Serum biomarker levels in smokers and non-smokers following periodontal therapy. A prospective cohort study.

BACKGROUND: To compare presence and levels of serum cytokines in smokers and non-smokers with periodontitis following periodontal therapy. METHODS: Thirty heavy smokers and 30 non-smokers with stage III or IV periodontitis were included in this prospective cohort study. Clinical data and blood serum were collected at baseline (T0), after step I-III (T1), and after 12 months step IV periodontal therapy (T2). Cytokine IL-1ß, IL-6, IL-8, TNF-α, IL-10, and IP-10 levels were measured using multiplex kit Bio-Plex Human Pro™ Assay. Linear regression models with cluster robust variance estimates to adjust for repeated observations were used to test intra- and intergroup levels for each marker, IL-6 and IL-8 defined as primary outcomes. RESULTS: Clinical outcomes improved in both groups following therapy (p < 0.05). IL-6 levels increased with 75.0% from T0-T2 among smokers (p = 0.004). No significant intra- or intergroup differences were observed for IL-8. Higher levels of TNF-α (44.1%) and IL-10 (50.6%) were detected in smokers compared with non-smokers at T1 (p = 0.007 and p = 0.037, respectively). From T1-T2, differences in mean change over time for levels of TNF-α and IL-10 were observed in smokers compared with non-smokers (p = 0.005 and p = 0.008, respectively). CONCLUSION: Upregulated levels of serum cytokines in smokers indicate a systemic effect of smoking following periodontal therapy. Differences in cytokine levels between smokers and non-smokers demonstrate a smoking induced modulation of specific systemic immunological responses in patients with severe periodontitis.

Bioactive adrenomedullin and interleukin-6 in COVID-19: potential biomarkers of acute kidney injury and critical illness.

BACKGROUND: The aim of this study was to investigate whether bioactive adrenomedullin (bio-ADM) and interleukin-6 (IL-6) are related to acute kidney injury (AKI) and severe illness in COVID-19 patients. METHODS: 153 patients with COVID-19 admitted to the emergency department (ED) were included. Blood samples were collected from each patient at admission. Bio-ADM and IL-6, as well as DPP3 and routinely measured markers were evaluated regarding the endpoints AKI (22/128 hospitalized patients) and a composite endpoint of admission to intensive care unit and/or in-hospital death (n = 26/153 patients). RESULTS: Bio-ADM and IL-6 were significantly elevated in COVID-19 patients with AKI compared to COVID-19 patients without AKI (each p < 0.001). According to ROC analyses IL-6 and bio-ADM had the largest AUC (0.84 and 0.81) regarding the detection of AKI. Furthermore, bio-ADM and IL-6 were significantly elevated in COVID-19 patients reaching the composite endpoint (each p < 0.001). Regarding the composite endpoint ROC analysis showed an AUC of 0.89 for IL-6 and 0.83 for bio-ADM in COVID-19 patients. In the multivariable logistic model bio-ADM and IL-6 presented as independent significant predictors regarding both endpoints AKI and the composite endpoint in COVID-19 patients (as well as creatinine regarding the composite endpoint; each p < 0.05), opposite to leukocytes, C-reactive protein (CRP) and dipeptidyl peptidase 3 (DPP3; each p = n.s.). CONCLUSION: Elevated levels of bio-ADM and IL-6 are associated with AKI and critical illness in patients with COVID-19. Therefore, both biomarkers may be potential tools in risk stratification in COVID-19 patients at presentation in the ED.

C-Reactive Protein, Interleukin-6, and Vascular Recurrence According to Stroke Subtype: An Individual Participant Data Meta-Analysis

BACKGROUND AND OBJECTIVES: Anti-inflammatory therapies reduce major adverse cardiovascular events (MACE) in coronary artery disease but remain unproven after stroke. Establishing the subtype-specific association between inflammatory markers and recurrence risk is essential for optimal selection of patients in randomized trials (RCTs) of anti-inflammatory therapies for secondary stroke prevention. METHODS: Using individual participant data (IPD) identified from a systematic review, we analyzed the association between high-sensitivity C-reactive protein, interleukin-6 (IL-6), and vascular recurrence after ischemic stroke or transient ischemic attack. The prespecified coprimary end points were (1) any recurrent MACE (first major coronary event, recurrent stroke, or vascular death) and (2) any recurrent stroke (ischemic, hemorrhagic, or unspecified) after sample measurement. Analyses were performed stratified by stroke mechanism, per quarter and per biomarker unit increase after loge transformation. We then did study-level meta-analysis with comparable published studies not providing IPD. Preferred Reporting Items for Systematic Review and Meta-Analyses IPD guidelines were followed. RESULTS: IPD was obtained from 10 studies (8,420 patients). After adjustment for vascular risk factors and statins/antithrombotic therapy, IL-6 was associated with recurrent MACE in stroke caused by large artery atherosclerosis (LAA) (risk ratio [RR] 2.30, 95% CI 1.21-4.36, p = 0.01), stroke of undetermined cause (UND) (RR 1.78, 1.19-2.66, p = 0.005), and small vessel occlusion (SVO) (RR 1.71, 0.99-2.96, p = 0.053) (quarter 4 [Q4] vs quarter 1 [Q1]). No association was observed for stroke due to cardioembolism or other determined cause. Similar results were seen for recurrent stroke and when analyzed per loge unit increase for MACE (LAA, RR 1.26 [1.06-1.50], p = 0.009; SVO, RR 1.22 [1.01-1.47], p = 0.04; UND, RR 1.18 [1.04-1.34], p = 0.01). High-sensitivity CRP was associated with recurrent MACE in UND stroke only (Q4 vs Q1 RR 1.45 [1.04-2.03], p = 0.03). Findings were consistent on study-level meta-analysis of the IPD results with 2 other comparable studies (20,136 patients). DISCUSSION: Our data provide new evidence for the selection of patients in future RCTs of anti-inflammatory therapy in stroke due to large artery atherosclerosis, small vessel occlusion, and undetermined etiology according to inflammatory marker profile.

Household air pollution and pneumococcal density related to nasopharyngeal inflammation in mothers and children in Ethiopia: A cross-sectional study.

BACKGROUND: Three billion people in low- and middle-income countries are exposed to household air pollution as they use biomass fuel for cooking. We investigated the associations between solid fuel use and nasopharyngeal (NP) inflammation, as well as the associations between high pneumococcal density and NP inflammation, in mothers and children in rural and urban Ethiopia. MATERIALS AND METHODS: Sixty pairs of mothers (median age, 30 years; range, 19-45 years) with a child (median age, 9 months; range, 1-24 months) were included from rural Butajira (n = 30) and urban Addis Ababa (n = 30) in Ethiopia. The cohort was randomly selected from a previous study of 545 mother/child pairs included 2016. Questionnaire-based data were collected which included fuel type used (solid: wood, charcoal, dung or crop waste; cleaner: electricity, liquefied petroleum gas). Nasopharyngeal (NP) samples were collected from all mothers and children and analyzed for the levels of 18 cytokines using a Luminex immunoassay. Pneumococcal DNA densities were measured by a real-time multiplex PCR and a high pneumococcal density was defined as a cyclic threshold (Ct) value ≤ 30. RESULTS: Mothers from rural areas had higher median CXCL8 levels in NP secretions than those from urban areas (8000 versus 1900 pg/mL; p < 0.01), while rural children had slightly higher IL-10 levels than those from the urban area (26 vs 13 pg/mL; p = 0.04). No associations between fuel type and cytokine levels were found. However, a high pneumococcal density was associated with higher levels of cytokines in both mothers (CCL4, CXCL8, IL-1ß, IL-6 and VEGF-A) and children (CCL4, CXCL8, IL-1ß, IL-6 and IL-18). CONCLUSIONS: No significant associations were found between solid fuel use and NP inflammation in Ethiopian mothers and children, but the inflammatory activity was higher in individuals living in the rural compared to the urban area. In addition, high cytokine levels were associated with high pneumococcal density in both mothers and children, indicating a significant impact of NP pathogens on inflammatory mediator levels in upper airways.

The biology of hope: Inflammatory and neuroendocrine profiles in ovarian cancer patients.

INTRODUCTION: Although the concept of hope is highly relevant for cancer patients, little is known about its association with cancer-relevant biomarkers. Here we examined how hope was related to diurnal cortisol and interleukin-6 (IL-6), a pro-inflammatory cytokine previously associated with tumor biology and survival in ovarian cancer. Secondly, we examined whether hope and hopelessness are distinctly associated with these biomarkers. METHOD: Participants were 292 high-grade ovarian cancer patients who completed surveys and provided saliva samples 4x/daily for 3 days pre-surgery to assess diurnal cortisol. Blood (pre-surgery) and ascites were assessed for IL-6. Hope and hopelessness were assessed using standardized survey items from established scales (Center for Epidemiological Studies Depression Scale; Profile of Mood States, Functional Assessment of Cancer Therapy). Two hopeless items were z-scored and combined into a composite for analysis. Regression models related these variables to nocturnal cortisol, cortisol slope, plasma and ascites IL-6, adjusting for cancer stage, BMI, age, and depression. RESULTS: Greater hope was significantly related to a steeper cortisol slope, ß = -0.193, p = 0.046, and lower night cortisol, ß = -0.227, p = 0.018, plasma IL-6, ß = -0.142, p = 0.033, and ascites IL-6, ß = -0.290, p = 0.002. Secondary analyses including both hope and hopelessness showed similar patterns, with distinct relationships of hope with significantly lower nocturnal cortisol ß = -0.233,p = 0.017 and ascites IL-6, ß = -0.282,p = 0.003, and between hopelessness and a flatter cortisol slope, ß = 0.211, p = 0.031. CONCLUSIONS: These data suggest a biological signature of hope associated with less inflammation and more normalized diurnal cortisol in ovarian cancer. These findings have potential clinical utility but need replication with more diverse samples and validated assessments of hope.

Preterm Delivery in Obese Mothers Predicts Tumor Necrosis Factor-α Levels in Breast Milk.

Background: Breast milk (BM) is a nutritive fluid that is rich in bioactive components such as hormones and cytokines that can shape the newborn's feeding habits and program the newborn's immature immune system. BM components can change under different scenarios that include maternal body mass index (BMI) and premature birth. This study aimed to study the interaction of premature status or maternal obesity on the hormonal and cytokine profile in BM according to the sex of the offspring. Materials and Methods: We recruited 31 women with preterm births from the Centro de Alta Especialidad Dr. Rafael Lucio in Mexico. Luminex multiplexing assay was used for quantifying cytokine profile of monocyte chemoattractant protein-1, tumor necrosis factor (TNF)-α, interferon-γ, interleukin (IL)1-ß, IL-2, IL-4, IL-6, IL-7, and hormones insulin, ghrelin, leptin, and glucagon in mature BM samples. Biological modeling was performed to predict the interaction between cytokines and hormones, maternal BMI status, infant birth sex, parity, and gestational age. Results: BM multiplex analysis showed positive correlations for TNF-α and increasing prematurity and for higher maternal BMI and IL-2, IL-4, and IL-6 cytokines. Multiple regression models identified an interaction between maternal BMI and gestational weeks in male infants that is associated to TNF-α accumulation in BM. Biological modeling predicts that preterm delivery in mothers with obesity modulates TNF- α levels in mature BM of women with male offspring. Conclusion: Prematurity and obesity modify BM's immune profile. TNF- α expression increases as prematurity increases, and maternal BMI correlates positively with increases in IL-2, IL-6, and IL-4. Our multiple regression model also shows that maternal BMI and gestational weeks in male infants predict TNF-α.

Obesity Is Associated with a Weakened Gingival Inflammatory Cytokine Response.

Background and Objectives: An obesity-related elevated body mass index (BMI) across life is associated with chronic low-grade inflammation and increased levels of C-reactive protein (CRP) in blood. CRP is a marker and promoter of inflammation. The objectives of this study were to examine the effect of obesity on the relationship between peripheral and gingival CRP levels and to examine the effects of gingival CRP levels on gingival fluid inflammatory cytokines in periodontitis-resistant obese individuals. Materials and Methods: Thirty-nine participants in good periodontal health were recruited. Twenty patients were classified as lean and nineteen as obese based on their BMI levels. A thorough periodontal assessment was carried out. Gingival crevicular fluid (GCF) and blood samples were collected. Both GCF and blood samples were analyzed for interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-17A (IL-17A), and CRP. Results: GCF CRP levels were significantly higher in the obese than in the lean individuals. No statistically significant differences were noted between the two groups in either GCF or blood in terms of any of the inflammatory cytokine levels. IL-17A was not detected in the GCF of most subjects in both groups. GCF CRP levels were positively associated with blood CRP levels, and the association tended to be stronger in the obese individuals. GCF CRP showed no associations with GCF IL-10 in both groups. Although GCF CRP levels were positively associated with multiple GCF inflammatory cytokines (e.g., IL-1ß, IL-6, IL-8, and TNF-α) in all subjects, the associations tended to be weaker in the obese individuals (e.g., IL-1ß, IL-6, and TNF-α). Furthermore, the levels of the GCF inflammatory cytokines IL-6 and TNF-α were decreased in the obese individuals. Conclusions: Obesity unfavorably influences the relationship between blood and GCF CRP levels and promotes increased CRP levels in GCF. Collectively, the findings suggest a weakened inflammatory cytokine response in the gingival tissues of obese individuals.

Role of selected salivary inflammatory cytokines in the diagnosis and prognosis of oral squamous cell carcinoma. A Systematic Review and Meta-analysis

Background: Oral squamous cell carcinoma (OSCC) is gradually increasing its incidence in our society. Unfortunately, this entity is diagnosed at an advanced stage in most patients, a fact that implies greater difficulty in its treatment and a worse prognosis. This systematic review aims to assess whether the cytokines IL-6, IL-8 and TNF-α are potential salivary biomarkers that allow early diagnosis of cancer. Material and methods: An electronic search was performed in three databases (Pubmed, Scopus and Web of Science). We used the following keywords: "salivary cytokines", "saliva cytokines", "salivary interleukins", "biomarkers", "oral squamous cell carcinoma" and "diagnosis", combined with the Boolean operators "AND" and "OR". Results: 128 publications were found and finally 23 articles were included in the review and 15 in the meta-analysis. It has been observed that the majority of OSCC patients express higher salivary concentrations of IL-6, IL-8 and TNF-α compared to the control (CL) and premalignant lesion (OPML) groups. It has also been observed that the different premalignant lesions do not have statistically significant differences in the salivary concentration of the cytokines, and on the other hand, differences have been observed between the different TNM stages. The meta-analysis has shown that the difference in concentration of IL-6, IL-8 and TNF-α is statistically significant between the CL group and the OSCC, and also between the CL group and OPML. Conclusions: There is sufficient evidence to affirm that IL-6, IL-8 and TNF-α are useful salivary cytokines in the early diagnosis and prognosis of OSCC. Although future studies are necessary to establish greater reliability of these biomarkers and thus be able to develop a valid diagnostic test. (AU)

Can M-30, M-65, and IL-6 serum levels be useful markers in the diagnosis of preeclampsia and gestational diabetes?

OBJECTIVE: We aimed to evaluate the maternal and fetal serum M-30, M-65 and IL-6 levels in preeclampsia and gestational diabetes mellitus (GDM) in both maternal and cord blood. PATIENTS AND METHODS: Women with preeclampsia (n=30), GDM (n=30), and uncomplicated pregnancy (n=28) were evaluated in a cross-sectional study. After clamping during delivery, the serum M-30, M-65, and IL-6 levels were measured in both maternal venous blood and cord blood. RESULTS: The serum M-30, M-65, and IL-6 levels were significantly higher in preeclampsia and GDM patients' maternal blood and cord blood samples compared to the control group. In the preeclampsia group, M-65 was significantly higher in cord blood compared with the level in maternal serum, but there was no significant difference between the GDM and control groups. The control group's IL-6 level in cord blood was statistically significantly lower than the other groups. Although the M-30 value in both maternal and cord blood was statistically lower in the control group than in the GDM group, there was no significant difference between the two groups when compared to the preeclampsia group. CONCLUSIONS: M-30 and M-65 molecules appear to have the potential to serve as biochemical markers in placental diseases, particularly preeclampsia and gestational diabetes. Due to the insufficient sample sizes, more research is needed.

Atomic-precise Pt2Cu4 cluster-based fluorescent sensor for rapid interleukin-6 detection.

Levonorgestrel protected Pt2Cu4 clusters were assembled with a polymer to prepare nanobeads (NBs) with intense red fluorescence. An immunofluorescence sensor based on Pt2Cu4NBs was established for the rapid and sensitive detection of interleukin-6 (IL-6) owing to its significance in inflammatory diseases, with a limit of detection of 42.66 pg mL-1. IL-6 spiked in serum was also accurately detected.

Volatile profiling coupled with multivariate analysis, antiproliferative and anti-inflammatory activities of rhizome essential oil of four Hedychium species from India.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Hedychium of family Zingiberaceae comprises several perennial rhizomatous species widely used in perfumery and traditional folk medicine to treat diseases related to asthma, diarrhoea, nausea, stomach disorders, inflammation and tumours. Several species of Hedychium have remained under-explored with respect to their chemical composition and biological activities. AIM OF THE STUDY: The current research aimed to explore the chemical composition and evaluate the antiproliferative and anti-inflammatory activities of rhizome essential oil from four Hedychium species (H. coccineum, H. gardnerianum, H. greenii and H. griffithianum). MATERIALS AND METHODS: Compound identification was accomplished using a Clarus 580 gas chromatography system in conjunction with mass spectrometry (GC-MS). The multivariate data statistics using chemometrics (PCA, PLS-DA, sPLS-DA) and cluster analysis (Dendrogram, Heat maps, K-means) were used to compare the similarity and relationship among Hedychium metabolomes. MTT assay was employed to visualize the antiproliferative property against MCF7, HepG2 and PC3 cancerous cell lines. The toxicity of essential oils was determined using 3T3-L1 non-tumorigenic/normal cells. Lipopolysaccharide (LPS)-induced RAW 264.7 cells were used to investigate the anti-inflammatory properties of Hedychium essential oils by measuring the production of nitric oxide (NO) using the Griess reagent method. Furthermore, the levels of prostaglandin (PGE2) and pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) was assessed using the ELISA technique. RESULTS: In total, 82 compounds were identified in four targeted species of Hedychium from which 1,8-cineole (52.71%), ß-pinene (32.83%), α-pinene (19.62%), humulene epoxide II (19.86%) and humulene epoxide I (19.10%) were the major constituents. Monoterpenes (8.5-59.9%) and sesquiterpenes (2.87-54.11%) were the two class of compounds, found as the most prevalent in the extracted essential oils. The multivariate analysis classified the four Hedychium species into three different clusters. Hedychium essential oils exhibited potent antiproliferative activity against MCF7, HepG2 and PC3 cancer cell lines with IC50 values less than 150 µg/mL where H. gardnerianum exhibited the highest selective cytotoxicity against human breast and prostate adenocarcinoma cells with an IC50 value of 44.04 ± 1.07 µg/mL and 56.11 ± 1.44 µg/mL, respectively. The essential oils on normal (3T3-L1) cells displayed no toxicity with higher IC50 values thereby concluding as safe to use for normal human health without causing any side effects. Besides, the essential oils at 100 µg/mL concentration revealed remarkable anti-inflammatory activity in LPS-activated RAW 264.7 murine macrophages by inhibiting the production of inflammatory mediators, with H. greenii exhibiting the maximum anti-inflammation response by significantly suppressing the levels of NO (84%), PGE2 (87%), TNF-α (94.3%), IL-6 (95%) and IL-1ß (85%) as compared to LPS treated group. CONCLUSION: The present findings revealed that the Hedychium species traditionally used in therapeutics could be a potential source of active compounds with antiproliferative and anti-inflammatory properties.

Pro- and anti-inflammatory cytokines and osteoclastogenesis-related factors in peri-implant diseases: systematic review and meta-analysis.

BACKGROUND: Pro- and anti-inflammatory cytokines are acknowledged, during inflammatory bone destruction, as key regulators of osteoclast and osteoblast differentiation and activity. However, evidence regarding the exact role of pro- and anti-inflammatory cytokines and osteoclastogenesis-related factors in peri-implant diseases is unclear. We aimed to execute a systematic review and meta-analysis about the pro- and anti-inflammatory cytokines and osteoclastogenesis-related factors levels in peri-implant diseases. METHODS: The focused question was elaborated to summarize the levels of pro-and anti-inflammatory cytokines and osteoclastogenesis-related factors in tissue samples (mRNA) and biofluids (protein levels) of patients with/without peri-implant diseases. Electronic searches of the PubMed, Cochrane Controlled Trials Registry, Web of Science, EMBASE, Scopus and Google scholar databases were conducted for publications up to March 2023. Meta-analysis evaluating the mediator´s levels (protein levels by ELISA) in peri-implant crevicular fluid (PICF) were made. The effect size was estimated and reported as the mean difference. The 95% confidence interval was estimated for each mediator, and the pooled effect was determined significant if two-sided p-values < 0.05 were obtained. RESULTS: Twenty-two publications were included in the systematic review (qualitative analysis), with nine of these subjected to meta-analyses (quantitative analysis). In the qualitative analysis, higher pro-inflammatory cytokines [Interleukin (IL)-1ß, IL-6] and pro-osteoclastogenic mediator [Receptor Activator of Nuclear Factor-Kappa B ligand (RANKL)] levels were observed in PICF of individuals with peri-implant diseases in comparison to healthy individuals. Higher RANKL/osteoprotegerin (OPG) ratios were observed in PICF from individuals with peri-implant diseases in comparison to healthy individuals. Meta-analysis showed higher RANKL levels in diseased groups compared to controls. CONCLUSIONS: The results showed that the levels of IL-1ß, IL-6, IL-10, and RANKL/OPG are not balanced in peri-implant disease, suggesting that these mediators are involved in the host osteo-immunoinflammatory response related to peri-implantitis.

Analysis of cytokine levels, cytological findings, and MP-DNA level in bronchoalveolar lavage fluid of children with Mycoplasma pneumoniae pneumonia.

BACKGROUND: The present study was conducted to determine the inflammatory response in the lungs of children with Mycoplasma pneumoniae pneumonia (MPP). METHODS: This study retrospectively analyzed cytokine levels, cytological findings, and M. pneumoniae (MP)-DNA level in the bronchoalveolar lavage fluid (BALF) of 96 children with MPP. The study utilized Spearman's correlation method to evaluate the contribution of BALF and blood parameters in MPP children. RESULTS: (1) A total of 96 MPP children were classified into the Low MP-DNA MPP group (BALF MP-DNA ≤ 105 copies/mL) and the High MP-DNA MPP group (BALF MP-DNA > 105 copies/mL); the Non-fever MPP group (no fever during the entire course of pneumonia) and the Fever MPP group; the Defervescence MPP group (fever had subsided at the time of bronchoscopy) and the Fervescence MPP group; and the Mild MPP group and the Severe MPP group. (2) The High MP-DNA MPP, Fever MPP, Fervescence MPP, and Severe MPP groups had higher levels of interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α) in their BALF (all p < .05). (3) The proportions of neutrophils and macrophages in the BALF of the High MP-DNA MPP and Fever MPP groups increased and decreased, respectively (all p < .05). (4) In the BALF of MPP children, MP-DNA, IL-6, IL-10, TNF-α, and interferon gamma (IFN-γ) levels positively correlated with neutrophil proportion while negatively correlated with macrophage proportion (all p < .05). (5) The MP-DNA, IL-6, IL-10, TNF-α, and IFN-γ levels in the BALF of MPP children were positively correlated with the levels of C-reactive protein, procalcitonin, lactic dehydrogenase, fibrinogen, and d-dimer, while they were negatively correlated with the albumin level (all p < .05). CONCLUSIONS: In children with MPP, the pulmonary inflammatory immune response was stronger in the High MP-DNA MPP, Fever MPP, Fervescence MPP, and Severe MPP groups. The relationship between pulmonary cytokine levels, MP-DNA load, and serum inflammatory parameters were found to be weak.

Role of selected salivary inflammatory cytokines in the diagnosis and prognosis of oral squamous cell carcinoma. A Systematic Review and Meta-analysis.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is gradually increasing its incidence in our society. Unfortunately, this entity is diagnosed at an advanced stage in most patients, a fact that implies greater difficulty in its treatment and a worse prognosis. This systematic review aims to assess whether the cytokines IL-6, IL-8 and TNF-α are potential salivary biomarkers that allow early diagnosis of cancer. MATERIAL AND METHODS: An electronic search was performed in three databases (Pubmed, Scopus and Web of Science). We used the following keywords: "salivary cytokines", "saliva cytokines", "salivary interleukins", "biomarkers", "oral squamous cell carcinoma" and "diagnosis", combined with the Boolean operators "AND" and "OR". RESULTS: 128 publications were found and finally 23 articles were included in the review and 15 in the meta-analysis. It has been observed that the majority of OSCC patients express higher salivary concentrations of IL-6, IL-8 and TNF-α compared to the control (CL) and premalignant lesion (OPML) groups. It has also been observed that the different premalignant lesions do not have statistically significant differences in the salivary concentration of the cytokines, and on the other hand, differences have been observed between the different TNM stages. The meta-analysis has shown that the difference in concentration of IL-6, IL-8 and TNF-α is statistically significant between the CL group and the OSCC, and also between the CL group and OPML. CONCLUSIONS: There is sufficient evidence to affirm that IL-6, IL-8 and TNF-α are useful salivary cytokines in the early diagnosis and prognosis of OSCC. Although future studies are necessary to establish greater reliability of these biomarkers and thus be able to develop a valid diagnostic test.

Lipid metabolites, interleukin-6 and oxidative stress markers in follicular fluid and their association with serum concentrations in mares.

The application of trans-vaginal ovum pick up (OPU) and intracytoplasmic sperm injection (ICSI) is well established for commercial in vitro embryo production in horses. These assisted reproductive techniques are especially applied during the non-breeding season of the mare. However, little is known about how the health of the oocyte donor may affect the biochemical composition of the follicular fluid (FF) in small and medium-sized follicles routinely aspirated during OPU. This study aimed to investigate associations between systemic and FF concentrations of interleukin-6 (IL-6), total cholesterol, triglycerides, non-esterified fatty acids (NEFA), reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), and oxidative stress index (OSI) during the non-breeding season in mares. At the slaughterhouse, serum and FF of small (5-10 mm in diameter), medium (> 10-20 mm in diameter), and large (> 20-30 mm in diameter) follicles were sampled from 12 healthy mares. There was a strong positive association (P < 0.01) between the concentration of IL-6 in serum and those measured in small (r = 0.846), medium (r = 0.999), and large (r = 0.996) follicles. Serum concentrations of NEFA were positively correlated (P < 0.05) with those measured in small (r = 0.726), medium (r = 0.720), and large (r = 0.974) follicles. Values of total cholesterol and OSI in serum and medium follicles were significantly associated (r = 0.736 and r = 0.696, respectively). The serum concentrations of all lipid metabolites were markedly higher than those measured in FF of small- and medium-sized follicles. Values of IL-6 and OSI did not change significantly between serum and all follicle classes (P ≥ 0.05). To conclude, changes in the blood composition associated with inflammation, oxidative stress, and disturbed lipid metabolism of mares may lead to an inadequate oocyte microenvironment, which could affect oocyte quality and the success rate of OPU/ICSI programs. Further research should indicate whether these changes may ultimately affect in vitro oocyte developmental capacity and subsequent embryo quality.

HPLC Analysis of Polyphenols Derived from Hungarian Aszú from Tokaj Wine Region and Its Effect on Inflammation in an In Vitro Model System of Endothelial Cells.

Many studies have been published in recent years regarding the fact that moderate wine consumption, as a part of a balanced diet can have a beneficial effect on human health. The biologically active components of wine continue to be the subject of intense research today. In this study, the bioactive molecules of Hungarian aszú from the Tokaj wine region were analyzed using high-performance liquid chromatography (HPLC) and investigated in an in vitro model system of endothelial cells induced by bacterial-derived lipopolysaccharide. The HPLC measurements were performed on a reversed phased column with gradient elution. The non-cytotoxic concentration of the active substance was determined based on 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT)-, apoptosis, and necrosis assays. The antioxidant effect of the extract was determined by evaluating its ability to eliminate ROS. The expressions of the interleukin-(IL)1α, IL1-ß, IL-6, and IL-8 pro-inflammatory cytokines and nitric oxide synthase (eNOS) at the mRNA level were evaluated using a quantitative polymerase chain reaction (qPCR). We found that the lipopolysaccharides (LPS)-induced increases in the expressions of the investigated cytokines were significantly suppressed by Hungarian aszú extract, excluding IL-6. In our experimental setup, our treatment had a positive effect on the eNOS expression, which was impaired as a result of the inflammatory manipulation. In our experimental model, the Hungarian aszú extract decreased the LPS-induced increases in the expression of the investigated cytokines and eNOS at the mRNA level, which presumably had a positive effect on the endothelial dysfunction caused by inflammation due to its strong antioxidant and anti-inflammatory effects. Collectively, this research contributes to a more thorough understanding of the bioactive molecules of aszú from the Tokaj wine region.

Evidence for the participation of CHCHD2/MNRR1, a mitochondrial protein, in spontaneous labor at term and in preterm labor with intra-amniotic infection.

OBJECTIVE: Intra-amniotic inflammation (IAI), associated with either microbe (infection) or danger signals (sterile), plays a major role in the pathophysiology of preterm labor and delivery. Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 2 (CHCHD2) [also known as Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1)], a mitochondrial protein involved in oxidative phosphorylation and cell survival, is capable of sensing tissue hypoxia and inflammatory signaling. The ability to maintain an appropriate energy balance at the cellular level while adapting to environmental stress is essential for the survival of an organism. Mitochondrial dysfunction has been observed in acute systemic inflammatory conditions, such as sepsis, and is proposed to be involved in sepsis-induced multi-organ failure. The purpose of this study was to determine the amniotic fluid concentrations of CHCHD2/MNRR1 in pregnant women, women at term in labor, and those in preterm labor (PTL) with and without IAI. METHODS: This cross-sectional study comprised patients allocated to the following groups: (1) mid-trimester (n = 16); (2) term in labor (n = 37); (3) term not in labor (n = 22); (4) PTL without IAI who delivered at term (n = 25); (5) PTL without IAI who delivered preterm (n = 47); and (6) PTL with IAI who delivered preterm (n = 53). Diagnosis of IAI (amniotic fluid interleukin-6 concentration ≥2.6 ng/mL) included cases associated with microbial invasion of the amniotic cavity and those of sterile nature (absence of detectable bacteria, using culture and molecular microbiology techniques). Amniotic fluid and maternal plasma CHCHD2/MNRR1 concentrations were determined with a validated and sensitive immunoassay. RESULTS: (1) CHCHD2/MNRR1 was detectable in all amniotic fluid samples and women at term without labor had a higher amniotic fluid CHCHD2/MNRR1 concentration than those in the mid-trimester (p = 0.003); (2) the amniotic fluid concentration of CHCHD2/MNRR1 in women at term in labor was higher than that in women at term without labor (p = 0.01); (3) women with PTL and IAI had a higher amniotic fluid CHCHD2/MNRR1 concentration than those without IAI, either with preterm (p < 0.001) or term delivery (p = 0.01); (4) women with microbial-associated IAI had a higher amniotic fluid CHCHD2/MNRR1 concentration than those with sterile IAI (p < 0.001); (5) among women with PTL and IAI, the amniotic fluid concentration of CHCHD2/MNRR1 correlated with that of interleukin-6 (Spearman's Rho = 0.7; p < 0.001); and (6) no correlation was observed between amniotic fluid and maternal plasma CHCHD2/MNRR1 concentrations among women with PTL. CONCLUSION: CHCHD2/MNRR1 is a physiological constituent of human amniotic fluid in normal pregnancy, and the amniotic concentration of this mitochondrial protein increases during pregnancy, labor at term, and preterm labor with intra-amniotic infection. Hence, CHCHD2/MNRR1 may be released into the amniotic cavity by dysfunctional mitochondria during microbial-associated IAI.

Dietary fiber intake and fecal short-chain fatty acid concentrations are associated with lower plasma lipopolysaccharide-binding protein and inflammation.

Consuming adequate dietary fiber is a promising strategy for reducing systemic inflammation. The objective was to evaluate relationships between dietary fiber intake, markers of metabolic endotoxemia, and systemic inflammation in adults. This was a cross-sectional study of 129 healthy participants (age 33.6 ± 6.1 yr, BMI 30.5 ± 6.9 kg/m2). Dietary fiber intake was assessed by food frequency questionnaire. Adiposity was measured using dual-energy X-ray absorptiometry (DXA). Fecal short-chain fatty acids (SCFA) were quantified using gas chromatography-mass spectrometry. Fecal microbiota sequence data (V4 region, 16S rRNA gene) were analyzed using DADA2 and QIIME2. Inflammatory cytokines were assessed with enzyme-linked immunosorbent assays; flow cytometry was conducted for monocyte surface marker quantification. Bivariate correlations and generalized step-wise linear modeling were used for statistical analyses. Plasma C-reactive protein (CRP) and interleukin (IL)-6 concentrations were positively related to whole body (CRP r = 0.45, P = <0.0001; IL-6 r = 0.34, P = 0.0002) and visceral adiposity (CRP r = 0.33, P = 0.0003; IL-6 r = 0.38, P = 0.0002). Plasma lipopolysaccharide-binding protein (LBP) concentrations were inversely related to dietary fiber intake (r = -0.22, P = 0.03) and fecal SCFA (acetate r = -0.25, P = 0.01; propionate r = -0.28, P = 0.003; butyrate r = -0.23, P = 0.02). Whole body adiposity, dietary fiber, and fecal SCFA were the most predictive of plasma LBS-BP concentrations. Novel findings included associations between dietary fiber intake, the gastrointestinal microbiota, and systemic inflammation.NEW & NOTEWORTHY Dietary fiber intake may reduce the inflammation associated with obesity and metabolic disease. Our cross-sectional analysis revealed that dietary fiber intake and fecal short-chain fatty acids are inversely associated with lipopolysaccharide-binding protein, a marker of systemic inflammation. In addition, plasma interleukin-6 and C-reactive protein were positively related to markers of adiposity.

Structural characterization of a heteropolysaccharide from the fruit of Crataegus pinnatifida and its bioactivity on the gut microbiota of immunocompromised mice.

Crataegus pinnatifida is a common food in China, Europe and North America. In order to confirm polysaccharide was the material basis for C. pinnatifida to exert immune regulation. A polysaccharide (CPP) with a molecular weight of 13.58 kDa was isolated from C. pinnatifida. The structure of CPP was determined to be a backbone composed of â†’ 3,5)-α-l-Araf-(1→, with two branches consisting of â†’ 4)-α-d-Galp-(1 â†’ and â†’ 5)-α-l-Araf-(1→, with α-l-Araf and α-d-Manp as the terminal unit. CPP (10 âˆ¼ 500 µg/mL) could promote the secretion of nitric oxide, interleukin-2, interleukin-6 and tumor necrosis factor-α in vitro. CPP could significantly restore the body weight of immunosuppressive mice and improve the immune organ index and interleukin-2, interleukin-6, and tumor necrosis factor-α secretion. In addition, CPP increased the abundance of Bacteroidetes and Verrucomicrobia and decreased the abundance of Proteobacteria at the phylum level. So CPP can regulate the gut microbiota and play an important role in immune regulation.

Role of ubiquitin-specific protease 5 in the inflammatory response of chronic periodontitis.

BACKGROUND: The systemic inflammatory response caused by chronic periodontitis is a risk factor for multiple diseases. Ubiquitin-specific protease 5 (USP5) is a kind of deubiquitinase which mainly responsible for dissociating unanchored polyubiquitin. However, the functions of USP5 in chronic periodontitis have not been reported. METHODS: Chronic periodontitis patients were recruited, and their periodontal samples were collected. The levels of USP5, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) in gingival crevicular fluid were evaluated by ELISA. The expression of USP5, TNF-α, IL-6, and IL-1ß in human periodontal ligament stem cells (PDLSCs) was estimated by qRT-PCR assay. The activation of STAT3 signaling was examined by Western blot. RESULTS: USP5 was upregulated in the gingival crevicular fluid and gingival tissues of chronic periodontitis patients. USP5 expression was positively correlated with the expression of proinflammatory factors. USP5 knockdown and deubiquitinase inhibitor inhibited LPS-induced inflammatory responses in PDLSCs. Suppressing USP5 inhibited STAT3 signaling in PDLSCs. CONCLUSION: Suppression deubiquitinase USP5 inhibits the inflammatory response of chronic periodontitis by suppressing STAT3 signaling.