The aim of this study was to determine the effect of quercetin on the indicators of chronic systemic inflammation (CSI) in stable coronary artery disease (CAD).
This study included 85 patients with ...CAD, stable angina pectoris, functional class (FC) II, and heart failure (НF) 0-І. Each patient was prescribed beta-blockers, statins, and aspirin. In addition, a total of 30 patients, forming the study group received quercetin at a daily dose of 120mg for two months, while the remaining 55 patients made up the control group. The levels of cytokines, such as tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin-10 (IL-10) in serum and the expression of the inhibitor of kappa B α (IkBα) gene in blood mononuclear cells, were determined.
The increased levels of IL-1β and TNF-α, as well as a moderate increase in IL-10 levels, were detected in the serum of patients with CAD. The expression of the IkBα gene (2–δСt) did not differ significantly between the groups. Under the influence of quercetin, levels of IL-1β and TNF-α were reduced and IL-10 levels tended to decrease. In contrast, the serum levels of these cytokines did not change significantly in the control group. The administration of quercetin decreased the expression of the IkBα gene (0.0092±0.0033 against 0.0261±0.0166, р=0.003; 2–δδСt, 2.82±1.39 times) in contrast to the control group.
Quercetin showed anti-inflammatory properties in patients with CAD, indicating a decrease in transcriptional activity of the nuclear factor of transcription kappa B (NF-kB).
•Gingival CD68+/CD163 + macrophage ratio increased in chronic periodontitis.•Azithromycin decreased the CD68+/CD163 + macrophage ratio in periodontal tissues.•Azithromycin can modulate gingival ...macrophages'functional rolein periodontitis.
The growing interest in the possibilities of macrophages modulation with therapeutic purposes promotes new approaches for periodontitis treatment.
The aim of this randomized controlled open clinical study was to evaluate the early clinical and immunological effects of the long-course azithromycin as an adjunct to scaling and root planing in periodontitis.
50 patients (with stage I-III, grade A/B periodontitis) and 22 periodontally healthy volunteers as the reference group were recruited. Following scaling and root planing (SRP), the patients were randomly assigned to one of two treatment modalities: SRP only (n = 25) and adjunct azithromycin (Az) treatment (n = 25). The patients were monitored at baseline, and 30 ± 5 days after therapy. Clinical attachment loss (CAL), periodontal probing depth (PPD) and bleeding on probing (BoP) were evaluated. Secondary outcome measures included mean changes in single-positive CD68 + and CD163 + macrophages (Mφs) density and ratio, evaluated by immunohistochemistry, and IL1-β, IL-6, IL-10, TGF-β levels, detected by ELISA.
At 1 month both groups showed significant improvements of CAL, PPD and BoP, without significant added benefit in terms of CAL, PPD and BoP of Az. But Az increased the density of CD68 + and CD163 + Mφs (P < 0.0001), decreased the CD68+/CD163 + ratio (P = 0.043), decreased IL-1β (P < 0.01), IL-6 (P < 0.001) levels, and increased IL-10 (P < 0.0001) and TGF-β (P < 0.001) levels compared to SRP and periodontitis at baseline.
The long course of Az demonstrated modulation of CD68 + and CD163 + Mφs towards M2 polarization, which may play a significant role in achieving favorable long-term treatment outcomes. ClinicalTrials.gov
Liraglutide (L) is the analogue of human glucagon-like peptide 1 which stimulates glucose-dependent insulin secretion and can modify the level of inflammatory biomarkers. L can influence NF-kB ...inflammatory cascade, but the mechanisms of anti-inflammatory activities of L remain to be determined. In animal models L influenced an activity of Sirtuin 1(SIRT1). Moreover, recent evidences strongly suggest that SIRT1 up-regulation may serve as a potent therapeutic approach against development and progression of diabetic complications. The aim of this study was to investigate L effects directed on the pro-inflammatory NF-kB pathway and expression of SIRT1 in obese patients with type 2 diabetes mellitus (DM).
15 obese patients with type 2 diabetes were studied, all using metformin (1-2 g/day) and sulfonylurea (glimiperide). All patients received L 1.2 mg daily add-on to stable therapy for 6 weeks. Blood samples were collected before, 6 weeks after start of treatment and after an overnight fast 6 weeks after stopping L, mononuclear cells (MNC) were isolated. The mRNA expressions of TNF-α, TLR2, TLR4, NOD1, IL-2 and SIRT1 were measured in MNC by RT-PCR. Ceruloplasmin concentration was measured in plasma by photometric method.
In this add-on pilot clinical investigation we received new data that L can inhibit proinflammatory NF-kB pathway by increased SIRT1 expression in obese patients with type 2 DM improving metabolic profile. The mRNA expression in MNC of TNF-α, IkB, TLR2, TLR4, and plasma ceruloplasmin fell after 6 weeks of L. Expressions of IL-2 and NOD-1 were stable. There was a significant increase of SIRT1 mRNA expression. The mRNA expression in MNC of TNF-α, IkB, TLR2, TLR4, NOD1, SIRT1 and ceruloplasmin concentrations did not reverse to baseline levels after 6 weeks stopping of L treatment. IL-2 expression decreased in comparison with basic level.
L has a potent anti-inflammatory effect as do GLP-1 agonists due to inhibition of NF-kB pathways and up-regulate SIRT1 expression, down-regulating pro-inflammatory factors including cytokines (TNF-α), extra- and intracellular receptors (TLR2, TLR4), and inflammation markers such as ceruloplasmin. Long lasting effects of L can be mediated by epigenetic regulation of NF-kB pathway by SIRT-1.
BackgroundWe examined the human toll and subsequent humanitarian crisis resulting from the Russian invasion of Ukraine, which began on 24 February 2022.MethodWe extracted and analysed data resulting ...from Russian military attacks on Ukrainians between 24 February and 4 August 2022. The data tracked direct deaths and injuries, damage to healthcare infrastructure and the impact on health, the destruction of residences, infrastructure, communication systems, and utility services – all of which disrupted the lives of Ukrainians.ResultsAs of 4 August 2022, 5552 civilians were killed outright and 8513 injured in Ukraine as a result of Russian attacks. Local officials estimate as many as 24 328 people were also killed in mass atrocities, with Mariupol being the largest (n=22 000) such example. Aside from wide swaths of homes, schools, roads, and bridges destroyed, hospitals and health facilities from 21 cities across Ukraine came under attack. The disruption to water, gas, electricity, and internet services also extended to affect supplies of medications and other supplies owing to destroyed facilities or production that ceased due to the war. The data also show that Ukraine saw an increase in cases of HIV/AIDS, tuberculosis, and Coronavirus (COVID-19).ConclusionsThe 2022 Russia-Ukraine War not only resulted in deaths and injuries but also impacted the lives and safety of Ukrainians through destruction of healthcare facilities and disrupted delivery of healthcare and supplies. The war is an ongoing humanitarian crisis given the continuing destruction of infrastructure and services that directly impact the well-being of human lives. The devastation, trauma and human cost of war will impact generations of Ukrainians to come.
Environmental stress can disturb the integrative functioning of the cardiovascular system and trigger a number of adaptive and/or maladaptive cell responses. Concomitant with the expanding use of ...mobile communication systems, public exposure to electromagnetic fields (EMFs) raises the question of the impact of 900 MHz EMFs on cardiovascular health. Therefore, in this study, we experimentally investigated whether 915 MHz EMF exposure influenced cardiac metabolic, antioxidant, apoptotic, and fibro-inflammatory profiles in a mouse model. Healthy mice were sham-exposed or exposed to EMF for 14 days. Western blot analysis using whole cardiac tissue lysates demonstrated that there was no significant change in the expression of oxidative phosphorylation (OXPHOS) complexes between the control and EMF-exposed mice. In addition, the myocardial expression of fibro-inflammatory cytokines, antioxidant enzymes, and apoptosis-related markers remained unchanged in the EMF-challenged hearts. Finally, the structural integrity of the cardiac tissues was preserved among the groups. These findings suggest that the apoptotic, antioxidant, metabolic, and fibro-inflammatory profiles of the heart remained stable under conditions of EMF exposure in the analyzed mice.
This study examined the influence of PPARG activation by pioglitazone (PG) on the mRNA of core clock, inflammation‐ and metabolism‐related genes in the mouse kidney medulla as well as urinary ...sodium/potassium excretion rhythms disrupted by reverse feeding. Mice were assigned to daytime feeding and nighttime feeding groups. PG 20 mg/kg was administered at 7 am or 7 pm. On day 8 of the feeding intervention, mice were killed at noon and midnight. Kidney medulla expression of Arntl, Clock, Nr1d1, Cry1, Cry2, Per1, Per2, Nfe2l2, Pparg, and Scnn1g was determined by qRT PCR. We measured urinary K+, Na+, urine volume, food, and H2O intake. The reverse feeding uncoupled the peripheral clock gene rhythm in mouse kidney tissues. It was accompanied by a decreased expression of Nfe2l2 and Pparg as well as an increased expression of Rela and Scnn1g. These changes in gene expressions concurred with an increase in urinary Na+, K+, water excretion, microcirculation disorders, and cell loss, especially in distal tubules. PG induced the restoration of diurnal core clock gene expression as well as Nfe2l2, Pparg, Scnn1g mRNA, and decreased Rela expressions, stimulating Na+ reabsorption and inhibiting K+ excretion. PG intake at 7 pm was more effective than at 7 am.
This study examined the influence of PPARG activation by pioglitazone (PG) on the mRNA of core clock, inflammation‐, and metabolism‐related genes in the mouse kidney medulla as well as urinary sodium/potassium excretion rhythms disrupted by reverse feeding. The reverse feeding induced disruption of mouse kidney diurnal expression pattern of core clock genes, increasing Rela and Scnn1g expression and urinary Na+, K+, water excretion, decreasing Nfe2l2 and Pparg expression. PG restores the diurnal core clock gene expression pattern, decreases Rela and Scnn1g expression, increases Nfe2l2 and Pparg mRNA, stimulates Na+ reabsorption, and inhibits K+ excretion.
Chronic inflammatory process is the main link in COPD pathogenesis, which causes structural changes in the respiratory tract and lungs. In overweight patients, an adipose tissue could contribute to ...activation of the inflammatory process. Therefore, it is highly important to identify potential biomarkers of inflammation for patients with COPD and obesity. The aim of this study was to investigate the role of interleukin-26 (IL-26) and evaluate the relationship between the level of systemic inflammation, lung function, and body mass index (BMI) in patients with COPD.
Eighty-three patients with COPD in the stable condition (stage 2 according to the 2016 Global Initiative for Chronic Obstructive Lung Disease recommendations), aged 40-70 years, were included in the study. All patients were divided into 2 groups: obese (n=53) (BMI - 30.0-39.9 kg/m
) and non-obese (n=30) (BMI - 18.5-24.9 kg/m
). We conducted patients' examination, spirometry, induced the sputum, determined the level of C-reactive protein (CRP), leptin in serum and IL-26 in sputum.
Obese and non-obese COPD patients had a significant increase in IL-26 compared with healthy subjects by 2.3 and 2.6 (
=0.0003). We also observed a higher level of CRP by 1.38 times (
=0.0008), compared with the rate in non-obese COPD patients, and by 1.8 times (
=0.015) higher concentration level of leptin compared with healthy subjects. The sputum IL-26 level had positive correlation with BMI, CRP, and leptin, and a negative - with forced expiratory volume in 1 second (FEV
) and FEV
/forced vital capacity. Leptin level had positive correlation with BMI and CRP, and negative with FEV
, FEV
/forced vital capacity.
Obese COPD patients had a higher level of persistent systemic inflammation than non-obese ones, which is confirmed by a significant increase of CRP and leptin in serum. The data confirm that IL-26 can be considered as a perspective marker to detect the inflammation level in lung tissue of COPD patients.
The circadian rhythm system regulates lung function as well as local and systemic inflammations. The alteration of this rhythm might be induced by a change in the eating rhythm. Peroxisome ...proliferator‐activated receptor gamma (PPARG) is a key molecule involved in circadian rhythm regulation, lung functions, and metabolic processes. We described the effect of the PPARG agonist pioglitazone (PZ) on the diurnal mRNA expression profile of core circadian clock genes (Arntl, Clock, Nr1d1, Cry1, Cry2, Per1, and Per2) and metabolism‐ and inflammation‐related genes (Nfe2l2, Pparg, Rela, and Cxcl5) in the male murine lung disrupted by reversed feeding (RF). In mice, RF disrupted the diurnal expression pattern of core clock genes. It decreased Nfe2l2 and Pparg and increased Rela and Cxcl5 expression in lung tissue. There were elevated levels of IL‐6, TNF‐alpha, total cells, macrophages, and lymphocyte counts in bronchoalveolar lavage (BAL) with a significant increase in vascular congestion and cellular infiltrates in male mouse lung tissue. Administration of PZ regained the diurnal clock gene expression, increased Nfe2l2 and Pparg expression, and reduced Rela, Cxcl5 expression and IL‐6, TNF‐alpha, and cellularity in BAL. PZ administration at 7 p.m. was more efficient than at 7 a.m.
The growing interest in the possibilities of modulating macrophages in inflammatory diseases with therapeutic purpose has prompted the development of new approaches for the treatment of ...periodontitis. This randomized add-on open preliminary clinical study evaluated the short-term effects of L-arginine or L-ornithine as an adjuvant to scaling and root planing (SRP) in patients with chronic periodontitis.
Seventy-five periodontitis patients were recruited and monitored clinically and immunologically at baseline (before SRP) and 30 ± 5 days after SRP. All patients were assigned by stratified randomization to SRP (SRP only, n = 25), Arg (SRP + L-arginine, n = 25) or Control (SRP + L-ornithine, n = 25) Group. The medicines were used according to available instructions for 10 and 15 days, respectively. During the study, all patients were on a stable diet, without changing their rations and regiments. As immunological monitoring immunohistochemical study of CD68+ and CD163 + single positive gingival macrophages for 5 patients per group in the same time-point was conducted. The data were statistically analyzed.
Reduction of periodontal pocket depth (PPD) and bleeding on probing (BoP) was observed in all groups, with significant between-group differences for BoP in the Arg Group (p < 0.0001) at 30 days. The SRP and Arg groups demonstrated nonsignificantly increased density of CD68+ and CD163 + cells. The Orn Group showed an increase in the density of CD68+ and CD163 + macrophages at intragroup (p = 0.0066 and p < 0.0001) and between-group levels (p = 0.001 and p < 0.0001), and these changes corresponded to clinical PPD and BoP reduction. In the Arg and Orn groups at 30 days, CD163 + macrophages significantly predominated over CD68+ (p = 0.013, p < 0.0001).
The use of L-arginine and L-ornithine as an adjunct to SRP promotes additional limited immunological benefit in the treatment of periodontitis. Metabolic stimulation with L-ornithine, but not L-arginine, is preferable for CD163+ Mφs subpopulation in periodontitis-affected gingiva.
CD163 + macrophage, CD68 + macrophage, Clinical trial, L-arginine, L-ornithine, Macrophages-targeted therapy, Periodontitis.
The demographic crisis that prevailed in Ukraine in recent years, the state of war as a result of the aggression of the Russian Federation, reproductive losses among women of childbearing age are one ...of the most urgent problems in modern obstetrics and gynecology. One of the most effective methods of correcting impaired reproductive function is in vitro fertilization.
is to develop a pharmacological complex for the prevention of imbalance of CD68+/CD163+ decidual macrophages in vitro fertilized women.
105 pregnant women who were divided into 3 groups took part in the study. The first group included 20 women whose pregnancy occurred and is proceeding physiologically. The second group consisted of 85 women who became pregnant as a result of in vitro fertilization, including 37 pregnant women who refused prophylactic correction of the threat of premature birth, and 48 pregnant women who received prophylactic correction of the threat of premature birth: complex prescription of vitamin D3 2000 IU orally 2 times a day, micronized progesterone 200 mg 2 times a day and l-arginine aspartate 1000 mg 4 times a day, starting from 18 to 20 weeks of pregnancy.
In women who refused prophylactic correction of the threat of premature birth, a local increase in the activity of inducible NO-synthase and concentration of tumor necrosis factor-α, and a decrease in the activity of arginase and in the level of interleukin-10 were observed in the cervical mucus. They have a lower expression of CD163+ on placental decidual macrophages and an increased expression of CD68+, which indicates a shift in the polarization of macrophages from an anti-inflammatory to a pro-inflammatory phenotype. The use of prophylactic treatment brings the studied parameters closer to the results of women in whom pregnancy occurred physiologically.
In women who became pregnant as a result of in vitro fertilization, at 28–30 weeks of pregnancy, changes specific for pro-inflammatory phenotype of decidual macrophages were observed. Complex administration of vitamin D3, micronized progesterone and l-arginine aspartate lead to restoration of anti-inflammatory phenotype of decidual macrophages.
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