macrophages from KO mice than in WT cells. Our study identified miR-144/451 as an anti-inflammatory factor in LPS-induced lung inflammation that acts by downregulating Rac1 and STAT-3.

CD56briCD38+ as a novel neutrophil-specific marker in chronic myeloid leukemia

BackgroundChronic myeloid leukemia (CML) is classified as a subtype of myeloproliferative neoplasm, and bone marrow flow cytometry does not reveal any specific immunophenotype. Interestingly, aberrant expression of cluster of differentiation (CD) markers such as CD56 and CD38 has been observed on neutrophils in CML patients. Therefore, we investigated the abnormal expression of CD56 and CD38 in CML neutrophils to explore their diagnostic value in identifying CML through flow cytometry. MethodsWe have developed a multi-parameter flow cytometry assay to identify aberrant immunophenotypes in CML neutrophils among bone marrow nucleated cells. ResultsCompared to healthy donors and patients with a reactive neutrophilia or other hematological malignancies, the percentage of CD56briCD38+ neutrophil subsets in CML patients exhibits a distinctive increase (cut-off value, 2.0 %). The specificity and sensitivity associated with the learning cohort (168 samples) were 90.8 % and 84.9 %, respectively, while in the validation cohort (194 samples), they were 90.7 % and 84.7 %. The accumulation of CD56briCD38+ neutrophil subsets, which demonstrate are abnormal characteristics, is independent of the neutrophil count, BCR/ABL1 fusions and risk stratification but associated with blast cells immunophenotype. Moreover, this increase disappears in CML patients after treatment with tyrosine kinase inhibitors when the curative effect was satisfactory. ConclusionsWe conclude that an increase in the proportion of CD56briCD38+ neutrophil subsets exceeding 2.0 % of total neutrophils serves as a highly sensitive and specific flow cytometry marker, enabling rapid and accurate identification of CML.

Immune Marker and C-Reactive Protein Dynamics and Their Prognostic Implications in Modulated Electro-Hyperthermia Treatment in Advanced Pancreatic Cancer: A Retrospective Analysis

Background: Previous research has suggested that modulated electro-hyperthermia (mEHT) can be used to induce anti-tumor immune effects and to extend patient survival. The use of mEHT in advanced pancreatic cancer is beneficial; however, its immune-mediating effects were never investigated. Methods: A retrospective observational study was conducted. Leukocyte counts, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and granulocyte-to-lymphocyte ratio (GLR) were measured at baseline, midpoint, and after mEHT treatment. Results: A total of 73 mEHT treated pancreatic cancer patients were included. The time elapsed between tumor diagnosis and the first mEHT treatment was 4.40 ± 5.70 months. While no change could be observed between the baseline and the first follow-up visits, the total white blood cell (WBC), neutrophil, and granulocyte count, CRP, NLR, and GLR were significantly higher at the second follow-up compared to both previous visits. Higher levels of the latter parameters following the last mEHT treatment were signaling significantly poor prognostic signs, and so were their longitudinal changes. Conclusions: After the initiation of mEHT, immune markers stabilize with the treatment, but this positive effect is eroded over time by progressive disease. Monitoring the changes in these markers and the occurrence of their increase is a prognostic marker of shorter survival.

Diagnostic value of baseline 18F-FDG PET/CT and peripheral blood inflammatory markers for aggressive lymphoma in non-Hodgkin's lymphoma.

This study aims to investigate the diagnostic value of baseline F18 fluorodeoxyglucose (FDG) PET/computed tomography (CT) parameters and peripheral blood inflammatory markers in aggressive lymphoma of non-Hodgkin lymphoma (NHL) and the correlation between peripheral blood inflammatory markers and maximum standardized uptake value (SUVmax). We conducted a retrospective analysis including 121 patients with NHL. Patients were divided into aggressive lymphoma group and indolent lymphoma group. Mann-Whitney U test, chi-square test and multivariate stepwise logistic regression were used to analyse. Subsequently, receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic performance. Additionally, Spearman correlation analysis was utilized to explore the correlation between peripheral blood inflammatory markers and SUVmax. Leptin mass criterion uptake value (SUL)max, SUVmax, SUVavg, SUVpeak, focal SUVmax/liver SUVmax, focal SUVmax/ mediastinal SUVmax, SULavg, SULpeak, systemic immune-inflammation, neutrophil ratio, total lesion glycolysis, neutrophils versus lymphocyte ratio, platelet-to-lymphocyte ratio, hemoglobin-to-white blood cell ratio, lactate dehydrogenase and lymphocyte ratio between two groups were statistically significant (P < 0.05). SUVmax was an independent influencing factor, and the area under the ROC curve was 0.862. There was a positive correlation between the platelet-to-lymphocyte ratio and SUVmax (r = 0.239; P = 0.008). PET/CT parameters and peripheral blood inflammatory markers have certain value in the diagnosis of aggressive lymphoma in NHL, among which SUVmax is an independent influencing marker and is positively correlated with PLR.

Clinical insights into Invasive Aspergillosis in Mexican children with cancer

Abstract Background In the last years Invasive Aspergillosis (IA) has become the most frequent invasive fungal infection (IFI) affecting children with hematological malignancies. This complication results in the delay of cancer treatment and/or poor prognosis mainly due to late diagnosis and late start of antifungal treatment. Therefore, antifungal prophylaxis and preemptive approaches have been proposed for these patients based on risk factors and local epidemiological data. For this reason, we performed a unicenter, descriptive and prospective study to determine the frequency and clinical course of IA in hospitalized cancer patients with fever and neutropenia. Methods we included events of fever and neutropenia of hospitalized patients with cancer and either with persistent febrile neutropenia (PFN: fever for &amp;gt;96h with total neutrophil count of &amp;lt;500cells/mm3) or profound prolonged neutropenia (PPN: total neutrophil count of &amp;lt;500cells/mm3 for &amp;gt;7 days). Informed consent was requested prior inclusion and follow up of these events was performed with weekly measurement of serum galactomannan antigen (until the recovery of neutrophil count), lung computed tomography (CT) and/or sinus and/or central nervous system (CNS) imaging, depending on clinical findings, and if feasible bronchoscopy to obtain bronchioalveolar lavage (BAL) samples. Clinical and laboratory data were obtained; with this information diagnosis of IA was classified as possible, probable, and proven, according to the EORTC/MSG guidelines. This protocol was approved by the hospital’s research and ethics committees (INP 041/2021). For data analysis categorical variables were presented as frequencies and numerical variables as median and range. Statistical analysis was made with X2 and U Mann Whitney tests. Results Seventy events were included, 14 (20%) had IA diagnosis; 2 possible, 11 probable and 1 proved. Median of age was 10.2y (5.5 – 17) and 64.3% were male. Acute lymphoblastic leukemia was the main oncologic diagnosis (71.4%), 35.7% during induction phase; followed by acute myeloblastic leukemia (21.4%). 92.9% of events with IA presented as PFN (p=0.001) with a fever duration of 3.5 days (1-8) (p=0.004). Pulmonary disease was evident in all events with IA, two had disseminated infection. In 5/14 events serum galactomannan antigen was positive in the first measurement. Only 8 events underwent bronchoscopy: BAL was positive in 6 and 4 had positive culture with Aspergillus spp. Lung CT scan showed different findings, lobar/segmental consolidation and nodule with halo sign were the most common; 85.7% of cases presented with more than one radiological sign (p=0.003). Voriconazole monotherapy was given to 78.5% of IA cases and 21.4% required combined antifungal therapy (added caspofungine or liposomal amphotericin B) due to disseminated disease or severe clinical course. Intensive care admission resulted with statistical significance for the events with diagnosis of IA (64.3% p= 0.019). Within the IA events survival at 60 days was of 78.6%. Conclusion Frequency of IA was high among our high risk cancer patients. This study demonstrates the importance of a complete work up for invasive fungal infection in high-risk patients with persistent febrile neutropenia. The information obtained is of great use for the implementation of pre-emptive approaches and antifungal prophylaxis in this patient population.

Cordyceps militaris Grown on Germinated Rhynchosia nulubilis (GRC) Encapsulated in Chitosan Nanoparticle (GCN) Suppresses Particulate Matter (PM)-Induced Lung Inflammation in Mice.

Cordyceps militaris grown on germinated Rhynchosia nulubilis (GRC) exerts various biological effects, including anti-allergic, anti-inflammatory, and immune-regulatory effects. In this study, we investigated the anti-inflammatory effects of GRC encapsulated in chitosan nanoparticles (CN) against particulate matter (PM)-induced lung inflammation. Optimal CN (CN6) (CHI: TPP w/w ratio of 4:1; TPP pH 2) exhibited a zeta potential of +22.77 mV, suitable for GRC encapsulation. At different GRC concentrations, higher levels (60 and 120 mg/mL) led to increased negative zeta potential, enhancing stability. The optimal GRC concentration for maximum entrapment (31.4 ± 1.35%) and loading efficiency (7.6 ± 0.33%) of GRC encapsulated in CN (GCN) was 8 mg/mL with a diameter of 146.1 ± 54 nm and zeta potential of +30.68. In vivo studies revealed that administering 300 mg/kg of GCN significantly decreased the infiltration of macrophages and T cells in the lung tissues of PM-treated mice, as shown by immunohistochemical analysis of CD4 and F4/80 markers. Additionally, GCN ameliorated PM-induced lung tissue damage, inflammatory cell infiltration, and alveolar septal hypertrophy. GCN also decreased total cells and neutrophils, showing notable anti-inflammatory effects in the bronchoalveolar lavage fluid (BALF) from PM-exposed mice, compared to GRC. Next the anti-inflammatory properties of GCN were further explored in PM- and LPS-exposed RAW264.7 cells; it significantly reduced PM- and LPS-induced cell death, NO production, and levels of inflammatory cytokine mRNAs (IL-1β, IL-6, and COX-2). GCN also suppressed NF-κB/MAPK signaling pathways by reducing levels of p-NF-κB, p-ERK, and p-c-Jun proteins, indicating its potential in managing PM-related inflammatory lung disease. Furthermore, GCN significantly reduced PM- and LPS-induced ROS production. The enhanced bioavailability of GRC components was demonstrated by an increase in fluorescence intensity in the intestinal absorption study using FITC-GCN. Our data indicated that GCN exhibited enhanced bioavailability and potent anti-inflammatory and antioxidant effects in cells and in vivo, making it a promising candidate for mitigating PM-induced lung inflammation and oxidative stress.

Derivation of Russian-specific reference intervals for complete blood count, iron markers and related vitamins.

This study aimed to establish reference intervals (RIs) for Russian adults for hematological parameters including related iron markers and vitamins. Sources of variation of reference values (RVs) and needs for secondary exclusion were explored for proper derivations of RIs. Following the harmonized protocol of the IFCC Committee on Reference Intervals and Decision Limits (C-RIDL), 506 healthy Russians (age 18-80; 46% male) were recruited. Complete blood counts (CBC) and leukocyte differentials, iron markers, vitamin B12, and folate were measured by Beckman Coulter's analyzers. Sources of variation were analyzed by multiple regression analysis, and ANOVAs, and the need for partitioning RVs was decided accordingly. Two schemes of excluding latent anemia were compared: (1) latent abnormal values exclusion method (LAVE) based on associations among CBC parameters, or (2) explicit exclusion of individuals with either ferritin or iron below the respective lower limit of the manufacturer. RIs were determined by the parametric method using two-parameter Box-Cox formula. Gender-specific RIs were required for most analytes, while age-specific RIs were set only for ferritin in females. A BMI-related increase in RVs was prominently observed for reticulocyte parameters, hence we chose to exclude individuals with BMI>28 kg/m2 when establishing the RIs. The LAVE method was more effective in excluding individuals with latent anemia, than exclusion based on low ferritin and/or iron values. International comparison revealed that Russian RIs featured a lower side shift of platelet counts. Similar to African countries, Russian RIs for total leukocyte and neutrophil counts were lower compared to most of other countries. RIs for the Russian population for 34 hematological and related parameters were established using up-to-date methods proposed by C-RIDL. Reducing the influences of latent anemia and obesity on RIs was crucial for erythrocyte parameters. Low levels of Russian RIs observed for platelet and neutrophil counts need further investigation.

Effect of betaine supplementation on immunity, energy, and lipid metabolites of growing Murrah buffalo calves

This study aimed to observe the effect of betaine (BET) supplementation on the growth, immunity, energy, and lipid metabolites of Murrah buffalo calves. Twenty-one Murrah buffalo calves were taken and randomly distributed into three groups (n=3) after blocking by body weight (98.70±1.31 kg) and age (8.12±0.55 months). The feeding regimen was the same in all the groups except that the Treatment groups were supplemented additionally with 0.0 (B0), 7.0 (B7), and 14.0 (B14) g/d BET in three respective groups for 90 d of the experiment period. Total leukocytes (TLC), neutrophils, lymphocytes, total immunoglobulin (TIG), total antioxidant activity (TAA), energy, and lipid metabolites were observed at fortnightly intervals during 90 d experimental periods. Adding BET up to 14 g/d did not exert (P&gt;0.05) any effect on total leukocytes and neutrophils concentration. Lymphocytes, TIG, and TAA were increased significantly (P&lt;0.05) in BET received groups either dose 7 or 14 g/d than in the control. No effect of dietary addition of BET was observed on the glucose, non-esterifies fatty acid (NEFA), total cholesterol (TCH), and high-density lipoprotein cholesterol (HDL-CH). The results of our study indicate that supplemental BET may play a role in regulating the immunity of growing Murrah buffalo calves.

Phytochemistry and Evaluation of the Anti-Inflammatory Activity of the Hydroethanolic Extract of Virola elongata (Benth.) Warb. Stem Bark.

Previous studies of the hydroethanolic extract of Virola elongata inner stem bark (HEVe) have demonstrated its antioxidant, gastroprotective, and antiulcer properties, but have not evaluated its anti-inflammatory potential. HEVe was obtained by maceration and phytochemically analyzed. Its systemic anti-inflammatory activity was assessed by its effect on lipopolysaccharide (LPS)-induced peritonitis in mice. HEVe gel (HEgVe) was employed to evaluate topical anti-inflammatory activity by measuring the ear edema resulting from croton-oil-induced dermatitis in mice. A cell viability assay was conducted to determine the non-cytotoxic concentrations of the HEVe. RAW 264.7 cells were stimulated by LPS to determinate cytokine and nitric oxide production. A phytochemical analysis of the HEVe revealed the presence of phenolic acids, neolignans, flavonoids, and monomeric catechins. The oral treatment of acute peritonitis with HEVe reduced the total leukocytes, neutrophils, TNF-α, and IL-1β and elevated IL-10 levels. The application of the HEgVe reduced local edema. The HEVe on the RAW 264.7 cells exhibited no cytotoxicity, and the cells with HEVe displayed reduced TNF-α, IL-1β, and NO levels and increased IL-13 levels. HEVe demonstrated systemic and topical multitarget anti-inflammatory activity, likely due to the combined effects of secondary metabolites. HEVe emerges as a promising herbal remedy for inflammation with minimal cytotoxicity, emphasizing its potential therapeutic significance.

Regulations of Immune Response by Astragalus in Animal Asthma Models: A Meta-analysis

Background Asthma is a chronic respiratory condition by airway inflammation. Traditional Chinese medicine, is commonly used to treat it. Astragalus is known for its immunoregulation, anti-inflammatory, and antioxidant effects. Purpose To systematically evaluate the efficacy of Astragalus in asthma animal models using meta-analysis methods. Methodology A systematic search was performed in various databases, such as China National Knowledge Infrastructure (CNKI), WanFang Data, PubMed, Web of Science, and Cochrane Library databases for animal studies on Astragalus intervention in asthma models, with the search period extending up to September 2023. Two researchers performed independent literature screening and data extraction. The quality of the included studies was assessed by the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) animal experiment bias risk assessment tool. Meta-analysis was performed with RevMan (version 3.6.1). Results A total of 25 experiments were included. Meta-analysis indicated that Astragalus can significantly reduce total leukocytes, neutrophils, lymphocytes, and eosinophils in animal models of asthma. It also downregulated the expression levels of interleukin-4 and interleukin-5, while upregulation of interferon-γ and interleukin-10 expression was observed; however, the impact on macrophages was found to be not statistically significant ( p &gt; 0.05). Conclusion Our systemic review suggested the potential efficiency of Astragalus in asthma treatment in China, although its mechanism is still unclear. The functions of Astragalus may be associated with attenuating airway inflammation through the regulation of immune response.

Neutrophil CD10 and CD16 as markers of generalized infection development in newborns

BACKGROUND: Neonatal sepsis remains a critical concern. Thus, predictors of infection development and generalization should be determined. AIM: This study aimed to determine novel neutrophil surface biomarkers for early prediction of the infections in newborns. MATERIALS AND METHODS: This observational, single-center, prospective, selective, uncontrolled, unblinded experimental study included 261 newborns, with a mean postconceptual age of 38.7 (38.4–39.0) weeks and a mean gestation age of 38.0 (37.7–38.2) weeks. Blood samples were collected into vacutainers on hospitalization day 1. Patients were enrolled between April 2022 and December 2023. The primary endpoints were length of stay in the ICU and total length of hospitalization in patients with normal and decreased values of CD16 and CD10 neutrophils and HLA-DR monocytes. The expression of CD16 on CD62Lhigh neutrophils, total neutrophil CD10, and monocyte HLA-DR were evaluated by flow cytometry. RESULTS: We assessed infants in the “control” (n = 96), “localized infection” (n = 95), and “generalized infection” (n = 70) subgroups. In all patients, a decrease in CD16 was associated with an increase in the median ICU stay from 4 to 8 days (p = 9.33 × 10–8) and total stay from 14 to 22 days (p = 1.58 × 10–7). A decrease in CD10 was associated with an increase in median ICU stay from 4 to 8 days (p = 3.01 × 10–6) and in the total stay from 14 to 19 days (p = 2.78 × 10–5). A decrease in monocytic HLA-DR was associated with a longer ICU and total hospital stay: 4 vs 8 days (p = 7.16 × 10–5) and 14 vs 21 days (p = 4.03 × 10–5), respectively. The median ICU stay in patients with a decrease in CD16 but normal CD10 was 4 days, whereas a decrease in both indicators was associated with prolonged hospital stay to 11 days (p = 2.13 × 10–5). The median hospital stay in patients with decreased CD16 but normal CD10 was 16 days, whereas the drop of both markers was related with increase of hospitalization stay to 23 days (p = 3.36 × 10–6). In the “localized infection” subgroup, low CD16 was associated with an increased median ICU stay from 4 to 6 days (p = 0.010) and the median hospital stay from 13 to 19 days (p = 4.14 × 10–4). In the “generalized infection” subgroup, decreased CD10 was related with prolongation of the median ICU stay from 7 to 11 days (p = 0.011) and the median total duration of hospitalization from 19 to 27 days (p = 0.037). CONCLUSIONS: A decrease in CD10 and CD16 on the neutrophils at the start of clinical is an unfavorable prognostic factor of infectious and septic complications in newborns.

Leukocyte-Poor Platelet-Rich Plasma for the Management of Knee Osteoarthritis: A Retrospective Study With 12 Months of Follow-Up.

Introduction The knee, the most frequently affected joint in osteoarthritis (OA), impacts the life quality of millions of individuals globally, resulting in a considerable healthcare burden. Conservative treatments are preferred, turning to surgical intervention when necessary. Nonetheless, these conventional modalities have drawbacks. Recently, the use of regenerative medicine therapies, including autologous peripheral blood-derived orthobiologics (APBOs), such as leukocyte-poor platelet-rich plasma (LP-PRP), has evolved and demonstrated the ability to manage knee OA. The primary objective of this investigation was to evaluate the efficacy of LP-PRP via widely used patient-reported outcome measures (PROMs) in grade I or II (on the Kellgren-Lawrence scale) knee OA patients. The secondary objective was to characterize the formulated LP-PRP and determine the efficiency of the leukodepletion filter used for leukocyte removal and platelet recovery. Methods This investigation was a retrospective analysis of data collected from patients treated at a single center over a period of 15 months.Data from 40 patients included in this study were intra-articularly injected with 3mL of formulated LP-PRPunder ultrasound guidance. PROMs questionnaires, including Kujala and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, were used and responses were documented at baseline and up to 12 months follow-up. The characterization of the formulated LP-PRP and the efficiency of the leukodepletion filter in removing leukocytes and recovering platelets were assessed via complete blood count (CBC) analysis. Results The intra-articular administration of LP-PRP resulted in statistically significant improvements in Kujala and WOMAC scores in patients with Grade I or II OA of the knee at all follow-up time points (four to 12 months) compared to the respective baseline scores. The subgroup analysis showed significant improvements in Kujala and WOMAC scores inboth male and female grade I or II knee OA patients with or without comorbidities, including diabetes and/or hypertension. The characterization of formulated PRP showedplatelet concentration to be at least 6x compared to the baseline whole blood levels, the absolute platelet count to be at least 5 billion, and total leukocytes, lymphocytes, neutrophils, and RBCs were depleted by over 88%, 82%, 98%, and 98%, respectively. In addition, the utilization of the PuriBlood leukocyte reduction filter (Puriblood Medical Co. Ltd., Baoshan Township, Taiwan) led to the depletion of approximately 93% of leukocytes and the recovery of about 83% of platelets. Conclusions Administration of LP-PRP resulted in significant improvements in pain and function of patients suffering from grade I or II OA of the knee. In addition, the leukodepletion filter used to formulate LP-PRP, successfully resulted in the depletion of leukocytes while recovering the platelets. More sufficiently powered, multi-center, prospective, non-randomized, and randomized controlled trials with long-term follow-up are needed to further establish the effectiveness of this formulation in knee OA patients.

Aconitate decarboxylase 1 mediates the acute airway inflammatory response to environmental exposures.

Environmental lipopolysaccharide (LPS) and microbial component-enriched organic dusts cause significant lung disease. These environmental exposures induce the recruitment and activation of distinct lung monocyte/macrophage subpopulations involved in disease pathogenesis. Aconitate decarboxylase 1 (Acod1) was one of the most upregulated genes following LPS (vs. saline) exposure of murine whole lungs with transcriptomic profiling of sorted lung monocyte/macrophage subpopulations also highlighting its significance. Given monocyte/macrophage activation can be tightly linked to metabolism, the objective of these studies was to determine the role of the immunometabolic regulator ACOD1 in environmental exposure-induced lung inflammation. Wild-type (WT) mice were intratracheally (i.t.) instilled with 10 μg of LPS or saline. Whole lungs were profiled using bulk RNA sequencing or sorted to isolate monocyte/macrophage subpopulations. Sorted subpopulations were then characterized transcriptomically using a NanoString innate immunity multiplex array 48 h post-exposure. Next, WT and Acod1-/- mice were instilled with LPS, 25% organic dust extract (ODE), or saline, whereupon serum, bronchoalveolar lavage fluid (BALF), and lung tissues were collected. BALF metabolites of the tricarboxylic acid (TCA) cycle were quantified by mass spectrometry. Cytokines/chemokines and tissue remodeling mediators were quantitated by ELISA. Lung immune cells were characterized by flow cytometry. Invasive lung function testing was performed 3 h post-LPS with WT and Acod1-/- mice. Acod1-/- mice treated with LPS demonstrated decreased BALF levels of itaconate, TCA cycle reprogramming, decreased BALF neutrophils, increased lung CD4+ T cells, decreased BALF and lung levels of TNF-α, and decreased BALF CXCL1 compared to WT animals. In comparison, Acod1-/- mice treated with ODE demonstrated decreased serum pentraxin-2, BALF levels of itaconate, lung total cell, neutrophil, monocyte, and B-cell infiltrates with decreased BALF levels of TNF-α and IL-6 and decreased lung CXCL1 vs. WT animals. Mediators of tissue remodeling (TIMP1, MMP-8, MMP-9) were also decreased in the LPS-exposed Acod1-/- mice, with MMP-9 also reduced in ODE-exposed Acod1-/- mice. Lung function assessments demonstrated a blunted response to LPS-induced airway hyperresponsiveness in Acod1-/- animals. Acod1 is robustly upregulated in the lungs following LPS exposure and encodes a key immunometabolic regulator. ACOD1 mediates the proinflammatory response to acute inhaled environmental LPS and organic dust exposure-induced lung inflammation.