Cellular Markers Of Inflammation Research Articles

Effects of electroconvulsive therapy on inflammatory markers and depressive symptoms in adolescents with major depressive disorder

ObjectiveLimited research exists on the use of electroconvulsive therapy (ECT) for adolescents with major depressive disorder (MDD). This study investigates the effects of ECT on inflammatory markers in adolescents aged 13-18 suffering from severe MDD, evaluating its efficacy in modulating cellular inflammatory markers and ameliorating depressive symptoms.MethodsA cohort of 38 adolescents with severe MDD received standard antidepressant therapy along with 6-8 ECT sessions spanning two weeks. A control group of 29 age-matched, healthy individuals was also assessed for comparative purposes. The investigation measured variations in depressive symptomatology and inflammatory marker levels (IL-1β, IL-6, IL-10) pre- and post-intervention.ResultsPost-ECT, a substantial decrease in pro-inflammatory cytokines (IL-1β and IL-6) and an increase in the anti-inflammatory cytokine (IL-10) were noted. Participants who responded to the treatment showed a significant decline in HAMD-17 scores, which accentuates ECT’s therapeutic potential. Comparative analysis indicated a significant correlation between post-treatment inflammatory marker alterations and clinical improvement, implying that shifts in inflammatory state might serve as predictors of treatment response. Moreover, the mitigation of depressive symptoms exhibited a moderate correlation with post-treatment decrements in IL-1β and IL-6 levels, underscoring MDD’s intricacy and ECT’s comprehensive impact.ConclusionWhile initial inflammatory marker levels did not predict the response to ECT, the post-treatment measures appeared to be linked to clinical improvement. These findings suggest ECT’s potential effectiveness in treating severe MDD in adolescents and point to the possible predictive value of inflammatory markers in therapeutic outcomes. The study contributes to our understanding of the biopsychosocial framework of MDD and indicates that ECT may be a viable treatment option for this population.

Evaluation of the prognostic significance of cellular markers of inflammation in patients with coronary artery atherosclerosis

Evaluation of the prognostic significance of cellular markers of inflammation in patients with coronary artery atherosclerosis

Prognostic role of the neutrophil/lymphocyte ratio in high-risk BCG-naïve non-muscle-invasive bladder cancer treated with intravesical gemcitabine/docetaxel.

To investigate the role of pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in the prediction of response to sequential intravesical therapy, gemcitabine and docetaxel (Gem/Doce), given to patients with bacille Calmette-Guérin (BCG)- naïve high-risk non-muscle-invasive bladder cancer (NMIBC). A retrospective analysis was conducted on 115 patients who received intravesical Gem/Doce for high-risk NMIBC between January 2011 and December 2021. Data were computed as the median (interquartile range [IQR]) or mean (standard deviation [sd]). Cox regression analysis was performed to determine if neutrophilia, NLR, platelet counts, and PLR before instillation therapy were predictive of recurrence-free survival (RFS) and overall survival (OS). Predictive performance was estimated using Uno's C-statistic. The median (IQR) follow-up for the overall cohort was 23 (13-36) months. The mean (sd) values for NLR, PLR and platelet counts were 3.4 (2.3), 142.2 (85.5), and 225.2 (75.1) × 109/L, respectively. NLR was associated with RFS, with a hazard ratio of 1.32 (95% confidence interval CI 1.19-1.46). Concordance analysis showed that NLR had a good ability to predict RFS (C-index: 0.7, P < 0.01). The PLR and platelet count were not associated with RFS and did not predict recurrence. In terms of OS, none of these cellular inflammatory markers showed any prediction value. Pre-treatment NLR provides some predictive accuracy for RFS in high-risk BCG-naïve patients receiving Gem/Doce. Further prospective trials are needed to validate this finding.

Prognostic value of platelet levels in patients with aneurysmal Subarachnoid Hemorrhage

Pathophysiological processes following aneurysmal subarachnoid hemorrhage (aSAH) include upregulated underlying systemic inflammation, which is reflected by changes in different peripheral blood cells and their sub-populations. As inflammation is a crucial process that contributes to post-aSAH complications and clincal outcome, blood cell numbers and ratios in systemic circulation may predict the outcome and provide rapid and easy to quantify point of care biomarkers for these critically ill patients. To identify blood-derived cellular inflammatory parameters which allow a precise prediction of patient outcome after aSAH. In this single-center retrospective study, 19 whole blood-derived cellular inflammatory markers and clinical and demographic parameters for 101 aSAH patients were recorded within 24 h after aSAH. Clinical outcome was quantified with modified Rankin scale (mRS) on discharge. Proportional odds logistic regression (POLR) was used to model the patient outcome as the function of clinical parameters and inflammatory markers. The results were validated on a separate hold-out dataset (220 patients). The on-admission platelet count, mean platelet volume (MPV) and mean platelet volume to platelet ratio (MPR) were found to be significant and predictive of patient outcome on discharge. Mean platelet volume (MPV) and mean platelet volume to platelet ratio (MPR) predicted clinical outcome and may serve as easy to quantify point of care biomarker. The findings are potentially relevant for the management of aSAH.

Kinetics of Immune Cell Mobilization during Acute Aerobic Exercise in Healthy Adults.

While pre-post differences in immune cell mobilization after acute aerobic exercise are well investigated, less is known about when and to what extent immune cells are mobilized during acute aerobic exercise. This experimental trial aimed to investigate the detailed kinetics of circulating immune cells in twelve healthy adults (n=6 females) who completed a 40-min aerobic exercise bout at 60% of the participants' V̇O2peak on a bicycle ergometer. Cellular inflammation markers and sex-dependent differences in circulating immune cells were analyzed. Blood samples were taken immediately before, after warm-up, during exercise after 5 min, 10 min, 15 min, 30 min, 40 min (cessation), and 60 min post exercise. Significant increases in leukocytes (p<0.001), lymphocytes (p<0.001), neutrophils (p=0.003) and platelets (p=0.047) can be observed after 5 min of exercise. The cellular inflammation markers show significant alterations only post exercise. Significant sex differences were observed for neutrophils (p=0.049) and neutrophil-to-lymphocyte ratio (p=0.007) one hour post exercise. These results indicate that i) leukocytes are already mobilized after 5 min of moderate-to-vigorous aerobic exercise, ii) the magnitude of exercise induced leukocyte mobilization is dependent on exercise duration, iii) integrative cellular inflammation markers are only altered after exercise cessation, and iv) the observed effects might be sex-dependent.

The association between genetically predicted systemic inflammatory regulators and endometriosis: A bidirectional Mendelian randomization study.

Elevated levels of various cellular inflammatory markers have been observed in patients with endometriosis (EMs). However, a causal relationship between these markers and EMS has not been firmly established. This study aimed to assess the causality between cellular inflammatory markers and the onset of EMS using a bidirectional Mendelian randomization approach. Genetic associations for EMs were derived from the largest and most recent genome-wide association study (GWAS) involving 1937 EMS cases and 245,603 controls of European ancestry. Single nucleotide polymorphisms associated with 41 cellular cytokines and other systemic inflammatory regulators were identified from 8293 Finnish participants. Estimates were obtained using inverse-variance weighted, with sensitivity analyses conducted using MR-Egger, weighted median, and MR-PRESSO. Among the 41 systemic inflammatory regulators included in the analysis, none were associated with the risk of EMs. Elevated levels of IL-6 were associated with an increased risk of EMs (OR = 1.351, 95%CI = 1.015-1.797). Conversely, genetically predicted elevated levels of platelet-derived growth factor (PDGF-BB) were associated with a reduced risk of EMs (OR = 0.856, 95%CI = 0.742-0.987). Genetically predicted elevations in IL-6 may contribute to an increased risk of EMs, while elevated PDGF-BB levels appear protective, suggesting potential therapeutic targets for EMs. Other systemic inflammatory regulators seem unrelated to EMs risk, potentially representing downstream effects or consequences of shared factors between inflammation and EMs.

2-(Piperidin-3-yl)phthalimides reduce classical markers of cellular inflammation in LPS-challenged RAW 264.7 cells and also demonstrate potentially relevant sigma and serotonin receptor affinity in membrane preparations

Herein, we report the synthesis of new 4-amino-2-(piperidin-3-yl)isoindoline-1,3-diones and their biological evaluation in a series of in vitro experiments. The synthetic production of these materials was initiated upon the condensation of appropriate nitrophthalic acid derivatives with various 3-aminopiperidines; subsequent reduction provided the final products in moderate to good yields. Readily available chiral pool reagents facilitated entry into optically enriched samples, while the piperidine scaffold furnished a variety of amide and alkylated entries. In total, 16 candidates were produced, and their ensuing treatment in LPS-challenged RAW cells effected slight reductions in secreted TNF-α but provided more robust and dose-dependent declines in nitrite and IL-6 levels relative to basal amounts, all concurrent with maintenance of cellular viability across the concentration ranges screened. The secondary amine cohort including rac-6, (R)-7, and (S)-8 rendered the most pronounced dose-dependent reductions in nitrite and IL-6. When dosed at 30 μM, (R)-7 demonstrated the most compelling effects, with decreases of 32 % and 40 % for nitrite and IL-6, respectively. Notable reductions in the inflammatory markers were also observed for 19 which effected declines in TNF-α (14 %), nitrite (19 %), and IL-6 (11 %) when treated at 30 μM. Additionally, four representative compounds were further evaluated against numerous CNS receptors, channels, and transporters, with 6, 9, and 19 demonstrating varying degrees of nanomolar-to-low-micromolar binding to the σ-1 and σ-2 receptors and also to serotonin receptors 5HT2A, 5HT2B and 5HT3. In this regard, 6 displayed perhaps the most noteworthy affinities, with binding at σ-2 (Ki = 2.2uM), 5HT2B (Ki = 561 nM) and 5HT3 (Ki = 536 nM). Furthermore, no pronounced or dose-dependent Cereblon/DDB1 binding was observed for the screened representative compounds 6, 9, 18 and 19.

Cellular Inflammatory Markers and the Castelli Risk Indices in Women with Gestational Diabetes Mellitus

Background: The clinical importance of early identification of potential predictors of cardiovascular events in women with gestational diabetes mellitus (GDM) cannot be overemphasized. Thus, this study was aimed to determine the levels of selected cellular inflammatory markers and Castelli I and II risk indices in women with GDM. Methods: A total of 40 pregnant women, consisting of 11 women with GDM and 29 women without GDM, were randomly enrolled in this case-control study using the convenient sampling method. After participants fasted overnight, venous blood samples were taken, and the plasma lipid profiles were determined using the spectrophotometric methods. Then, differential white blood cells counting was done using a microscope. Thereafter, plasma low-density lipoprotein cholesterol (LDL-C) levels, Castelli risk index-I (CRI-I) and CRI-II, neutrophil-lymphocyte ratio (NLR), and monocyte lymphocyte ratio (MLR) were calculated using the appropriate formula. Student’s t-test, Mann Whitney U, Chi-square, and Spearman’s rho correlations were used for statistical analysis. P-values less than 0.05 were considered statistically significant.Results: Mean age, gestational weight, fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), LDL-C, and neutrophil count were significantly higher in women with GDM. Likewise with the Castelli I and II risk indices values, as well as the NLR. In contrast, HDL-C levels, lymphocytes, and monocytes counts were significantly lower in women with GDM. However, the two groups observed no difference in the MLR ) .Conclusion: Gestational diabetes mellitus is associated with dyslipidemia and systemic inflammation, which are forerunners of cardiovascular diseases.

The immunomodulating activity of trimodulin (polyvalent IgM, IgA, IgG solution): a post hoc analysis of the phase II CIGMA trial

BackgroundThe phase II CIGMA trial performed in 160 patients with severe community-acquired pneumonia (sCAP) found treatment with trimodulin (human polyvalent immunoglobulin [Ig]: ~ 23% IgM, ~ 21% IgA, ~ 56% IgG) was associated with a lower mortality in those patients with elevated baseline serum levels of C-reactive protein (CRP) and/or subnormal IgM.MethodsIn this post hoc analysis, the pharmacodynamic effects of trimodulin treatment (182.6 mg/kg/day for 5 days) were investigated on Ig replenishment, cellular markers of inflammation (absolute neutrophil [ANC] and lymphocyte [ALC] count, neutrophil-to-lymphocyte ratio [NLR]), and soluble markers of inflammation (procalcitonin [PCT] and CRP). The impact of these pharmacodynamic effects on mortality was also evaluated.ResultsCompared with healthy subjects, baseline serum levels of IgM, IgG, and ALC were significantly lower, and ANC, NLR, PCT and CRP significantly higher in sCAP patients (p < 0.0001). Low Ig concentrations increased with trimodulin. Normalization of ANC (analysis of variance [ANOVA] p = 0.016) and PCT (ANOVA p = 0.027) was more rapid with trimodulin compared with placebo. These and other effects were more evident in patients with low baseline IgM levels. Normalization of PCT and CRP levels was both steadier and faster with trimodulin treatment. In patients with low baseline ALC, trimodulin was associated with a lower 28-day all-cause mortality rate (14.5% vs 32.1% in placebo, p = 0.043) and more ventilator-free days ([VFD]; median VFD: 3.5 vs 11 in placebo, p = 0.043). These numerical differences were greater if baseline IgM was also low (low ALC, low IgM: 8.1% mortality vs 34.1% placebo, p = 0.006; 3 VFD vs 15 VFD, p = 0.009, respectively). Results were consistent in patients with high baseline CRP (low ALC, high CRP: 10.9% mortality vs 34.1% placebo, p = 0.011).ConclusionsThis post hoc pharmacodynamic analysis of a blinded phase II trial suggests that trimodulin compensates for, and more rapidly modifies, the dysregulated inflammatory response seen in sCAP patients. Trimodulin was associated with significantly lower mortality and more VFD in subgroups with high CRP and low ALC. This effect was particularly marked in patients who also had low baseline IgM values. These findings require confirmation in prospective trials.

Effect of Oleoylethanolamide-Based Dietary Supplement on Systemic Inflammation in the Development of Alimentary-Induced Obesity in Mice.

The complex effect of oleoylethanolamide-based dietary supplement (OEA-DS) was studied in a model of diet-induced obesity in mice. Physiological, biochemical, and immunohistochemical methods were used to reveal differences in the changes in the weight of experimental animals, morphological changes in the spleen tissues, and changes in the cytokine expression profile in the spleen, blood plasma, and macrophage cell culture. First, it is shown that a hypercaloric diet high in carbohydrates and cholesterol led to the development of systemic inflammation, accompanied by organ morphological changes and increased production of proinflammatory cytokines. In parallel, the use of OEA-DS reduced the intensity of cellular inflammatory reactions, accompanied by a decrease in markers of cellular inflammation and proliferation, such as CD68, Iba-1, and Ki67 in the spleen tissue, and stabilized the level of proinflammatory cytokines (IL-1β, IL-6, TNFα) both in animals and in cell culture. In addition, in the macrophage cell culture (RAW264.7), it was shown that OEA-DS also suppressed the production of reactive oxygen species and nitrites in LPS-induced inflammation. The results of this study indicate the complex action of OEA-DS in obesity, which includes a reduction of systemic inflammation.

Salsolinol improves angiotensin II‑induced myocardial fibrosis invitro via inhibition of LSD1 through regulation of the STAT3/Notch‑1 signaling pathway.

The clinical incidence of congestive heart failure (CHF) is very high and it poses a significant threat to the health of patients. The traditional Chinese medicine monomer salsolinol is widely used to treat similar symptoms of CHF. However, there have been no reports on the effect of salsolinol for the management of CHF and its effects on myocardial fibrosis. In the present study, salsolinol was used to treat angiotensin II (AngII)-induced human cardiac fibroblasts (HCFs) and cell proliferation and migration were assessed using a CCK-8, EdU staining assay and wound healing assay. Subsequently, immunofluorescence, western blotting and other techniques were used to detect indicators associated with cell fibrosis and relevant kits were used to detect markers of cellular inflammation and reactive oxygen species (ROS) production. Molecular docking analysis was used to predict the relationship between salsolinol and lysine-specific histone demethylase 1A (LSD1). Subsequently, the expression of LSD1 in the serum of CHF patients was detected by reverse transcription-quantitative PCR. Finally, LSD1 was overexpressed in cells to explore the regulatory mechanism of salsolinol in AngII-induced HFCs. Salsolinol reduced the proliferation and migration. Salsolinol reduced the expression of fibrosis marker proteins α-smooth muscle actin, Collagen I and Collagen III in a concentration-dependent manner, thereby reducing cell fibrosis. In addition, salsolinol reduced the levels of TNF-α and IL-6 in the cell supernatant and ROS production following AngII induction. Salsolinol inhibited LSD1 expression and regulated the STAT3/Notch-1 signaling pathway. Upregulation of LSD1 reversed the effects of salsolinol on AngII-induced HCFs. Salsolinol inhibited LSD1 via regulation of the STAT3/Notch-1 signaling pathway to improve Ang II-induced myocardial fibrosis in vitro.

2,4-Dinitrophenol does not exert neuro-regenerative potential in experimental autoimmune neuritis

ObjectiveWe evaluated the potential neuro-regenerative effects of the mitochondrial uncoupler 2,4-Dinitrophenol in experimental autoimmune neuritis, an animal model for an acute autoimmune neuropathy. MethodsExperimental autoimmune neuritis was induced in Lewis rats. Different concentrations of 2,4-Dinitrophenol (1 mg/kg, 0.1 mg/kg and 0.01 mg/kg) were applied during the recovery phase of the neuritis (at days 18, 22 and 26) and compared to the vehicle. Any effects were assessed through functional, electrophysiological, and morphological analysis via electron microscopy of all groups at day 30. Additional immune-histochemical analysis of inflammation markers and remyelination of the sciatic nerves were performed for the dosage of 1 mg/kg and control. ResultsNo enhancement of functional or electrophysiological recovery was observed in all 2,4-Dinitrophenol-treated groups. Cellular inflammation markers of T cells (CD3+) were comparable to control, and an increase of macrophages (IbA1+) invasion in the sciatic nerves was observed. Treatment with 2,4-Dinitrophenol reduced axonal swelling in myelinated and unmyelinated fibers with an increased production of brain-derived neurotrophic factor. ConclusionOur findings do not support the hypothesis that repurposing of the mitochondrial uncoupler 2,4-Dinitrophenol exerts functionally relevant neuro-regenerative effects in autoimmune neuritis.

Exposure to long wavelength light that improves aged mitochondrial function shifts acute cytokine expression in serum and the retina.

Aged mitochondrial function can be improved with long wavelength light exposure. This reduces cellular markers of inflammation and can improve system function from fly through to human. We have previously shown that with age there are increases in cytokine expression in mouse serum. Here, we ask what impact 670nm light has on this expression using a 40 cytokine array in blood serum and retina in C57Bl6 mice. 670nm exposure was delivered daily for a week in 12 month old mice. This shifted patterns of cytokine expression in both serum and retina inducing a selective increase. In serum examples of significant increases were found in IL (interleukins) 1α, IL-7, 10, 16, 17 along with TNF-α and CXCL (chemokines) 9 and 10. In retina the increases were again mainly in some IL's and CXCL's. A few cytokines were reduced by light exposure. Changes in serum cytokines implies that long wavelengths impact systemically even to unexposed tissues deep in the body. In the context of wider literature, increased cytokine expression may be protective. However, their upregulation by light merits further analysis as cytokines upregulation can also be negative and there are probably complex patterns of interaction in the dynamics of their expression.

Scar formation in the presence of mitomycin C and the anti-fibrotic antibody in a rabbit model of glaucoma microsurgery: A pilot study

PurposeThis study aimed to evaluate the utility of a rationally engineered antibody that directly blocks collagen fibrillogenesis to reduce scar tissue formation associated with subconjunctival glaucoma surgery. Material and methodsFourteen eyes of 7 adult rabbits underwent glaucoma filtering surgery using XEN 45 Gel Stent. The rabbits’ eyes were divided randomly into three treatment groups: (i) treated with the antibody, (ii) treated with mitomycin C, and (iii) treated with the antibody and mitomycin C. Following surgeries, the intraocular pressure and bleb appearance were evaluated in vivo. The rabbits were sacrificed 8 weeks after the surgery, and their eyes were harvested and processed for tissue analysis. Subsequently, tissue samples were analyzed microscopically for fibrotic tissue and cellular markers of inflammation. Moreover, the collagen-rich fibrotic tissue formed around the stents was analyzed using quantitative histology and infrared spectroscopy. The outcomes of this study were analyzed using the ANOVA test. ResultsThis study demonstrated no significant differences in intraocular pressure, bleb appearance, or presence of complications such as bleb leak among the treatment groups. In contrast, we observed significant differences among the subpopulations of collagen fibrils formed within scar neo-tissue. Based on the spectroscopic analyses, we determined that the relative content of mature collagen cross-links in the antibody-treated group was significantly reduced compared to other groups. ConclusionsDirect blocking of collagen fibrillogenesis with the anti-collagen antibody offers potentially beneficial effects that may reduce the negative impact of the subconjunctival scarring associated with glaucoma filtering surgery.

Platin-C containing nanoparticles: a recipe for the delivery of curcumin-cisplatin combination chemotherapeutics to mitochondria.

The success story of cisplatin spans over six decades now and yet it continues to be the key player in most chemotherapeutic regimens. Numerous efforts have been made to improve its efficacy, address its shortcomings, and overcome drug resistance. One such strategy is to develop new platinum(IV)-based prodrugs with functionally active ligands to deliver combination therapeutics. This strategy not only enables the drug candidate to access multiple drug targets but also enhances the kinetic inertness of platinum complexes and thereby ensures greater accumulation of active drugs at the target site. We report the synthesis of Platin-C, a platinum(IV)-based cisplatin prodrug tethered to the active component of ancient herbal medicine, curcumin, as one of the axial ligands. This combination complex showed improved chemotherapeutic efficacy in cisplatin resistant A2780/CP70 cell lines compared with the individual components. An amine-terminated biodegradable polymer was suitably functionalized with the triphenylphosphonium (TPP) cation to obtain a mitochondria-directed drug delivery platform. Quantification of Platin-C loading into these NPs using complementary techniques employing curcumin optical properties in high-performance liquid chromatography and platinum-based inductively coupled plasma mass spectrometry evidenced efficacious payload incorporation resulting in functional activities of both the components. Stability studies for a period of one week indicated that the NPs remain stable, enabling substantial loading and controlled release of the prodrug. The targeting nanoparticle (NP) platform was utilized to deliver Platin-C primarily in the mitochondrial network of cancer cells as monitored using confocal microscopy employing the green fluorescence of the curcumin pendant. Our studies showed that amine terminated NPs were relatively less efficient in their ability to target mitochondria despite being positively charged. This re-validated the importance of lipophilic positively charged TPP surface functionalities to successfully target cellular mitochondria. We validated the capabilities of Platin-C and its mitochondria-targeting nanoparticles towards inflicting mitochondria-directed activity in cisplatin-sensitive and cisplatin-resistant cell lines. Furthermore, our studies also demonstrated the effectiveness of Platin-C incorporated targeting NPs in attenuating cellular inflammatory markers by utilizing the curcumin component. This study advances our understanding of the cisplatin prodrug approach to combine chemotherapeutic and inflammatory effects in accessing combinatory pathways.

Red Cell Distribution Width and Absolute Lymphocyte Count Associate With Biomarkers of Inflammation and Subsequent Mortality in Rheumatoid Arthritis.

Morbidity and mortality in rheumatoid arthritis (RA) is partly mitigated by maintaining immune and hematologic homeostasis. Identification of those at risk is challenging. Red cell distribution width (RDW) and absolute lymphocyte count (ALC) associate with cardiovascular disease (CVD) and mortality in the general population, and with disease activity in RA. How these variables relate to inflammation and mortality in RA was investigated. In a retrospective single Veterans Affairs (VA) Rheumatology Clinic cohort of 327 patients with RA treated with methotrexate (MTX)+/- a tumor necrosis factor (TNF) inhibitor (TNFi), we evaluated RDW and ALC before and during therapy and in relation to subsequent mortality. Findings were validated in a national VA cohort (n = 13,914). In a subset of patients and controls, we evaluated inflammatory markers. In the local cohort, high RDW and low ALC prior to MTX treatment was associated with subsequent mortality over 10 years (both P < 0.001). The highest mortality was observed in those with both high RDW and low ALC. This remained after adjusting for age and comorbidities and was validated in the national RA cohort. In the immunology cohort, soluble and cellular inflammatory markers were higher in patients with RA than in controls. ALC correlated with age, plasma TNF receptor II, natural killer HLA-DR mean fluorescence intensity, and CD4CM/CD8CM HLA-DR/CD38%, whereas RDW associated with age and ALC. MTX initiation was followed by an increase in RDW and a decrease in ALC. TNFi therapy added to MTX resulted in an increase in ALC. RDW and ALC before disease-modifying antirheumatic drug therapy are associated with biomarkers of monocyte/macrophage inflammation and subsequent mortality. The mechanistic linkage between TNF signaling and lymphopenia found here warrants further investigation.

Fluoride exposure and blood cell markers of inflammation in children and adolescents in the United States: NHANES, 2013–2016

BackgroundIngestion of fluoride in drinking water has been shown to result in increased cellular markers of inflammation in rodent models. However, the approximately 5–10 × increase in water fluoride concentrations required in rat and mouse models to obtain plasma fluoride concentrations similar to those found in humans has made relevant comparisons of animal to human studies difficult to assess. As an increased white blood cell count (WBC) is a marker of inflammation in humans, we used available NHANES survey data to assess the associations between plasma fluoride levels in the U.S. and blood cell counts children and adolescents. MethodsMultiple linear regressions were done to determine the association of blood cell counts and plasma fluoride in publicly available NHANES survey data from the 2013–2014 and 2015–2016 cycles. Plasma fluoride concentration measurements were available only for children aged 6 to 19, inclusive, and therefore this subpopulation was used for all analyses. Covariate predictors along with plasma fluoride were age, ethnicity, gender, and Body Mass Index (BMI). ResultsPlasma fluoride was significantly positively associated with water fluoride, total WBC count, segmented neutrophils, and monocytes, and negatively associated with red blood cell count when adjusted for age, gender and BMI.ConclusionOur finding that neutrophils and monocytes are associated with higher plasma fluoride in U.S. children and adolescents is consistent with animal data showing fluoride related effects of increased inflammation. These findings suggest the importance of further studies to assess potential mechanisms that are involved in absorption and filtration of ingested fluoride, particularly in tissues and organs such as the small intestine, liver and kidney.

The Levels of the Human-β-Defensin-2 and LL-37 in the Sputum of Children with Cystic Fibrosis: A Case–control Study and Literature Review

BACKGROUND: Cystic fibrosis (CF) is a genetic disorder with an autosomal-recessive type of inheritance. Based on their host-defending and pro-inflammatory functions, antimicrobial peptides (AMPs) likely have one of the central roles in the pathogenesis of lung disease in CF. AIM: The purpose of the study was to measure the concentration of AMPs in the sputum of children with CF and evaluate any correlation with a bacterial profile of the lungs. METHODS: Lung colonization was evaluated using a culture-dependent method, sputum was utilized. A sandwich-ELISA was used to measure hBD-2 and hCAP-18/LL-37 in the sputum. RESULTS: There were 27 children enrolled in the study group, median age of inclusion was 11.4 (8.5; 14.8) years old. The control group consisted of 14 children, 11.6 (8.6; 12.6) years old. The concentration of AMPs was not correlating with participants` age (rs = −0.286, p = 0.148 – defensin hDB-2; rs = −0.084, p = 0.676 – cathelicidin hCAP-18/LL-37). The concentration of hBD-2 was from 64.01 to 813.61 pg/mL. The concentration of hCAP-18/LL-37 was from 3.24 to 35.98 ng/mL. There were significant differences in the content of AMPs on respiratory samples between study and control group (U = 976.5, p = 0.001 – for hBD-2; U = 1080.5, p &lt; 0.001). The correlation between current infection Pseudomonas aeruginosa and concentration of hBD-2 (rs = 0.167; p = 0.406) was not found. However, the presence of P. aeruginosa correlated with density of neutrophilic infiltration (rs = 0.622; p = 0.001). The concentration of hBD-2 showed direct medium correlation with total cells count (rs = 0.881, p &lt; 0.001). Correlation between current infection P. aeruginosa and concentration of hCAP-18/LL-37 (rs = 0.788; p &lt; 0.001) was observed. With increases in total cell count and relative neutrophils count, the concentration of hCAP-18/LL-37 was increased and the power of the association was medium (rs = 0.453; p = 0,018; rs = 0,592; p = 0,001). The correlation between concentrations of hBD-2 and hCAP-18/LL-37 (rs = 0.316, p &gt; 0.1) was not found. CONCLUSIONS: Measured AMPs correlated with cellular inflammatory markers and, probably, their overexpression is dedicated to stimulating a cellular component of innate immune response; there was no correlation between bacterial colonization of lungs and levels of hBD-2, so our findings sustain that P. aeruginosa is a leading but non-single contributor to persistent local inflammation in polymicrobial lungs.

Thionated aminofluorophthalimides reduce classical markers of cellular inflammation in LPS-challenged RAW 264.7 cells

Herein, we present the synthesis of several fluorinated pomalidomide derivatives and their thionated counterparts with subsequent biological evaluation against classical markers of cellular inflammation. Treatment in LPS-challenged cells effected varying reductions in levels of secreted TNF-α and nitrite relative to basal amounts. While arene fluorination and thioamidation had marginal and sporadic effects on TNF-α production, specific 7-position fluorination combined with subsequent increases in carbonyl thionation produced compounds 11, 14, and 15 which demonstrated corresponding and escalating anti-nitrite activities concurrent with minimal cellular toxicity. In this regard, compound 15 displayed roughly 96 % cell viability combined with a 65 % drop in nitrite production when supplied to RAW cells challenged with 60 ng/mL LPS. When a focused family of fluorinated isomers were directly compared, the analogous 5-fluorinated isomer 17 displayed comparable minimal toxicity but markedly less anti-nitrite activity versus 15 in RAW cells challenged with 70 ng/mL LPS. Compound 15 was subsequently screened in human liver microsomes for preliminary Phase 1 analysis where it demonstrated heightened stability relative to its non-fluorinated counterpart 3,6′-dithiopomalidomide 4, a result in line with the expected metabolic fortitude provided by fluorination at the sensitive pomalidomide 7-position.

Genotypes and Variants of BKPyV in Organ Donors after Brain Death.

Kidney transplantation from a donor with latent BKPyV might be the cause of serious complications, such as BK virus-associated nephropathy. The aim of the study was to determine the prevalence of BKPyV infection in donors after brain death (DBDs), to analyse the molecular variation of BKPyV and to compare clinical and inflammation parameters of DBDs infected with various genotypes of BKPyV. BKPyV was investigated in blood and urine samples of 103 DBDs using PCR followed by sequencing and bioinformatic analysis, and the viral load was assessed by qPCR. Clinical parameters, including cellular markers of inflammation were assessed. The results confirm high prevalence of BKPyV (48%),and genotype IV (49%) over genotype I (43%) and the co-infection with genotypes I and IV in 8.2%. Viral load ranged from 102 to 107 copies/mL, with an average of 1.92 × 106 copies/mL. No specific markers for BKPyV infection were detected among the parameters tested. Infection with genotype I may be associated with the adverse impact on thekidney function, while infection with genotype IV was associated with the anemia Not only the viral load but also the genotype of BKPyV may have an impact on the course of infection.