Inflammation Dysfunction Research Articles

The associations between dietary fibers intake and systemic immune and inflammatory biomarkers, a multi-cycle study of NHANES 2015-2020.

In recent years, there has been considerable growth in abnormal inflammatory reactions and immune system dysfunction, which are implicated in chronic inflammatory illnesses and a variety of other conditions. Dietary fibers have emerged as potential regulators of the human immune and inflammatory response. Therefore, this study aims to investigate the associations between dietary fibers intake and systemic immune and inflammatory biomarkers. This cross-sectional study used data from the National Health and Nutrition Examination Survey (2015-2020). Dietary fibers intake was defined as the mean of two 24-h dietary recall interviews. The systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), red blood cell distribution width-to-albumin ratio (RA), ferritin, high-sensitivity C-reactive protein (hs-CRP), and white blood cell (WBC) count were measured to evaluate systemic immune and inflammatory states of the body. The statistical software packages R and EmpowerStats were used to examine the associations between dietary fibers intake and systemic immune and inflammatory biomarkers. Overall, 14,392 participants were included in this study. After adjusting for age, gender, race, family monthly poverty level index, alcohol consumption, smoking status, vigorous recreational activity, body mass index, hyperlipidemia, hypertension, diabetes, and dietary inflammatory index, dietary fibers intake was inversely associated with SII (β = -2.19885, 95% CI: -3.21476 to -1.18294, p = 0.000248), SIRI (β = -0.00642, 95% CI: -0.01021 to -0.00263, p = 0.001738), NLR (β = -0.00803, 95% CI: -0.01179 to -0.00427, p = 0.000284), RA (β = -0.00266, 95% CI: -0.00401 to -0.00131, p = 0.000644), ferritin (β = -0.73086, 95% CI: -1.31385 to -0.14787, p = 0.020716), hs-CRP (β = -0.04629, 95% CI: -0.0743 to -0.01829, p = 0.002119), WBC (β = -0.01624, 95% CI: -0.02685 to -0.00563, p = 0.004066), neutrophils (β = -0.01346, 95% CI: -0.01929 to -0.00764, p = 0.000064). An inverse association between dietary fibers and PLR was observed in the middle (β = -3.11979, 95% CI: -5.74119 to -0.4984, p = 0.028014) and the highest tertile (β = -4.48801, 95% CI: -7.92369 to -1.05234, p = 0.016881) and the trend test (βtrend = -2.2626, 95% CI: -3.9648 to -0.5604, Ptrend = 0.0150). The observed associations between dietary fibers intake and SII, SIRI, NLR, RA, ferritin, hs-CRP, WBC, and neutrophils remained robust and consistent in the sensitivity analysis. No significant interaction by race was found. Dietary fibers intake is associated with the improvement of the parameters of the immune response and inflammatory biomarkers, supporting recommendations to increase dietary fibers intake for enhanced immune health.

Dexmedetomidine ameliorates acute brain injury induced by myocardial ischemia-reperfusion via upregulating the HIF-1 pathway.

Neurological complications after myocardial ischemia/reperfusion (IR) injury remain high and seriously burden patients and their families. Dexmedetomidine (Dex), an α2 agonist, is endowed with analgesic-sedative and anti-inflammatory effects. Therefore, our study aims to explore the mechanism and effect of Dex on brain damage following myocardial IR injury. C57BL/6 mice were randomly divided into Sham, IR, and IR + Dex groups, and myocardial IR models were established. The impact of Dex on brain injury elicited by myocardial IR was assessed via enzyme-linked immunosorbent assay (ELISA) for inflammatory factors in serum and brain; Evans blue for blood-brain barrier (BBB) permeability; Hematoxylin-eosin (H&E) staining for pathological injury in brain; Immunofluorescence for microglia activation in brain; Morris water maze for cognitive dysfunction; Western blot for the expression level of HIF-1α, Occludin, Cleaved caspase-3, NF-κB p65 and p-NF-κB p65 in brain. In addition, HIF-1α knockout mice were used to verify whether the neuroprotective function of Dex is associated with the HIF-1 pathway. Dex was capable of reducing myocardial IR-induced brain damage including inflammatory factor secretion, BBB disruption, neuronal edema, microglial activation, and acute cognitive dysfunction. However, the protective role of Dex was attenuated in HIF-1α knockout mice. Dex protects against myocardial IR-induced brain injury, and the neuroprotection of Dex is at least partially dependent on the activation of the HIF-1 pathway.

Stearic Acid, but not Palmitic Acid, is Associated with Inflammatory and Endothelial Dysfunction Biomarkers in Individuals at Cardiovascular Risk.

Several studies have associated dietary saturated fatty acids (SFAs) with cardiovascular risk but there are still many controversies. Most of these studies have focused on the effects of palmitic acid on circulating lipids. Stearic acid usually shows a neutral effect on blood lipids, however, there is a lack of clinical studies assessing the link with inflammatory and endothelial dysfunction markers. To evaluate the association of red blood cell (RBC) SFA (palmitic and stearic acids) with circulating inflammatory and endothelial dysfunction biomarkers. Cross-sectional study of 79 adults of both sexes with at least one cardiovascular risk factor but without previous events (acute myocardial infarction or stroke). Plasma biomarkers - lipids, glucometabolic markers, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) - and RBC palmitic and stearic fatty acids were analyzed. The associations were assessed by correlation and multiple linear regression analyses, with statistical significance set at p < 0.05. Palmitic acid showed no significant associations with traditional cardiovascular risk factors or inflammatory markers. Stearic acid, on the other hand, was inversely correlated with blood cholesterol and triglycerides, but independently associated with hs-CRP, IL-6, and TNF-α. Stearic acid is associated with inflammatory and endothelial dysfunction biomarkers in individuals with at least one cardiovascular risk factor.

Identifying prognostic biomarker related to immune infiltration in acute myeloid leukemia.

The immune cells of tumor microenvironment (TME) constitute a vital element of the tumor tissue. There is increasing evidence for their clinical significance in predicting prognosis and therapeutic outcomes. However, the TME immune cell infiltrating pattern of the bone marrow in acute myeloid leukemia (AML) patients remains unclear. Here, RNA-sequencing results of AML patients from TCGA database were used to quantify the abundance of 28 types of immune cells in the TME using the single-sample gene set enrichment analysis algorithm. We comprehensively evaluated the immune infiltration status in the TCGA-LAML cohort and defined two immunophenotypes: the immune hot and immune cold subtypes. Additionally, we constructed a TME score reflecting the immune infiltrating pattern of the patients using Cox regression algorithm. Subtypes with high TME score were characterized by over-activation of immune inflammation-related pathways, release of inflammatory factors, T-cell dysfunction, and poor prognosis. Subtypes with a low TME score were characterized by relatively low immune infiltration and immune exclusion. Our analysis indicated that patients in the low TME score group were more sensitive to chemotherapeutic drugs, and those in high TME score were more likely to respond to immunotherapy. Our study provides a new direction to evaluate anti-tumor therapy from immune infiltration of the TME, and the individualized scoring system in this study has important clinical significance in identifying patients who respond to immunotherapy.

T-cells roles and potentials as a therapeutic target in human sepsis

Sepsis is a severe syndrome that is associated with both inflammatory responses and immune system dysfunctions. The most frequent location of injuries caused by sepsis is the respiratory system, followed by the digestive system, and the circulatory system. Researchers have revealed the relationship between T cells and sepsis. To be specific, during the pathology of sepsis, T cells could be damaged, deactivated, and inhibited, while they could also act as an agent that amplifies the sepsis syndrome. This paper focuses on analyzing 3 types of T cells: CD4+ T cells, CD8+ T cells, and regulatory T cells. The populations of the first two types would be reduced, while the functions of regulatory T cells could lead to further immunosuppression during sepsis. Although to date there is no effective treatment to cure this disease, treatment plans targeting immune stimulation and Treg suppression are also examined and analyzed in depth in this paper.

Lipid oxidation dysregulation: an emerging player in the pathophysiology of sepsis.

Sepsis is a life-threatening organ dysfunction caused by abnormal host response to infection. Millions of people are affected annually worldwide. Derangement of the inflammatory response is crucial in sepsis pathogenesis. However, metabolic, coagulation, and thermoregulatory alterations also occur in patients with sepsis. Fatty acid mobilization and oxidation changes may assume the role of a protagonist in sepsis pathogenesis. Lipid oxidation and free fatty acids (FFAs) are potentially valuable markers for sepsis diagnosis and prognosis. Herein, we discuss inflammatory and metabolic dysfunction during sepsis, focusing on fatty acid oxidation (FAO) alterations in the liver and muscle (skeletal and cardiac) and their implications in sepsis development.

The dynamics of the lipopolysaccharide-binding protein (LBP) level in assessing the risk of adverse outcomes in operated colorectal cancer patients

BackgroundThe main aim of this study is to analyze changes in the lipopolysaccharide-binding protein (LBP) level in blood serum over time and assess it as a potential risk factor for the development of SIRS, infectious and inflammatory complications, organ dysfunction and mortality in patients operated on colorectal cancer (CRC). Methods90 CRC patients were divided into 2 groups: Group 1–50 patients operated on for CRC without acute bowel obstruction (ABO); Group 2–40 patients operated on for CRC with ABO. To determine LBP by ELISA method venous blood was taken 1 h before surgery and 72 h after it (3rd day). ResultsLBP level on the 3rd day after surgery was lower in CRC patients with SIRS, postoperative complications, organ dysfunction and in dead patients. With an LBP value on the 3rd day after surgery being at ≤821.95 ng/mL, the risk of SIRS occurrence is 3.5 times higher, that of the postoperative complications is 5.2 times higher and death is 12.9 times higher than with its higher level (OR 3.5, CI 1.46–8.4; OR 5.2, CI 1.80–15.12; OR 12.9, CI 1.54–108.21, respectively). If the LBP value on the 3rd day after surgery is ≤ 700.15 ng/mL, the risk of organ dysfunctions is 13.5 times higher than with its higher level (OR 13.5, CI 3.536–51.54). ConclusionsThis study demonstrated that in the patients with CRC, the LBP can be used as a predictive criterion for the development of SIRS, postoperative infectious and inflammatory complications, organ dysfunction, and mortality.

Small extracellular vesicles-transported lncRNA TDRKH-AS1 derived from AOPPs-treated trophoblasts initiates endothelial cells pyroptosis through PDIA4/DDIT4 axis in preeclampsia.

Substantial studies have demonstrated that oxidative stress placenta and endothelial injury are considered to inextricably critical events in the pathogenesis of preeclampsia (PE). Systemic inflammatory response and endothelial dysfunction are induced by the circulating factors released from oxidative stress placentae. As a novel biomarker of oxidative stress, advanced oxidation protein products (AOPPs) levels are strongly correlated with PE characteristics. Nevertheless, the molecular mechanism underlying the effect of factors is still largely unknown. With the exponential knowledge on the importance of placenta-derived extracellular vesicles (pEVs), we carried out lncRNA transcriptome profiling on small EVs (sEVs) secreted from AOPPs-treated trophoblast cells and identified upregulated lncRNA TDRKH-AS1 as a potentially causative factor for PE. We isolated and characterized sEVs from plasma and trophoblast cells by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blotting. The expression and correlation of lncRNA TDRKH-AS1 were evaluated using qRT-PCR in plasmatic sEVs and placentae from patients. Pregnant mice injected with TDRKH-AS1-riched trophoblast sEVs was performed to detect the TDRKH-AS1 function in vivo. To investigate the potential effect of sEVs-derived TDRKH-AS1 on endothelial function in vitro, transcriptome sequencing, scanning electron Microscopy (SEM), immunofluorescence, ELISA and western blotting were conducted in HUVECs. RNA pulldown, mass spectrometry, RNA immunoprecipitation (RIP), chromatin isolation by RNA purification (ChIRP) and coimmunoprecipitation (Co-IP) were used to reveal the latent mechanism of TDRKH-AS1 on endothelial injury. The expression level of TDRKH-AS1 was significantly increased in plasmatic sEVs and placentae from patients, and elevated TDRKH-AS1 in plasmatic sEVs was positively correlated with clinical severity of the patients. Moreover, pregnant mice injected with TDRKH-AS1-riched trophoblast sEVs exhibited a hallmark feature of PE with increased blood pressure and systemic inflammatory responses. Pyroptosis, an inflammatory form of programmed cell death, is involved in the development of PE. Indeed, our in vitro study indicated that sEVs-derived TDRKH-AS1 secreted from AOPPs-induced trophoblast elevated DDIT4 expression levels to trigger inflammatory response of pyroptosis in endothelial cells through interacting with PDIA4. Herein, results in the present study supported that TDRKH-AS1 in sEVs isolated from oxidative stress trophoblast may be implicated in the pathogenesis of PE via inducing pyroptosis and aggravating endothelial dysfunction.

Long noncoding RNA (taurine upregulated gene 1) and micro RNA-377: emerging players in the development of metabolic syndrome among psoriasis patients

BackgroundPsoriasis (PsO) is an immune-mediated dermatosis and systemic inflammatory condition that can affect the skin, joints, and other organs and tissues with a range of comorbidities. The activation of proinflammatory cytokines is the primary cause of the development of skin lesions in PsO. Patients with PsO have a higher risk of developing cardiovascular metabolic comorbidities; among these is the metabolic syndrome (MetS). Particularly, MetS is characterized by abdominal obesity, hypertension, hyperglycemia, and hyperlipidemia, has been linked to PsO. The connection between PsO and MetS is believed to be caused by PsO generating systemic inflammation, which then results in elevated inflammatory adipokines, endothelial dysfunction, and insulin resistance. Micro RNA-377 and long noncoding RNA taurine upregulated 1 (TUG1) are both involved in the control of a variety of inflammatory disorders in humans and can be employed as biomarkers for the diagnosis and prognosis of psoriasis. The aim of the present study is to establish a panel of biomarkers for the early diagnosis of MetS incidence in psoriasis and thereby, reducing its lethal consequences.ResultsIn this study, 120 patients: 40 psoriatic patients, 40 psoriatic patients with metabolic syndrome, and 40 healthy subjects were conducted. Expressions of Long noncoding RNA Taurine Upregulated Gene-1 (TUG1), miRNA-377 and Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) were assessed in tissue lesion by real-time PCR. ELISA technique was carried out for the detection of serum levels of plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor β (TGFβ). Moreover, miRNA-377 expression was significantly elevated with the simultaneous down-regulation of both TUG-1 and PPAR-γ in PsO-MetS group when compared to those of PsO and control groups. Furthermore, PAI-1 and TGFβ levels were higher in PsO-MetS than PsO.ConclusionsThe dysregulated levels of TUG-1, miRNA-377, PPAR-γ, PAI-1, and TGFβ, biomarkers may provide information about their potential role in the emergence of MetS in psoriasis patients.

MESNA (2-Mercaptoethanesulfonate) Attenuates Brain, Heart, and Lung Injury Induced by Carotid Ischemia-Reperfusion in Rats.

Ischemia-reperfusion (I/R) causes organ dysfunction as a result of the increased formation of various reactive oxygen metabolites, infiltration of inflammatory cells, interstitial edema, cellular dysfunction, and tissue death. The study aimed to investigate the cytoprotective effect of 2-mercaptoethanesulfonate (MESNA) against tissue damage in rats exposed to carotid ischemia-reperfusion. Twenty-four male Wistar albino rats were divided into four groups (n = 6): sham, carotid I/R, I/R + MESNA (75 mg/kg), and I/R + MESNA (150 mg/kg) groups. To induce ischemia in rats, the carotid arteries were ligated with silk sutures for 10 min; the silk suture was then opened, and 1 h reperfusion was done. MESNA (75 and 150 mg/kg) was administered intraperitoneally 30 min before ischemia-reperfusion. Tissue samples from the animals were taken for histological examination, while the serum levels of some biochemical parameters were utilized to evaluate the systemic alterations. ANOVA and Tukey's post hoc tests were applied with a significance level of 5%. The ischemia-reperfusion-induced tissue damage as evidenced by increase in serum levels of alanine transaminase, aspartate aminotransferase, alkaline phosphatase, malondialdehyde, lactate dehydrogenase, and matrix metalloproteinases (MMP-1, -2, -8) was significantly (P < 0.05-0.0001) reversed after treatment with MESNA in a dose-dependent manner. Treatment with MESNA (75 and 150 mg/kg), significantly (P < 0.05-0.0001) decreased the I/R-induced increase in serum tumor necrosis factor-alpha (TNF-α) and Interleukin-1-beta (IL-1 β). The results of this study suggest that MESNA has a protective effect on tissues by suppressing cellular responses to oxidants and inflammatory mediators associated with carotid ischemia-reperfusion.

Long term follow-up of a multicentre cohort of COVID-19 patients with pulmonary embolism: Anticoagulation management and outcomes

Background and aimsPulmonary embolism (PE) is a frequent complication in COVID19 hospitalized patients. Inflammatory storm and endothelial dysfunction due to the virus seem to be the two major risk factors for PE. Consequently, PE related to COVID19 could be consider as triggered by a transient inflammatory acute phase and treated for no longer than 3 months. However, few data are available on management of anticoagulation and risk of venous thromboembolic (VTE) recurrences in these patients and guidelines are still undefined.Aim of the present study is to evaluate the long-term follow-up of a cohort of covid-19 patients with PE. MethodsWe conducted a retrospective multicenter study in four Italian hospitals between March 1st, 2020, and May 31st, 2021 in patients who experienced a PE during hospitalization for a COVID-19 pneumonia, excluding patients who died during hospitalization. Baseline characteristics were collected and patients were grouped according to duration of anticoagulant treatment (< 3 months or > 3 months). The primary outcome was incidence of VTE recurrence while secondary outcome was the composite of deaths, major hemorrhages and VTE recurrence during follow-up. Results106 patients with PE were discharged, of these 95 (89.6 %) had follow up longer than 3 months (seven patients were lost to follow up and four died within three months). The median follow-up was 13 months (IQR 1–19). Overall, 23 % of subjects (22/95) were treated for 3 months or less and 76.8 % (73/95) received anticoagulation for >3 months. Of patients in the short treatment group, 4.5 % died, compared with 5.5 % of those in the longer treatment group (p = NS); no difference was shown in risk of VTE recurrence (0 % vs 4.1 %, p = NS), major bleeding (4.5 % vs 4.1 %, p = NS) or in composite outcome (9.1 % vs 11 %, p = NS). No difference was found between the two treatment groups for composite outcome using the Kaplan-Meier analysis (Log Rank Test p = 0.387). ConclusionIn our retrospective multi-center cohort, prolongation of duration of anticoagulation seems not to affect risk of VTE recurrences, deaths and bleeding after a PE related to COVID-19.

Inflammatory and endothelial dysfunction markers in hypertensive patients with type 2 diabetes mellitus

Hypertension and diabetes are two of the main risk factors for the development of cardiovascular disease, and both pathologies overlap significantly in their pathophysiological mechanisms. The aim of this study was to determine the concentration of inflammatory markers and endothelial dysfunction in patients with hypertension and type 2 diabetes mellitus, to compare with healthy individuals, and to determine whether the coexistence of both pathologies has a different effect on the behavior of these markers. A descriptive, correlational, cross-sectional research was carried out from July 2022 to February 2023. A total of 120 individuals were selected for this study (30 controls, 30 with type 2 diabetes mellitus, 30 with hypertension and 30 with diabetes plus hypertension). Each subject had a fasting blood sample drawn for determination of total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, ultrasensitive C-reactive protein (hs-CRP), glycosylated hemoglobin, sICAM-1, sE-selectin, IL-6 and TNF-α. A significant increase in the concentration of sICAM-1, sE-selectin, IL-6 and TNF-α was found in diabetic, hypertensive and diabetic patients with hypertension when compared to controls (p&lt;0.0001). The coexistence of diabetes and hypertension did not represent a significant elevation in the concentration of markers of endothelial dysfunction and inflammation. In conclusion, our results suggest endothelial activation as well as an inflammatory state in patients with diabetes and hypertension, indicated by elevated levels of circulating adhesion molecules and proinflammatory cytokines. The simultaneous presence of diabetes and hypertension did not have an additive effect on the levels of these molecules.

Inflammatory and endothelial dysfunction markers in females with metabolic syndrome aged 50–75 years

Introduction: The prevalence of metabolic syndrome (MetS) in Indonesia is 39% and it is higher in females than in males (46% vs. 28%). Features of this syndrome comprise low-grade chronic inflammation and endothelial dysfunction from cardiometabolic abnormalities. High-sensitive C-reactive protein (HsCRP) is a biomarker of cardiovascular disease, whereas ferritin and pentraxin-3 (PTX-3) are markers of chronic inflammation. One of the markers of endothelial dysfunction is an intercellular cell adhesion molecule-1 (ICAM-1). Studies on MetS in women aged 50–70 years and using several markers of inflammation and endothelial dysfunction are rare. The study aimed to determine differences in HsCRP, ferritin, PTX-3, and ICAM-1 level between females with and without MetS aged 50–75 years. Methods: For this cross-sectional study, 160 females aged 50–75 years from South Jakarta were recruited, divided into MetS and non-MetS (control) groups, 80 participants each. Participants that met the inclusion criteria were assessed for vital signs and metabolic parameters (e.g., lipid profile, fasting blood glucose level, and waist circumference [WC]). The groups were compared using an independent t-test for inflammatory (i.e., HsCRP, PTX-3, and ferritin) and endothelial dysfunction (ICAM-1) (p &lt; 0.05) biomarkers. Results: The mean age of the MetS and control groups was 59.6 ± 5.6 and 59.2 ± 5.5 years. MetS criteria included WC of ≥80 cm (95.2%), increased blood pressure level (90.6%); and high-density lipoprotein cholesterol of &lt;50 mg/dL (76.2%). Significant differences were found between the MetS and control groups for ferritin (p = 0.027), PTX-3 (p = 0.045), and ICAM-1 (p = 0.004) but not for HsCRP (p = 0.136). Conclusion: Elevated ferritin, PTX-3 level, and ICAM-1 level are significantly associated with an increased Mets risk in females aged 50–75 years; however, the same is not true for HsCRP.

Genesis of clinical and subclinical endometritis in dairy cows.

Up to half of dairy cows may develop one or more types of reproductive tract inflammatory disease within 5 weeks after calving. Clinical endometritis (CE) results from uterine bacterial dysbiosis with increased relative abundance of pathogenic bacteria associated with luminal epithelial damage. These bacteria cause endometrial stromal cell lysis, followed by massive polymorphonuclear neutrophil (PMN) migration, and pyogenesis. Clinical endometritis is defined as endometrial inflammation accompanied by purulent discharge. Purulent discharge is not always accompanied by uterine inflammation (being (rarely) vaginitis or (commonly) cervicitis), hence referred to as purulent vaginal discharge (PVD). Subclinical endometritis (SCE) is an asymptomatic uterine disease defined by a threshold of PMN on cytology that is associated with worse reproductive performance; it has not been linked with bacterial dysbiosis. Current evidence suggests that SCE is a result of metabolic and inflammatory dysfunction that impairs innate immune function and the ability of endometrial PMN to undergo apoptosis, necrosis, and ultimately achieve resolution of inflammation. Clinical endometritis and SCE are diagnosed between 3 and 5 weeks postpartum and commonly overlap, but they are considered distinct manifestations of reproductive tract inflammatory disease. This review addresses the genesis of CE and SCE in postpartum dairy cows considering metabolic stress, innate immune dysfunction, and shifts in the composition of the uterine microbiota.

Shexiang Tongxin Dropping Pill alleviates M1 macrophage polarization-induced inflammation and endothelial dysfunction to reduce coronary microvascular dysfunction via the Dectin-1/Syk/IRF5 pathway

Ethnopharmacological relevanceShexiang Tongxin Dropping Pill (STDP), a traditional Chinese medicine compound, is fragrant, invigorates the qi, unblocks pulses, activates the blood circulation, removes blood stasis, and relieves pain. It is used clinically to treat coronary heart disease and angina pectoris. Coronary microvascular dysfunction (CMD) is associated with increased morbidity and mortality from cardiovascular events. Endothelial dysfunction and inflammation have been verified as its underlying causes. STDP can ameliorate CMD, but the mechanism has not been fully elucidated. Aim of the studyTo explore the effects of STDP on M1 macrophage polarization-induced inflammation and endothelial dysfunction as an inhibitor of CMD, and to determine its mechanisms of action. Materials and methodsThe CMD rat model was established by left anterior descending artery (LAD) ligation. The efficacy of STDP against CMD was evaluated by echocardiography, optical microangiography, Evans blue staining, and histological examination. The OGD/R-induced endothelial injury model, the endothelial injury-induced sterile inflammation model, the Dectin-1 overexpression model, and the Dectin-1-overexpressing RAW264.7 macrophage supernatant-stimulated HUVEC-induced secondary injury of endothelial function model were established to confirm the efficacy of STDP against M1 macrophage polarization-induced inflammation and endothelial dysfunction. ResultsSTDP blunted the deterioration of cardiac function and ameliorated CMD by reducing inflammatory cell infiltration and endothelial dysfunction in CMD rats. Endothelial injury and Dectin-1 overexpression induced M1 macrophage polarization and inflammation. Mechanically, STDP hindered M1 macrophage polarization and inflammation by inhibiting the Dectin-1/Syk/IRF5 pathway both in vivo and in vitro. STDP alleviated endothelial dysfunction induced by Dectin-1 overexpression in macrophages. ConclusionSTDP can alleviate M1 macrophage polarization-induced inflammation and endothelial dysfunction against CMD via the Dectin-1/Syk/IRF5 pathway. Dectin-1-associated M1 macrophage polarization might be developed as a novel target for ameliorating CMD.

Late Decrease in Cerebral Blood Flow in Bacterial Meningitis: More than a Simple Normalization of Acute Inflammatory Vessel Wall Architecture?

Acute bacterial meningitis is a disease with an overwhelmingly high mortality rate and high incidence of adverse neurological sequelae and poor neurological recovery amongst survivors. Amongst the numerous complications of bacterial meningitis, the presence of cerebrovascular disease represents a severe disease form. Vascular involvement during bacterial meningitis has long been established by numerous pathological and angiographic studies. Cerebrovascular changes known to occur in bacterial meningitis ranging from narrowing of large arteries by vasospasm to critical stenosis/obliteration of small to medium sized arteries/arterioles by vasculitis. Not surprisingly, alterations in CBF velocities have commonly been described during the inflammatory process and may represent an important component of brain injury during meningitis. In accordance with previous studies observing a biphasic cerebral flow pattern characterized by an early but transient increase in flow velocity, mostly due to reflexive vasospasm, and later by a sustained decrease in flow velocity, likely attributable to stenotic vasculitis, cerebral ischemia is a notable complication of bacterial meningitis during the advanced disease phase. Impaired cerebral perfusion during the late stages of disease may result from a variety of factors that contribute to a vital component of cerebral injury in bacterial meningitis. The pathogenesis of cerebral ischemia with progression of disease course is less clearly understood but may involve a complex interaction between inflammatory processes, systemic dysfunction, energy impairment, neuronal damage and intracranial pressure, factors of which we aim to more precisely understand and assign a more definite contributory role in the development of cerebrovascular ischemic consequences with advanced stages of bacterial meningitis.

Analysis of factors associated with sterile inflammation in women with pe receiving different antihypertensive treatment strategies

Systemic inflammation alongside endothelial dysfunction is considered to play a crucial role in PE pathogenesis. Endothelial dysfunction can be assessed by endothelial glycocalyx (eGC) damage. eGC is a superficial layer of cells associated with endothelial membrane that provides all endothelial cells functions. Its damage can be evaluated by the levels of its circulating components in blood. Patients with PE generally receive methyldopa (Dopegyt) solely or in combination with nifedipine (Cordaflex), and there is no understanding of their effect on proinflammatory state of blood vessels. Our study aimed to assess levels of IL-6, IL-18, TNFα, galektin-3 and homocysteine as well as levels of syndecan-1, eCG structural component, representing system inflammatory response and endothelial dysfunction development in blood of women with early- and late-onset PE receiving different antihypertensive treatment strategies. Eighty-two patients were enrolled into this interventional longitudinal pilot study. The comparison group included 15 patients before 34 gestational weeks and 15 patients after 34 weeks. Study subgroup 1 included 12 patients with early- onset PE receiving Dopegyt solely and 16 patients with early-onset PE receiving Dopegyt together with Cordaflex. Study subgroup 2 included 12 patients with late-onset PE receiving Dopegyt solely and 12 patients with late-onset PE receiving combined therapy. As for early-onset PE, only IL-6 demonstrated statistically significant differences in patients receiving both treatment strategies compared to control. Proinflammatory state was more profound in late-onset PE. IL-6 levels were significantly increased in late-onset PE treated with Dopegyt. IL-6 and TNFa levels were significantly higher in late-onset PE patients treated with Dopegyt + Cordaflex compared to control. Syndecan-1 levels were statistically significantly higher in patients with early-onset PE treated with Dopegyt solely. There were no statistically significant differences between the groups despite elevated mean values of syndecan-1 in late-onset PE. Galectin-3 and homocysteine levels did not differ significantly between the groups, representing lack of pronounced inflammatory response and endothelial dysfunction.

ОЦЕНКА ЗНАЧИМОСТИ ВЗАИМОСВЯЗИ МЕЖДУ ПОКАЗАТЕЛЯМИ РЕМОДЕЛИРОВАНИЯ СОСУДОВ, ВОСПАЛИТЕЛЬНОГО ОТВЕТА И ПОЛИМОРФИЗМА ГЕНОВ ДИСФУНКЦИИ ЭНДОТЕЛИЯ У ПАЦИЕНТОВ МУЖСКОГО ПОЛА С ИНФАРКТОМ МИОКАРДА В ЗАВИСИМОСТИ ОТ НАЛИЧИЯ ИЛИ ОТСУТСТВИЯ ГИПЕРТОНИЧЕСКОГО АНАМНЕЗА

Introduction. Endothelial dysfunction, arterial hypertension and surrogate events of myocardial infarction are interrelated phenomena, while the genetic predisposition in these patients is an independent risk factor for the development of cardiovascular pathology. Aim. The aim of the study was to evaluate the significance of the interaction of associations of polymorphic loci of adhesion molecule genes (immunoglobulin VCAM1), MCP-1 chemokine, vascular endothelial growth factor (VEGFA), nitric oxide control enzyme (DDAH1), markers of the inflammatory response, vascular remodeling and endothelial dysfunction in patients with male myocardial infarction, depending on the presence or absence of arterial hypertension in history in the development of myocardial infarction. Material and methods. 667 male patients and 621 practically healthy individuals in the comparison group were examined. Patients underwent determination of general clinical parameters, serum concentrations of monocyte-chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGFA), cytokines (IL-1,6; TNF-α), molecular genetic study, measurement of media intima thickness of the common carotid artery. Selected in the group of patients with myocardial infarction, individuals with or without a history of arterial hypertension. Results and discussion. As a result of a comparative analysis of groups of patients with and without a history of arterial hypertension with a group of healthy individuals, significant differences in the frequencies of genotypes and alleles for the following polymorphic gene loci were revealed: MCP-1, VEGFA, DDAH1, VCAM1. The serum concentration of cytokines (IL-1,6; TNF-α) in patients, regardless of the presence or absence of a history of hypertension, significantly exceeded the level in the comparison group. The VEGFA index in patients with myocardial infarction with arterial hypertension was significantly increased compared to the serum level in patients with myocardial infarction without arterial hypertension. Conclusion. A higher significance of the interaction between indicators of vascular remodeling, inflammation, endothelial dysfunction gene polymorphism in the development of myocardial infarction in patients with a history of hypertension, in contrast to non-hypertensive patients with myocardial infarction, was revealed, which indicates a powerful contribution of arterial hypertension to the etiology and implementation of myocardial infarction.

Acute exercise modulates the inflammatory response in adipose tissue in both lean and obese mice

ObjectivesAcute physical exercise acts as a metabolic stressor, promoting activation of the immune system, and this response could be relevant in the adipose tissue remodeling process. In addition, some cytokines have important functions in lipolysis. Because chronic exercise improves obesity-related metabolic and inflammatory dysfunction, herein we investigated the effect of acute exercise on the inflammatory responses in the adipose tissues of lean and obese mice. MethodsLean mice were fed a standard chow diet, whereas obese mice were fed a high-refined carbohydrate diet for 8 wk. Both groups were subjected to 60 min of moderate-intensity exercise. ResultsIn the epididymal adipose tissue of lean mice, exercise enhanced interleukin (IL)-6 and tumor necrosis factor-α levels, which correlated positively with increased serum free fatty acid concentrations. In vivo confocal imaging of epididymal adipose tissue vessels revealed higher recruitment of neutrophils after exercise. Also, the number of leukocytes expressing CD11b+F480– was elevated 6 h after exercise. Similarly, the chemokine (C-X-C motif) ligand 1 level increased at 6 h and remained high until 24 h after exercise. Myeloperoxidase activity was increased at 6, 12, and 24 h after exercise. Surprisingly, however, no changes were observed in epididymal adipose tissue from obese mice, considering proinflammatory cytokines (IL-6 and tumor necrosis factor-α). On the other hand, IL-13, IL-4, and IL-10 levels were higher in obese mice after exercise. ConclusionsThese data suggest that acute exercise promotes an inflammatory response in the adipose tissue of lean mice that is observed as part of its role in adipose tissue remodeling. In contrast, acute exercise promotes an antiinflammatory response in adipose tissue from obese mice, likely as an important tool for restoring homeostasis.

Effect of Ornithine α-Ketoglutarate on Intestinal Microbiota and Serum Inflammatory Cytokines in Dextran Sulfate Sodium Induced Colitis.

Ornithine α-ketoglutarate (OKG), a nutritional compound, is an amino acid salt with anti-oxidative and anti-inflammatory effects on humans and animals. Ulcerative colitis (UC), as an inflammatory bowel disease (IBD), leads to chronic intestinal inflammatory dysfunction. This study evaluated the optimal dosage of OKG in healthy mice. Then, a mouse model of acute colitis was established using dextran sodium sulfate (DSS), and the preventive effect of OKG on DSS-induced colitis in mice was explored through analysis of serum inflammatory cytokines and fecal microbiota. Initially, the mice were randomly divided into a control group, a group given a low dose of OKG (LOKG: 0.5%), a group given a medium dose of OKG (MOKG: 1%), and a group given a high dose of OKG (HOKG: 1.5%); they remained in these groups for the entire 14-day experimental period. Our results demonstrated that 1% OKG supplementation increased body weight, serum growth hormone (GH), insulin (INS), alkaline phosphatase (ALP), Tyr, and His and decreased urea nitrogen (BUN), NH3L, and Ile. Then, a 2 × 2 factor design was used for a total of 40 mice, with diet (a standard diet or a 1% OKG diet) and challenge (4% DSS or not) as the main factors. During days 14 to 21, the DSS mice were administered 4% DSS to induce colitis. The results revealed that OKG alleviated weight loss and reversed the increases in colonic histological damage induced by DSS. OKG also increased serum IL-10 secretion. Moreover, OKG enhanced the abundance of Firmicutes and decreased that of Bacteriodetes at the phylum level and particularly enhanced the abundance of Alistipes and reduced that of Parabacterioides at the genus level. Our results indicated that OKG promotes growth performance and hormone secretion and regulates serum biochemical indicators and amino acid concentrations. Furthermore, 1% OKG supplementation prevents DSS-induced colitis in mice via altering microbial compositions and reducing the secretion of inflammatory cytokines in serum.