Acute Inflammatory Response Research Articles

Evaluation of per- and polyfluoroalkyl substances (PFAS) toxic effects on the acute inflammatory response in the medicinal leech Hirudoverbana

Per- and polyfluoroalkyl (PFAS) substances are a large group of chemicals with elevated water and oil-resistance properties, widely implicated in various applicative fields. Due to the extensive use and high resistance to degradative factors, these compounds pose a significant risk of environmental spreading, bioaccumulating also in living organisms. In this context, despite many researches have been performed to demonstrate “legacy” PFAS harmfulness, only few data are still available about all the emerging fluorinated molecules, industrially introduced to replace the previous ones. For this reason, we proposed the medicinal leech Hirudo verbana as consolidated invertebrate model to assess the effects of four different PFAS (HFPO-DA, PFMoBa, PFOA and PFMOPrA) following freshwater dispersion. Morphological, immunohistochemical and molecular analyses demonstrate that, despite all the compounds basically induce an acute inflammatory and oxidative stress response, a different cellular and molecular response has been observed. Whereas for PFOA and PFMOPrA an increase in the tested concentration leads to a corresponding rise in the immune response, HFPO-DA and PFMoBa trigger an entirely opposite effect. Indeed, the significant recruitment of both granulocytes and macrophage like cells, typically involved in the removal of non-self, is inhibited with increasing concentrations of these compounds. The data collected revealed a different sensitivity of the leech immune system following PFAS exposure, requiring to deepen the current knowledge on the potential toxicity of these compounds.

A Novel Intravaginal Contraceptive Plug for Cats: A Preliminary Biocompatibility Assessment on Haematology and Vaginal Swab.

This preliminary study evaluated the biocompatibility of a novel degradable intravaginal plug contraceptive composed of PEG 4000 and chitosan in cats using haematological profiling and vaginal cytology. Five healthy, non-pregnant female cats were fully anaesthetised and fitted with an intravaginal plug (10 × 0.3 mm) using an applicator, following oestrogen administration 3 h prior. Blood samples were collected from the cephalic vein on days 0 (pre-insertion) and 3 and 7 (post-insertion). Vaginal cytology examinations were conducted on day 0 (pre- and post-oestrogen injection) and days 1, 3 and 7 post-insertion. Haematological parameters, including red blood cell count, haemoglobin levels, haematocrit values, total white blood cell count and differentiation, showed no significant changes after contraceptive insertion (p > 0.05). Vaginal cytology indicated an acute inflammatory response in one out of five subjects on day three post-insertion. The distribution of vaginal epithelial cells (parabasal, intermediate and superficial) remained unaffected by contraception. Oestrogen injection resulted in the dominance of superficial cells up to day 7 of observation (p < 0.05). Overall, PEG 4000 and chitosan-based intravaginal plug contraceptives demonstrated sufficient biocompatibility, indicating their potential as viable contraceptive options for feline use.

Insoluble proteomics analysis of acute intracranial large vessel occlusive thrombus

BackgroundAcute large vessel occlusion (LVO) stroke is highly prevalent and severe. Despite thrombolytic therapy, many patients experience substantial complications. Understanding the origins, constituents, and pathologic processes involved in thrombus formation in acute intracranial large artery occlusion is crucial. ObjectivesTo identify the characteristics of insoluble proteins from different sources of cerebral thrombus. MethodsThis study included 13 patients with cardiogenic embolic (CE) thrombus and 15 with large artery atherosclerotic (LAA) thrombus. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry were used to analyze insoluble proteins in thrombi. Bioinformatics analyses explored differential proteins and associated functional pathways. Least absolute shrinkage and selection operator and random forest identified biomarkers for diagnosing thrombus sources, validated by parallel reaction monitoring. ResultsWe constructed an insoluble protein atlas of cerebral thrombi, identifying 6975 insoluble proteins, including 143 extracellular matrix (ECM)-related proteins. The enrichment pathways considerably varied between thrombi from different sources. Inflammation-related pathways, such as acute inflammatory response, along with ECM-related pathways such as laminin interactions, were notably upregulated in LAA compared with CE. Additionally, 2 biomarkers (IDH2 and HSPG2) exhibited strong diagnostic performance (area under the curve = 1) and robustness. ConclusionIn the insoluble proteomics of thrombus, we highlighted the crucial roles of immune responses and ECM proteins in thrombus formation, providing new insights into its mechanisms and potential drug development. Additionally, we identified 2 biomarkers that offer new methods for determining thrombus sources in patients with LVO.

A randomized controlled cross-over trial investigating the acute inflammatory and metabolic response after meals based on red meat, fatty fish, or soy protein: the postprandial inflammation in rheumatoid arthritis (PIRA) trial.

Rheumatoid Arthritis (RA) has a point prevalence of around 20million people worldwide. Patients with RA often believe that food intake affects disease activity, and that intake of red meat aggravate symptoms. The main objective of the Postprandial Inflammation in Rheumatoid Arthritis (PIRA) trial was to assess whether postprandial inflammation and serum lipid profile are affected differently by a meal including red meat, fatty fish, or a soy protein (vegan) meal. Using a randomized controlled crossover design, 25 patients were assigned to eat isocaloric hamburger meals consisting of red meat (60% beef, 40% pork), fatty fish (salmon), or soy protein for breakfast. Blood samples were taken before meals and at intervals up to 5h postprandial. The analysis included the inflammation marker interleukin 6 (IL-6) and serum lipids. No significant differences in postprandial IL-6 or triglyceride concentrations were found between meals. However, the area under the curve of very low density lipoprotein (VLDL) particle counts, as well as VLDL-4-bound cholesterol, triglycerides, and phospholipids, was higher after the fatty fish compared to both red meat and soy protein. Postprandial inflammation assessed by IL-6 did not indicate any acute negative effects of red meat intake compared to fatty fish- or soy protein in patients with RA. The fatty fish meal resulted in a higher number of VLDL-particles and more lipids in the form of small VLDL particles compared to the other protein sources.

Assessing the predictive value of pre- and post-operative inflammatory markers in patients undergoing total knee arthroplasty

Background and objectiveTotal Knee Arthroplasty (TKA) has proven highly effective in improving quality of life for patients with severe knee conditions. Despite advancements, surgical complications such as periprosthetic joint infections (PJIs) pose risks. The potential predictive value of pre- and post-operative inflammatory markers like neutrophil-to-lymphocyte ratio (NLR), D-dimer, and albumin levels on surgical outcomes is garnering attention. There is a growing interest in leveraging these markers to enhance patient selection and outcome prediction in the context of TKA.Focusing on the natural course of these markers, and the incidence of PJIs and to refine perioperative care strategies, improve patient outcomes, and identify high-risk patients for targeted intervention.MethodsThe study included 94 patients who underwent total knee arthroplasty (TKA) between 2019 and 2023. Blood tests were conducted before surgery and at 1, 3, 7, and 15 days after surgery to assess various parameters including white blood cell count, neutrophils, lymphocytes, platelets, hemoglobin, C-reactive protein, D-dimers, total protein, albumin, and total cholesterol values and ratios.ResultsFollowing total knee arthroplasty (TKA), key observations in blood markers included a sharp rise in white blood cell (WBC) counts from 5.81 to 10.22 (*10^9/L) on the first day post-surgery, with levels returning close to preoperative values by day-15. Neutrophil counts similarly increased from 3.46 to 8.50 (*10^9/L) on day-1, decreasing to 4.01 by day-15. Hemoglobin levels significantly decreased from 115.70 g/L to 90.62 by day-3 before improving to 100.30 by day-15. C-reactive protein (CRP) levels also saw a significant rise from 6.15 mg/L to a peak of 47.07 on day-3, then reducing to 10.55 by day-15, indicating a response to inflammation.ConclusionFollowing total knee arthroplasty (TKA), a significant initial postoperative increase in white blood cell count, neutrophils, and C-reactive protein levels, indicative of an acute inflammatory response, before returning towards baseline values by day 15. Hemoglobin levels displayed a notable dip post-surgery, gradually improving by the study’s end. These patterns emphasize the dynamic nature of inflammatory and hematological responses after TKA, highlighting their potential role in predicting surgical outcomes and guiding postoperative care.

Facial cooling improves thermal perceptions and maintains the interleukin-6 response during passive heating: A sex comparison

ABSTRACT Passively elevating body temperature can trigger a potentially beneficial acute inflammatory response. However, heat therapy often causes discomfort and negative thermal perceptions, particularly in females who generally have lower heat tolerance than males. This study aimed to evaluate the impact of facial cooling on thermal comfort and interleukin-6 concentration in response to 60 minutes of dry heat exposure, and to investigate sex differences in physiological responses and perceptions. 22 healthy young adults (10 females, 12 males; age: 24.4 ± 3.3 years) completed three trials in randomized order using a dry sauna device: 1) Hyperthermia (71.1 ± 1.9°C; HEAT), 2) Hyperthermia with facial cooling via fans (71.1 ± 3.0°C; FAN), and 3) Normothermia (27.0 ± 0.9°C; CON). Blood samples to determine interleukin-6 (IL-6) plasma concentration were collected before and after exposure; basic affect and thermal comfort, rectal and skin temperature were assessed throughout the intervention. Rectal temperature following HEAT (38.0 ± 0.3°C) and FAN (37.8 ± 0.3°C) did not differ between males and females (p = 0.57). Females had higher forehead skin temperatures than males (p ≤ 0.019). Thermal comfort remained more positive in FAN compared to HEAT (p ≤ 0.002). Females felt more thermal discomfort than males in HEAT (p ≤ 0.03), but not in FAN (p = 0.28). The increase in IL-6 plasma concentration was similar between HEAT and FAN (p = 1.00), and higher than CON (p ≤ 0.02); there was no difference between males and females (p = 0.69). This study showed that facial cooling alleviated the thermal discomfort during heat exposure, particularly benefitted females, and did not impede the acute IL-6 response.

How does fetal inflammatory response syndrome change fetalresponse to hypoxia? An experimental study in a fetal sheep model.

Fetal inflammatory response syndrome associated with acidosis during labor is a high-risk situation for the fetus. This study evaluated hemodynamic, gasometric, and heart rate variability changes during acute fetal inflammatory response syndrome associated with hypoxia, compared with isolated hypoxia. Acute fetal inflammatory response syndrome was obtained via anintravenously injection of lipopolysaccharide derived from Escherichia coli. Hypoxia was induced by repeated umbilical cord occlusions during three phases: mild, moderate, and severe umbilical cord occlusions. Two groups were created with chronically instrumented near-term fetal sheep: one group with isolated hypoxia, the other with hypoxia and fetal inflammatory response syndrome. Hemodynamic, gas parameters, and fetal heart rate variability were compared between the groups. The hypoxia and fetal inflammatory response syndrome group had a higher mortality rate (n = 4/9) compared with the hypoxia group (n = 0/9). Gasometric state was altered earlier in case of lipopolysaccharide injection (pH = 7.22 (7.12-7.24) vs 7.28 (7.23-7.34) p = 0.01; lactate = 10.3 mmol/L (9.4-11.0) vs 6.0 mmol/L (4.1-8.2) p < 0.001 after mild occlusions). After mild occlusions, the hypoxia and fetal inflammatory response syndrome group had higher values on seven heart rate variability parameters compared with the hypoxia group. After moderate occlusions, two parameters remained significantly higher. During fetal inflammatory response syndrome, fetal adaptation to hypoxia is impaired. In case of fetal infection, acidosis during labor is likely to become severe more rapidly, requiring closer fetal monitoring during labor.

Markers of systemic inflammation in hemorrhagic stroke with effective and ineffective cerebral blood flow

Neuroinflammation during intracerebral hemorrhage is initiated by blood breakdown products in the subarachnoid space and/or brain parenchyma. In this case, neuroinflammation can cause the development of systemic inflammation. In some cases, intracerebral hemorrhage is accompanied by the appearance of the phenomenon of ineffective cerebral blood flow and clinical manifestations of brain death. The purpose of the study is to identify markers of systemic inflammation in severe hemorrhagic stroke with or without effective cerebral blood flow. The study included patients with intracerebral hemorrhage and the presence of multiple organ failure syndrome, as well as coma on the first day of manifestation, to determine markers of systemic inflammation. A total of 3 groups were analyzed: patients with ineffective cerebral blood flow (Group 2); with effective cerebral blood flow (Group 3); and control group (Group 1) – healthy blood donors. Criteria for non-inclusion in the study: the presence in patients with hemorrhagic stroke of septic complications during hospitalization and acute infectious diseases during the manifestation of intracerebral hemorrhage. In frozen blood plasma samples (anticoagulant – citrate), the levels of IL-6, IL-8, IL-10, TNFá, procalcitonin, neuron-specific enolase, cortisol, myoglobin, troponin I and D-dimers were determined. Enzyme immunoassay was carried out on an automatic analyzer “Dynex Lazurite” (Dynex Technologies, VA, USA). The Kolmogorov–Smirnov test was used to confirm the normality of data distribution. Further comparison of quantitative data was carried out using the nonparametric Mann–Whitney U test. All results were considered statistically significant at p 0.05. In patients with effective and ineffective cerebral blood flow, statistically significant differences were observed in almost all studied markers of systemic inflammation, except for troponin I. However, in the presence of effective cerebral blood flow, significantly higher values of a number of indicators were noted, which may indicate a more rapidly occurring acute systemic inflammatory response in case of effective cerebral blood flow. At the same time, 28 day mortality and SOFA scores in the group with effective blood flow were lower than in the group with ineffective blood flow. This discrepancy may indicate a greater contribution to 28 day mortality and patient severity from direct loss of brain function than from systemic inflammation in patients with ineffective blood flow. On the other hand, the lack of severity of systemic inflammation in this category of patients is most likely due to impaired blood outflow from the damaged brain and the entry of tissue breakdown products and other pro-inflammatory factors into the systemic circulation. That is, intracerebral hemorrhage is accompanied by the development of neuroinflammation, which may be an important component of systemic inflammation. However, disruption of the inflow and outflow of blood in the main great vessels of the brain reduces the likelihood and severity of the development of systemic inflammation.

Blockage of ATGL-mediated breakdown of lipid droplets in microglia alleviates neuroinflammatory and behavioural responses to lipopolysaccharides

Lipid droplets (LD) are triglyceride storing organelles that have emerged as an important component of cellular inflammatory responses. LD lipolysis via adipose triglyceride lipase (ATGL), the enzyme that catalyses the rate-limiting step of triglyceride lipolysis, regulates inflammation in peripheral immune and non-immune cells. ATGL elicits both pro- and anti-inflammatory responses in the periphery in a cell-type dependent manner. The present study determined the impact of ATGL inhibition and microglia-specific ATGL genetic loss-of-function on acute inflammatory and behavioural responses to pro-inflammatory insult. First, we evaluated the impact of lipolysis inhibition on lipopolysaccharide (LPS)-induced expression and secretion of cytokines and phagocytosis in mouse primary microglia cultures. Lipase inhibitors (ORlistat and ATGListatin) and LPS led to LD accumulation in microglia. Pan-lipase inhibition with ORlistat alleviated LPS-induced expression of IL-1β and IL-6. Specific inhibition of ATGL had a similar action on CCL2, IL-1β and IL-6 expression in both neonatal and adult microglia cultures. CCL2 and IL-6 secretion were also reduced by ATGListatin or knockdown of ATGL. ATGListatin increased phagocytosis in neonatal cultures independently from LPS treatment. Second, targeted and untargeted lipid profiling revealed that ATGListatin reduced LPS-induced generation of pro-inflammatory prostanoids and modulated ceramide species in neonatal microglia. Finally, the role of microglial ATGL in neuroinflammation was assessed using a novel microglia-specific and inducible ATGL knockout mouse model. Loss of microglial ATGL in adult male mice dampened LPS-induced expression of IL-6 and IL-1β and microglial density. LPS-induced sickness- and anxiety-like behaviours were also reduced in male mice with loss of ATGL in microglia. Together, our results demonstrate potent anti-inflammatory effects produced by pharmacological or genetic inhibition of ATGL-mediated triglyceride lipolysis and thereby propose that supressing microglial LD lipolysis has beneficial actions in acute neuroinflammatory conditions.

Tumor microbiota of renal cell carcinoma affects clinical prognosis by influencing the tumor immune microenvironment

Despite reported influences of the intratumoral microbiome on cancer progression, its role in this subtype remains unclear. This study aimed to characterize the microbial landscape and signatures of kidney renal clear cell carcinoma using RNA-Seq data from The Cancer Genome Atlas. Following microbial decontamination, differential microbial analysis was conducted between tumorous and adjacent non-tumorous samples. Compared to non-tumorous samples, tumorous microbiota exhibited reduced α and β diversity and distinct phylum-level communities. Differential microbial analysis between patients exhibiting long and short overall survival revealed ten significant differential microbial genera, with six genera correlating with a positive prognosis (Plasmodium, Babesia, Toxoplasma, Cytobacillus, Alicyclobacillus, Verrucomicrobium) and four with a negative prognosis (Colletotrichum, Leuconostoc, Gluconobacter, and Parabacteroides). Employing Cox regression analysis and support vector machines, a prognosis-related microbiome risk signature was developed, achieving an AUC of 0.809. Based on this risk signature, two microbiome-based subtypes were found to be significantly associated with distinct clinical prognoses and immune microenvironments. These findings were corroborated by significant correlations between prognostic-relevant microorganisms and 30 immune-related differentially expressed genes. Specifically, microbial genera associated with a negative prognosis were linked to a pro-tumor acute inflammatory immune response, whereas genera related to a positive prognosis were associated with an anti-tumor adaptive immune response. In conclusion, microbiome-based subtyping revealed correlations between tumor microbiome, clinical prognosis, and tumor microenvironment, indicating intratumoral microbiota as a promising prognostic biomarker for kidney renal clear cell carcinoma.

A mouse model of overexpression of human IL-6 by tissue-resident macrophages in the context of LPS-induced inflammation

Chronic inflammation caused by overexpression of IL-6 underlies a number of pathological conditions Mouse models of systemic chronic inflammation with overexpression of human IL-6 (hIL-6) are in demand not only in the context of studying the molecular mechanisms of inflammation, but also in assessing the effectiveness of clinically approved or newly developed IL-6 inhibitors. One experimental approach in addressing such models in mice relies on the induction of systemic acute inflammation in response to lipopolysaccharide (LPS) administration. This work describes mice with tamoxifen-dependent overexpression of human IL-6 in CX3CR1+ myeloid cells in the context of systemic inflammation induced by LPS administration. Our study demonstrates that the highest expression of the transgene carrying IL6 was observed in the heart, while high production of this cytokine was detected in the blood serum. In response to LPS administration, the production of hIL-6 in the blood increased in transgenic mice, while the production of mIL-6 also increased and was comparable to that in wild-type mice. The consequences of high systemic production of hIL-6, which in our model originates from CX3CR1+ tissue-resident macrophages, were noticeable even in the organs in which these cells are not present. Thus, significant amounts of hIL-6 were detected in tissue lysates of the lungs of transgenic mice after LPS administration. Evaluation of the expression of genes encoding cytokines and markers of tissue remodeling upon injury using quantitative real-time PCR showed significant changes in their expression in the context of LPS-induced systemic inflammation. Thus, this work demonstrates the feasibility of using a mouse model with tamoxifen-dependent transgene activation in CX3CR1+ tissue-resident macrophages to study the effects of systemic overexpression of IL-6 and pharmacological blockade of this cytokine with clinically approved or newly developed inhibitors in the context of experimentally induced diseases.

Mast cells: a double-edged sword in inflammation and fibrosis.

As one of the key components of the immune system, mast cells are well known for their role in allergic reactions. However, they are also involved in inflammatory and fibrotic processes. Mast cells participate in all the stages of acute inflammatory responses, playing an immunomodulatory role in both innate and adaptive immunity. Mast cell-derived histamine, TNF-α, and IL-6 contribute to the inflammatory processes, while IL-10 mediates the suppression of inflammation. Crosstalk between mast cells and other immune cells is also involved in the development of inflammation. The cell-cell adhesion of mast cells and fibroblasts is crucial for fibrosis. Mast cell mediators, including cytokines and proteases, play contradictory roles in the fibrotic process. Here, we review the double-edged role of mast cells in inflammation and fibrosis.

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.

The Role of Hydroxyeicosatetraenoic Acids in the Regulation of Inflammation in Bronchial Asthma.

Hydroperoxyeicosatetraenoic acids (HETEs) are metabolites of arachidonic acid that are oxidized by a family of enzymes including cyclooxygenase, lipoxygenase, and cytochrome P450 enzymes. These enzymes are widely present in various organs and tissues, and the HETEs they synthesize perform an important function in the regulation of immune reactions and haemostasis processes under physiological and pathophysiological conditions. More researchers confirm the role of these oxidized metabolites in modulating inflammation in asthma. The high production of HETEs in allergic and severe asthma indicates their involvement in the processes of an acute inflammatory response. On the other hand, disturbance of the metabolic transformation of arachidonic acid contributes to the development of chronic inflammation due to insufficient synthesis of mediators that resolve inflammatory processes. Several HETEs have both pro-inflammatory and anti-inflammatory effects, which underscores the ongoing interest in their involvement in the pathogenesis of asthma. At the same time, research results are scarce. Based on an analysis of the literature, the pathways of metabolic transformation of 5-HETE, 12-HETE, and 15-HETE with the participation of cyclooxygenases, lipoxygenases, and cytochrome P-450, as well as their role in asthma pathogenesis, were discussed. The PubMed database was searched for information covering the last five years using selected inclusion criteria. Information queries included the following set of keywords: "bronchial asthma, hydroxyeicosatetraenoic acids, 5-HETE, 12-HETE, 15-HETE." Literature data indicate that the role of HETEs in human physiology and pathology, including the modulation of inflammation in asthma, requires comprehensive study to selectively modulate the enzymatic pathways of arachidonic acid metabolism leading to the production of these mediators.

Acute exercise-induced inflammatory and thrombotic response in hypertensive patients.

Vigorous physical activity may acutely trigger the onset of an acute coronary syndrome especially in sedentary persons with established cardiovascular risk factors such as arterial hypertension. The rupture of an inflamed coronary plaque and the activation of the coagulation cascade are the main underlying mechanisms. The present study aimed to determine the effect of acute exercise on the inflammatory and thrombotic response in patients with arterial hypertension as compared to normotensive peers. After excluding patients with any inflammatory or/and coronary artery disease, a total of 60 non-treated hypertensive patients and 65 normotensive individuals underwent a maximal treadmill exercise testing. Βlood samples were drawn at rest and immediately after peak exercise. High-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), white blood cell (WBC), interleukin-6 (IL-6), and total fibrinogen (TF) levels, as well as plasminogen activator inhibitor-1 (PAI-1) activity, were measured. All biomarkers increased with exercise, except PAI-1, which decreased (P < 0.05 for the change between resting and peak exercise for all biomarkers). Αfter adjusting for relevant confounders (duration of exercise, metabolic equivalents, systolic BP, and rate-pressure product achieved at peak exercise), the normotensive group had less marked (P < 0.05) exercise-induced changes than the hypertensive group in hsCRP (7.7 vs. 8.6%), SAA (5.6 vs. 11.9%), WBC (45.0 vs. 51.7%), and PAI-1 (-17.3 vs. -20.1%) and a similar (P = NS) change in IL-6 (23.8 vs. 23.0%) and TF (8.5 vs. 8.5%). In conclusion, the acute exercise-induced inflammatory and thrombotic response seems to be more pronounced in non-treated hypertensive patients than in normotensive controls. Possible clinical implications of this finding merit further examination.

Elevated Leukocyte Count and Platelet-Derived Thrombogenicity Measured Using the Total Thrombus-Formation Analysis System in Patients with ST-Segment Elevation Myocardial Infarction.

High platelet-derived thrombogenicity during the acute phase of ST-segment elevation myocardial infarction (STEMI) is associated with poor outcomes; however, the associated factors remain unclear. This study aimed to examine whether acute inflammatory response after STEMI affects platelet-derived thrombogenicity. This retrospective observational single-center study included 150 patients with STEMI who were assessed for platelet-derived thrombogenicity during the acute phase. Platelet-derived thrombogenicity was assessed using the area under the flow-pressure curve for platelet chip (PL-AUC), which was measured using the total thrombus-formation analysis system (T-TAS). The peak leukocyte count was evaluated as an acute inflammatory response after STEMI. The patients were divided into two groups: the highest quartile of the peak leukocyte count and the other three quartiles combined. Patients with a high peak leukocyte count (＞15,222/mm3; n=37) had a higher PL-AUC upon admission (420 [386-457] vs. 385 [292-428], p=0.0018), higher PL-AUC during primary percutaneous coronary intervention (PPCI) (155 [76-229] vs. 96 [29-170], p=0.0065), a higher peak creatine kinase level (4200±2486 vs. 2373±1997, p＜0.0001), and higher PL-AUC 2 weeks after STEMI (119 [61-197] vs. 88 [46-122], p=0.048) than those with a low peak leukocyte count (≤ 15,222/mm3; n=113). The peak leukocyte count after STEMI positively correlated with PL-AUC during primary PPCI (r=0.37, p＜0.0001). A multivariable regression analysis showed the peak leukocyte count to be an independent factor for PL-AUC during PPCI (β=0.26, p=0.0065). An elevated leukocyte count is associated with high T-TAS-based platelet-derived thrombogenicity during the acute phase of STEMI.

PROTEIN ELECTROPHORESIS AND REFERENCE INTERVALS OF SERUM PROTEINS OF A CAPTIVE POPULATION OF ROTI ISLAND SNAKE-NECKED TURTLES (CHELODINA MCCORDI).

Protein electrophoresis (PEP) is an important tool in mammals to characterize specific dysproteinemias and detect acute and chronic inflammatory responses. In reptiles, PEP is the gold standard method for globulin fraction determination and albumin measurement. In this study, preliminary reference intervals were established for serum PEP in 22 clinically healthy adult Roti Island snake-necked turtles (Chelodina mccordi), a critically endangered species, kept in captivity and sampled over two monsoon seasons. The species has a prominent prealbumin fraction and β-globulins were the dominant globulin fraction. Significant differences between females and males were found in prealbumin (P < 0.01), albumin (P = 0.02), α1-globulin (P = 0.05) and γ-globulin (P = 0.01). Gravid females had significantly lower total protein (P < 0.01), prealbumin (P < 0.01), albumin (P < 0.01) and albumin:globulin ratio (P = 0.01). These preliminary reference intervals should aid in clinical investigation in this species as well as further research studies seeking to understand the application of PEP in reptilian species.

Latent profile analysis of newborn dried blood spot (DBS) cyto-and chemo-kines and growth factors and maternal and fetal acute inflammatory responses to amniotic fluid infection.

Latent profile analysis of newborn dried blood spot (DBS) cyto-and chemo-kines and growth factors and maternal and fetal acute inflammatory responses to amniotic fluid infection.

Oral manifestations of COVID-19 in children: a narrative literature review

COVID-19 triggers an acute inflammatory response in organs, tissues, tongue mucosa, and salivary glands. Some symptoms such as lesions on the tongue and oral mucosa, oral pseudomembranous candidiasis, pharyngitis, taste alteration, gingivitis, canker sores, and even multisystem inflammatory syndrome have been reported in children with COVID-19. Early diagnosis of oral manifestations improves patients' prognosis and quality of life. A narrative literature review was conducted based on studies published in PubMed and LiLacs from January 2020 to April 2024, related to oral manifestations in COVID-19 in children. Of the 68 articles found, 7 were selected after analysis. The main manifestations presented were: abscesses, mucositis, ulcerative lesions, gingivitis, pseudomembranous candidiasis, mucosal lesions, lip and tongue fissures, hemorrhagic crust, inflammation of salivary glands, lip swelling, and reactive infectious mucocutaneous eruption. The selected articles showed that these oral manifestations of COVID-19 can affect children in various age groups, serving as indicators of the disease and signs of worsening infection.

Maternal immune activation exerts long-term effects on activity and sleep in male offspring mice.

Exposure to infectious or non-infectious immune activation during early development is a serious risk factor for long-term behavioural dysfunctions. Mouse models of maternal immune activation (MIA) have increasingly been used to address neuronal and behavioural dysfunctions in response to prenatal infections. One commonly employed MIA model involves administering poly(I:C) (polyriboinosinic-polyribocytdilic acid), a synthetic analogue of double-stranded RNA, during gestation, which robustly induces an acute viral-like inflammatory response. Using electroencephalography (EEG) and infrared (IR) activity recordings, we explored alterations in sleep/wake, circadian and locomotor activity patterns on the adult male offspring of poly(I:C)-treated mothers. Our findings demonstrate that these offspring displayed reduced home cage activity during the (subjective) night under both light/dark or constant darkness conditions. In line with this finding, these mice exhibited an increase in non-rapid eye movement (NREM) sleep duration as well as an increase in sleep spindles density. Following sleep deprivation, poly(I:C)-exposed offspring extended NREM sleep duration and prolonged NREM sleep bouts during the dark phase as compared with non-exposed mice. Additionally, these mice exhibited a significant alteration in NREM sleep EEG spectral powerunder heightened sleep pressure. Together, our study highlights the lasting effects of infection and/or immune activation during pregnancy on circadian activity and sleep/wake patterns in the offspring.