IL-6 Protein Research Articles

Anti-inflammatory effects of eupatilin on Helicobacter pylori CagA-induced gastric inflammation.

Eupatilin, a flavone isolated from Artemisia species, exerts anti-inflammatory, anti-oxidative, and anti-neoplastic activities. However, the effects of eupatilin on H. pylori-associated gastritis remain unclear. Thus, this study aimed to investigate the anti-inflammatory effects of eupatilin on gastric epithelial cells infected with cytotoxin-associated gene A (CagA)-positive Helicobacter pylori. AGS human gastric carcinoma cells were infected with a CagA-positive H. pylori strain and then treated with 10, 50, or 100 ng of eupatilin. After 24 h, the expression levels of CagA, phosphoinositide 3-kinase 1 (PI3K), nuclear factor (NF)-κB, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α in the cell lysates were measured using western blotting, and the mRNA levels of IL-6, IL-8, and monocyte chemoattractant protein (MCP)-1 were measured using real-time polymerase chain reaction. CagA translocation into AGS cells resulted in an elongated cell morphology, which was significantly suppressed by eupatilin treatment in a dose-dependent manner. Immunofluorescence staining for anti-CagA showed that eupatilin treatment dose-dependently inhibited CagA expression in the H. pylori-infected AGS cells. H. pylori infection increased the levels of pro-inflammatory cytokines including IL-1β, TNF-α, IL-6, IL-8, and MCP-1, and eupatilin treatment significantly reduced the levels of these cytokines in a dose-dependent manner. Additionally, eupatilin treatment dose-dependently suppressed the expression of PI3K and NF-κB. Eupatilin treatment demonstrated anti-inflammatory effects on CagA-positive H. pylori-infected gastric epithelial cells by inhibiting CagA translocation, thereby suppressing the NF-κB signaling pathway. These results suggest that eupatilin plays a protective role against CagA-positive H. pylori-induced gastritis.

Evidence of Browning and Inflammation Features in Visceral Adipose Tissue of Women with Endometriosis

Patients with endometriosis tend to have a low body mass index, suggesting an inverse relationship between body fat and risk of disease. This is supported by evidence that miRNAs differentially expressed in endometriosis induce browning of pre-adipocytes in vitro. Thus, we hypothesize that endometriosis may underlie adipose tissue (AT) dysfunction and browning. Identify inflammation and browning processes in AT collected from endometriosis patients. Visceral and subcutaneous AT samples were obtained during endometriosis (n = 32) or uterine myoma (n = 14; controls) surgery. Blood catecholamines were determined by high-performance liquid chromatography while IL-6 and TGF-β levels were quantified by ELISA. Adipocyte cross-sectional areas were analyzed in H&E-stained sections by computer-assisted morphometry. Macrophages (F4/80; Galectin-3) and browning activation (UCP-1; PGC-1α) in tissues were identified by dual label immunofluorescence. Expression of inflammatory (IL-6; MCP-1; Galectin-3; CD206; TIMP1; TGF-β) and browning-related (UCP-1; PGC-1α; DIO2; CITED1; CIDEA; TMEM26; TBX1; PRDM16; PPAR-γ) molecules in AT were assessed by RT-PCR and Western blotting. Compared to controls, patients presented smaller adipocytes, especially in VAT, and lower norepinephrine levels. Serum IL-6, but not TGF-β, was increased in patients. UCP-1, PGC-1α, IL-6, and MCP-1 were upregulated in VAT from endometriosis women, which also evidenced a reduction of CD206, relative to controls. However, no differences were found in mRNA expression of IL-6, TIMP1, and TGF-β nor Galectin-3 protein levels. In SAT, protein expression remained unchanged between patients and controls. Our findings support an endometriosis' role as a pro-catabolic state along with local signals of VAT browning and inflammation.

Activation of the Innate Immune System in Brain-Dead Donors Can Be Reduced by Luminal Intestinal Preservation During Organ Procurement Surgery - A Porcine Model

Organs obtained from brain dead donors can have suboptimal outcomes. Activation of the innate immune system and translocation of intestinal bacteria could be causative. Thirty two pigs were assigned to control, brain death (BD), BD + luminal intestinal polyethylene glycol (PEG), and BD + luminal intestinal University of Wisconsin solution (UW) groups. Animals were observed for 360 min after BD before organ retrieval. 2,000 mL luminal intestinal preservation solution was instilled into the duodenum at the start of organ procurement. Repeated measurements of plasma C3a, Terminal Complement Complex (TCC), IL-8, TNF, and lipopolysaccharide binding protein were analysed by immunoassays. C3a was significantly higher in the BD groups compared to controls at 480 min after brain death. TCC was significantly higher in BD and BD + UW, but not BD + PEG, compared to controls at 480 min. TNF was significantly higher in the BD group compared to all other groups at 480 min. LPS binding protein increased following BD in all groups except BD + PEG, which at 480 min was significantly lower compared with all other groups. Brain death induced innate immune system activation was decreased by luminal preservation using PEG during organ procurement, possibly due to reduced bacterial translocation.

Recombinant expression, downstream optimization, and therapeutic evaluation of recombinant human interleukin-37 for cancer therapy.

Interleukin-37 is a cytokine with potent immunosuppressive properties that has been shown to have potential to treat autoimmune and chronic inflammatory diseases, as well as certain types of cancer. IL-37 is a 19kDa protein which interacts with proteins in receptor-dependent and receptor-independent pathways. The expression of the IL-37 protein cloned into the pET-28a vector was optimized in Rosetta 2(DE3) after comparing its expression with Rosetta-gami 2(DE3) and Rosetta 2(DE3) pLysS, which was then used for the large-scale production of IL-37. IMAC purification of IL-37 yielded > 97% pure 0.9mg/mL protein from auto-induced fermentation. The IC50 value of IL-37 was < 1µM, which was similar to that of doxorubicin, and proliferation of > 80% of all cancer cells was inhibited by 100µg/mL of IL-37 protein. IL-37 may be a promising theragnostic target for cancer due to its comparable IC50 value with that of doxorubicin.

In-silico analysis predicts disruption of normal angiogenesis as a causative factor in osteoporosis pathogenesis

Angiogenesis-osteogenesis coupling is critical for proper functioning and maintaining the health of bones. Any disruption in this coupling, associated with aging and disease, might lead to loss of bone mass. Osteoporosis (OP) is a debilitating bone metabolic disorder that affects the microarchitecture of bones, gradually leading to fracture. Computational analysis revealed that normal angiogenesis is disrupted during the progression of OP, especially postmenopausal osteoporosis (PMOP). The genes associated with OP and PMOP were retrieved from the DisGeNET database. Hub gene analysis and molecular pathway enrichment were performed via the Cytoscape plugins STRING, MCODE, CytoHubba, ClueGO and the web-based tool Enrichr. Twenty-eight (28) hub genes were identified, eight of which were transcription factors (HIF1A, JUN, TP53, ESR1, MYC, PPARG, RUNX2 and SOX9). Analysis of SNPs associated with hub genes via the gnomAD, I-Mutant2.0, MUpro, ConSurf and COACH servers revealed the substitution F201L in IL6 as the most deleterious. The IL6 protein was modeled in the SWISS-MODEL server and the substitution was analyzed via the YASARA FoldX plugin. A positive ΔΔG (1.936) of the F201L mutant indicates that the mutated structure is less stable than the wild-type structure is. Thirteen hub genes, including IL6 and the enriched molecular pathways were found to be profoundly involved in angiogenesis/endothelial function and immune signaling. Mechanical loading of bones through weight-bearing exercises can activate osteoblasts via mechanotransduction leading to increased bone formation. The present study suggests proper mechanical loading of bone as a preventive strategy for PMOP, by which angiogenesis and the immune status of the bone can be maintained. This in silico analysis could be used to understand the molecular etiology of OP and to develop novel therapeutic approaches.

Preliminary Evidence Supports that Long-Term Consumption of Higher-Protein Breakfast Promotes Higher Expression of Select miRNA Associated with Cardiometabolic Health in Adolescents

BackgroundIncreased dietary protein at breakfast promotes cardiometabolic health; however, whether these improvements occur at the molecular level is unknown. ObjectivesThe objective was to examine whether long-term consumption of breakfast, varying in protein quantity, alters the expression of circulating microRNAs (miRNAs) associated with cardiometabolic health in “breakfast-skipping” adolescents. MethodsThirty adolescents (age: 19 ± 1 y; body mass index: 25.4 ± 3 kg/m2) completed a 6-mo tightly controlled breakfast trial in which participants consumed 350 kcal normal-protein (NP, 10 g protein) or higher-protein (HP, 30 g protein) breakfasts or continued to BS for 6 mo. Fasting blood samples were collected at baseline (PRE) and 6 mo (POST) for assessment of 12 a priori circulating plasma miRNA expression levels (real-time quantitative polymerase chain reaction), glucose, insulin, IL-6, and C-reactive protein. ResultsNo main effects of group were observed for any miRNAs; however, a time-by-group interaction was detected for the expression of miR-126-3p (P = 0.05). HP breakfast tended to increase miR-126-3p expression throughout the study (POST-PRE, P = 0.09) leading to greater expression at POST compared with BS (P = 0.03), whereas NP breakfast did not. Additionally, several miRNAs predicted fasting concentrations of IL-6: miR-320a-3p, -146a-5p, -150-5p, -423-5p, -122-5p, glucose: miR-24-3p, -126-3p; insulin: miR-24-3p, -126-3p, -15b-5p; insulin sensitivity: miR-24-3p, -126-3p, -199a-5p, -15b-5p; and β-cell function: miR-15b-5p (R2 between 0.2 and 0.39; P < 0.05) from PRE and POST samples across groups. ConclusionsThese data support the daily consumption of a HP breakfast to promote cardiometabolic health, potentially through changes in miRNA expression, in a sensitive life-stage where early intervention strategies are critical to reduce the risk of adult-onset chronic disease. Trial registration numberNCT03146442.

A weekly 4-methylpyrazole treatment attenuates the development of non-obese metabolic dysfunction-associated steatotic liver disease (MASLD) in male mice: Role of JNK.

4-methylpyrazole (4MP, fomepizole) is a competitive inhibitor of alcohol dehydrogenase (ADH) preventing the metabolism of ethylene glycol and methanol, respectively, into their toxic metabolites. 4MP seems also to possess a potential in the treatment of intoxication from other substance, for example, acetaminophen, and to modulate JNK-dependent signalling. Here, we determined if a treatment with 4MP once weekly affects the development of diet-induced non-obese metabolic dysfunction-associated steatotic liver disease (MASLD) in C57BL/6 mice. Male C57BL/6 mice (6-8 weeks old, n = 7-8/group) were pair-fed either a liquid control diet (C) or a liquid sucrose-, fat- and cholesterol-rich diet (SFC) for 8 weeks while being concomitantly treated with 4MP (50 mg/kg bw i.p.) or vehicle once a week. Liver damage, inflammatory markers and glucose tolerance were assessed. Moreover, in endotoxin-challenged J774A.1 cells pretreated with 4MP, pro-inflammatory markers were assessed. The concomitant treatment of SFC-fed mice with 4MP attenuated the increase in JNK phosphorylation and pro-inflammatory markers like IFNγ, IL-6 and 3-nitrotyrosine protein adducts in liver tissue found in vehicle-treated SFC-fed mice, while not affecting impairments of glucose tolerance or the increase in portal endotoxin levels. Moreover, a pretreatment of endotoxin-stimulated J774A.1 cells with 4MP significantly attenuated the increases in JNK phosphorylation and pro-inflammatory mediators like IL-6 and Mcp1. Taken together, our results suggest that a treatment with 4MP once weekly attenuates the activation of JNK and dampens the development of non-obese MASLD in mice.

Reducing the excessive inflammation after burn injury in aged mice by maintaining a healthier intestinal microbiome.

One in six people are projected to be 65 years or older by 2050. As the population ages, better treatments for injuries that disproportionately impact the aged population will be needed. Clinical studies show that people aged 65 and older experience higher rates of morbidity and mortality after burn injury, including a greater incidence of pulmonary complications when compared to younger burn injured adults, which we and others believe is mediated, in part, by inflammation originating in the intestines. Herein, we use our clinically relevant model of scald burn injury in young and aged mice to determine whether cohousing aged mice with young mice or giving aged mice oral gavage of fecal material from young mice is sufficient to alter the microbiome of the aged mice and protect them from inflammation in the ileum and the lungs. Aged burn injured mice have less DNA expression of Bacteroidetes in the feces and an unhealthy Firmicutes/Bacteroidetes ratio. Both Bacteroidetes and the ratio of these two phyla are restored in aged burn injured by prior cohousing for a month with younger mice but not fecal transfer from young mice. This shift in the microbiome coincides with heightened expression of danger-associated molecular patterns (DAMP), and pro-inflammatory cytokine interleukin-6 (il6) in the ileum and lung of aged, burn injured mice, and heightened antimicrobial peptide camp in the lung. Cohousing reverses DAMP expression in the ileum and lung, and cathelicidin-related antimicrobial peptide protein (camp) in the lung, while fecal transfer heightened DAMPs while reducing camp in the lung, and also increased IL-6 protein in the lungs. These results highlight the importance of the intestinal microbiome in mediating inflammation within the gut-lung axis, giving insights into potential future treatments in the clinic.

Effects of an Extract of Physalis Peruviana Linnaeus on the Expression of Inflammatory Markers in the Caco-2 Intestinal Epithelium-like Cell Line

Objective: Physalis Peruviana Linnaeus (PPL) is an herbaceous species characterized by a wide variety of bioactive compounds to which anti-inflammatory properties have been attributed. This makes this fruit a possible complementary therapy for diseases that involve chronic inflammation, such as inflammatory bowel diseases (IBD). In the present study, the effect of a PPL extract on the expression of inflammatory markers in the Caco-2 cell line was evaluated. Methods: An in vitro gastric digest (50 g PPL pulp) was performed, obtaining an extract that was used to challenge Caco-2 cells for 24 and 72 hours. This extract was characterized by LC-MS/MS. Then, the relative mRNA expression of NF-kB, TLR4, IL-18 and MCP-1 was determined through qRT-PCR and the protein levels of TNF-α, IL-6, IL-8, IL-18 and MCP-1 through Luminex Immunoassay. Results: From the characterization of the extract, compounds with bioactive potential such as isothiocyanates, indoles and coumarins were found. Treatment of Caco-2 cells with PPL extract (80 µg/ml), particularly for 72 hours, produced a reduction of IL-18 and MCP-1 mRNA expression (p < 0.01), in addition to IL-18 (p < 0.01), IL-8 (p < 0.0001) and MCP-1 (p < 0.01) protein levels, however, no effects on NF-kB p65 (p = 0.09) and TLR4 (p = 0.20) mRNA expression were observed. Conclusion: The results obtained in this study open the possibility that the regular consumption of 50 g of PPL could constitute a possible complementary therapy for the treatment of IBD, improving the quality of life of these patients.

A square planar cobalt(II)-thiosemicarbazone complex. Synthesis, characterization, antiviral and anti-inflammatory potential

Considering the possible antiviral effect of cobalt compounds and known pharmacological potential of thiosemicarbazones, a new combination containing cobalt(II) ions and tetradentate thiosemicarbazone was synthesized and structurally analyzed. In the complex structure (Co1), the cobalt ion is in 2+ oxidation state and is coordinated with ONNO donor set on the thiosemicarbazone backbone. The complex molecule crystallizes in the space group P21/m and the environment of the cobalt center tends to square planar geometry. The inhibitory performance of SARS-CoV-2 and the anti-inflammatory impact of the complex molecule were investigated. It was found that Co1 has high inhibitory effects on the SARS-CoV-2 virus's 3CL main protease enzyme, ACE2:SARS-CoV2 Spike RBD interaction, and IL8. Also, it showed significant anti-inflammatory effects on the release of IL6, IL8, IL10, and TGFβ1 cytokines and wound healing during in vitro TNF-α-induced inflammation. Experimental evidence demonstrates that Co1 diminishes both IL8 gene expression and protein levels. According to in silico and experimental results, it has a drug potential. Assessing the in vivo impacts of Co1 might contribute to understanding its potential as an antiviral and anti-inflammatory agent.

Dexamethasone, Remdesivir and Azithromycin modulate ACE2 and IL-6 in Lung Epithelial Cells.

The optimal use of steroids in COVID-19 patients remains challenging. Current S3-guidelines "Recommendations for patients with COVID-19" recommend dexamethasone (DEX) for patients requiring respiratory support, remdesivir (RD) in the early disease phase and azythromycin (AZ) is no longer recommended. We investigated effects of DEX, RD and AZ in a lipopolysaccharide induced inflammation in lung cells in vitro and analyzed publicly available datasets with a focus on the Angiotensin-converting enzyme 2 (ACE2) to better understand drugs' mechanisms of action. human bronchial (Calu) and alveolar (A549) lung epithelial cells were treated with DEX, AZ or RDV in the presence of lipopolysaccharides (LPS). Gene expression (GE) of ACE2, IL-6 and the IL-6 protein release were measured. Publicly available GE data from lung tissues of COVID-19 patients and from lung cells treated with DEX were analyzed for the GE of ACE2. DEX increased and RDV and AZ reduced the GE of ACE2 in LPS-stimulated bronchial and alveolar epithelial cells. Only DEX significantly reduced LPS-induced IL-6 releases in alveolar cells substantially. The database analyses showed an, albeit not always significant, increase in ACE2 for lung tissue or cell lines treated with DEX. Lung tissue from patients after COVID-19 infection as well as bronchial cell cultures after COVID-19 infection showed lower GEs of ACE2. DEX can increase ACE2 expression in vitro and thereby the portal of entry of SARS-CoV-2 into lung cells during an LPS induced inflammation. Simultaneously the inflammatory marker IL-6 is reduced. Comparative database analyses indicate that these processes can also take place in vivo.

Associations of Placental Inflammation and Oxidative Stress Biomarkers with Glucolipid Metabolism in Children: A Birth Cohort Study in China.

The maternal intrauterine immune environment may affect offspring long-term health. We aimed to investigate the association between the intrauterine placental immunological milieu and glycolipid metabolic health in children. This study enrolled 1803 mother-child pairs from the Ma'anshan birth cohort (2013-2014). Placental mRNA expression of inflammatory cytokines (interleukin-1β [IL-1β], IL-10, monocyte chemoattractant protein-1, tumor necrosis factor-α, IL-4, IL-6, IL-8, C-reactive protein, and interferon-γ) and oxidative stress biomarkers (heme oxygenase-1, hypoxia-inducible factor-1alpha, and glucose-related protein 78) was quantified using real-time quantitative polymerase chain reaction. Fasting blood glucose, insulin, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol were assessed at 5 to 6 years old. Statistical analyses included multiple linear regression, binary logistic regression, restricted cubic spline model, and the Bayesian kernel machine regression model. Placental inflammatory cytokines (IL-1β, monocyte chemoattractant protein-1, C-reactive protein, IL-6, IL-8, IL-10) and oxidative stress biomarkers (heme oxygenase-1, hypoxia-inducible factor-1alpha, glucose-related protein 78) showed positive associations with children's fasting blood glucose levels. Heme oxygenase-1 and glucose-related protein 78 exhibited negative correlations with children's fasting insulin levels. Elevated IL-6, heme oxygenase-1, hypoxia-inducible factor-1alpha, and glucose-related protein 78 were associated with increased risk of prediabetes in children. Overall upregulation of placental proinflammatory cytokines and oxidative stress factors mRNA expression correlated with higher prediabetes risk in children. Bayesian kernel machine regression analysis indicated a joint positive effect of the 12 placental inflammation and oxidative stress mixtures on children's risk of high fasting blood glucose. This exploratory study underscores significant correlations between maternal intrauterine placental inflammation, oxidative stress markers, and offspring fasting blood glucose and insulin levels. These findings highlight the potential role of intrauterine holistic immunity in shaping offspring glucose metabolism health.

Influence of stress-specific interventions on biomarker levels and cognitive function in cancer patients: Systematic review and meta-analysis.

Cancer patients' psycho-physiological health is seriously affected by long-term exposure to stress. Many studies have explored the impact of stress-specific interventions on cancer patients' biomarker levels and cognitive functions. However, the current research findings are inconsistent, and their statistical power is limited by the small samples. Therefore, we conducted this meta-analysis to verify the effect of stress-specific interventions on cancer patients. The literature involved nine databases from the inception until January 13, 2024, extracted 19 randomized controlled trials (RCTs). Review Manager (RevMan) 5.4 software was used to perform a meta-analysis, and the revised Cochrane risk of bias tool (RoB2) was utilized for quality evaluation. Nine RCTs were assessed as having a low risk of bias, and others had a moderate risk. The results showed that stress-specific interventions had beneficial effects on patients' subjective cognition but uncertain impacts on their executive function, tumour necrosis factor-α level, morning cortisol level, and no effect on cortisol at other times, interleukin (IL)-10, IL-8, IL-6, IL-1, and C-reactive protein. More rigorous studies are required to elucidate the influence of stress-specific interventions on biomarker levels. The potential mechanism by which stress-specific interventions affect the cancer patient's cognitive function remains unclear.

Anti-inflammatory Effect of Novel 2-Phenylphthalazin-2-ium Bromides on LPS-induced RAW264.7 Cells and their Mechanism

Background: Inspired by natural anti-inflammatory quaternary benzo[C]phenanthridine alkaloids, novel 2-phenylphthalazin-2-ium bromides were previously designed and synthesized. Objective: The anti-inflammatory effect of 2-phenylphthalazin-2-ium bromides was evaluated based on inflammatory cytokines, and their possible mechanism was explored through the NF-κB, TLR4 and MAPK signaling pathways. Methods: The tested concentrations of two compounds were assessed using MTT assay in vitro. Griess assay was used to determine the changes in nitric oxide (NO) in the cell culture supernatant. qRT‒PCR was used to detect the mRNA levels of inflammatory cytokines, such as IL-6, IL-1ß, IL-10, TNF-α, TLR4 and iNOS. The secretion levels of TNF-α and IL-1β were detected by ELISA. Western blot test was used to detect the protein expression of IL-6, IL-10, TLR4, iNOS, NF-κB, p-P38/P38, p- ERK/ERK and p-JNK/JNK. Results: 2-(3,5-Dichlorophenyl)phthalazin-2-ium bromide (2) with a concentration below 1 μg/mL showed no significant effect on the growth inhibition of RAW264.7 cells, so the concentrations of compound 2 used for experiments were set to 0, 0.25, 0.5 and 1 μg/mL. Compared with the blank control group, the model group showed increased release of NO, transcription levels of IL-6, IL-1ß, IL-10, TNF-α, TLR4 and iNOS (p&lt; 0.05), and ratios of p-P38/P38, p-ERK/ERK, p-JNK/JNK (p&lt; 0.05). Compared with the model group, the sample groups displayed decreased NO release and reduced transcriptional levels of IL-6, IL-1ß, IL-10, TNF-α, TLR4, and iNOS and reduced protein expression ratios of IL-6, IL-1ß, IL-10, TNF-α, NF-κB, TLR4, iNOS, p-P38/P38, p-ERK/ERK and p- JNK/JNK (p&lt; 0.05). Conclusion: This study showed that 2-phenylphthalazin-2-ium bromides partially protected macrophages from the LPS-induced inflammatory response by suppressing TLR4-NF-κB/MAPK signaling and reducing NO production.

Effects of stannous fluoride dentifrice on gingival health and oxidative stress markers: a prospective clinical trial

BackgroundPeriodontal disease results in oral dysbiosis, increasing plaque virulence and oxidative stress. Stannous fluoride (SnF2) binds lipopolysaccharides to reduce plaque virulence. This study prospectively assessed SnF2 effects on oxidative stress in adults with gingivitis.MethodsThis was a 2-month, single-center, single-treatment clinical trial. Twenty “disease” (> 20 bleeding sites with ≥ 3 pockets 3 mm-4 mm deep) and 20 “healthy” (≤ 3 bleeding sites with pockets ≤ 2 mm deep) adults were enrolled. All participants were instructed to use SnF2 dentifrice twice daily for 2 months. An oral examination, Modified Gingival Index (MGI) examination and Gingival Bleeding Index (GBI) examination were conducted at baseline, 1 month and 2 months. Gingival crevicular fluid (GCF), saliva, oral lavage and supragingival plaque were collected at each visit to evaluate: Endotoxins, Protein Carbonyls, L-lactate dehydrogenase (LDH), Ferric reducing antioxidant power (FRAP), Oxidized low density lipoproteins (oxi-LDL), IL-6 and C-reactive protein (CRP). A subset-analysis examined participants considered at higher risk of cardiovascular disease. Change-from-baseline analyses within each group were of primary interest.ResultsThe disease group showed statistically significant reductions in GBI at Month 1 (67%) and Month 2 (85%) and in MGI at Month 1 (36%) and Month 2 (51%) versus baseline (p < 0.001). At baseline, the disease group showed greater LDH in GCF and oxi-LDL levels in saliva versus the healthy group (p ≤ 0.01). Total antioxidant capacity (FRAP) in saliva increased versus baseline for the disease group at Months 1 and 2 (p < 0.05), and levels for the disease group were greater than the healthy group at both timepoints (p < 0.05). SnF2 treatment reduced endotoxins (lavage) for both disease and healthy groups at Month 2 (p ≤ 0.021) versus baseline. There was a reduction in oxidative stress markers, namely protein carbonyl in saliva, at Months 1 and 2 (p < 0.001) for both groups and a reduction in cytokine IL-6 (lavage) in the disease group at Month 2 (p = 0.005). A subset analysis of participants at higher coronary disease risk showed reductions in endotoxins in lavage, oxi-LDL, and CRP in saliva at Month 2 (p ≤ 0.04).ConclusionSnF2 dentifrice use reversed gingival inflammation, suppressed endotoxins and reduced some harmful oxidant products in saliva and gingiva.Clinical trial registrationClinicaltrials.gov NCT05326373, registered on 13/04/2022.

CD9 and Aryl Hydrocarbon Receptor Are Markers of Human CD19+CD14+ Atypical B Cells and Are Dysregulated in Systemic Lupus Erythematous Disease.

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor whose expression regulates immune cell differentiation. Single-cell transcriptomic profiling was used to ascertain the heterogeneity of AHR expression in human B cell subpopulations. We identified a unique population of B cells marked by expression of AHR, CD9, and myeloid genes such as CD14 and CXCL8. Results were confirmed directly in human PBMCs and purified B cells at the protein level. TLR9 signaling induced CD14, CD9, and IL-8 protein expression in CD19+ B cells. CD14-expressing CD9+ B cells also highly expressed AHR and atypical B cell markers such as CD11c and TBET. In patients with active lupus disease, CD14+ and CD9+ B cells are dysregulated, with loss of CD9+ B cells strongly predicting disease severity and demonstrating the relevance of CD9+ B cells in systemic lupus erythematosus and autoimmune disease.

Nutraceutical formulation based on a synergic combination of melatonin and palmitoylethanolamide for the management of allergic events.

The management of allergic events is a growing global health issue, especially in industrialized countries. This disease is an immune-mediated process, regulated by the interaction of IgE with an allergen, resulting in mast cell activation, which concerns the release of several immune-inflammatory modulators, i.e., histamine, β-hexosaminidase, COX-2, IL-6, and TNF-α, responsible for the main allergic-reaction associated symptoms. The aim of the present study was the efficacy evaluation of an alternative remedy, an innovative nutraceutical formulation (NF) based on the synergic combination of melatonin (MEL) and palmitoylethanolamide (PEA) for the prevention and treatment of immune disease. At first, the intestinal bioaccessibility of PEA and MEL in NF was assessed at 1.6 and 36%, respectively. Then the MEL and PEA ability to modulate the release of immune-inflammatory modulators in the human mast cell line (HMC-1.2) at their bioaccessible concentration was investigated. Our results underline that NF treatment was able to reduce COX-2 mRNA transcription levels (-30% vs. STIM, p < 0.0001) in stimulated HMC-1.2 and to contract COX-2 enzymatic activity directly (IC50: 152 μg/mL). Additionally, NF showed valuable ability in reducing histamine and β-hexosaminidase release in stimulated HMC-1.2, as well as in decreasing TNF-α and IL-6 mRNA transcription levels and protein production.

In vitro evidence of antioxidant and anti-inflammatory effects of a new nutraceutical formulation explains benefits in a clinical setting of COPD patients.

Background and Aim: Increased oxidative stress within the airways is associated to epithelial damage and amplification of inflammatory responses that in turn contribute to Chronic Obstructive Pulmonary Disease (COPD) progression. This study was aimed to identify whether a new formulation of N-acetylcisteine (NAC), carnitine, curcumin and B2 vitamin could counteract oxidative stress and downstream pro-inflammatory events promoted by cigarette smoke extract (CSE) exposure in primary bronchial epithelial cells (PBEC), both submerged/undifferentiated (S-PBEC) and cultured at the air-liquid interface (ALI-PBEC). Methods: PBEC were exposed to CSE with/without the new formulation or NAC alone and ROS production, IL-8 and IL-6 gene expression and protein release were evaluated. Results: CSE increased ROS, IL-8 and IL-6 gene expression and protein release and the new formulation counteracted these effects. NAC alone was not effective on IL-8 and IL-6 release. The effects of a similar nutraceutical formulation were evaluated in COPD patients treated for six months. The results showed that the treatment reduced the concentration of IL-8 in nasal wash and improved quality of life. Conclusion: The tested formulation, exerting antioxidant and anti-inflammatory effects, can preserve airway epithelial homeostasis and improve clinical symptoms in COPD.

Comparison of the effect of consuming the prepared cakes with acorn flour and wheat flour following a hypocaloric diet on serum levels of leptin, endothelin, inflammatory factors, and oxidative stress parameters in obese and overweight patients with metabolic syndrome: A double-blind clinical trial.

Metabolic syndrome (MetS), which is a major consequence of obesity, increases mortality risks. Evidence shows favorable effects of nutritional approaches in the management of MetS. Accordingly, the use of functional foods has increased to enhance weight loss and reduce the risk factors associated with MetS. So, we aimed to investigate the effects of daily consumption of a functional acorn-based cake in conjunction with energy-restricted diet on some complications of patients with MetS. The study included 66 participants who were randomly assigned to either (A) a calorie-restricted diet + functional cake (FC) (n = 33) or (B) a calorie-restricted diet + a placebo cake (PC) (n = 33). Sociodemographic information, anthropometric measurements, dietary intakes, and serum biochemical parameters (inflammatory and oxidative stress markers, leptin, and endothelin) were measured before and after 8 weeks of intervention. Sixty-three participants completed this trial. After adjustment for baseline levels, consumption of FC compared to the PC resulted in a significant decrease in IL-6 (p = .03) and high-sensitivity C-reactive protein (p = .04) levels. No differences were observed between groups with regard to serum malondialdehyde, total antioxidant capacity, endothelin, and leptin levels (p > .05). Acorn-based cake could improve inflammation as an adjunct to an energy-restricted diet in overweight and obese patients with MetS. However, it is not clear whether acorn-based cake can be used to prevent or treat MetS because of indecisive findings regarding its ability to manage oxidative stress and serum hormones.

Thermosensitive and pH-responsive quercus infectoria gall-containing gel with long-lasting anti-inflammatory activity for ulcerative colitis

In the study, quercus infectoria gall (QIG) was used to develop a pH/thermosensitive gel in situ delivery system for enema administration of to treat acute ulcerative colitis (UC). The QIG ethanol extract pH/temperature-sensitive gel (QIG-pH-TSG) was characterized by using DSC, SEM, rheological and drug release analyses. The therapeutic effect in UC mice of the obtained gel were studied. The gel was maintained in a flowing liquid state under nonphysiological conditions (25 °C) to facilitate drug administration, and was transformed into a pseudoplastic liquid state under physiological conditions (37 °C), which prolonged its retention time in the colon. The gel drug was completely released within 24 h, and the temperature and viscosity of the gel were within the required range. In the in vitro anti-inflammatory test, QIG-pH-TSG decreased the level of TNF-α and IL-6, and increased IL-10 in RAW 264.7 actived by LPS. Moreover, the administration of QIG-pH-TSG resulted in a decrease in the colon histopathological score and an increase in colonic length, and also could reduce the IL-6, TNF-α, and C-reactive protein (CRP) levels in UC mice along with significant increases in IL-10 level in the colon. The QIG-pH-TSG could increase the concentration of QIG at the local inflammatory site and lead to an effective repair of the colonic mucosa. Therefore, the pH/thermosensitive in situ gel may serve as a drug delivery system for QIG to treat UC and overcome the limitations of some existing formulations. These results indicated that this composite gel was effectively in UC mice and the study provided a practical reference for the application of QIG-pH-TSG in the treatment of UC.