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International Journal of Molecular... Jun 2024The aim of this study was to test the molecular expression profile (senescence-associated secretory phenotype; SASP) in gingival crevicular fluid (GCF) prior to surgery...
The aim of this study was to test the molecular expression profile (senescence-associated secretory phenotype; SASP) in gingival crevicular fluid (GCF) prior to surgery in relation to the distribution of clinical success of periodontal regeneration. Forty consecutive patients presenting sites with residual probing pocket depth (PPD) ≥ 6 mm and intrabony defects ≥ 3 mm were treated through a minimally invasive surgical technique. Pre-operatively, GCF was sampled for inflammatory biomarker analysis related to SASP [interleukin (IL)-1β, IL-6, and IL-12; matrix-metalloproteinases (MMP)-8 and -9]. Better or worse responders were classified depending on the achievement of a composite outcome measure at 1-year [COM; PPD ≤ 4 mm and clinical attachment gain (CAL) gain ≥ 3 mm]. Correlation analyses and logistic regression models were performed. Periodontal regeneration led to significant improvements in mean clinical and radiographic parameters. Teeth achieving COM presented significantly lower amounts of SASP factors compared with non-successful teeth. Higher CAL gain, PPD reduction, and radiographic bone fill were negatively correlated with IL-1β and MMP-8 and -9 ( < 0.001), while IL-12 showed a direct relationship with CAL gain ( = 0.005) and PPD reduction ( = 0.038). Sites expressing higher SASP expression in the GCF before periodontal regeneration achieved worse clinical and radiographic outcomes.
Topics: Humans; Gingival Crevicular Fluid; Male; Female; Middle Aged; Biomarkers; Adult; Regeneration; Matrix Metalloproteinase 8; Phenotype; Matrix Metalloproteinase 9; Inflammation; Treatment Outcome; Interleukin-1beta; Aged
PubMed: 38928390
DOI: 10.3390/ijms25126687 -
International Journal of Molecular... Jun 2024Treatment of critically ill patients with venovenous (V-V) extracorporeal membrane oxygenation (ECMO) has gained wide acceptance in the last few decades. However, the...
New Insights into Hepatic and Intestinal Microcirculation and Pulmonary Inflammation in a Model of Septic Shock and Venovenous Extracorporeal Membrane Oxygenation in the Rat.
Treatment of critically ill patients with venovenous (V-V) extracorporeal membrane oxygenation (ECMO) has gained wide acceptance in the last few decades. However, the use of V-V ECMO in septic shock remains controversial. The effect of ECMO-induced inflammation on the microcirculation of the intestine, liver, and critically damaged lungs is unknown. Therefore, the aim of this study was to measure the hepatic and intestinal microcirculation and pulmonary inflammatory response in a model of V-V ECMO and septic shock in the rat. Twenty male Lewis rats were randomly assigned to receive V-V ECMO therapy or a sham procedure. Hemodynamic data were measured by a pressure-volume catheter in the left ventricle and a catheter in the lateral tail artery. Septic shock was induced by the intravenous infusion of lipopolysaccharide (1 mg/kg). During V-V ECMO therapy, rats received lung-protective ventilation. The hepatic and intestinal microcirculation was assessed by micro-lightguide spectrophotometry after median laparotomy for 2 h. Systemic and pulmonary inflammation was measured by enzyme-linked immunosorbent assays of plasma and bronchoalveolar lavage (BAL), respectively, which included tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-10, C-X-C motif ligand 2 (CXCL2), and CXCL5. Reduced oxygen saturation and relative hemoglobin concentration were measured in the hepatic and intestinal microcirculation during treatment with V-V ECMO. These animals also showed increased systolic, mean, and diastolic blood pressures. While no differences in left ventricular ejection fraction were observed, animals in the V-V ECMO group presented an increased heart rate, stroke volume, and cardiac output. Blood gas analysis showed dilutional anemia during V-V ECMO, whereas plasma analysis revealed a decreased concentration of IL-10 during V-V ECMO therapy, and BAL measurements showed increased concentrations of TNF-α, CXCL2, and CXCL5. Rats treated with V-V ECMO showed impaired microcirculation of the intestine and liver during septic shock despite increased blood pressure and cardiac output. Despite lung-protective ventilation, increased pulmonary inflammation was recognized during V-V ECMO therapy in septic shock.
Topics: Animals; Microcirculation; Extracorporeal Membrane Oxygenation; Male; Rats; Shock, Septic; Rats, Inbred Lew; Intestines; Liver; Disease Models, Animal; Pneumonia; Hemodynamics; Tumor Necrosis Factor-alpha
PubMed: 38928327
DOI: 10.3390/ijms25126621 -
International Journal of Molecular... Jun 2024Bosentan, an endothelin receptor antagonist (ERA), has potential anti-atherosclerotic properties. We investigated the complementary effects of bosentan and atorvastatin...
Bosentan, an endothelin receptor antagonist (ERA), has potential anti-atherosclerotic properties. We investigated the complementary effects of bosentan and atorvastatin on the progression and composition of the atherosclerotic lesions in diabetic mice. Forty-eight male mice were fed high-fat diet (HFD) for 14 weeks. At week 8, diabetes was induced with streptozotocin, and mice were randomized into four groups: (1) control/COG: no intervention; (2) ΒOG: bosentan 100 mg/kg/day per os; (3) ATG: atorvastatin 20 mg/kg/day per os; and (4) BO + ATG: combined administration of bosentan and atorvastatin. The intra-plaque contents of collagen, elastin, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-a (TNF-a), matrix metalloproteinases (MMP-2, -3, -9), and TIMP-1 were determined. The percentage of lumen stenosis was significantly lower across all treated groups: BOG: 19.5 ± 2.2%, ATG: 12.8 ± 4.8%, and BO + ATG: 9.1 ± 2.7% compared to controls (24.6 ± 4.8%, < 0.001). The administration of both atorvastatin and bosentan resulted in significantly higher collagen content and thicker fibrous cap versus COG ( < 0.01). All intervention groups showed lower relative intra-plaque concentrations of MCP-1, MMP-3, and MMP-9 and a higher TIMP-1concentration compared to COG ( < 0.001). Importantly, latter parameters presented lower levels when bosentan was combined with atorvastatin compared to COG ( < 0.05). Bosentan treatment in diabetic, atherosclerotic mice delayed the atherosclerosis progression and enhanced plaques' stability, showing modest but additive effects with atorvastatin, which are promising in atherosclerotic cardiovascular diseases.
Topics: Animals; Bosentan; Atorvastatin; Mice; Male; Atherosclerosis; Endothelin Receptor Antagonists; Diabetes Mellitus, Experimental; Drug Therapy, Combination; Collagen; Diet, High-Fat; Chemokine CCL2; Tumor Necrosis Factor-alpha; Plaque, Atherosclerotic; Mice, Knockout; Tissue Inhibitor of Metalloproteinase-1
PubMed: 38928320
DOI: 10.3390/ijms25126614 -
International Journal of Molecular... Jun 2024The inflammasome regulates the innate inflammatory response and is involved in autoimmune diseases. In this study, we explored the levels of IL-18 and IL-1β in serum...
Evaluating Single-Nucleotide Polymorphisms in Inflammasome Proteins and Serum Levels of IL-18 and IL-1β in Kidney Interstitial Damage in Anti-Neutrophilic Cytoplasmic Antibody-Associated Vasculitis.
The inflammasome regulates the innate inflammatory response and is involved in autoimmune diseases. In this study, we explored the levels of IL-18 and IL-1β in serum and urine and the influence of various single-nucleotide polymorphisms (SNPs) on kidney lesions at diagnosis in patients with ANCA-associated vasculitis (AAV) and their clinical outcomes. Ninety-two patients with renal AAV were recruited, and blood and urine were collected at diagnosis. Serum and urine cytokine levels were measured by ELISA. DNA was extracted and genotyped using TaqMan assays for SNPs in several inflammasome genes. Lower serum IL-18 ( = 0.049) and the rs187238 G-carrier genotype ( = 0.042) were associated with severe fibrosis. The rs1946518 TT genotype was associated with an increased risk of relapse ( = 0.05), whereas GG was related to better renal outcomes ( = 0.031). The rs187238 GG genotype was identified as a risk factor for mortality within the first year after AAV diagnosis, independent of the requirement for dialysis or lung involvement ( = 0.013). We suggest that decreased cytokine levels could be a surrogate marker of scarring and chronicity of the renal lesions, together with the rs187238 GG genotype. If our results are validated, the rs1946518 TT genotype predicts the risk of relapse and renal outcomes during follow-up.
Topics: Humans; Polymorphism, Single Nucleotide; Interleukin-18; Male; Female; Inflammasomes; Middle Aged; Interleukin-1beta; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Aged; Kidney; Genotype; Adult; NLR Family, Pyrin Domain-Containing 3 Protein
PubMed: 38928186
DOI: 10.3390/ijms25126479 -
International Journal of Molecular... Jun 2024Activation of the transcription factor NF-κB in cardiomyocytes has been implicated in the development of cardiac function deficits caused by diabetes. NF-κB controls...
Activation of the transcription factor NF-κB in cardiomyocytes has been implicated in the development of cardiac function deficits caused by diabetes. NF-κB controls the expression of an array of pro-inflammatory cytokines and chemokines. We recently discovered that the stress response protein regulated in development and DNA damage response 1 (REDD1) was required for increased pro-inflammatory cytokine expression in the hearts of diabetic mice. The studies herein were designed to extend the prior report by investigating the role of REDD1 in NF-κB signaling in cardiomyocytes. REDD1 genetic deletion suppressed NF-κB signaling and nuclear localization of the transcription factor in human AC16 cardiomyocyte cultures exposed to TNFα or hyperglycemic conditions. A similar suppressive effect on NF-κB activation and pro-inflammatory cytokine expression was also seen in cardiomyocytes by knocking down the expression of GSK3β. NF-κB activity was restored in REDD1-deficient cardiomyocytes exposed to hyperglycemic conditions by expression of a constitutively active GSK3β variant. In the hearts of diabetic mice, REDD1 was required for reduced inhibitory phosphorylation of GSK3β at S9 and upregulation of IL-1β and CCL2. Diabetic REDD1 mice developed systolic functional deficits evidenced by reduced ejection fraction. By contrast, REDD1 mice did not exhibit a diabetes-induced deficit in ejection fraction and left ventricular chamber dilatation was reduced in diabetic REDD1 mice, as compared to diabetic REDD1 mice. Overall, the results support a role for REDD1 in promoting GSK3β-dependent NF-κB signaling in cardiomyocytes and in the development of cardiac function deficits in diabetic mice.
Topics: Animals; Myocytes, Cardiac; NF-kappa B; Signal Transduction; Mice; Diabetes Mellitus, Experimental; Transcription Factors; Glycogen Synthase Kinase 3 beta; Humans; Mice, Knockout; Male; Chemokine CCL2; Interleukin-1beta; Mice, Inbred C57BL; Tumor Necrosis Factor-alpha; Phosphorylation; Gene Deletion
PubMed: 38928166
DOI: 10.3390/ijms25126461 -
Biomolecules May 2024Schnitzler syndrome is a rare disorder characterized by a chronic urticarial rash associated with immunoglobulin M (IgM) monoclonal gammopathy. Schnitzler syndrome... (Review)
Review
Schnitzler syndrome is a rare disorder characterized by a chronic urticarial rash associated with immunoglobulin M (IgM) monoclonal gammopathy. Schnitzler syndrome shares strong clinicopathologic similarities with monogenic IL-1-mediated autoinflammatory disorders and is now considered an acquired adult-onset autoinflammatory disease. The spectacular effect of interleukin-1 inhibitors demonstrates the key role of this cytokine in the pathogenesis of the disease. However, the physiopathology of Schnitzler syndrome remains elusive, and the main question regarding the relationship between autoinflammatory features and monoclonal gammopathy is still unanswered. The purpose of this narrative review is to describe what is currently known about the pathogenesis of this peculiar disease, as well as to address its diagnosis and management.
Topics: Schnitzler Syndrome; Humans; Immunoglobulin M; Interleukin-1
PubMed: 38927050
DOI: 10.3390/biom14060646 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To screen interleukin (IL)-1β secretion-related membrane transporters by macrophage experiment and conventional knockout mice.
OBJECTIVE
To screen interleukin (IL)-1β secretion-related membrane transporters by macrophage experiment and conventional knockout mice.
METHODS
THP-1 cell line was differentiated to obtain human THP-1-derived macrophages, and the primary macrophages were obtained from human peripheral blood. wild-type mice with the same sex and age were used as the controls of knockout mice. The macrophages in abdominal cavity and bone marrow of mice were cultivated. The cells were treated with ABCC1/MRP1, ABCG2/BCRP, ABCB1/P-gp, OATP1B1, and MATE transporter inhibitors, then stimulated by lipopolysaccharide and adenosine triphosphate. The secretion level of IL-1β was detected by ELISA, Western blot, and immunofluorescence.
RESULTS
After inhibiting ABCC1/MRP1 transporter, the secretion of IL-1β decreased significantly, while inhibition of the other 4 transporters had no effect. In animal experiment, the level of IL-1β secreted by macrophages in bone marrow of knockout mice was significantly lower than control group ( < 0.05).
CONCLUSION
ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway, which is expected to become a new target for solving clinical problems such as cytokine release syndrome.
Topics: Interleukin-1beta; Mice; Animals; Humans; Multidrug Resistance-Associated Proteins; Mice, Knockout; Macrophages; Down-Regulation; THP-1 Cells; Lipopolysaccharides
PubMed: 38926988
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.040 -
Discovery Medicine Jun 2024Rotator cuff injury is a common injury that includes inflammation, partial tearing, or complete tearing of the rotator cuff tendon. In cases of rotator cuff tears...
OBJECTIVE
Rotator cuff injury is a common injury that includes inflammation, partial tearing, or complete tearing of the rotator cuff tendon. In cases of rotator cuff tears (RCTs), Tumor Necrosis Factor-alpha (TNF-α) can trigger the release of nerve growth factor (NGF). TNF-α is an important inflammatory mediator that affects rotator cuff activity and increased NGF expression is observed in RCTs. Therefore, this study aimed to investigate whether inhibition of TNF-α could reduce behavioural responses and inflammation levels in rats through NGF.
METHODS
A rat RCT model was established, and the CatWalk gait analysis system was used for behavioural assessment. Immunohistochemistry was used to detect NGF protein levels in tendon tissue. Hematoxylin eosin (HE) staining was used to observe histopathological changes. The expressions of Interleukin-1beta (IL-1β) and Cyclooxygenase-2 (COX2) were detected by western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR). The expression of apoptosis protein Bcl-2-associated X (Bax), B-cell lymphoma 2 (Bcl-2), and Cysteine-aspartic acid protease-3 (Caspase-3) were detected using WB. Oxidative stress markers, namely Reactive Oxygen Species (ROS), Malondialdehyde (MDA), and Superoxide Dismutase (SOD) were quantified in tissues using an ELISA kit.
RESULTS
In the RCT model, elevated NGF protein expression, noticeable atrophy in the supraspinatus muscle tissue, and substantial fat infiltration were observed. The levels of IL-1β, COX2, apoptosis, and oxidative stress were all increased. TNF-α inhibition resulted in decreased NFG expression, decreased tissue fibrosis, and improved tendon atrophy. Moreover, when TNF-α was inhibited, the expressions of IL-1β and Cox2 were reduced and both apoptosis and oxidative stress were decreased. The results showed that inhibiting TNF-α had the potential to reduce inflammation levels and behavioural responses in rats.
CONCLUSION
TNF-α can affect behaviour and inflammation in rats with RCTs through NGF, and TNF-α inhibition can improve rotator cuff injury.
Topics: Animals; Nerve Growth Factor; Rotator Cuff Injuries; Rats; Tumor Necrosis Factor-alpha; Inflammation; Rats, Sprague-Dawley; Male; Oxidative Stress; Behavior, Animal; Disease Models, Animal; Apoptosis; Interleukin-1beta; Cyclooxygenase 2
PubMed: 38926110
DOI: 10.24976/Discov.Med.202436185.114 -
PloS One 2024Obsessive-compulsive disorder (OCD) is a highly prevalent neuropsychiatric disorder. Recently, there has been a growing interest in investigating the association between...
BACKGROUND
Obsessive-compulsive disorder (OCD) is a highly prevalent neuropsychiatric disorder. Recently, there has been a growing interest in investigating the association between pro-inflammatory cytokines and the pathogenesis of OCD. However, studies targeting interleukin-1β (IL-1β) and interleukin-6 (IL-6) in OCD are limited. Therefore, the present study aimed to explore the potential role of pro-inflammatory cytokines IL-1β and IL-6 in the pathophysiology and development of OCD.
METHODS
This study recruited 58 OCD patients and 30 age-sex-matched healthy controls (HCs). A qualified psychiatrist diagnosed OCD patients and assessed HCs based on the Diagnostic and Statistical Manual for Mental Health Disorders, 5th edition (DSM-5) criteria. We measured the severity of OCD using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Serum IL-1β and IL-6 levels were measured using ELISA kits following the appropriate methods.
RESULTS
The results showed that serum IL-1β levels were significantly elevated in OCD patients compared to HCs (23.68±1.65 pg/ml vs. 15.75±1.02 pg/ml; p = 0.002). Similarly, OCD patients exhibited significantly higher serum IL-6 levels than HCs (44.97±0.73 pg/ml vs. 37.04±0.35 pg/ml; p<0.001). We observed both cytokines were positively correlated with the Y-BOCS scores in OCD patients (IL-1β: r = 0.380, p = 0.015; IL-6: r = 0.324, p = 0.026) which indicates their role in disease pathophysiology.
CONCLUSION
These results suggest that serum IL-1β and IL-6 levels may be associated with the pathophysiology of OCD. Also, these cytokines levels in blood samples can serve as early risk assessment tools for the development of OCD. We recommend further studies in a large and homogeneous population to support these findings.
Topics: Humans; Obsessive-Compulsive Disorder; Interleukin-1beta; Interleukin-6; Female; Male; Adult; Case-Control Studies; Young Adult; Middle Aged
PubMed: 38924009
DOI: 10.1371/journal.pone.0306125 -
Skin Research and Technology : Official... Jul 2024Acne vulgaris (AV) is a chronic inflammatory skin condition affecting the pilosebaceous unit, commonly presenting as comedones, papules, pustules, or nodules on the...
BACKGROUND
Acne vulgaris (AV) is a chronic inflammatory skin condition affecting the pilosebaceous unit, commonly presenting as comedones, papules, pustules, or nodules on the face, upper limbs, torso, and back, with comedones formation being the primary pathology leading to disfiguring inflammation, hyperpigmentation, scarring, and psychological impact.
AIM
The purpose of this study was to investigate the significance of two genetic variants in the promoter region of the tumor necrosis factor-alpha (TNF-α) gene and their association with insulin resistance (IR) in acne patients. To understand how these variants contribute to AV and its associated IR.
SUBJECTS AND METHODS
An analytical cross-sectional study with a case-control design and research evaluation was carried out on 87 AV patients and 73 healthy volunteers. The medical histories of both groups were obtained, as well as the severity and duration of inflammation among acne sufferers, as well as demographic data. Biochemical analysis was performed on both sets of participants, including fasting blood glucose levels, insulin levels while fasting, IR, and serum TNF-α. PCR-RFLP analysis identified -863 G > A (rs1800630) and -308 G > A (rs1800629) variations, and real-time PCR analysis evaluated TNF-α gene expression in both patients and healthy people.
RESULTS
Acne patients exhibited significantly higher levels of IR, fasting glucose, fasting insulin, serum TNF-α, and TNF-α folding change, when compared to healthy controls. The co-dominant model for -863 G > A and -308 G > A variants exhibited significant variations between the two groups. Severe acne patients who had the A/A genotype for -308 variants exhibited higher levels of IR, serum TNF-α, and TNF-α folding change. Highly significant positive linear correlation between IR, serum TNF-α, and TNF-α folding change in severe AV.
CONCLUSION
There is a correlation between AV, especially severe acne, and the -863 G > A and -308 G > A polymorphism, which influences TNF-α gene expression and serum TNF-α levels.
Topics: Humans; Acne Vulgaris; Insulin Resistance; Tumor Necrosis Factor-alpha; Male; Female; Case-Control Studies; Cross-Sectional Studies; Adult; Young Adult; Adolescent; Severity of Illness Index; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease
PubMed: 38923681
DOI: 10.1111/srt.13811