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Diabetes mellitus is a common metabolic disorder affecting different body organs; one of its serious complications is diabetic cardiomyopathy (DCM). Thus, finding more cardiopreserving agents to protect the heart against such illness is a critical task. For the first time, we planned to study the suspected role of diacerein (DIA) in ameliorating DCM in juvenile rats and explore different mechanisms mediating its effect including inflammasome/caspase1/interleukin1β pathway. Four-week-aged juvenile rats were randomly divided into groups; the control group, diacerein group, diabetic group, and diabetic-treated group. Streptozotocin (45 mg/kg) single intraperitoneal (i.p.) dose was administered for induction of type 1 diabetes on the 1st day which was confirmed by detecting blood glucose level. DIA was given in a dose of 50 mg/kg/day for 6 weeks to diabetic and non-diabetic rats, then we evaluated different inflammatory, apoptotic, and oxidative stress parameters. Induction of DCM succeeded as there were significant increases in cardiac enzymes, heart weights, fasting blood glucose level (FBG), and glycosylated hemoglobin (HbA1c) associated with elevated blood pressure (BP), histopathological changes, and increased caspase 3 immunoexpression. Furthermore, there was an increase of malondialdehyde (MDA), inflammasome, caspase1, angiotensin II, nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNFα), and interleukin 1β (IL1β). However, antioxidant parameters such as reduced glutathione (GSH) and total antioxidant capacity (TAC) significantly declined. Fortunately, DIA reversed the diabetic cardiomyopathy changes mostly due to the observed anti-inflammatory, antioxidant, and anti-apoptotic properties with regulation of blood glucose level.DIA has an ability to regulate DCM-associated biochemical and histopathological disturbances. [ABSTRACT FROM AUTHOR]

Globally, an estimated 50 million people are affected by epilepsy, a persistent, noncommunicable neurological ailment. Quercetin (QR) is a prevalent flavonoid substance extensively dispersed throughout agricultural life. In a pilocarpine (PILO)-induced epilepsy model in mice, this investigation aimed to determine whether QR has an antiepileptic effect and explore its putative mechanism of action. Fifty mice were allocated into seven groups, with six in every group. The first group received physiological saline, the second group was given diazepam (1 mg/kg), and four groups were administered QR at 50, 100, 150, and 200 mg/kg, respectively. The seventh group (the induction group) received normal saline. After 30 min, all groups were injected intraperitoneally with PILO. The impact of QR on motor coordination was assessed using the rotarod test, while measures such as latency to first seizure, generalized tonic-clonic seizures (GTCS), number of convulsions, and mortality were recorded. Serum samples were collected through the retro-orbital route to measure prostaglandin E2 (PGE2) and interleukin 1 beta (IL-1β) levels. QR showed no significant difference in motor impairment, but increased duration until the initial seizure occurred and declined the mortality rate, duration of GTCS, and incidence of convulsions. All doses of QR significantly reduced PGE2 levels (P ≤ 0.05). However, QR’s effect on IL-1β reduction was statistically insignificant (P > 0.05). QR’s capacity to inhibit PILO-induced epilepsy by decreasing IL-1 and PGE2 levels is supported by this study. The results of this work indicate that QR could have a function to treat acute epilepsy.

Background: The pro-inflammatory cytokine IL-1 plays an important role in severe COVID-19. A change in IL-1 production may be associated with a mutation in the IL1Β gene. Our study analyzed the impact of the IL1Β gene variants (rs1143634) on disease progression in patients with severe COVID-19 pneumonia, taking into account treatment strategies. Methods and results: The study enrolled 117 patients with severe COVID-19 pneumonia. The IL1Β gene variants were identified using the polymerase chain reaction-restriction fragment length polymorphism method. In the group of patients, the following genotype frequencies were found based on the investigated rs1143634 variant of the IL1Β gene: CC–65.8%, CT–28.2%, and TT–6.0%. Our results showed that the group of patients with the T allele of the IL1Β gene had higher leukocyte counts (p = 0.040) and more pronounced lymphopenia (p = 0.007). It was determined that patients carrying the T allele stayed on ventilators significantly longer (p = 0.049) and required longer treatment with corticosteroids (p = 0.045). Conclusion: Identifying variants of the IL1Β gene can be used as a predictive tool for assessing the severity of COVID-19 pneumonia and tailoring personalized treatment strategies. Further research with a larger patient cohort is required to validate these findings. [ABSTRACT FROM AUTHOR]

Murine macrophages activated by the Toll-like receptor 4 agonist lipopolysaccharide (LPS) polarize to the M1 type by inducing proinflammatory marker proteins and changing their energy metabolism to increased aerobic glycolysis and reduced respiration. We here show that the aliphatic isothiocyanate sulforaphane (Sfn) diminishes M1 marker expression (IL-1β, IL-6, TNF-α, iNOS, NO, and ROS) and leads to highly energetic cells characterized by both high glycolytic and high respiratory activity as assessed by extracellular flux analysis. Focusing on a potential connection between high glycolytic activity and low IL-1β expression in M1 (LPS/Sfn) macrophages, we reveal that Sfn impedes the moonlighting function of pyruvate kinase M2 (PKM2) in M1 macrophages. Sfn limits mono/dimerization and nuclear residence of PKM2 accompanied by reduced HIF-1a levels, Stat3 phosphorylation at tyrosine 705, and IL-1β expression while preserving high levels of cytosolic PKM2 tetramer with high glycolytic enzyme activity. Sfn prevents glutathionylation of PKM2 in LPS-stimulated macrophages which may account for the reduced loss of PKM2 tetramer. Overall, we uncover PKM2 as a novel affected hub within the antiinflammatory activity profile of Sfn. [ABSTRACT FROM AUTHOR]

Autologous fat transfers show promise in treating fibrotic skin diseases, reversing scarring and stiffness, and improving quality of life. Adipose-derived stem cells (ADSCs) within these grafts are believed to be crucial for this effect, particularly their secreted factors, though the specific mechanisms remain unclear. This study investigates transcriptomic changes in ADSCs after in vitro fibrotic, inflammatory, and hypoxic conditioning. High-throughput gene expression assays were conducted on ADSCs exposed to IL1-β, TGF-β1, and hypoxia and in media with fetal bovine serum (FBS). Flow cytometry characterized the ADSCs. RNA-Seq analysis revealed distinct gene expression patterns between the conditions. FBS upregulated pathways were related to the cell cycle, replication, wound healing, and ossification. IL1-β induced immunomodulatory pathways, including granulocyte chemotaxis and cytokine production. TGF-β1 treatment upregulated wound healing and muscle tissue development pathways. Hypoxia led to the downregulation of mitochondria and cellular activity. [ABSTRACT FROM AUTHOR]

Simple Summary: According to the literature, 35–71% of multiple myeloma patients have nutritional disorders. In the development of cachexia and malnutrition, the inflammatory process, accompanied by an increase in the level of proinflammatory cytokines, plays a key role. Interleukin-1β is a cytokine that plays an important role in the mechanisms responsible for muscle and adipose tissue breakdown during malnutrition and cachexia. This study aimed to investigate the association of IL1B gene polymorphism and interleukin-1β plasma concentration with the occurrence of nutritional disorders and survival in patients with multiple myeloma. The presence of the CC genotype of the IL1B gene was associated with a higher plasma concentration of interleukin-1β, a higher risk of cachexia, and poor prognosis. Determination of IL1B polymorphism may be a useful predictive marker of the risk of cachexia and prognostic factor in multiple myeloma patients. Background: Multiple myeloma (MM) is a hematological neoplasm of the early precursor of B-cells. The most characteristic symptoms observed during MM include hypocalcemia, anemia, bacterial infections, and renal damage. Nutritional disorders, especially malnutrition, are noted in about 35–71% of MM patients. Interleukin 1 beta (IL-1β) is a proinflammatory cytokine responsible for muscle atrophy and lipolysis during malnutrition and cachexia. This study aimed to evaluate the usefulness of the IL1B single-nucleotide polymorphism (SNP) (rs1143634) and plasma concentration of IL-1β in the assessment of the risk of nutritional disorders and prognosis in patients with MM. Methods: In our study, 93 patients with the de novo MM were enrolled. The real-time PCR with specific TaqMan probes method was used in genotyping. The IL-1β ELISA kit was used to determine IL-1β concentration in plasma samples. Results: Patients with the CC genotype, compared to the carriers of the other variants of the IL1B, demonstrated significantly higher concentrations of IL-1β in plasma (7.56 vs. 4.97 pg/mL), a significantly higher risk of cachexia (OR = 5.11), and a significantly higher risk of death (HR = 2.03). Moreover, high IL-1β plasma level was related to a significantly higher risk of cachexia (OR = 7.76); however, it was not significantly associated with progression-free survival (PFS) or overall survival (OS). Conclusions: Determination of the IL1B SNP (rs1143634) and plasma concentration of IL-1β may be useful in the assessment of the risk of cachexia and prognosis in patients with MM. [ABSTRACT FROM AUTHOR]

Globally, an estimated 50 million people are affected by epilepsy, a persistent, noncommunicable neurological ailment. Quercetin (QR) is a prevalent flavonoid substance extensively dispersed throughout agricultural life. In a pilocarpine (PILO)-induced epilepsy model in mice, this investigation aimed to determine whether QR has an antiepileptic effect and explore its putative mechanism of action. Fifty mice were allocated into seven groups, with six in every group. The first group received physiological saline, the second group was given diazepam (1 mg/kg), and four groups were administered QR at 50, 100, 150, and 200 mg/kg, respectively. The seventh group (the induction group) received normal saline. After 30 min, all groups were injected intraperitoneally with PILO. The impact of QR on motor coordination was assessed using the rotarod test, while measures such as latency to first seizure, generalized tonic-clonic seizures (GTCS), number of convulsions, and mortality were recorded. Serum samples were collected through the retro-orbital route to measure prostaglandin E2 (PGE2) and interleukin 1 beta (IL-1ß) levels. QR showed no significant difference in motor impairment, but increased duration until the initial seizure occurred and declined the mortality rate, duration of GTCS, and incidence of convulsions. All doses of QR significantly reduced PGE2 levels (P = 0.05). However, QR's effect on IL-1ß reduction was statistically insignificant (P > 0.05). QR's capacity to inhibit PILO-induced epilepsy by decreasing IL-1 and PGE2 levels is supported by this study. The results of this work indicate that QR could have a function to treat acute epilepsy. [ABSTRACT FROM AUTHOR]

Background: Diabetic nephropathy (DN) is a common complication of type 2 diabetes. Okra (Abelmoschus esculentus L) is reported to have anti-diabetic effects. The present study aimed to investigate the effects of dried okra extract (DOE) supplementation on lipid profile, renal function indices, and expression of inflammatory genes, as well as serum level of soluble Receptor for Advanced glycation end products (sRAGE) in patients with DN. Methods: In this triple-blind randomized placebo-controlled clinical trial, 64 eligible patients with DN received either 125 mg of DOE or placebo daily along with DN-related nutritional recommendations for 10 weeks. Changes in kidney indices including proteinuria and estimated glomerular filtration rate (eGFR), lipid profile, serum SRAGE, as well as the expression of RAGE, ICAM-1, and IL-1 genes were measured over 10 weeks. Results: After adjustment for the potential confounders, between-group analyses showed no significant differences in terms of lipid profile, kidney function indices, sRAGE, and RAGE-related inflammatory genes expression after 10 weeks. Conclusion: Daily 125 mg DOE along with nutritional recommendations on top of usual care did not lead to significant changes in renal function indices, lipid profile, and inflammatory genes expression in patients with DN.

Purpose: To the assess whole salivary cotinine and interleukin 1β (IL-1β) levels among individuals involuntarily exposed to vapor from electronic nicotine delivery systems (ENDS) (test group) and unexposed individuals (control group). Materials and Methods: Demographic data and information related to ENDS vapor exposure were collected using a questionnaire. Unstimulated whole saliva samples were collected, unstimulated whole-saliva flow rate (UWSFR) was calculated, and cotinine and IL-1β levels were determined using enzyme-linked immunosorbent assay. Samplesize estimation and statistical analysis were performed. Regression analysis was performed to determine the correlation between whole salivary cotinine and IL-1β levels. Statistical significance was set at p < 0.05. Results: Forty-eight individuals (24 and 24 in test and control groups, respectively) were included. Mean ages of individuals in the test and control groups were comparable. In the test group, the mean duration for which the individuals inhaled vapor from ENDS in each session was 22.3 ± 9.5 min and they were exposed to ENDS vapor 12.2 ± 2.4 times daily. There was no difference in the UWSFR between patients in the test (0.21 ± 0.02 ml/min) and control (0.22 ± 0.04 ml/min) groups. Whole salivary cotinine (p < 0.001) and IL-1β (p < 0.001) levels were significantly higher in the test than control group. Conclusion: Young adults involuntarily exposed to vapor from ENDS express elevated whole salivary cotinine and IL-1β levels. Long-term exposure to ENDS vapor may potentially predispose vulnerable populations to oral and systemic inflammatory diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Feeding approaches to increase production efficiency using new feed additives are essential for sustainable poultry production. This study aimed to evaluate the dietary addition of microbial muramidase (MMUR) on broiler chickens' nutritional and health aspects. The study suggested that MMUR could enhance the chicken growth rate and improve their antioxidant, inflammatory, and anti-inflammatory responses. The impact of microbial muramidase (MMUR) addition to broiler chicken rations was evaluated through growth parameters, liver histoarchitecture, antioxidant status, biochemical analysis, and expression of pro-inflammatory cytokines for 35 days. Four hundred three-day-old chicks (97.68 ± 0.59 g) were distributed to four distinct groups with ten duplicates each (100 chicks/group) consisting of: group 1 (G1): a basal diet without MMUR (control group); G2: a basal diet + 200 mg MMUR kg−1 G3: a basal diet + 400 mg MMUR kg−1; and G4: a basal diet + 600 mg MMUR kg−1. The results showed that the final body weight and total weight gain were increased (p = 0.015) in birds fed with diets supplemented with MMUR at 600 mg kg−1. The feed conversion ratio (FCR) was improved in all treatment groups compared with the control group. Birds fed with a diet supplemented with 600 mg MMUR kg−1 showed the highest body weight gain and improved FCR. The values of thyroxin hormones and growth hormones were increased in all MMUR-supplemented groups. Dietary MMUR increased the activities of antioxidant enzymes (total antioxidant activity, catalase, and superoxide dismutase) and decreased the activity of malondialdehyde (p < 0.05). In addition, it increased the values of interleukin 1 beta and interferon-gamma compared with the control group. Furthermore, dietary MMUR increased the expression of transforming growth factor-beta immunostaining in the liver and spleen tissues. Our results show that supplementing broilers' diets with 600 mg MMUR kg−1 could enhance the chicken growth rate and improve their antioxidant, inflammatory, and anti-inflammatory responses. [ABSTRACT FROM AUTHOR]

Persistent inflammation biologically alters signaling molecules and ultimately affects osteogenic differentiation, including in modern-day broilers with unique physiology. Lipopolysaccharides (LPS) are Gram-negative bacterial components that activate cells via transmembrane receptor activation and other molecules. Previous studies have shown several pathways associated with osteogenic inductive ability, but the pathway has yet to be deciphered, and data related to its dose-dependent effect are limited. Primary mesenchymal stem cells (MSCs) were isolated from the bones of day-old broiler chickens, and the current study focused on the dose-dependent variation (3.125 micrograms/mL to 50 micrograms/mL) in osteogenic differentiation and the associated biomarkers in primary MSCs. The doses in this study were determined using a cell viability (MTT) assay. The study revealed that osteogenic differentiation varied with dose, and the cells exposed to higher doses of LPS were viable but lacked differentiating ability. However, this effect became transient with lower doses, and this phenotypic character was observed with differential staining methods like Alizarin Red, Von Kossa, and alkaline phosphatase. The data from this study revealed that LPS at varying doses had a varying effect on osteogenic differentiation via several pathways acting simultaneously during bone development. [ABSTRACT FROM AUTHOR]

1. Abstract: Objective: Osteoarthritis (OA), the most prevalent form of arthritis, impacts approximately 10% of men and 18% of women aged above 60 years. Currently, a complete cure for OA remains elusive, making clinical management challenging. The traditional Chinese herb Notopterygium incisum, integral to the Juanbi pill for rheumatism, shows promise in safeguarding chondrocytes through its strong anti-inflammatory effects. Methods: To explore the protective effect of notopterol and miRNA (has-miR-4248) against inflammation, we simulated an inflammatory environment in chondrocytes cell lines C20A4 and C28/12, focusing on inflammasome formation and pyroptosis. Results: Our finding indicates notopterol significantly reduced interleukin (IL)-18 and tumor necrosis factor (TNF)-alpha levels in inflamed cells, curtailed reactive oxygen species (ROS) production post-inflammation, and inhibited the JAK2/STAT3 signaling pathway, thus offering chondrocytes protection from inflammation. Importantly, notopterol also hindered inflammasome assembly and pyroptosis by blocking the NF-κB/NLRP3 pathway through hsa-miR-4282 modulation. In vivo experiments showed that notopterol treatment markedly decreased Osteoarthritis Research Society International (OARSI) scores in OA mice and boosted hsa-miR-4282 expression compared to control groups. Conclusions: This study underscores notopterol's potential as a therapeutic agent in OA treatment, highlighting its capacity to shield cartilage from inflammation-induced damage, particularly by preventing pyroptosis.

Abstract Background The role of pro-resolving mediators in inflammation is a new concern in research. The effect of low-dose aspirin on production of a special kind of these mediators named aspirin triggered lipoxin (ATL) has been studied on different tissues. This randomized clinical trial evaluated the effect of low-dose aspirin on ATL and pro-inflammatory mediators’ level in periapical fluid of necrotic teeth with large lesions. Methods Twenty-four patients with necrotic pulp and periapical lesion were randomly assigned to low-dose aspirin and placebo groups. In the first appointment, canals were shaped up to F3 size and #40 K-file and cleaned with 10 milliliters 2.5% sodium hypochlorite and 17% Ethylenediaminetetraacetic acid. Periapical fluid was sampled by a paper cone. The tooth was temporized without any intracanal medication. Tablets were administered for 7 days, then the teeth were re-opened and the sampling were repeated. Interleukin-1 beta (IL-1β), prostaglandin E2 (PGE2) and ATL were analyzed by enzyme-linked immunosorbent assay. Data were analyzed with paired t-test using SPSS statistical software, version 21 (α = 0.05). Results A significant reduction in PGE2 and IL-1β was noted in the aspirin-treated group while an increase in ATL was observed (P 0.05). Conclusion Low-dose aspirin can influence the inflammatory process by reducing pro-inflammatory mediators such as PGE2 and IL-1β, as well as increasing the pro-resolving mediators such as ATL. Trial registration IRCT20191211045702N1.

Autologous fat transfers show promise in treating fibrotic skin diseases, reversing scarring and stiffness, and improving quality of life. Adipose-derived stem cells (ADSCs) within these grafts are believed to be crucial for this effect, particularly their secreted factors, though the specific mechanisms remain unclear. This study investigates transcriptomic changes in ADSCs after in vitro fibrotic, inflammatory, and hypoxic conditioning. High-throughput gene expression assays were conducted on ADSCs exposed to IL1-β, TGF-β1, and hypoxia and in media with fetal bovine serum (FBS). Flow cytometry characterized the ADSCs. RNA-Seq analysis revealed distinct gene expression patterns between the conditions. FBS upregulated pathways were related to the cell cycle, replication, wound healing, and ossification. IL1-β induced immunomodulatory pathways, including granulocyte chemotaxis and cytokine production. TGF-β1 treatment upregulated wound healing and muscle tissue development pathways. Hypoxia led to the downregulation of mitochondria and cellular activity.

Background: Fibrin glue has shown to be a pioneering remedy to overcome the inconvenience of suturing. Autologous products reduce the risk of contamination and immunological responses compared to commercial fibrin glue. Hence using autologous fibrin glue (AFG) as a tissue sealant in periodontal flap closure would be of added value for a predictable outcome. Objective: To evaluate and compare the efficacy of AFG with 4-0 silk sutures in periodontal flap closure and healing. Material and methods: Total of 17 patients diagnosed with generalized periodontitis in the age group of 18 to 60 years with probing pocket depth of ≥ 6 mm and clinical attachment level of ≥5 mm in at least two quadrants were categorized into test group (AFG) and control group (4-0 silk sutures). Primary outcome measures [modified gingival index (MGI), early wound index (EHI) and interleukin 1 beta (IL-1ß) and secondary outcome measures (oral hygiene index, plaque index and visual analog scale (VAS) were recorded at baseline, 1, 2, 3 and 4 weeks. Results: A statistically significant reduction of IL-1ß value (p =.005); MGI (p =.02); EHI (p =.004), VAS scores (p <.001) and a positive Spearman's correlation (rho = 0.15) was seen between EHI scores & IL-1ß levels in test group at 1week period in comparison to control group. Conclusion: AFG showed promising results as an alternative to sutures. The use of AFG significantly improved clinical parameters and reduced the levels of pro-inflammatory cytokines making it an effective adhesive with healing properties in the era of suture-less periodontal flap surgery. [ABSTRACT FROM AUTHOR]

Background: The role of pro-resolving mediators in inflammation is a new concern in research. The effect of low-dose aspirin on production of a special kind of these mediators named aspirin triggered lipoxin (ATL) has been studied on different tissues. This randomized clinical trial evaluated the effect of low-dose aspirin on ATL and pro-inflammatory mediators' level in periapical fluid of necrotic teeth with large lesions. Methods: Twenty-four patients with necrotic pulp and periapical lesion were randomly assigned to low-dose aspirin and placebo groups. In the first appointment, canals were shaped up to F3 size and #40 K-file and cleaned with 10 milliliters 2.5% sodium hypochlorite and 17% Ethylenediaminetetraacetic acid. Periapical fluid was sampled by a paper cone. The tooth was temporized without any intracanal medication. Tablets were administered for 7 days, then the teeth were re-opened and the sampling were repeated. Interleukin-1 beta (IL-1β), prostaglandin E2 (PGE2) and ATL were analyzed by enzyme-linked immunosorbent assay. Data were analyzed with paired t-test using SPSS statistical software, version 21 (α = 0.05). Results: A significant reduction in PGE2 and IL-1β was noted in the aspirin-treated group while an increase in ATL was observed (P < 0.001). There was no significant difference in the mediator scores before and after in the placebo-treated group (P > 0.05). Conclusion: Low-dose aspirin can influence the inflammatory process by reducing pro-inflammatory mediators such as PGE2 and IL-1β, as well as increasing the pro-resolving mediators such as ATL. Trial registration: IRCT20191211045702N1. [ABSTRACT FROM AUTHOR]

Background: Multiple myeloma (MM) is a hematological neoplasm of the early precursor of B-cells. The most characteristic symptoms observed during MM include hypocalcemia, anemia, bacterial infections, and renal damage. Nutritional disorders, especially malnutrition, are noted in about 35–71% of MM patients. Interleukin 1 beta (IL-1β) is a proinflammatory cytokine responsible for muscle atrophy and lipolysis during malnutrition and cachexia. This study aimed to evaluate the usefulness of the IL1B single-nucleotide polymorphism (SNP) (rs1143634) and plasma concentration of IL-1β in the assessment of the risk of nutritional disorders and prognosis in patients with MM. Methods: In our study, 93 patients with the de novo MM were enrolled. The real-time PCR with specific TaqMan probes method was used in genotyping. The IL-1β ELISA kit was used to determine IL-1β concentration in plasma samples. Results: Patients with the CC genotype, compared to the carriers of the other variants of the IL1B, demonstrated significantly higher concentrations of IL-1β in plasma (7.56 vs. 4.97 pg/mL), a significantly higher risk of cachexia (OR = 5.11), and a significantly higher risk of death (HR = 2.03). Moreover, high IL-1β plasma level was related to a significantly higher risk of cachexia (OR = 7.76); however, it was not significantly associated with progression-free survival (PFS) or overall survival (OS). Conclusions: Determination of the IL1B SNP (rs1143634) and plasma concentration of IL-1β may be useful in the assessment of the risk of cachexia and prognosis in patients with MM.

Bronchial asthma is the most common chronic respiratory disease of childhood. Cough is one of its defining symptoms. This study investigated the associations between selected inflammatory biomarkers and cough reflex sensitivity after capsaicin inhalation in children with mild and moderate well-controlled type 2 endotype asthma compared with non-asthmatic probands. Sensitivity to the cough reflex was measured by recording the cough response after capsaicin inhalation. The sandwich ELISA method was used to measure serum concentrations of the investigated potential inflammatory biomarkers (interleukin 13, interleukin 1β, eosinophil-derived neurotoxin). The acquired data were statistically evaluated according to descriptive analyses for summarization and comparison between cough reflex sensitivity parameters and individual biomarker values in the observed and control groups modeled by a simple linear regression model. Statistical significance was defined as p<0.05. We showed a statistically significant association (p-value 0.03) between cough reflex sensitivity – C2 value (capsaicin concentration required for two cough responses) and interleukin 1β serum concentrations in the asthma group compared with the control group of non-asthmatic children. Our results support the possibility of interleukin 1β as a potential additive inflammatory biomarker used in clinical practice in children with asthma because of its correlation with the activity of the afferent nerve endings in the airways. [ABSTRACT FROM AUTHOR]

The study aims to determine the relationship of migraine and chronic tension-type headache (TTHs) with alterations in the salivary markers of inflammation. - The prospective study involved 75 patients. The concentrations of inflammatory markers (CRP, IL-1 β, and IL-6) in migraine and chronic TTH patients were determined in distinct time points: headache-free period (interictal period), during headache (ictal period), day after headache attack. The STAI-Y (State Trait Anxiety Inventory – Y) and BDI (Beck Depression Inventory) questionnaires were used to measure the level of anxiety and depression in the interictal and ictal periods. The interictal levels of CRP, IL1-β, and IL-6 were significantly higher in headache groups compared to healthy controls (p < 0.001). Differences in the ictal concentrations were even stronger. Twenty-four hours after headache attack, patients with migraine and chronic TTH experienced a decrease in CRP, IL1-β, and IL-6 levels; yet, those levels were still higher compared with the interictal ones. The repeated analysis of variance revealed no significant statistical differences in CRP, IL-β, and IL-6 levels between the migraine and TTH groups over time (p > 0.05). Statistically higher levels of anxiety and depression were seen in unhealthy groups (p < 0.01). The relationship of CRP, IL1-β, and IL-6 concentrations with migraine and chronic TTH has been established. No statistically significant differences were found in the dynamics between migraine and chronic TTH groups. There was a direct correlation of migraine and chronic TTH with anxiety and depression. [ABSTRACT FROM AUTHOR]

The impact of microbial muramidase (MMUR) addition to broiler chicken rations was evaluated through growth parameters, liver histoarchitecture, antioxidant status, biochemical analysis, and expression of pro-inflammatory cytokines for 35 days. Four hundred three-day-old chicks (97.68 ± 0.59 g) were distributed to four distinct groups with ten duplicates each (100 chicks/group) consisting of: group 1 (G1): a basal diet without MMUR (control group); G2: a basal diet + 200 mg MMUR kg−1 G3: a basal diet + 400 mg MMUR kg−1; and G4: a basal diet + 600 mg MMUR kg−1. The results showed that the final body weight and total weight gain were increased (p = 0.015) in birds fed with diets supplemented with MMUR at 600 mg kg−1. The feed conversion ratio (FCR) was improved in all treatment groups compared with the control group. Birds fed with a diet supplemented with 600 mg MMUR kg−1 showed the highest body weight gain and improved FCR. The values of thyroxin hormones and growth hormones were increased in all MMUR-supplemented groups. Dietary MMUR increased the activities of antioxidant enzymes (total antioxidant activity, catalase, and superoxide dismutase) and decreased the activity of malondialdehyde (p < 0.05). In addition, it increased the values of interleukin 1 beta and interferon-gamma compared with the control group. Furthermore, dietary MMUR increased the expression of transforming growth factor-beta immunostaining in the liver and spleen tissues. Our results show that supplementing broilers’ diets with 600 mg MMUR kg−1 could enhance the chicken growth rate and improve their antioxidant, inflammatory, and anti-inflammatory responses.

Persistent inflammation biologically alters signaling molecules and ultimately affects osteogenic differentiation, including in modern-day broilers with unique physiology. Lipopolysaccharides (LPS) are Gram-negative bacterial components that activate cells via transmembrane receptor activation and other molecules. Previous studies have shown several pathways associated with osteogenic inductive ability, but the pathway has yet to be deciphered, and data related to its dose-dependent effect are limited. Primary mesenchymal stem cells (MSCs) were isolated from the bones of day-old broiler chickens, and the current study focused on the dose-dependent variation (3.125 micrograms/mL to 50 micrograms/mL) in osteogenic differentiation and the associated biomarkers in primary MSCs. The doses in this study were determined using a cell viability (MTT) assay. The study revealed that osteogenic differentiation varied with dose, and the cells exposed to higher doses of LPS were viable but lacked differentiating ability. However, this effect became transient with lower doses, and this phenotypic character was observed with differential staining methods like Alizarin Red, Von Kossa, and alkaline phosphatase. The data from this study revealed that LPS at varying doses had a varying effect on osteogenic differentiation via several pathways acting simultaneously during bone development.

Background: Orthodontic tooth movement is mediated by the inflammation process. Inflammation induces pain and increases the level of cortisol hormone as it triggers stress. The aim of this research was to observe the effects of vitamin E (VE) supplementation in reducing stress levels from orthodontic force in Wistar rats (Rattus norvegicus). Methods: Wistar rats (n = 56) were divided into two groups: group 1 as the control group, and group 2 as the experimental group (VE group). VE supplemented for 14 days prior application of the separator as an orthodontic force. Each group was divided into four subgroups (n = 7), corresponding to the duration in days that force was applied, i.e., 0, 1, 3, and 7 days. Stress were measured by cortisol levels, and inflammation were measured by interleukin-1 beta (IL-1β) levels in blood plasma. Results: The VE group had lower cortisol levels than the control group, and significant found on days 3 and 7 (p = 0.026 and p = 0.037). The cortisol level in the VE group decreased faster, beginning on day 1, whilst the control group occurred on day 3. Statistical analysis of IL-1β levels found insignificant differences between the two groups. Conclusion: Vitamin E helps reduce stress caused by orthodontic force due to tooth movement.

Barbara Choroma&nacute;ska,1 Piotr My&sacute;liwiec,1 Tomasz Koz&lstrok;owski,1 Magdalena &Lstrok;uba,1 Piotr Wojskowicz,1 Jacek Dadan,1 Hanna My&sacute;liwiec,2 Katarzyna Choroma&nacute;ska,3 Katarzyna Makarewicz,4 Anna Zalewska,5 Mateusz Maciejczyk6 1 1st Department of General and Endocrine Surgery, Medical University of Bialystok, Bialystok, Poland; 2Department of Dermatology and Venereology, Medical University of Bialystok, Bialystok, Poland; 3Department of Oral Surgery, Medical University of Gdansk, Gdansk, Poland; 4Regional Centre for Transfusion Medicine in Bialystok, Bialystok, Poland; 5Experimental Dentistry Laboratory, Medical University of Bialystok, Bialystok, Poland; 6Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, Bialystok, PolandCorrespondence: Mateusz Maciejczyk Email mat.maciejczyk@gmail.comBackground: Adrenal masses are the most common of all human tumors. The role of nitrosative stress and inflammation in cancer development has already been demonstrated. However, it is not known whether they are involved in the pathogenesis of adrenal tumors. The aim of the study was to investigate a cross-talk between nitrosative stress, inflammation and hypoxia-inducible factor (HIF-1α) in 75 patients with different types of adrenal masses (non-functional incidentaloma, pheochromocytoma and Cushing’s/Conn’s adenoma).Methods: The plasma concentrations of total nitric oxide (NO), S-nitrosothiols, peroxynitrite nitrotyrosine and the activity of serum myeloperoxidase (MPO) were measured spectrophotometrically, whereas concentrations of interleukin 1 beta (IL-1β), tumor necrosis factor α (TNF-α) and hypoxia-inducible factor 1 alpha (HIF-1α) were measured using commercial ELISA kits. The control group consisted of 50 healthy people matched by age and sex to the study group. The number of subjects was determined a priori based on our previous experiment (power of the test = 0.9; α = 0.05).Results: We found significantly higher nitrosative stress (↑nitric oxide, ↑peroxynitrite, ↑S-nitrosothiols and ↑nitrotyrosine) in the plasma of patients with adrenal tumors, which was accompanied by increased inflammatory (↑myeloperoxidase, ↑interleukin 1 beta and ↑tumor necrosis factor α) and hypoxia (HIF-1α) biomarkers. Peroxynitrite and nitrotyrosine were positively correlated with aldosterone level. Nitrosative stress was also associated with inflammation and HIF-1α. Interestingly, plasma nitrotyrosine and serum MPO differentiated patients with adrenal tumor from healthy individuals with high sensitivity and specificity. Moreover, using multivariate regression analysis, we showed that ONOO− and IL-1β depended on cortisol level, while ONOO−, nitrotyrosine and HIF-1α were associated with aldosterone. Unfortunately, none of the assessed biomarkers differentiated between tumor types studied, suggesting that the severity of nitrosative damage and inflammation are similar in patients with incidentaloma, pheochromocytoma, and Cushing’s or Conn’s adenoma.Conclusion: Adrenal tumors are associated with increased protein nitration/S-nitrosylation and inflammation.Keywords: adrenal tumors, nitrosative stress, nitric oxide, peroxynitrite, S-nitrosothiols, nitrotyrosine, myeloperoxidase, interleukin 1 beta, tumor necrosis factor, α hypoxia-inducible factor

Aims: Tert-butylhydroquinone (tBHQ) has been identified as an inhibitor of oxidative stress-induced injury and apoptosis in human neural stem cells. However, the role of tBHQ in osteoarthritis (OA) is unclear. This study was carried out to investigate the role of tBHQ in OA. Methods: OA animal model was induced by destabilization of the medial meniscus (DMM). Different concentrations of tBHQ (25 and 50 mg/kg) were intraperitoneally injected in ten-week-old female mice. Chondrocytes were isolated from articular cartilage of mice and treated with 5 ng/ml lipopolysaccharide (LPS) or 10 ng/ml interleukin 1 beta (IL-1β) for 24 hours, and then treated with different concentrations of tBHQ (10, 20, and 40 μM) for 12 hours. The expression levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in blood were measured. The expression levels of interleukin 6 (IL-6), IL-1β, and tumour necrosis factor alpha (TNF-α) leptin in plasma were measured using enzyme-linked immunoabsorbent assay (ELISA) kits. The expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathway proteins, and macrophage repolarization-related markers, were detected by western blot. Results: Tert-butylhydroquinone significantly attenuated cartilage destruction in DMM-induced mice in vivo. It demonstrated clear evidence of inhibiting IL-1β-induced chondrocyte apoptosis, inflammation, and differentiation defect in vitro. Meanwhile, tBHQ inhibited LPS-induced activation of NF-κB and MAPK signalling pathways, and also inhibited LPS-induced reactive oxygen species production and macrophages repolarization in vitro. Conclusion: Taken together, tBHQ might be a potential therapeutic strategy for protecting against OA development. Cite this article: Bone Joint Res 2021;10(11):704–713.

Inflammatory processes contribute to osteoarthritis (OA) severity and progression. Mesenchymal stem cells, particularly those derived from adipose tissue (ASCs), are able to sense and control the inflammatory environment. This immunomodulatory potential can be boosted by different priming strategies based on inflammatory stimulation. The aim of the present study is to investigate the transcriptional modulation of a huge panel of genes and functionally verify the predicted immunomodulatory ability of ASCs after interleukin one beta (IL-1β) priming. ASCs were isolated from adipose tissue obtained from three donors and expanded. After stimulation with 1 ng/ml of IL-1β for 48 h, cells were collected for gene array and functional tests. Pooled cells from three donors were used for RNA extraction and gene array analysis. Gene Ontology (GO) enrichment analysis and Gene Set Enrichment Analysis (GSEA) were performed to assess the involvement of the modulated genes after priming in specific biological processes and pathways. Functional co-culture tests of ASCs with T cells and macrophages were performed to assess the ability of primed ASCs to modulate immune cell phenotype. Among the overall genes analyzed in the gene array, about the 18% were up- or down-regulated in ASCs after IL-1β priming. GO enrichment analysis of up- or down-regulated genes in ASCs after IL-1β priming allowed identifying specific pathways involved in the modulation of inflammation and extracellular matrix remodeling. The main processes enriched according to the GSEA are related to the inflammatory response and cell proliferative processes. Functional tests on immune cells showed that primed and non-primed ASCs induced a decrease in the CD3+ T lymphocytes survival rate and an anti-inflammatory macrophage polarization. In conclusion, IL-1β priming represents a tailored strategy to enhance the ability of ASCs to direct macrophages towards an anti-inflammatory phenotype and, consequently, improve the efficacy of ASCs in counteracting the OA inflammatory component.

Murine macrophages activated by the Toll-like receptor 4 agonist lipopolysaccharide (LPS) polarize to the M1 type by inducing proinflammatory marker proteins and changing their energy metabolism to increased aerobic glycolysis and reduced respiration. We here show that the aliphatic isothiocyanate sulforaphane (Sfn) diminishes M1 marker expression (IL-1β, IL-6, TNF-α, iNOS, NO, and ROS) and leads to highly energetic cells characterized by both high glycolytic and high respiratory activity as assessed by extracellular flux analysis. Focusing on a potential connection between high glycolytic activity and low IL-1β expression in M1 (LPS/Sfn) macrophages, we reveal that Sfn impedes the moonlighting function of pyruvate kinase M2 (PKM2) in M1 macrophages. Sfn limits mono/dimerization and nuclear residence of PKM2 accompanied by reduced HIF-1α levels, Stat3 phosphorylation at tyrosine 705, and IL-1β expression while preserving high levels of cytosolic PKM2 tetramer with high glycolytic enzyme activity. Sfn prevents glutathionylation of PKM2 in LPS-stimulated macrophages which may account for the reduced loss of PKM2 tetramer. Overall, we uncover PKM2 as a novel affected hub within the anti-inflammatory activity profile of Sfn. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative and painful inflammatory joint disease affecting the cartilage, bone, and synovial membranes, without any effective treatment that targets the underlying mechanisms of OA. Our study evaluated the therapeutic effects of a live probiotic strain, Clostridium butyricum GKB7, administered for 6 weeks to rats with knee OA (KOA) induced by anterior cruciate ligament transection (ACLT) of the right knee. All rats underwent weekly weight-bearing behavioral testing and body weight measurements. At 6 weeks, all rats were sacrificed, and the right hind knees were collected for micro-computed tomography imaging and histopathological and immunohistochemical analyses. Compared with rats in the ACLT-only group, ACLT rats administered the probiotic exhibited dramatic improvements in pain-related behavior from postoperative week 2, had significantly less osseous and cartilaginous damage at week 6, and significantly lower levels of the inflammatory markers interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in cartilage and synovium sections. C. butyricum GKB7 appeared to slow or even reverse OA progression and is worth investigating as a novel therapeutic for OA. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is an age-related disorder that affects the joints and causes functional disability. Hericium erinaceus is a large edible mushroom with several known medicinal functions. However, the therapeutic effects of H. erinaceus in OA are unknown. In this study, data from Sprague-Dawley rats with knee OA induced by anterior cruciate ligament transection (ACLT) indicated that H. erinaceus mycelium improves ACLT-induced weight-bearing asymmetry and minimizes pain. ACLT-induced increases in articular cartilage degradation and bone erosion were significantly reduced by treatment with H. erinaceus mycelium. In addition, H. erinaceus mycelium reduced the synthesis of proinflammatory cytokines interleukin-1β and tumor necrosis factor-α in OA cartilage and synovium. H. erinaceus mycelium shows promise as a functional food in the treatment of OA. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune disease that causes persistent inflammation involving the joints, cartilage, and synovium. In individuals with RA, alterations in the composition of intestinal bacteria suggest the vital role of gut microbiota in immune dysfunction. Multiple therapies commonly used to treat RA can also alter the diversity of gut microbiota, further suggesting the modulation of gut microbiota as a prevention or treatment for RA. Therefore, a better understanding of the changes in the gut microbiota that accompany RA should facilitate the development of novel therapeutic approaches. In this study, B. coagulans BACO-17 not only significantly reduced paw swelling, arthritis scores, and hind paw and forepaw thicknesses but also protected articular cartilage and the synovium against RA degeneration, with a corresponding downregulation of TNF-α expression. The inhibition or even reversing of RA progression highlights B. coagulans BACO-17 as a novel therapeutic for RA worth investigating., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Murine macrophages activated by the Toll-like receptor 4 agonist lipopolysaccharide (LPS) polarize to the M1 type by inducing proinflammatory marker proteins and changing their energy metabolism to increased aerobic glycolysis and reduced respiration. We here show that the aliphatic isothiocyanate sulforaphane (Sfn) diminishes M1 marker expression (IL-1β, IL-6, TNF-α, iNOS, NO, and ROS) and leads to highly energetic cells characterized by both high glycolytic and high respiratory activity as assessed by extracellular flux analysis. Focusing on a potential connection between high glycolytic activity and low IL-1β expression in M1 (LPS/Sfn) macrophages, we reveal that Sfn impedes the moonlighting function of pyruvate kinase M2 (PKM2) in M1 macrophages. Sfn limits mono/dimerization and nuclear residence of PKM2 accompanied by reduced HIF-1α levels, Stat3 phosphorylation at tyrosine 705, and IL-1β expression while preserving high levels of cytosolic PKM2 tetramer with high glycolytic enzyme activity. Sfn prevents glutathionylation of PKM2 in LPS-stimulated macrophages which may account for the reduced loss of PKM2 tetramer. Overall, we uncover PKM2 as a novel affected hub within the anti-inflammatory activity profile of Sfn.

Objective: Periodontitis is a chronic inflammatory disease initiated by dysbiotic microbiota. Conventional mechanical debridement often needs adjunctive measures to control the disease process. The objective of the present study was to find out benefit of ozonized water irrigation along with nonsurgical periodontal therapy for the management of periodontitis. Methods: We have conducted a randomized controlled, triple‐blinded, parallel‐group clinical trial. The test group (n = 25) was treated with ozonized water irrigation, whereas the control group (n = 25) received normal saline irrigation along with mechanical debridement. Full mouth plaque score, bleeding score, probing pocket depth and clinical attachment loss were evaluated at baseline and 4 weeks after treatment. Salivary interleukin 1 beta was analysed using enzyme linked immunosorbent assay. Analysis of covariance, t test and chi‐square test were used for intergroup comparison. Intragroup comparison was done using the paired t test. Results: Adjunctive ozone water irrigation resulted in significant improvement in all clinical parameters, except probing pocket depth after adjusting the extraneous effects due to initial confounding factors (p < 0.001). But as per subgroup analysis, ozone water irrigation resulted in significant reduction in pocket depth in deep pockets (p = 0.01) and the number of sites with a pocket depth ≥4 mm with bleeding on probing. Salivary interleukin 1 beta also reduced significantly in the test group after therapy. Conclusion: Ozone irrigation provides adjunctive benefit along with nonsurgical periodontal therapy in reducing clinical parameters and inflammatory mediators in saliva. But long‐term benefits need to be assessed with future studies. The study was registered in the Clinical Trial Registry of India (CTRI no: CTRI/2020/06/026275). [ABSTRACT FROM AUTHOR]

The current work assessed the inclusion impacts of oilseed camelina meal (CM) as a protein source in red sea bream (Pagrus major) diets. A 45 day assessment period with 180 juveniles (6.47 ± 0.17 g) were allocated in triplicates to 4 experimental groups and fed formulated diets in which fish meal (FM) was subrogated at graded series of 0% (T1), 20.5% soybean meal (T2), 20.5% camelina meal (T3), and 33% camelina meal (T4). No noticeable alterations were observed in specific growth rate, feed intake, survival rate, hepatosomatic index, and Fulton's condition factor among the experimental groups. Fish fed the T4 diet showed considerably reduced (P 0.05) in glucose, total bilirubin, total protein, total cholesterol, triglyceride, glutamyl oxaloacetic transaminase, and glutamic pyruvate transaminase. Hematocrit levels decreased noticeably (P

Diabetic nephropathy (DN) is a common complication of type 2 diabetes. Okra (Abelmoschus esculentus L) is reported to have anti-diabetic effects. The present study aimed to investigate the effects of dried okra extract (DOE) supplementation on lipid profile, renal function indices, and expression of inflammatory genes, as well as serum level of soluble Receptor for Advanced glycation end products (sRAGE) in patients with DN. In this triple-blind randomized placebo-controlled clinical trial, 64 eligible patients with DN received either 125 mg of DOE or placebo daily along with DN-related nutritional recommendations for 10 weeks. Changes in kidney indices including proteinuria and estimated glomerular filtration rate (eGFR), lipid profile, serum SRAGE, as well as the expression of RAGE, ICAM-1, and IL-1 genes were measured over 10 weeks. After adjustment for the potential confounders, between-group analyses showed no significant differences in terms of lipid profile, kidney function indices, sRAGE, and RAGE-related inflammatory genes expression after 10 weeks. Daily 125 mg DOE along with nutritional recommendations on top of usual care did not lead to significant changes in renal function indices, lipid profile, and inflammatory genes expression in patients with DN. • The present clinical trial for the first time investigated the effects of okra in Diabetic nephropathy patients. • Flame-photometer analysis indicated the amounts of potassium and sodium in the Dried okra extract. • the type and value of bioactive compounds in okra vary among each native variance. • In our study, the dried hydroalcoholic extract of okra was used, which is different from those supplemented in most of the previous studies. [ABSTRACT FROM AUTHOR]

Background: Paraquat (PQ) has been reported to have a high mortality rate. The major target organ of PQ poisoning is the lungs. The pathogenesis of PQ-induced lung injury involves oxidative stress and inflammation. Unfortunately, there is still no effective antidote for PQ poisoning. We hypothesized that aqueous Thunbergia laurifolia (TL) leaf extract is a possible antidote for PQ-induced lung injury. Methods: The total phenolic content and caffeic acid content of an aqueous extract of TL leaves were analyzed. Male Wistar rats were randomly divided into four groups (n = 4 per group): the control group (administered normal saline), the PQ group (administered 18 mg/kg body weight (BW) PQ dichloride subcutaneously), the PQ + TL-low-dose (LD) group (administered PQ dichloride subcutaneously and 100 mg/kg BW aqueous TL leaf extract by oral gavage) and the PQ + TL-high-dose (HD) group (administered PQ dichloride subcutaneously and 200 mg/kg BW aqueous TL leaf extract by oral gavage). Malondialdehyde (MDA) levels and lung histopathology were analyzed. In addition, the mRNA expression of NADPH oxidase (NOX), interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) was assessed using reverse transcription-polymerase chain reaction (RT-PCR), and the protein expression of IL-1β and TNF-α was analyzed using immunohistochemistry. Results: The total phenolic content of the extract was 20.1 ± 0.39 μg gallic acid equivalents (Eq)/mg extract, and the caffeic acid content was 0.31 ± 0.01 μg/mg. The PQ group showed significantly higher MDA levels and NOX, IL-1β and TNF-α mRNA expression than the control group. Significant pathological changes, including alveolar edema, diffuse alveolar collapse, hemorrhage, leukocyte infiltration, alveolar septal thickening and vascular congestion, were observed in the PQ group compared with the control group. However, the aqueous TL leaf extract significantly attenuated the PQ-induced increases in MDA levels and NOX, IL-1β and TNF-α expressions. Moreover, the aqueous TL leaf extract ameliorated PQ-induced lung pathology. Conclusion: This study indicates that aqueous TL leaf extract can ameliorate PQ-induced lung pathology by modulating oxidative stress through inhibition of NOX and by regulating inflammation through inhibition of IL-1β and TNF-α expressions. We suggest that aqueous TL leaf extract can be used as an antidote for PQ-induced lung injury. [ABSTRACT FROM AUTHOR]

During orthodontic tooth movement (OTM), there is the release of cytokines in the gingival crevicular fluid (GCF) that are supposed to participate in the bone remodeling. This systematic review aimed at assessing the effects of photobiomodulation (PBM) on the levels of these cytokines during OTM. This systematic review according to Cochrane Collaboration guidelines aimed to answer the clinical question following the PICOS strategy. The broad search in the literature was performed before 05 April, 2021 in six electronic databases (Pubmed, Web of Science, Scopus, Embase, Cochrane, Biblioteca Virtual de Saúde) and supplemented by the grey literature. The risk of bias of randomized and non-randomized clinical trials was evaluated by two tools: RoB 2 and ROBINS-I. Mean and standard deviation of cytokine levels was extracted to meta-analysis, and the GRADE system was applied to assess the quality of the evidence. Nine studies were included in this review. Low-level laser therapy (LLLT) was the photobiomodulation type used in most of the studies (n = 8). The wavelengths used varied from 618 to 980 nm and also differed concerning the light emission pattern. LLLT increased the levels of IL-1β, IL-8, OPN, and PGE2, but not TNF-α1, TGF-β1. The levels of IL6, RANKL, and OPG presented conflicting results. LLLT was statistically associated with an increase of IL-1β levels (standard mean difference [SMD] = 1.99; 95% confidence interval = 0.66 to 3.33; p < 0.001) with low certainty of evidence. LLLT may increase the levels of IL-1β and other cytokines; however, the results should be interpreted with caution due to protocol variations between studies, and the few studies added in the meta-analysis. [ABSTRACT FROM AUTHOR]

Bruxism is occlusal behaviour that often leads to stomatognathic system overload. Inflammatory markers in the periodontium are detectable in the gingival crevicular fluid (GCF). GCF production fluctuates due to various factors. Our study aimed to assess the effect of tooth clenching or grinding on GCF volume and proinflammatory IL-1β concentration in GCF. This pilot study was carried out on 20 participants aged 21 to 28 with good general health (per 10 people studied and control groups). GCF volume was measured with Periotron 8010 after absorbing for 30 s with PerioPaper strips. Twelve samples were collected from each patient—the buccal and lingual surfaces of teeth 16, 11, 24, 36, 31, and 44 were included. Laboratory examination of IL-1β concentration was performed. In patients with pathological tooth wear, a tendency to increase GCF secretion and IL-1β concentration in GCF was found. GCF volumes were higher in posterior teeth, while IL-1β levels were higher in anterior teeth. Crevices at the molars seem to have a potential predictive value in diagnosing periodontal microinflammation in patients with probable bruxism. Due to occlusal overload, these bruxists are more prone to microinflammatory processes in the periodontium. Further studies in a broader group are required to confirm this correlation. [ABSTRACT FROM AUTHOR]

Extracts from Taiwan's traditional medicinal mushroom, Antrodia cinnamomea , exhibit anti-inflammatory activities in cellular and preclinical studies. However, this paper is the first to report that Antcin K, a triterpenoid isolated from A. cinnamomea , inhibits proinflammatory cytokine production in human rheumatoid synovial fibroblasts (RASFs), which are major players in rheumatoid arthritis (RA) disease. In our analysis of the mechanism of action, Antcin K inhibited the expression of three cytokines (tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL-1β] and IL-8) in human RASFs; cytokines that are crucial to RA synovial inflammation. Notably, incubation of RASFs with Antcin K reduced the phosphorylation of the focal adhesion kinase (FAK), phosphoinositide 3-kinase (PI3K), protein kinase B (AKT) and nuclear factor-κB (NF-κB) signaling cascades, all of which promote cytokine production in RA. Intraperitoneal injections of Antcin K (10 mg/kg or 30 mg/kg) attenuated paw swelling, cartilage degradation and bone erosion, and decreased serum levels of TNF-α, IL-1β, IL-8 in collagen-induced arthritis (CIA) mice; in further experiments, IL-6 levels were similarly reduced. The inhibitory effects of Antcin K upon TNF-α, IL-1β and IL-8 expression in human RASFs was achieved through the downregulation of the FAK, PI3K, AKT and NF-κB signaling cascades. Our data support clinical investigations using Antcin K in RA disease. [ABSTRACT FROM AUTHOR]

Orthodontic tooth movement is mediated by the inflammation process. Inflammation induces pain and increases the level of cortisol hormone as it triggers stress. The aim of this research was to observe the effects of vitamin E (VE) supplementation in reducing stress levels from orthodontic force in Wistar rats (Rattus norvegicus). Wistar rats (n = 56) were divided into two groups: group 1 as the control group, and group 2 as the experimental group (VE group). VE supplemented for 14 days prior application of the separator as an orthodontic force. Each group was divided into four subgroups (n = 7), corresponding to the duration in days that force was applied, i.e., 0, 1, 3, and 7 days. Stress were measured by cortisol levels, and inflammation were measured by interleukin-1 beta (IL-1β) levels in blood plasma. The VE group had lower cortisol levels than the control group, and significant found on days 3 and 7 (p = 0.026 and p = 0.037). The cortisol level in the VE group decreased faster, beginning on day 1, whilst the control group occurred on day 3. Statistical analysis of IL-1β levels found insignificant differences between the two groups. Vitamin E helps reduce stress caused by orthodontic force due to tooth movement. [ABSTRACT FROM AUTHOR]

The mucopolysaccharidoses (MPS) are a heterogeneous group of inborn errors of metabolism with an increased deposition of glycosaminoglycans in lysosomes (GAGs). In MPS, GAG leads to inflammatory pathway activation. In MPS models, studies have shown that accumulation of glycosaminoglycans in lysosomes causes activation of oxidative stress, and then apoptosis is triggered. In this study, the aim was to show whether GAG deposition could trigger the inflammatory processes via cytokines. Forty-three MPS patients as patient group and 29 healthy children as control group were included in the study. Samples were taken before and after ERT from 8 MPS patients. 15 patients were treated with enzyme replacement and 28 patients could not be treated with the enzyme. Tumor necrosis alpha (TNF-α), interleukin 1-beta (IL-1β), interleukin 6 (IL-6) levels were studied by ELISA method. When cytokine levels of MPS patients and control groups were compared, cytokines were found to significantly increased (p≤0.05) in MPS patients. Pretreatment IL-6 and posttreatment IL-6 and IL-1β levels of patients treated with enzyme replacement therapy (ERT) were found near to control group. Pre-treatment and post-treatment TNF-α levels were found significantly higher in MPS patients than the control group that was significantly higher in the post-treatment group. In the MPS group of ERT treatment, IL-1β and TNF-α levels decreased significantly after ERT(p≤0.05). MPS patients had higher levels of IL-6 and TNF-α levels than the control group that revealed inflammatory pathway activation in MPS patients. The inflammatory process is prominent in MPS patients that GAG deposition leads to increase pro-inflammatory cytokines and oxidative stress. Although enzyme replacement therapy reduces glycosaminoglycan accumulation by preventing cytokine production, it might be more effective when given with antiinfllammatory mediators. [ABSTRACT FROM AUTHOR]

Preterm neonates have under-developed immune-regulatory system; consequently, there is a risk for developing chronic inflammation. Necrotizing enterocolitis (NEC) is an acute devastating neonatal intestinal inflammatory disorder. Due to the obscure multifactorial etiology, early diagnosis and effective treatment of NEC are limited. Consequently, effective strategies in the prevention of NEC, including nutritional approaches, are critically needed. The current study was conducted to assess the potential immunomodulatory effect of Docosahexaenoic Acid (DHA) supplementation in preterm neonates at neonatal intensive care unit (NICU) and subsequently its effect on preventing or reducing NEC incidence. This was a prospective randomized controlled study. A total of 67 neonates, with gestational age equal or less than 32 weeks at birth and weight less than or equal 1500 g, were randomly assigned to either DHA group or the control group. Modified Bell's staging criteria for NEC was used as an objective tool for diagnosis and staging of NEC. Levels of Interleukin 1 beta (IL-1β) were measured at baseline and after 10 days. Mortality and NICU length of stay (LOS) were also monitored. Thirty neonates of each group completed the study. A statistically significant difference was observed between the two groups regarding diagnosis and staging of NEC (p = 0.0001). There was also a statistically significant difference between DHA group 22(73.3), 95% CI [55.9, 86.5] and the control group 8 (26.7), 95% CI [13.5, 44.1] in the percentage change in IL-1β levels (p = 0.0001). A statistically significant association was found between IL and 1 β change and NEC diagnosis (p = 0.001). NICU LOS was significantly lower among DHA group 21.63 ± 6.67 compared to the control group 25.07 ± 4.67 (p = 0.025). Mortality n (%) among the control group 4 (11.8) was higher than DHA group 3 (9.1), however, no significant difference was detected (p = 1.0). Findings of this study suggest that enteral DHA supplementation can reduce NEC incidence in preterm neonates through its immunoregulatory effect that modulates production of regulatory cytokines. Trial registration: Registered at clinical trials.gov (NCT03700957), 6 October 2018. [ABSTRACT FROM AUTHOR]

The pro‐inflammatory cytokine interleukin 1 beta (IL‐1β) plays a critical role in osteoarthritis (OA) disease pathogenesis. MicroRNA (miRNA) activity is related to inflammation in OA and some miRNAs specifically regulate IL‐mediated degradation of cartilage type II collagen. Previous studies have indicated that miR‐144‐3p is a useful target in the regulation of pro‐inflammatory cytokines in different diseases. However, the role of miR‐144‐3p in OA is unclear. In this study, we observed a negative correlation between miR‐144‐3p and IL‐1β expression in OA. miR‐144‐3p mimic transfection of OA synovial fibroblasts downregulated levels of IL‐1β expression, while blocking the MAPK, PI3K/Akt, and NF‐κB signaling pathways relating to IL‐1β production, and effectively increased miR‐144‐3p expression in OASFs. Findings from an anterior cruciate ligament transection rat model revealed that administration of miR‐144‐3p mimic effectively ameliorated OA progression and reduced the numbers of IL‐1β‐positive cells in synovial tissue. This study suggests that miR‐144‐3p is a useful therapeutic target in OA disease. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Methotrexate (MTX) is one of the most commonly used anti-cancer drugs for various types of neoplasms. It is associated with multiple cytotoxic effects including nephrotoxicity, hepatotoxicity and cardiotoxicity. Liraglutide (LIR) is a potent anti-diabetic drug and also has antioxidant and anti-inflammatory properties. In this study, we tried to investigate the protective effect of LIR on MTX induced cardiotoxicity and to identify the molecular mechanisms for this protection. MATERIALS AND METHODS: Rats were divided into 4 groups, including control group, LIR group, MTX group and LIR + MTX group. ECG was measured then blood samples were taken, and hearts were excised for biochemical and histological investigations. RESULTS: MTX group exhibited a mild non-significant irregular bradycardia, an increase of CK-MB besides a decrease of total antioxidant capacity. MTX administration also resulted in downregulation of vascular endothelial growth factor (VEGF), while caused upregulation of interleukin 1 beta (IL-1B) and interleukin 6 (IL-6) in comparison to the control group. Also, MTX group showed histological abnormalities besides negative VEGF and positive iNOS as detected by immunohistochemical staining compared to the control group. LIR administration could reverse these results. CONCLUSIONS: LIR prevented MTX induced cardiotoxicity through its antioxidant and anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

Inflammation represents an important factor leading to metabolic imbalance within the intervertebral disc (IVD), conducive to degenerative changes. Therefore, a thorough knowledge of the IVD and endplate (EP) cell behaviour in such pathological environments is essential when designing regenerative therapeutic strategies. The present study aimed at assessing the molecular response of the IVD constitutive nucleus pulposus (NPCs)-, annulus fibrosus (AFCs)- and endplate (EPCs)-derived cells to interleukin (IL)-1β treatment, through large-scale, high-throughput microarray and protein analysis, identifying the differentially expressed genes and released proteins. Overall, the inflammatory stimulus downregulated stemness genes while upregulating pro-inflammatory, pro-angiogenic and catabolic genes, including matrix metalloproteases, which were not balanced by a concomitant upregulation of their inhibitors. Upregulation of anti-inflammatory and anabolic tumour necrosis factor inducible gene 6 protein (TNFAIP6), of IL-1 receptor antagonist (IL-1Ra) (at gene and protein levels) and of trophic insulin-like growth factor 1 (IGF1) was also observed in all cell types; IGF1 particularly in AFCs. An overall inhibitory effect of tumour necrosis factor alpha (TNFα) signal was observed in all cell types; however, EPCs showed the strongest anti-inflammatory behaviour. AFCs and EPCs shared the ability to limit the activation of the signalling mediated by specific chemokines. AFCs showed a slightly senescent attitude, with a downregulation of genes related to DNA repair or pro-mitosis. Results allowed for the identification of specific molecular targets in IVD and EP cells that respond to an inflammatory environment. Such targets can be either silenced (when pathological targets) or stimulated to counteract the inflammation.

Karim Mahmoud Nabil,1 Ghada Mohamed Elhady,2 Heba Morsy2 1Department of Ophthalmology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt; 2Department of Human Genetics, Medical Research Institute, University of Alexandria, Alexandria, EgyptCorrespondence: Karim Mahmoud NabilDepartment of Ophthalmology, Faculty of Medicine, University of Alexandria, Sultan Hussein Street, Khartoum Square, Alexandria 21523, EgyptTel +2034869545Fax +2034255781Email Karim_nabil_ophth@yahoo.comPurpose: In the present study, we investigated whether interleukin 1 beta (IL1B) promoter polymorphisms are associated with keratoconus in an Egyptian population and their association with disease severity.Methods: A total of 95 Egyptian keratoconus patients and 126 Egyptian healthy controls were enrolled in the study. Two IL1B single nucleotide polymorphisms (SNPs) (rs1143627 and rs16944) were genotyped using Taqman real-time PCR to compare haplotype, genotype, and allele frequencies between cases and controls (primary outcome) and their association with disease severity (secondary outcome).Results: Statistically significant association was observed for rs1143627 and rs16944; the T allele of rs1143627 and the G allele of rs16944 were associated with an increased risk of keratoconus (p < 0.001, odds ratio = 3.313, 4.770, respectively). The TT genotype of rs1143627 and the GG genotype of rs16944 were strongly associated with an increased risk of keratoconus (p < 0.001, odds ratio = 5.631, 11.478, respectively). The G allele of rs16944 was associated with an increased curvature of the flattest corneal meridian Kf in keratoconus (p = 0.041). The GG genotype of rs16944 was associated with an increased curvature of the flattest corneal meridian Kf, steepest corneal meridian Ks and average corneal curvature Kavg in keratoconus (p = 0.01, 0.046, 0.023, respectively).Conclusion: IL1B is suspected to play a crucial role, both in development and severity of keratoconus in Egyptian population.Keywords: interleukin 1 beta, promoter polymorphisms, keratoconus, Egypt

Extracts from Taiwan’s traditional medicinal mushroom, Antrodia cinnamomea, exhibit anti-inflammatory activities in cellular and preclinical studies. However, this paper is the first to report that Antcin K, a triterpenoid isolated from A. cinnamomea, inhibits proinflammatory cytokine production in human rheumatoid synovial fibroblasts (RASFs), which are major players in rheumatoid arthritis (RA) disease. In our analysis of the mechanism of action, Antcin K inhibited the expression of three cytokines (tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL-1β] and IL-8) in human RASFs; cytokines that are crucial to RA synovial inflammation. Notably, incubation of RASFs with Antcin K reduced the phosphorylation of the focal adhesion kinase (FAK), phosphoinositide 3-kinase (PI3K), protein kinase B (AKT) and nuclear factor-κB (NF-κB) signaling cascades, all of which promote cytokine production in RA. Intraperitoneal injections of Antcin K (10 mg/kg or 30 mg/kg) attenuated paw swelling, cartilage degradation and bone erosion, and decreased serum levels of TNF-α, IL-1β, IL-8 in collagen-induced arthritis (CIA) mice; in further experiments, IL-6 levels were similarly reduced. The inhibitory effects of Antcin K upon TNF-α, IL-1β and IL-8 expression in human RASFs was achieved through the downregulation of the FAK, PI3K, AKT and NF-κB signaling cascades. Our data support clinical investigations using Antcin K in RA disease.

Glomerular mesangial cell (GMC)‐derived pleiotropic cytokine, interleukin‐1 (IL‐1), contributes to hypercellularity in human and experimental proliferative glomerulonephritis. IL‐1 promotes mesangial proliferation and may stimulate extracellular matrix accumulation, mechanisms of which are unclear. The present study shows that the beta isoform of IL‐1 (IL‐1β) is a potent inducer of IL‐1 type I receptor‐dependent Ca2+ entry in mouse GMCs. We also demonstrate that the transient receptor potential ankyrin 1 (TRPA1) is an intracellular store‐independent diacylglycerol‐sensitive Ca2+ channel in the cells. IL‐1β‐induced Ca2+ and Ba2+ influxes in the cells were negated by pharmacological inhibition and siRNA‐mediated knockdown of TRPA1 channels. IL‐1β did not stimulate fibronectin production in cultured mouse GMCs and glomerular explants but promoted Ca2+‐dependent cell proliferation. IL‐1β also stimulated TRPA1‐dependent ERK mitogen‐activated protein kinase (MAPK) phosphorylation in the cells. Concomitantly, IL‐1β‐induced GMC proliferation was attenuated by TRPA1 and RAF1/ MEK/ERK inhibitors. These findings suggest that IL‐1β‐induced Ca2+ entry via TRPA1 channels engenders MAPK‐dependent mesangial cell proliferation. Hence, TRPA1‐mediated Ca2+ signaling could be of pathological significance in proliferative glomerulonephritis. [ABSTRACT FROM AUTHOR]