Interleukin-1 Activity Research Articles

The Effects of Whole-Body Photobiomodulation Light-Bed Therapy on Creatine Kinase and Salivary Interleukin-6 in a Sample of Trained Males: A Randomized, Crossover Study.

Photobiomodulation therapy (PBMT) can be applied to the whole body as compared to the application of using single hand-held devices that isolate a smaller muscle area. The purpose of this study was to examine the effects of an acute dose of whole-body PBMT pre- and post-high-intensity resistance training on creatine kinase (CK) and salivary interleukin-6 (IL-6) in a sample of trained males. Twelve males (31 ± 8.3 years, 177.2 ± 5.4 cm, and 86.0 ± 7.5 kg) were part of a randomized, counterbalanced, cross-over design, whereby each participant performed a high-intensity resistance training session that consisted of the bench press, chin-up, and repeated sprints on two separate occasions. Each participant was assigned to either the PBMT or control condition on two separate weeks, with a 10-days washout period between the weeks. Creatine kinase was measured at baseline, 24, 48, and 72 h post-exercise. Salivary IL-6 was measured at baseline, 60, 90, and 120 min. A paired t-test showed no significant difference (p = 0.669) in the area under the curve (AUC) for CK during the PBMT (191.7 ± 48.3) and control conditions (200.2 ± 68.0). A Wilcoxon signed-rank test also showed no significant median difference (p = 0.155) in the AUC for salivary IL-6 during the PBMT (Mdn = 347.7) and control conditions (Mdn = 305.8). An additional Wilcoxon signed-rank test for CK percentage change from 24 to 72 h showed the PBMT condition (Mdn = −45%) to have a −18% median difference as compared to the control condition (Mdn = −41%). As such, whole-body PBMT does not significantly reduce the activity of salivary IL-6 or CK concentration during the 24 to 72-h recovery post-high-intensity resistance training.

Role of Interleukin-6 in Depressive Disorder.

Major depressive disorder (MDD), which is a leading psychiatric illness across the world, severely affects quality of life and causes an increased incidence of suicide. Evidence from animal as well as clinical studies have indicated that increased peripheral or central cytokine interleukin-6 (IL-6) levels play an important role in stress reaction and depressive disorder, especially physical disorders comorbid with depression. Increased release of IL-6 in MDD has been found to be a factor associated with MDD prognosis and therapeutic response, and may affect a wide range of depressive symptomatology. However, study results of the IL6 genetic effects in MDD are controversial. Increased IL-6 activity may cause depression through activation of hypothalamic-pituitary-adrenal axis or influence of the neurotransmitter metabolism. The important role of neuroinflammation in MDD pathogenesis has created a new perspective that the combining of blood IL-6 and other depression-related cytokine levels may help to classify MDD biological subtypes, which may allow physicians to identify the optimal treatment for MDD patients. To modulate the IL-6 activity by IL-6-related agents, current antidepressive agents, herb medication, pre-/probiotics or non-pharmacological interventions may hold great promise for the MDD patients with inflammatory features.

Leukocyte Telomere Length Independently Predicts 3-Year Diabetes Risk in a Longitudinal Study of Chinese Population.

Cellular aging markers, including telomere length and mitochondrial function, as well as oxidative stress and inflammation markers influence each other and form a complex network, which is affected in diabetes. However, it remains unknown whether these markers could independently predict future diabetes after adjustment for their mutual effects. We conducted a 3-year longitudinal study in a Chinese cohort that comprised 108 nondiabetic individuals at baseline. The 2-hour 75 g oral glucose tolerance tests were performed at baseline and at 3-year follow-up. At baseline, leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) in leukocytes were determined using the polymerase chain reaction method. Tumor necrosis factor (TNF-α), interleukin-6, 8-hydroxy-2-deoxyguanosine levels, and superoxide dismutase (SOD) activity were measured by the enzyme-linked immunosorbent assay. Participants who developed diabetes at the 3-year follow-up (n = 28) had shorter LTL and higher levels of TNF-α and SOD activity at baseline. Baseline LTL was found to be independently associated with the development of diabetes at the 3-year follow-up after the adjustment for mtDNAcn, markers of oxidative stress and inflammation, and conventional diabetes risk factors. Our findings suggest that LTL is an independent predictor for 3-year diabetes risk, which might inform timely prevention and treatment of diabetes. Telomere shortening might be involved in the pathogenesis of diabetes independently of conventional diabetes risk factors, mtDNAcn, or oxidative stress and inflammation pathways.

Inhibitory Effect of 1,5-Dimethyl Citrate from Sea Buckthorn (Hippophae rhamnoides) on Lipopolysaccharide-Induced Inflammatory Response in RAW 264.7 Mouse Macrophages.

Hippophae rhamnoides L. (Elaeagnaceae; commonly known as “sea buckthorn” and “vitamin tree”), is a spiny deciduous shrub whose fruit is used in foods and traditional medicines. The H. rhamnoides fruit (berry) is rich in vitamin C, with a level exceeding that found in lemons and oranges. H. rhamnoides berries are usually washed and pressed to create pomace and juice. Today, the powder of the aqueous extract of H. rhamnoides berries are sold as a functional food in many countries. As part of our ongoing effort to identify bioactive constituents from natural resources, we aimed to isolate and identify those from the fruits of H. rhamnoides. Phytochemical analysis of the extract of H. rhamnoides fruits led to the isolation and identification of six compounds, namely, a citric acid derivative (1), a phenolic (2), flavonoids (3 and 4), and megastigmane compounds (5 and 6). Treatment with compounds 1–6 did not have any impact on the cell viability of RAW 264.7 mouse macrophages. However, pretreatment with these compounds suppressed lipopolysaccharide (LPS)-induced NO production in RAW 264.7 mouse macrophages in a concentration-dependent manner. Among the isolated compounds, compound 1 was identified as the most active, with an IC50 of 39.76 ± 0.16 μM. This value was comparable to that of the NG-methyl-L-arginine acetate salt, a nitric oxide synthase inhibitor with an IC50 of 28.48 ± 0.05 μM. Western blot analysis demonstrated that compound 1 inhibited the LPS-induced expression of IKKα/β (IκB kinase alpha/beta), I-κBα (inhibitor of kappa B alpha), nuclear factor kappa-B (NF-κB) p65, iNOS (inducible nitric oxide synthase), and COX-2 (cyclooxygenase-2) in RAW 264.7 cells. Furthermore, LPS-stimulated cytokine production was detected using a sandwich enzyme-linked immunosorbent assay. Compound 1 decreased interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) production in LPS-stimulated RAW 264.7 cells. In summary, the mechanism of action of 1 included the suppression of LPS-induced NO production in RAW 264.7 cells by inhibiting IKKα/β, I-κBα, NF-κB p65, iNOS, and COX-2, and the activities of IL-6 and TNF-α.

RETRACTED: MicroRNA-208-5p regulates myocardial injury of sepsis mice via targeting SOCS2-mediated NF-κB/HIF-1α pathway

Accumulating evidence has revealed the roles of microRNAs (miRs) in sepsis, hence, the aim of the present study was to investigate whether miR-208a-5p affects sepsis whilst attempting to elucidate the mechanisms by which the suppressors of cytokine signaling 2 (SOCS2)-mediated nuclear factor-kappaB/hypoxia-inducible factor-1α (NF-κB/HIF-1α) pathway is implicated in this process. The sepsis model was established by cecal ligation and puncture in mice. Serum levels of myocardial enzyme cardiac Troponin-I (cTnI) and brain natriuretic peptide (BNP) in mice were measured. Malondialdehyde (MDA), lactate dehydrogenase (LDH) activity, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), NF-κB p65, HIF-1α and superoxidedismutase (SOD) activity in myocardial tissues were determined. Furthermore, the swelling degree of mitochondria and the apoptosis of cardiomyocytes was measured. The expression of miR-208a-5p, SOCS2, Bcl-2, Bax, NF-κB p65 and HIF-1α in myocardial tissues of mice were detected. Down-regulation of miR-208a-5p and up-regulation of SOCS2 raised the activity of SOD, while reduced the activity of LDH and MDA and the concentrations of cTnI, BNP, TNF-α, IL-6, NF-κB p65 and HIF-1α in mice with sepsis. Down-regulated miR-208a-5p and up-regulated SOCS2 reduced degree of mitochondria swelling, and suppressed cardiomyocytes apoptosis in mice with sepsis. MiR-208a-5p, NF-κB p65 and HIF-1α expression were raised while SOCS2 expression was depressed in myocardial tissues of mice with sepsis. This study suggests that high expression of SOCS2 or inhibition of miR-208a-5p alleviates the myocardial injury of sepsis mice via modulating NF-κB/HIF-1α pathway, which are potential candidate markers and therapeutic targets for sepsis mice.

Analysis of the relationship between the activity of inducible nitric oxide synthase and interleukin-1 in the pathogenesis of experimental diabetic retinopathy

The purpose of the study: analysis of changes in the development of hypoxia and endothelial dysfunction in experimental diabetic retinopathy. Our results indicate endothelial dysfunction and dysfunction of nitric oxide synthesis on the 30th day of development of experimental diabetic retinopathy. An increase in the activity of inducible nitric oxide synthase in the 2nd group (p <0.001) in the first stage of the experiment with further progression of pathological changes on the 60th and 180th day of the study. The development of the inflammatory process in experimental diabetic retinopathy has been revealed and its relationship with the increase in the activity of inducible nitric oxide synthase has been confirmed. The most pronounced increase in the studied cytokine was detected in the 3rd stage of the experiment (p <0,001).

Effects of Coconut Water on Retina in Diabetic Rats.

Coconut water (CW) is a natural aseptic nutritious beverage, containing several biologically active compounds. This study aimed to determine the antiretinopathy effects of CW on diabetic Sprague Dawley (SD) rats using streptozotocin (STZ) and explore its potential mechanism. After allowing the rats to acclimatize for 7 days, 48 healthy adult male SD rats were selected and randomly divided into 4 groups, involving control (Ctrl), diabetic rats (DM), diabetic rats treated with CW (DM-CW), and diabetic rats treated with glibenclamide (DM-Gli). The diabetic models were established by an intraperitoneal injection of STZ (60 mg/kg). The Ctrl group was injected with an equal volume of sodium citrate solution. The experiment was totally conducted during 20 weeks, and then, all rats were sacrificed. The serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were measured; additionally, the activities of interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) in the retina were investigated using biochemical assays. Hematoxylin and eosin (H&E) staining was performed to observe pathological changes of retinal tissues. In presence of treatment with CW, serum level of MDA was decreased, while serum levels of SOD and GSH-Px were increased; besides, the activities of IL-6 and ICAM-1 in the retina were reduced compared with the DM group. The antiretinopathy feature of CW was confirmed by the increased number of neurons in the ganglion cell layer (GCL), total retina thickness (TRT), and thickness of the retinal nuclear layer (RNL) in diabetic rats. CW can be protective against diabetic retinopathy (DR), and its effects are comparable to Gli. The possible underlying mechanism may be partly explained by decreasing oxidative stress and anti-inflammatory activities in the retina. However, further research should be conducted to reveal the exact mechanism.

The Possible Protective Role of Sesame Oil on Skeletal Muscle Regeneration in Induced Red-Bull Injury: Experimental Study

Background: Energy drinks (Eds), including Red Bull, were introduced to United States markets in 1997. Consumption hasincreased worldwide mainly consumed by athletes and teenagers as they are seeking for increase their energy level. Seasme oil(SO) has been known to have anti-inflammatory and antioxidant properties.Aim: The current study was designed to elucidate study the possible protective role of SO on skeletal muscle regeneration inRed Bull experimentally induced injury.Materials and Methods: Twenty adult albino rats were divided into four groups, control, sham control, RB and RB+SO.Skeletal muscle sections were subjected to histological, morphometric, biochemical and statistical studies.Results: RB induced various histological changes in skeletal muscle in the form of congestion, atypical fibre, multiple fibroblastand dark nuclei. RB also caused a sig increase in area % collagen, area % of caspase3 immunoexpression (IE), count of alphasmooth muscle actin IE(no I SMA) and count of +ve CD34 IE were recorded. Sig increase in the activity of interleukin-6(IL-6)and PI3K and AKT proteins. Concomitant administration with SO improved sig the previously mentioned changes.Conclusion: It can be concluded that SO enhanced skeletal muscle regeneration in RB induced muscle injury expressed as adefinite ameliorating effect to the induced inflammatory and degenerative changes.

Soluble interleukin-6 receptor in young adults and its relationship with body composition and autonomic nervous system.

BackgroundThe immune system generates inflammatory responses through cytokines like Interleukin 6 (IL‐6) and the Tumor Necrosis Factor alpha (TNF α); these cytokines mediate cellular responses aided by the presence of soluble receptors such as: Soluble Interleukin 6 Receptor (sIL6R) and Soluble Tumor Necrosis Factor Receptors Type 1 and 2 (sTNFR1, sTNFR2); the literature is limited about the relationship between this cytokines and the role of its soluble receptors.ObjectivesThis study is to determine a possible relationship between specific inflammatory markers and their soluble receptors with the autonomic nervous system's activity and body composition.Methods27 subjects (13 men of 19.3 ± 1.6 years old and 14 women of 19.1 ± 1.7 years old) were evaluated. Body composition, autonomic nervous system activity and plasma concentration of inflammatory markers IL‐6, TNF α, sIL6R, sTNFR1 and sTNFR2 were measured using bio‐impedance, heart rate variability and ELISA respectively.ResultsA positive association between body‐fat percentage and the sIL6R (0.47, p = .013) as well as inverse relationship between muscular mass and the sIL6R (−0.45, p = .019) were found. The sIL6R was also positively correlated with sympathetic activity markers: Relation LF/HF (0.52, p = .006), cardiac sympathetic index (0.45, p = .008), and cardiac vagal index (−0.44, p = .022).ConclusionThis study suggested that the IL‐6 trans‐signaling involving both the soluble receptor, sIL6R, and gp130 membrane co‐receptor could produce inflammatory responses that generate an impact on the autonomic nervous system, possibly due to its direct action on the hypothalamus, the solitary tract nucleus, or the heart.

The Prognostic Value of Troponin in Pediatric Polytrauma.

Introduction: Severe trauma accounts for a great number of deaths among children and adolescents. The diagnostic value of troponin serum levels of severely injured patients has been reported for adults, but data on pediatric polytrauma (PT) are scarce. Therefore, we conducted a retrospective monocentered study analyzing the prognostic value of troponin T (TnT) in pediatric trauma patients at the time point of hospital admission.Methods: Data of 88 polytraumatized pediatric patients admitted to the emergency room of the University Hospital of Ulm, Germany, between 2007 and 2016 were analyzed retrospectively. The data source was the written and digital patient records. Interleukin-6 (IL-6), creatine kinase activity (CK activity), and lactate and TnT levels were measured by a certified clinical diagnostic laboratory; and patients were stratified for the Injury Severity Score (ISS). The prognostic value for lung contusion, organ dysfunction, and fatal outcome was statistically explored. The study was approved by the independent ethical committee of the University of Ulm (#44/18).Results: TnT levels were significantly increased in patients after severe PT compared with mild or moderate trauma severity as assessed by ISS values. Patients with TnT levels above the cutoff showed significantly increased levels of IL-6 and CK activity and a significantly prolonged stay in the intensive care unit. However, TnT levels did not correlate with absolute ISS values. TnT levels were significantly increased in patients with chest trauma and lung contusion. The incidence of lung contusion was associated with elevation of TnT. So was the onset of organ dysfunction, defined as a Sequential Organ Failure Assessment (SOFA) score ≥ 2 and fatal outcome, with a significant enhancement of plasma levels in children with organ dysfunction and in non-survivors.Conclusion: These descriptive data suggest that evaluation of TnT on admission of multiply injured children may help in predicting severity of injury and mortality in the clinical course after trauma and thus may be a useful addition to established prognostic parameters in the future.

Platinum Nanoparticles As A Therapeutic Agent Against Dextran Sodium Sulfate-Induced Colitis In Mice.

PurposeThis study aimed to evaluate the anti-colitis potential of platinum nanoparticles (PtNPs).Materials and methods5-, 30- and 70-nm PtNPs were administered to C57BL/6 mice once daily by intragastric gavage for 8 d during and after 5-d dextran sodium sulfate treatment.ResultsAccording to body weight change, stool blood and consistency, and colon length and histopathology, PtNPs size-dependently alleviated DSS-induced murine colitis. PtNPs enhanced gut-barrier function by upregulating the colonic expressions of heat-shock protein 25 and tight junction proteins. Based on colonic myeloperoxidase activity, colonic and peripheral levels of interleukin-6 and tumor necrosis factor-α, and peripheral counts of white blood cells, PtNPs attenuated colonic and systemic inflammation. By suppressing lipopolysaccharide-triggered production of proinflammatory mediators, including nitric oxide, tumor necrosis factor-α and interleukin-6, PtNPs exerted direct anti-inflammatory activities in RAW264.7 macrophages through a mechanism involving intracellular reactive oxygen species scavenging and Toll-like receptor 4/NF-κB signaling suppression. High-throughput 16S rRNA sequencing of fecal samples unveiled that PtNPs induced gut dysbiosis by unfavorably altering α-diversity, Firmicutes/Bacteroidetes ratio, and richness of certain specific bacteria.ConclusionPtNPs are a promising anti-colitis agent, but may negatively impact gut-microbiota.

SDHA gain-of-function engages inflammatory mitochondrial retrograde signaling via KEAP1-Nrf2.

Whether screening the metabolic activity of immune cells facilitates discovery of molecular pathology remains unknown. Here we prospectively screened the extracellular acidification rate as a measure of glycolysis and the oxygen consumption rate as a measure of mitochondrial respiration in B cells from patients with primary antibody deficiency. The highest oxygen consumption rate values were detected in three study participants with persistent polyclonal B cell lymphocytosis (PPBL). Exome sequencing identified germline mutations in SDHA, which encodes succinate dehydrogenase subunit A, in all three patients with PPBL. SDHA gain-of-function led to an accumulation of fumarate in PPBL B cells, which engaged the KEAP1-Nrf2 system to drive the transcription of genes encoding inflammatory cytokines. In a single patient trial, blocking the activity of the cytokine interleukin-6 in vivo prevented systemic inflammation and ameliorated clinical disease. Overall, our study has identified pathological mitochondrial retrograde signaling as a disease modifier in primary antibody deficiency.

Investigation of oxidative stress markers and antioxidant enzymes activity in newly diagnosed type 2 diabetes patients and healthy subjects, association with IL-6 level.

Oxidative stress and inflammation play an important role in the pathogenesis of diabetes and its complication. In this study, we aimed to evaluate and compare oxidative stress markers and antioxidant enzymes activity, as well as Interleukin 6 (IL-6) level in newly diagnosed type 2 diabetes mellitus (T2DM) patients and healthy subjects. 30 newly diagnosed type 2 diabetes patients and 30 healthy subjects (age and sex matched) were recruited in this study. After anthropometric parameters measurement, blood sample were collected from all participant. Serum and plasma were isolated. Biochemical parameters were evaluated in serum. Plasma was used to measure malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC) levels, as well as superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity. Also, IL-6 level was investigated in plasma using ELISA method. MDA and TOS levels were significantly higher in T2DM patients than the control group (p < 0.05). However, TAC and SOD were significantly lower in T2DM as compared with healthy subjects (p < 0.05). Also, IL-6 level was higher in T2DM in comparison to healthy subjects (p = 0.004). Furthermore, there was a significant positive correlation between IL-6 with MDA (p = 0.031, r = 0.482) and TOS (p < 0.001, r = 0.744). In addition, a negative correlation was observed between IL-6 and SOD activity (p = 0.002, r = -0.660). Reducing oxidative stress and inflammation could be effective in improvement of T2DM.

Placental growth factor regulates the generation of TH17 cells to link angiogenesis with autoimmunity.

Helper T cells actively communicate with adjacent cells by secreting soluble mediators, yet crosstalk between helper T cells and endothelial cells remains poorly understood. Here we found that placental growth factor (PlGF), a homolog of the vascular endothelial growth factor that enhances an angiogenic switch in disease, was selectively secreted by the TH17 subset of helper T cells and promoted angiogenesis. Interestingly, the 'angio-lymphokine' PlGF, in turn, specifically induced the differentiation of pathogenic TH17 cells by activating the transcription factor STAT3 via binding to its receptors and replaced the activity of interleukin-6 in the production of interleukin-17, whereas it suppressed the generation of regulatory T cells. Moreover, T cell-derived PlGF was required for the progression of autoimmune diseases associated with TH17 differentiation, including experimental autoimmune encephalomyelitis and collagen-induced arthritis, in mice. Collectively, our findings provide insights into the PlGF-dictated links among angiogenesis, TH17 cell development and autoimmunity.

Butorphanol attenuates inflammation via targeting NF-κB in septic rats with brain injury.

To observe the therapeutic effect of butorphanol on brain tissue injury in rats with sepsis through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Sprague-Dawley rats were divided into control group (n=20), sepsis model group [cecal ligation and perforation (CLP) group, n=20], and butorphanol treatment group (n=20). After successful modeling, the blood and brain tissues were collected from rats at 24 h. The content of serum brain injury indexes was detected. Hematoxylin-eosin (HE) staining assay and enzyme-linked immunosorbent assay (ELISA) were separately carried out to observe the pathological changes and measure the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and myeloperoxidase (MPO) activity. The neurological function was scored in rats. Glial fibrillary acidic protein (GFAP), S100, and NF-κB signaling pathway genes and proteins in brain tissues were detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and Western blotting. CLP group showed remarkably increased levels of serum glucosuria (GLU), creatinine (CR), and Na+ but an evidently reduced level of K+ in comparison with the control group (p<0.05), while the treatment group displayed contrary trends. Histopathological observations showed that the rats in the CLP group suffered a brain injury, while those in the treatment group had mild pathological changes. The MPO in the CLP group was significantly increased compared with that in the control group (p<0.05). The levels of TNF-α and IL-6 were overtly higher in the CLP group than those in the control group, and these indexes in the treatment group were close to those in the control group. The messenger ribonucleic acid (mRNA) expression levels of S100, GFAP, Toll-like receptor 2 (TLR2), and NF-κB in CLP group were evidently higher than those in the control group and treatment group (p<0.05). The results of Western blotting revealed that the protein expression of NF-κB was significantly higher in CLP group than that in the control group, and it declined in the treatment group, which was close to that in the control group. Butorphanol can reduce the content of inflammatory factors TNF-α, IL-1, and IL-6 through the NF-κB signaling pathway, thereby relieving the brain injury caused by sepsis.

Methyl jasmonate abrogates rotenone-induced parkinsonian-like symptoms through inhibition of oxidative stress, release of pro-inflammatory cytokines, and down-regulation of immnopositive cells of NF-κB and α-synuclein expressions in mice

Oxidative stress and neuroinflammation play key roles in the initiation and progression of Parkinson's disease (PD), a neurodegenerative disorder, associated with the loss of nigrostriatal dopaminergic pathway. Thus, compounds that can mitigate oxidative stress and neuroinflammation are being investigated as promising agents for the treatment of PD. This study was designed to evaluate the effects of methyl jasmonate (MJ), a potent antioxidant and anti-inflammatory compound on parkinsonian-like symptoms and the underlying biochemical changes induced by rotenone (Rot) in mice. To this end, the effects of graded doses of MJ (25, 50 and100 mg/kg, i.p.) on motor dysfunctions, cognitive and depressive-like disorders induced by Rot (2.5 mg/kg, i.p.) were evaluated. The specific brain regions (striatum, prefrontal cortex and hippocampus) of the animals were processed for various biochemical studies. Rot-treated mice showed reduced motor activity, postural instability, cognitive and depressive-like disorders. Rot also increased brain levels of malondialdehyde (MDA), nitrite, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and acetyl-cholinesterase (AChE) activity. Moreover, Rot reduced the concentration of glutathione (GSH) and increased immnopositive cells of NF-κB and α-synuclein expressions in these brain regions. However, pretreatment with MJ, attenuated the parkinsonian-like symptoms and reduced the brain levels of MDA/nitrite, TNF-α and IL-6 induced by Rot. MJ also reduced AChE activity and down-regulate the expressions of NF-κB and α-synuclein in the brain of Rot-treated mice. These findings suggest that MJ has anti-parkinsonian-like activity, which may be related to the inhibition of oxidative stress, release of pro-inflammatory cytokines, and down regulation of NF-κB and α-synuclein expressions.

Effects of saikosaponin b_2 on inflammation and energy metabolism in mice with acute liver injury induced by LPS/GalN

To study the effects of saikosaponin b2( SS-b2) on inflammatory factors and energy metabolism against lipopolysaccharide/galactosamine( LPS/Gal N) induced acute liver injury in mice. Mice were randomly divided into normal group( equal amount of normal saline),model group( 100 g·kg~(-1) LPS and 400 mg·kg~(-1) Gal N),low,medium,high dose group of SS-b2( SS-b25,10,20 mg·kg~(-1)·d-1) and positive control group( dexamethasone,10 mg·kg~(-1)). All of the groups except for the normal group were treated with LPS/Gal N though intraperitoneally injection to establish the acute liver injury model. The organ indexes were calculated. The levels of serum transaminases( ALT and AST) and the activities of ATPase( Na+-K+-ATPase,Ca2+-Mg2+-ATPase) in liver were detected. The activity of tumor necrosis factor-α( TNF-α),interleukin-1β( IL-1β) and interleukin-6( IL-6) were determined by the enzyme-linked immunosorbent assay( ELISA). The contents of lactate dehydrogenase( LDH) in liver were determined by micro-enzyme method. HE staining was used to observe the histopathological changes of the liver. Histochemical method was used to investigate the protein expression of liver lactate dehydrogenase-A( LDH-A). The protein expressions of Sirt-6 and NF-κB in the liver were detected by Western blot. According to the results,compared with the model group,there were significant changes in organ indexes in the high-dose group of SS-b2( P<0. 05). The level of ALT,AST,TNF-α,IL-1β,IL-6 and the activities of LDH in serum of mice with liver injury were significantly reduced in the medium and high dose groups of SS-b2( P<0. 01). With the increase of the concentration of SS-b2,the range of hepatic lesions and the damage in mice decreased. The activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in liver of mice were significantly enhanced in each dose group( P<0. 01). The expression of NF-κB in liver tissues was significantly down-regulated in the medium and high dose group( P<0. 01). Meanwhile,the expression of Sirt-6 protein in the liver of mice with acute liver injury was significantly increased in each dose group( P<0. 01).In summary,SS-b2 has a significant protective effect on LPS/Gal N-induced acute liver injury in mice,which may be related to the down-regulation of NF-κB protein expression and up-regulation of Sirt-6 protein expression to improve inflammatory injury and energy metabolism.

Correlation between Serum Level of Interleukin-6 and Osteoarthritis Disease Activity and Disability in Beni-Suef University Hospital

Correlation between Serum Level of Interleukin-6 and Osteoarthritis Disease Activity and Disability in Beni-Suef University Hospital

Nagarines A and B, two novel 8,15-seco diterpenoid alkaloids from Aconitum nagarum

Two novel 8,15-seco C19-diterpenoid alkaloids, nagarines A (1) and B (2), were isolated from the roots of Aconitum nagarum Stapf (Ranunculaceae), a folk herbal medicine used to treat rheumatism and arthritis in Southwestern China, Northern Burma and Northeastern India. They are the first C19-diterpenoid alkaloids possessing unprecedented opened D ring formed by the cleavage of the bond between C-8 and C-15. Compounds 1 and 2 showed certain inhibition activities of interleukin-6 in LPS-activated RAW 264.7 cells with IC50 values of 72.63 ± 0.39 μM and 52.98 ± 0.50 μM, respectively.

Targeting of IL-6-Relevant Long Noncoding RNA Profiles in Inflammatory and Tumorous Disease.

Interleukin-6 (IL-6) is a critical cytokine with a diverse repertoire of physiological functions. Dysregulation of IL-6 signaling is associated with inflammatory disorders as well as cancers. However, blockade of IL-6 activity via antibodies directed against the IL-6 signaling pathway may compromise the efficacy of the immune system; therefore, patients may not have a uniformly satisfactory response to treatment. Long noncoding RNAs (lncRNAs) have been discovered to be evolutionary conserved transcripts of noncoding DNA sequences and have emerged as biomarkers with great predictive and prognostic value, further employed as a targeted anticancer therapy. LncRNAs have been recently implicated in the regulation of IL-6-related signaling and function; they are tightly linked to the development of a range of IL-6 dysregulated diseases. Here, we will highlight those lncRNAs involved in IL-6 signaling, with an emphasis on the mechanisms of lncRNAs that interact with IL-6. Targeting of such lncRNAs related to IL-6 regulation could be, in the near future, a promising therapeutic strategy in the treatment of inflammatory- and tumor-related diseases.