Search results for: inflammatory cytokines

Authors: Shahira M. Ezzat, Marwa I. Ezzat, Mona M. Okba, Esther T. Menze, Ashraf B. Abdel-Naim, Shahnas O. Mohamed

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Background: In order to decrease the burden of the high cost of synthetic drugs, it is important to focus on phytopharmaceuticals. The aim of our study was to search for the mechanism of ginger (Zingiber officinale Roscoe) anti-inflammatory potential and to correlate it to its biophytochemicals. Methods: Various extracts viz. water, 50%, 70%, 80%, and 90% ethanol were prepared from ginger rhizomes. Fractionation of the aqueous extract (AE) was accomplished using Diaion HP-20. In vitro anti-inflammatory activity of the different extracts and isolated compounds was evaluated by protein denaturation inhibition, membrane stabilization, protease inhibition, and anti-lipoxygenase assays. In vivo anti-inflammatory activity of AE was estimated by assessment of rat paw oedema after carrageenan injection. Prostaglandin E2 (PGE2), certain inflammation markers (TNF-α, IL-6, IL-1α, IL-1β, INFr, MCP-1MIP, RANTES, and Nox) levels and MPO activity in the paw edema exudates were measured. Total antioxidant capacity (TAC) was also determined. Histopathological alterations of paw tissues were scored. Results: All the tested extracts showed significant (p < 0.1) anti-inflammatory activities. The highest percentage of heat induced albumin denaturation (66%) was exhibited by the 50% ethanol (250 μg/ml). The 70 and 90% ethanol extracts (500 μg/ml) were more potent as membrane stabilizers (34.5 and 37%, respectively) than diclofenac (33%). The 80 and 90% ethanol extracts (500 μg/ml) showed maximum protease inhibition (56%). The strongest anti-lipoxygenase activity was observed for the AE. It showed more significant lipoxygenase inhibition activity than that of diclofenac (58% and 52%, respectively) at the same concentration (125 μg/ml). Fractionation of AE yielded four main fractions (Fr I-IV) which showed significant in vitro anti-inflammatory. Purification of Fr-III and IV led to the isolation of 6-poradol (G1), 6-shogaol (G2); methyl 6- gingerol (G3), 5-gingerol (G4), 6-gingerol (G5), 8-gingerol (G6), 10-gingerol (G7), and 1-dehydro-6-gingerol (G8). G2 (62.5 ug/ml), G1 (250 ug/ml), and G8 (250 ug/ml) exhibited potent anti-inflammatory activity in all studied assays, while G4 and G5 exhibited moderate activity. In vivo administration of AE ameliorated rat paw oedema in a dose-dependent manner. AE (at 200 mg/kg) showed significant reduction (60%) of PGE2 production. The AE at different doses (at 25-200 mg/kg) showed significant reduction in inflammatory markers except for IL-1α. AE (at 25 mg/kg) is superior to indomethacin in reduction of IL-1β. Treatment of animals with the AE (100, 200 mg/kg) or indomethacin (10 mg/kg) showed significant reduction in TNF-α, IL-6, MCP-1, and RANTES levels, and MPO activity by about (31, 57 and 32% ) (65, 60 and 57%) (27, 41 and 28%) (23, 32 and 23%) (66, 67 and 67%) respectively. AE at 100 and 200 mg/kg was equipotent to indomethacin in reduction of NOₓ level and in increasing the TAC. Histopathological examination revealed very few inflammatory cells infiltration and oedema after administration of AE (200 mg/kg) prior to carrageenan. Conclusion: Ginger anti-inflammatory activity is mediated by inhibiting macrophage and neutrophils activation as well as negatively affecting monocyte and leukocyte migration. Moreover, it produced dose-dependent decrease in pro-inflammatory cytokines and chemokines and replenished the total antioxidant capacity. We strongly recommend future investigations of ginger in the potential signal transduction pathways.

Keywords: anti-lipoxygenase activity, inflammatory markers, 1-dehydro-6-gingerol, 6-shogaol

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Authors: Demosthenes Panagiotakos

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The aim of the present work was to evaluate dietary habits’ inflammatory potential with various components of arterial blood pressure (hypertension, mean arterial pressure (MAP) and pulse pressure (PP)) in a sample of older Mediterranean people without known cardiovascular disease. During 2005-2011, 2,813 older (aged 65-100 years) individuals from 21 Mediterranean islands and the rural Mani region (Peloponnesus) were voluntarily enrolled. Standard procedures were used to determine arterial blood pressure, as well as PP and MAP, and for the evaluation of dietary habits, lifestyle, anthropometric and clinical characteristics of the participants. A dietary inflammatory index (DII) was assessed based on the participants specific dietary habits, and its calculation was based on a standard procedure. It was reported that the higher the DII level of a diet (adherence to a more pro-inflammatory diet) the greater was the likelihood of having an older adult hypertension [OR=3.82 (95% CI): 1.24 to 11.71]. Moreover, the higher the level of DII (more pro-inflammatory dietary habits) the greater were the levels of MAP [b-coefficient (95% CI): 7.23 (+1.86 to +12.59)] and PP, [b-coefficient (95% CI): 10.86 (+2.70 to +19.01)]. Diet’s inflammatory potential is related with various components of arterial pressure. Adherence to a more pro-inflammatory diet seems to be associated with increased arterial peripheral resistance and arterial stiffness.

Keywords: dietary inflammatory index, hypertension, mean arterial pressure, elderly

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Authors: Aditya Arya, Hairin Taha, Ataul Karim Khan, Nayiar Shahid, Hapipah Mohd Ali, Mustafa Ali Mohd

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This study has investigated the antidiabetic and antioxidant potential of Pseudovaria macrophylla bark extract on streptozotocin–nicotinamide induced type 2 diabetic rats. LCMS-QTOF and NMR experiments were done to determine the chemical composition in the methanolic bark extract. For in vivo experiments, the STZ (60 mg/kg/b.w, 15 min after 120 mg/kg/1 nicotinamide, i.p.) induced diabetic rats were treated with methanolic extract of Pseuduvaria macrophylla (200 and 400 mg/kg∙bw) and glibenclamide (2.5 mg/kg) as positive control respectively. Biochemical parameters were assayed in the blood samples of all groups of rats. The pro-inflammatory cytokines, antioxidant status and plasma transforming growth factor βeta-1 (TGF-β1) were evaluated. The histological study of the pancreas was examined and its expression level of insulin was observed by immunohistochemistry. In addition, the expression of glucose transporters (GLUT 1, 2 and 4) were assessed in pancreas tissue by western blot analysis. The outcomes of the study displayed that the bark methanol extract of Pseuduvaria macrophylla has potentially normalized the elevated blood glucose levels and improved serum insulin and C-peptide levels with significant increase in the antioxidant enzyme, reduced glutathione (GSH) and decrease in the level of lipid peroxidation (LPO). Additionally, the extract has markedly decreased the levels of serum pro-inflammatory cytokines and transforming growth factor beta-1 (TGF-β1). Histopathology analysis demonstrated that Pseuduvaria macrophylla has the potential to protect the pancreas of diabetic rats against peroxidation damage by downregulating oxidative stress and elevated hyperglycaemia. Furthermore, the expression of insulin protein, GLUT-1, GLUT-2 and GLUT-4 in pancreatic cells was enhanced. The findings of this study support the anti-diabetic claims of Pseudovaria macrophylla bark.

Keywords: diabetes mellitus, Pseuduvaria macrophylla, alkaloids, caffeic acid

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Authors: Md. Mizanur Rahman, Anquan Liu, Anna Frostegård, Johan Frostegård

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The role of the human immune system is essential in cardiovascular diseases and atherosclerosis. Activated cells in atherosclerosis produce abundant amounts of cytokines, but the exact mechanisms involved in the effects of these inflammatory cytokines are not clear in atherosclerosis. In a large clinical cohort, we have previously determined that antibodies against phosphorylcholine (anti-PC) are negatively and independently associated with both development of atherosclerosis and also a low risk of cardiovascular disease. Further, we reported that rheumatoid arthritis patients who were non-responders to TNF-inhibitors, where those with low anti-PC levels. Upon anti-TNF treatment, anti-PC levels increased. We, therefore, hypothesised that proinflammatory cytokines such as TNF could play a role in anti-PC regulation. Peripheral blood mononuclear cells (PBMC) were cultured with or without TNF and anti-TNF. The cell supernatants were collected after six days for ELISA measurements. In separate experiments, cells were cultured for 24 hours in both polystyrene plates and ELISPOT plates under a similar condition for ELISA and ELISPOT assays respectively. Total RNA was extracted after 6 hours of cell culture to perform RT-qPCR. Cell viability was confirmed by trypan blue staining and MTT assays. ELISA measurements detected less than 40% of anti-PC in TNF-treated cells, in comparison to control cells, whereas anti-PC production was recovered by anti-TNF treatment. ELISPOT assays showed that TNF suppresses anti-PC production by inhibiting anti-PC producing B-cells. In addition, RT-qPCR and ELISA showed that TNF also has effects also on B-cell activation as BAFF expression was inhibited by TNF treatment. Atherosclerosis is a major cause of cardiovascular diseases, but anti-PC is a protection marker for atherosclerosis development. Our findings show that TNF is a negative regulator of anti-PC production. Immune modulation and rising of anti-PC could be of major significance for the patients.

Keywords: anti-PC, Anti-TNF, atherosclerosis, cardiovascular diseases, phosphorylecholine

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Authors: A. N. Gornostaeva, P. I. Bobyleva, E. R. Andreeva, L. B. Buravkova

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Multipotent mesenchymal stromal cells (MSCs) possess immunomodulatory properties. The effect of MSCs on the crucial cellular immunity compartment – T-cells is of a special interest. It is known that MSC tissue niche and expected milieu of their interaction with T- cells are characterized by low oxygen concentration, whereas the in vitro experiments usually are carried out at a much higher ambient oxygen (20%). We firstly evaluated immunomodulatory effects of MSCs on T-cells at tissue-related oxygen (5%) after interaction implied cell-to-cell contacts and paracrine factors only. It turned out that MSCs under reduced oxygen can effectively suppress the activation and proliferation of PHA-stimulated T-cells and can provoke decrease in the production of proinflammatory and increase in anti-inflammatory cytokines. In hypoxia some effects were amplified (inhibition of proliferation, anti-inflammatory cytokine profile shift). This impact was more evident after direct cell-to-cell interaction; lack of intercellular contacts could revoke the potentiating effect of hypoxia.

Keywords: MSCs, T-cells, activation, low oxygen, cell-to-cell interaction, immunosuppression

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Authors: S. K. Hemalata, M. N. Shiva Kameshwari

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The present work focusses on anti-inflammatory action of Urginea wightii in-vitro. Urginea wightii is a member of Hyacinthaceae and considered to be wonder plant because of its varied important medicinal properties. The plant is endemic to India, Africa, and Mediterranian regions. Presence of alkaloids, flavonoid-glycosides especially flavonone derivatives are responsible for the strong anti-inflammatory activity of Urginea wightii. In present research work, anti-inflammatory activity of methanol extract of the bulb powder was tested on Male Wistar Rats. In these test animals, inflammation was induced by injecting carrageenan as the irritant to induce paw edema in Wistar rats. Inflammation of Paw edema was treated with both plant extract and Pyrox gel a known synthetic anti-inflammatory drug through external application. The result indicated that anti-inflammatory activity of Urginea wightii extract was almost similar to the synthetic Pyrox gel. This disproves the modern world's scepticism towards the herbal medicines and encourages to rely on natural plant extracts.

Keywords: anti-inflammatory activity, flavonoid-glycosides, Pyrox gel, Urginia wightii

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Authors: Liu Yuhong, Hussen Mansai, Mei Chunli

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Inflammatory discitis is a sterile inflammatary disease that typically presents with abnormalities in two adjacent vertebral bodies and the intervening disk. Diagnosis this disorder is usually difficult and ideal management remains controversial. In this report，we examine a case of inflammatory discitis in a 56 year old female in which treatment with adalimumab ameliorated symptoms. The 56-year-old female patient developed repeatedly inflammatory discitis in the past three years, presenting with severe back pain, an elevated C-reactive protein and erythrocyte sedimentation rate, radiological erosive changes in vertebral and intervertebral disk of the spine. Surgical treatment, antibiotics and non steroidal anti-inflammatory drugs(NSAIDs) were used, but the patient still suffered from recurrent onset of unbearable backache. Three years later from the patient’s first admission，adalimumab was prescribed due to the third occurrence of Anderson lesions, which she had been suffering from for years. Soon after the same day of adalimumab therapy, her symptoms had a dramatic improvement. On the following day she could stand and walk slowly, her CRP and ESR were decreased to nearly normal levels in 4 weeks. Human leukocyte antigen (HLA)-typing analysis revealed a positive result for HLA-B27, the patient’s inflammatory discitis was considered to be associated with spondyloarthropathy.

Keywords: adalimumab, inflammatory discitis, spondyloarthropathy, patient

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Authors: Aroonsri Priprem, Sucharat Limsitthichaikoon, Suttasinee Thappasarapong

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Anthocyanins are natural pigments with effective UV protection but their topical use could be limited due to their physicochemical characteristics. An attempt to overcome such limitations by complexation of 2 major anthocyanin-rich sources, C. ternatea, and Z. mays, for investigation on potential use as topical anti-inflammatory. Cell studies indicate no cytotoxicity of the anthocyanin complex (AC) up to 1 mg/ml tested in HaCaT and human forehead fibroblasts by MTT. Croton oil-induced ear edema in Wistar rats suggests an effective dose of 5 mg/cm2 of AC as a topical anti-inflammatory in comparison to 0.5 mg/cm2 of fluocinolone acetonide. Niosomal encapsulation of the AC significantly prolonged the anti-inflammatory activity particularly at 8 h after topical application (p = 0.0001). The AC was not cytotoxic and its anti-inflammatory and activity was dose-dependent and prolonged by niosomal encapsulation. It has also shown to promote collagen type 1 production in cell culture. Thus, AC could be a potential candidate for topical anti-inflammatory agent from natural resources.

Keywords: anthocyanin complex, ear edema, inflammation, niosomes, skin

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Authors: Soumeya Krimat, Tahar Dob, Aicha Kesouri, Ahmed Nouasri, Hafidha Metidji

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Lavandula antineae Maire is an endemic medicinal plant of Algeria which is traditionally used for the treatment of chills, bruises, oedema and rheumatism. The objective of this study is to evaluate the anti-inflammatory of hydromethanolic aerial parts extract of Lavandula antineae for the first time using carrageenan-paw edema and croton oil-ear odema models. The plant extract, at the dose of 200 mg/kg, showed a significant anti-inflammatory activity (P˂0.05) in the carrageenan induced edema test in mice, showing 80.74% reduction in the paw thikness comparable to that produced by the standard drug aspirin 83.44% at 4h. When it was applied topically at a dosage of 1 and 2 mg per ear, the percent edema reduction in treated mice was 29.45% and 74.76%, respectively. These results demonstrate that Lavandula antineae Maire extract possess remarkable anti-inflammatory activity, supporting the folkloric usage of the plant to treat various inflammatory and pain diseases.

Keywords: lavandula antineae maire, medicinal plant, anti-inflammatory activity, carrageenan-paw edema, croton oil-ear edema

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Authors: Gaweł Magdalena, Lipkowska Anna, Olbert Magdalena, Frąckiewicz Ewelina, Librowski Tadeusz, Nowak Gabriel, Pilc Andrzej

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Heme oxygenase-1 (HO-1), also known as heat shock protein 32 (HSP32), has been shown to be implicated in cytoprotection in various organs. Its activation plays a significant role in acute and chronic inflammation, protecting cells from oxidative injury and apoptosis. This inducible isoform of HO catalyzes the first and rate-limiting step in heme degradation to produce equimolar quantities of biologically active products: carbon monoxide (CO), free iron and biliverdin. CO has been reported to possess anti-apoptotic properties. Moreover, it inhibits the production of proinflammatory cytokines and stimulates the synthesis of the anti-inflammatory interleukin-10 (IL-10), as well as promotes vasodilatation at sites of inflammation. The second product of catalytic HO-1 activity, free cytotoxic iron, is promptly sequestered into the iron storage protein ferritin, which lowers the pro-oxidant state of the cell. The third product, biliverdin, is subsequently converted by biliverdin reductase into the bile pigment bilirubin, the most potent endogenous antioxidant among the constituents of human serum, which modulates immune effector functions and suppresses inflammatory response. Furthermore, being one of the so-called stress proteins, HO-1 adaptively responds to different stressors, such as reactive oxygen species (ROS), inflammatory cytokines and heavy metals and thus protects cells against such conditions as ischemia, hemorrhagic shock, heat shock or hypoxia. It is suggested that pharmacologic modulation of HO-1 may represent an effective strategy for prevention of stress and drug-induced gastrointestinal toxicity. HO-1 is constitutively expressed in normal gastric, intestinal and colonic mucosa and up-regulated during inflammation. It has been proven that HO-1 up-regulated by hemin, heme and cobalt-protoporphyrin ameliorates experimental colitis. In addition, the up-regulation of HO-1 partially explains the mechanism of action of 5-aminosalicylic acid (5-ASA), which is used clinically as an anti-colitis agent. In 2009 Ueda et al. has reported for the first time that mucosal protection by Polaprezinc, a chelate compound of zinc and L-carnosine used as an anti-ulcer drug in Japan, is also attributed to induction of HO-1 in the stomach. Since then, inducers of HO-1 are desired subject of research, as they may constitute therapeutically effective anti-ulcer drugs.

Keywords: heme oxygenase-1, gastric lesions, gastroprotection, Polaprezinc

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Authors: Amos Sunday Onikanni, Bashir Lawal, Babatunji Emmanuel Oyinloye, Gomaa Mostafa-Hedeab, Mohammed Alorabi, Simona Cavalu, Augustine O. Olusola, Chih-Hao Wang, Gaber El-Saber Batiha

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The increasing global burden of diabetes mellitus has called for the search for a therapeutic alternative that offers better activities and safety than conventional chemotherapy. Herein, we evaluated the neuroprotective and antioxidant properties of different fractions (ethyl acetate, N-butanol and residual aqueous) of Clompanus pubescens leaves in streptozotocin (STZ)-induced diabetic rats. Our results revealed a significant elevation in the levels of blood glucose, pro-inflammatory cytokines, lipid peroxidation, neuronal activities of acetylcholinesterase, butyrylcholinesterase, nitric oxide, epinephrine, norepinephrine, and Na+/K+-ATPase in diabetic non treated rats. In addition, decreased levels of enzymatic and non-enzymatic antioxidants were observed. Treatment with different fractions of C. pubescens leaves resulted in a significant reversal of the biochemical alteration and improved the neurocognitive deficit in STZ-induced diabetic rats. However, the ethyl-acetate fraction demonstrated higher activities than the other fractions and was characterized for its phytoconstituents, revealing the presence of Gallic acid (713.00 ppm), catechin (0.91 ppm), ferulic acid (0.98 ppm), rutin (59.82 ppm), quercetin (3.22 ppm) and kaempferol (4.07 ppm). Our molecular docking analysis revealed that these compounds exhibited different binding affinities and potentials for targeting BChE/AChE/ IL-1 β/Na+-K+-ATPase. However, only Kampferol and ferulic exhibited good drug-like, ADMET, and permeability properties suitable for use as a neuronal drug target agent. Hence, the ethyl-acetate fraction of C. pubescent leaves could be considered a source of promising bioactive metabolite for the treatment and management of cognitive impairments related to type II diabetes mellitus.

Keywords: diabetes mellitus, neuroprotective, antioxidant, pro-inflammatory cytokines

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Authors: A. N. Ukwuani, M. G. Abubakar, S. W. Hassan

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Grewia crenata is used locally in the treatment of fractured bones, wound healing and inflammatory conditions. The anti-inflammatory activity of hydromethanolic extract of G. crenata leaves was investigated using egg albumin induced-hind paw oedema model in albino rat. The extract produced a time-dependent inhibition of egg albumin induced-hind paw oedema at 30th minutes up to 150th minutes in all the groups compared to the control. Significant reduction (p<0.05) of hind paw oedema was observed 150 minutes after egg albumin injection. The percentage inhibition produced by the extract at 200 mg/kg (22.1%) was comparable to that produced by 10 mg/kg indomethacin (24.9%) at the 150th minutes of post-egg albumin injection. Preliminary qualitative phytochemical analysis revealed the presence of saponins, steroids, flavonoids, anthraquinones and glycosides. The results obtained in this study suggest that Grewia crenata can be a potential source of anti-inflammatory agent and validates its use in the treatment of inflammatory conditions.

Keywords: Grewia crenata, anti-inflammatory, hind paw, oedema

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Authors: Lívia Pimentel Sant'ana Dourado, Raquel Das Neves Almeida, Luís Henrique Costa Corrêa Neto, Nayara Soares, Kelly Grace Magalhães

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Introduction: Obesity and high-fat diet intake have a crucial impact on immune cells and inflammatory profile, highlighting an emerging realization that obesity is an inflammatory disease. In the present work, we aimed to characterize the role of caspase-1/11 and NLRP3 inflammasome in the establishment of mice obesity and modulation of inflammatory lipid metabolism induced by high fat diet intake. Methods and results: Wild type, caspase-1/11 and NLRP3 knockout mice were fed with standard fat diet (SFD) or high fat diet (HFD) for 90 days. The weight of animals was measured weekly to monitor the weight gain. After 90 days, the blood, peritoneal lavage cells, heart and liver were collected from mice studied here. Cytokines were measured in serum by ELISA and analyzed in spectrophotometry. Lipid antigen presentation molecule CD1d expression, reactive oxygen species (ROS) generation and lipid droplets biogenesis were analyzed in cells from mice peritoneal cavity by flow cytometry. Liver histopathology was performed for morphological evaluation of the organ. The absence of caspase-1/11, but not NLRP3, in mice fed with HFD favored the mice weight gain, increased liver size, induced development of hepatic steatosis and IL-12 secretion in mice compared to mice fed with SFD. In addition, caspase-1/11 knockout mice fed with HFD presented an increased CD1d molecule expression, as well as higher levels of lipid droplets biogenesis and ROS generation compared to wild type mice also fed with HFD. Conclusion: Our data suggest that caspase-1/11 knockout mice have greater susceptibility to obesity as well as increased activation of lipid metabolism and inflammatory markers.

Keywords: caspase 1, caspase 11, inflamassome, obesity, lipids

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Authors: Razieh Zarei, Hassan zm, Abolghasem Ajami, Darush Moslemi, Narges Afsary, Amrollah Mostafa-zade

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Introduction: IL-23 is responsible for the differentiation and expansion of Th17/ThIL-17 cells from naive CD4+ T cells. Therefore, may be IL-23/IL17 axis involve in a variety of allergic and autoimmune diseases, such as RA, MS, inflammatory bowel disease (IBD), and asthma. TGF-β is also share for the differentiation Th17 producing IL-17 and CD4+CD25+Foxp3hiT regulatory cells from naïve CD4+ T cells which are involved in the regulation of immune response, maintaining immunological self-tolerance and immune homeostasis ,and the control of autoimmunity and cancer surveillance. Therefore, T regulatory cells play a key role in autoimmunity, allergy, cancer, infectious disease, and the induction of transplantation tolerance. Vitamin A and it's derivatives (retinoids) inhibit or reverse the carcinogenic process in some types of cancers in oral cavity,head and neck, breast, skin, liver, and blood cells. Shark is a murine organism and its cartilage has antitumor peptides to prevent angiogenesis, in vitro. Our purpose is whether simultaneous oral treatment vitamin A and shark cartilage can modulate IL-23/IL-17 and CD4CD25Foxp3 T regulatory cell/TGF-β pathways and Th1/Th2 immunity in patients with gastric cancer. Materials and Methods: First investigated an imbalanced supernatant of cytokines exist in patients with gastric cancer by ELISA. Associated with cytokines measuring such as IL-23,IL-17,TGF-β,IL-4 and γ-IFN, then flow cytometry was employed to determine whether the peripheral blood mononuclear cells such as CD4+CD25+Foxp3highT regulatory cells in patients with gastric cancer were changed correspondingly. Results: An imbalance between IL-17 secretion and TGF-β/Foxp3 t regulatory cell pathway and so, Th1 immunity (γ-IFN production) and TH2 immunity (IL-4 secretion) was not seen in patients with gastric cancer treated by vitamin A and shark cartilage. But, the simultaneously presented down-regulation of IL-23 indicated, at least cytokine level. Conclusion: Il-23, as a pro-angiogenesis cytokine, probably, help to tumor growth. Hence, suggested that down-regulation of IL-23, at least cytokine level, is useful for anti-tumor immune responses in patients with gastric cancer.

Keywords: IL-23/IL17 axis, TGF-β/CD4CD25Foxp3 T regulatory pathway, γ-IFN, IL-4, shark cartilage and gastric cancer

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Authors: Alireza Barari, Ahmad Abdi

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Regular body trainings cause adaption in various system in body. One of the important effect of body training is its effect on immune system. It seems that cytokines usually release after long period exercises or some exercises which cause skeletal muscular damages. If some of the cytokines which cause responses such as inflammation of cells in skeletal muscles, with manipulating of training program, it can be avoided or limited from those exercises which induct cytokines release. Ginger plant is a kind of medicinal plants which is known as a anti inflammation plant. This plant is as most precedence medicinal plants in medicine science especially in inflammation cure. The aim of the present study was the effect of selected resistance training and consumption of ginger extract on IL-1α and TNFα untrained young women. The population includes young women interested in participating in the study with the average of 30±2 years old from Abbas Abad city among which 32 participants were chosen randomly and divided into 4 four groups, resistance training (R), resistance training and ginger consumption(RG), Ginger consumption(G)and Control group(C). The training groups performed circuit resistance training at the intensity of 65-75% one repeat maximum, 3 days a week for 6 weeks. Besides resistance training, subjects were given either ginseng (5 mg/kg per day) or placebo. Prior to and 48 hours after interventions body composition was measured and blood samples were taken in order to assess serum levels of IL-1α and TNFα. Plasma levels of cytokines were measured with commercially available ELISA Kits.IL-1α kit and TNFα kit were used in this research. To demonstrate the effectiveness of the independent variable and the comparison between groups, t-test and ANOVA were used. To determine differences between the groups, the Scheffe test was used that showed significant changes in any of the variables. we observed that circuit resistance training in R and RG groups can significant decreased in weight and body mass index in untrained females (p<0.05). The results showed a significant decreased in the mean level of IL-1α levels before and after the training period in G group (p=0.046) and RG group (p=0.022). Comparison between groups also showed there was significant difference between groups R-RG and RG-C. Intergroup comparison results showed that the mean levels of TNFα before and after the training in group G (p=0.044) and RG (p=0.037), significantly decreased. Comparison between groups also showed there was significant difference between groups R–RG , R-G ,RG-C and G-C. The research shows that circuit resistance training with reducing overload method results in systemic inflammation had significant effect on IL-1α levels and TNFα. Of course, Ginger can counteract the negative effects of resistance training exercise on immune function and stability of the mast cell membrane. Considerable evidence supported the anti-inflammatory properties of ginger for several constituents, especially gingerols, shogaols, paradols, and zingerones, through decreased cytokine gene TNF α and IL-1Α expression and inhibition of cyclooxygenase 1 and 2. These established biological actions suggest that ingested ginger could block the increase in IL-1α.

Keywords: resistance training, ginger, IL-1α , TNFα

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Authors: Khadijeh Abhari, Seyed Shahram Shekarforoush, Saeid Hosseinzadeh

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Probiotics have been considered as an approach to treat and prevent a wide range of inflammatory diseases. The spore forming probiotic strain Bacillus coagulans has demonstrated anti-inflammatory and immune-modulating effects in both animals and humans. The prebiotic, inulin, also potentially affects the immune system as a result of the change in the composition or fermentation profile of the gastrointestinal microbiota. An in vivo trial was conducted to evaluate the effects of probiotic B. coagulans, and inulin, either separately or in combination, on down regulate immune responses and progression of rheumatoid arthritis using induced arthritis rat model. Forty-eight male Wistar rats were randomly divided into 6 groups and fed as follow: 1) control: Normal healthy rats fed by standard diet, 2) Disease control (RA): Arthritic induced (RA) rats fed by standard diet, 3) Prebiotic (PRE): RA+ 5% w/w long chain inulin, 4) Probiotic (PRO): RA+ 109 spores/day B. coagulans by orogastric gavage, 5) Synbiotic (SYN): RA+ 5% w/w long chain inulin and 109 spores/day B. coagulans and 6) Treatment control: (INDO): RA+ 3 mg/kg/day indomethacin by orogastric gavage. Feeding with mentioned diets started on day 0 and continued to the end of study. On day 14, rats were injected with complete Freund’s adjuvant (CFA) to induce arthritis. Arthritis activity was evaluated by biochemical parameters and paw thickness. Biochemical assay for Fibrinogen (Fn), Serum Amyloid A (SAA), TNF-α and Alpha-1-acid glycoprotein (α1AGp) was performed on day 21, 28 and 35 (1, 2 and 3 weeks post RA induction). Pretreatment with PRE, PRO and SYN diets significantly inhibit SAA and Fn production in arthritic rats (P < 0.001). A significant decrease in production of pro-inflammatory cytokines, TNF-α, was seen in PRE, PRO and SYN groups (P < 0.001) which was similar to the effect of the anti-inflammatory drug Indomethacin. Further, there were no significant anti-inflammatory effects observed following different treatments using α1AGp as a RA indicator. Pretreatment with all supplied diets significantly inhibited the development of paw swelling induced by CFA (P < 0.001). Conclusion: Results of this study support that oral intake of probiotic B. coagulans and inulin are able to improve biochemical and clinical parameters of induced RA in rat.

Keywords: rheumatoid arthritis, bacillus coagulans, inulin, animal model

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Authors: Razieh Zareia, Hassan ZMB, Darush Moslemic, Amrollah Mostafa-Zaded

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Introduction: Shark is a murine organism and its cartilage has antitumor peptides to prevent angiogenesis, at least, in vitro. The purpose of our research was to evaluate the immune-effectiveness on imbalance between IL-23/IL-17 axis, as an inflammatory pathway and TGF/Foxp3 T regulatory as a inhibitory pathway of commercial shark cartilage that is available as a non-common dietary supplement in IRAN. Materials and Methods: First investigated an imbalanced supernatant of cytokines exist in patients with gastric cancer by ELISA. Associated with cytokines measuring such as IL-23, IL-17, TGF-β, IL-4, and γ-IFN, then flow cytometry was employed to determine whether the peripheral blood mononuclear cells such as CD4+CD25+Foxp3highT regulatory cells in patients with gastric cancer were changed correspondingly. Results: The simultaneously presented up-regulation IL-17A indicated, at least cytokine level without changing in TGF-β amount or CD4+CD25+Foxp3 T regulatory cells, that there are not a direct correlation between IL-23/IL-17 axis and Treg/TGF-β pathway in patients with gastric cancer treated by shark cartilage, but IL-23 was not expressed differentially in this group. So, accompany these changes, an imbalance between Th1 immunity (γ-IFN production) and TH2 immunity (IL-4 secretion) evaluated in patients with gastric cancer treated by shark cartilage. Conclusion: On the basis of results, we propose that shark cartilage, by reducing IL-4, decreasing IL-17 a central cytokine in angiogenesis and increasing γ-IFN amplify anti-tumor immune responses in patients with gastric cancer.

Keywords: IL-23/IL17 axis, TGF-β/CD4+CD25+Foxp3high T regulatory pathway, γ-IFN, IL-4, shark cartilage, gastric cancer

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Authors: Masaki Yamaguchi, Daimei Sasayama, Shinsuke Washizuka

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The goal of this study was to examine the possibility of salivary cytokines for the screening of attention deficit hyperactivity disorder (ADHD) in children. We carried out a case-control study, including 19 children with ADHD and 17 healthy children (controls). A multiplex bead array immunoassay was used to conduct a multi-analysis of 27 different salivary cytokines. Six salivary cytokines (interleukin (IL)-1β, IL-8, IL12p70, granulocyte colony-stimulating factor (G-CSF), interferon gamma (IFN-γ), and vascular endothelial growth factor (VEGF)) were significantly associated with the presence of ADHD (p < 0.05). An informative salivary cytokine panel was developed using VEGF by logistic regression analysis (odds ratio: 0.251). Receiver operating characteristic analysis revealed that assessment of a panel using VEGF showed “good” capability for discriminating between ADHD patients and controls (area under the curve: 0.778). ADHD has been hypothesized to be associated with reduced cerebral blood flow in the frontal cortex, due to reduced VEGF levels. Our study highlights the possibility of utilizing differential salivary cytokine levels for point-of-care testing (POCT) of biomarkers in children with ADHD.

Keywords: cytokine, saliva, attention deficit hyperactivity disorder, child

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Authors: Khadse Saurabh, Talele Gokul, Surana Sanjay

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In an endeavor to find a new class of anti-inflammatory agents, a series of novel benzamides (ab1-ab16) were synthesized by utilizing some arylideneoxazolones (az1-az4) having 2-acetyloxyphenyl substitution on their second position. Structures of these synthesized compounds were confirmed by IR, 1H-NMR, 13C NMR, and HRMS. Among the tested benzamide compounds 3ab1, 3ab2, 3ab11, and 3ab16 showed promising anti-inflammatory activity with lessened propensity to cause gastro-intestinal hypermotility and ulceration when compared with standard Indomethacin. Virtual screening was performed by docking the designed compounds into the ATP binding site of COX-2 receptor to predict if these compounds have analogous binding mode to the COX-2 inhibitor.

Keywords: benzamides, anti-inflammatory, gastro-intestinal hypermotility, ulcerogenic activity, docking

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Authors: Leyla Sattarzadeh, Shahin Fathi Molk Kian, Maghsoud Peeri, Mohammadali Azarbaijani, Hasan Matin Homaee

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Inflammation by various mechanisms may cause atherosclerosis. Systemic circulating inflammatory markers such as C-reactive protein (CRP), pro-inflammatory cytokines such as Interleukin-6 (IL-6), vascular inflammatory markers as adhesion molecules like Intracellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1) are the predictors of cardiovascular diseases. Regarding the conflicting results about the effect of different patterns of resistance exercise training on these inflammatory markers, present study aimed to examine the effect of different patterns of eight week resistance exercise training on CRP, IL-6, ICAM-1 and VCAM-1 levels in healthy untrained women. 56 healthy volunteered untrained female university students (aged: 21 ± 3 yr., Body Mass Index: 21.5 ± 3.5 kg/m²) were selected purposefully and divided into four groups. At the end of training protocol and after subject drop during the protocol, upper body exercise training (n=11), lower body (n=12) and whole body resistance exercise training group (n=11) completed the eight weeks of training period although the control group (n=7) did anything. Blood samples gathered pre and post-experimental period and CRP, IL-6, ICAM-1 and VCAM-1 levels were evaluated using special laboratory kits, then the difference of pre and post values of each indices analyzed using one-way analysis of variance (α < 0.05). The results of one way ANOVA for difference of pre and post values of CRP, ICAM-1 and VCAM-1 showed no significant changes due to the exercise training, but there were significant differences between groups about IL-6. Tukey post- hoc test indicated that there is significant difference between the differences of pre and post values of IL-6 between lower body exercise training group and control group, and eight weeks of lower body exercise training lead to significant changes in IL-6 values. There were no changes in anthropometric indices. The findings show that the different patterns of upper, lower and whole body exercise training by involving the different amounts of muscles altered the IL-6 values in lower body exercise training group probably because of engaging the bigger amount of muscles, but showed any significant changes about CRP, ICAM-1 and VCAM-1 probably due to intensity and duration of exercise or the lower levels of these markers at baseline of healthy people.

Keywords: resistance training, C-reactive protein, interleukin-6, intracellular adhesion molecule-1, vascular cell adhesion molecule-1

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Authors: Belgheis Ebrahimi, Jun Lu

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In recent years, there has been a growing recognition of the potential of marine-based functional foods and combination therapies in promoting a healthy lifestyle and exploring their effectiveness in preventing or treating diseases. The combination of marine bioactive compounds or extracts offers synergistic or enhancement effects through various mechanisms, including multi-target actions, improved bioavailability, enhanced bioactivity, and mitigation of potential adverse effects. Both the green-lipped mussel (GLM) and fucoidan derived from brown seaweed are rich in bioactivities. These two, mussel and fucoidan, have not been previously formulated together. This study aims to combine GLM oil from Perna canaliculus with low molecular weight fucoidan (LMWF) extracted from Undaria pinnatifida to investigate the unique mixture’s anti-inflammatory and antioxidant properties. The cytotoxicity of individual compounds and combinations was assessed using the MTT assay in (THP-1 and RAW264.7) cell lines. The anti-inflammatory activity of mussel-fucoidan was evaluated by treating LPS-stimulated human monocyte and macrophage (THP1-1) cells. Subsequently, the inflammatory cytokines released into the supernatant of these cell lines were quantified via ELISA. Antioxidant activity was determined by using the free radical scavenging assay (DPPH). DPPH assay demonstrated that the radical scavenging activity of the combinations, particularly at concentrations exceeding 1 mg/ml, showed a significantly higher percentage of inhibition when compared to the individual component. This suggests an enhancement effect when the two compounds are combined, leading to increased antioxidant activity. In terms of immunomodulatory activity, the individual compounds exhibited distinct behaviors. GLM oil displayed a higher ability to suppress the cytokine TNF- compared to LMWF. Interestingly, the LMWF fraction, when used individually, did not demonstrate TNF- suppression. However, when combined with GLM, the TNF- suppression (anti-inflammatory) activity of the combination was better than GLM or LWMF alone. This observation underscores the potential for enhancement interactions between the two components in terms of anti-inflammatory properties. This study revealed that each individual compound, LMWF, and GLM, possesses unique and notable bioactivity. The combination of these two individual compounds results in an enhancement effect, where the bioactivity of each is enhanced, creating a superior combination. This suggests that the combination of LMWF and GLM has the potential to offer a more potent and multifaceted therapeutic effect, particularly in the context of antioxidant and anti-inflammatory activities. These findings hold promise for the development of novel therapeutic interventions or supplements that harness the enhancement effects.

Keywords: combination, enhancement effect, perna canaliculus, undaria pinnatifida

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Authors: Dzatur Rizqi Fathienah Syarifuddin, Isharyah Sunarno, Eddy Hartono, Siti Maisuri T. Chalid

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Introduction: The potential impact of coronavirus disease 2019 (COVID-19) on the health of expectant mothers and fetuses has strained attention. Pregnant women are considered a vulnerable category to respiratory infections. Moreover, several inflammatory cytokines are 2-100 times more abundant in COVID-19 with cytokine storms than in normal individuals; interleukin 6 (IL-6) exhibits much higher elevations. Investigating potential relationships between IL-6 serum levels and the severity of COVID-19 symptoms in pregnant women is the aim of this study. Material and Methods: Sixty-two eligible pregnant women were divided into a positive COVID-19 group (n=31) and a negative COVID-19 group (n=31) in this cross-sectional study. The research subjects were selected using consecutive sampling. The IL-6 was measured from a vein blood specimen using ELISA methods. Results: The COVID-19 positive group had a higher median IL-6 serum level (45.35 (35.15- 153.99) vs. 38.86 ± 11.43 (15.02-59.52), p=0.03) than the negative group. On the other hand, the IL-6 serum level had comparable value according to the COVID-19 symptoms severity (88.35 ± 36.14 ng/mL vs. 51.09 ± 25.48 ng/mL vs. 56.02 ± 33.20 ng/mL in moderate symptoms, mild symptoms, and asymptomatic, respectively; p=0.152). Conclusion: Although the IL-6 serum levels are not related to COVID-19 symptoms severity, an elevated of this biomarker was found in pregnant women with affected diagnoses.

Keywords: interleukin-6, pregnancy, COVID-19, several inflammatory

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Authors: Antonio Munar-Frau, Sascha Klismoch, Manfred Schmolz, Federico Hernandez-Alfaro, Jordi Caballe-Serrano

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Introduction: Biocompatibility of biomaterials has been proposed as one of the main criteria for treatment success. For guided bone regeneration (GBR), barrier membranes present a conflict given the number of origins and modifications of these materials. The biologic response to biomaterials is orchestrated by a series of events leading to the integration or rejection of the biomaterial, posing questions such as if a longer occlusive property may trigger an inflammatory reaction. Whole blood cultures are a solution to study the immune response to drugs or biomaterials during the first 24-48 hours. The aim of this study is to determine the early immune response of different origins and chemical modifications of barrier membranes. Materials & Methods: 5 different widely used barrier membranes were included in this study: Acellular dermal matrix (AlloDerm, LifeCell®), Porcine Peritoneum (BioGide, Geistlich Pharma®), Porcine Pericardium (Jason, Botiss Biomaterials GmbH®), Porcine Cross-linked collagen (Ossix Plus, Datum Dental®) and d-PTFE (Cytoplast TXT, Osteogenics Biomedical®). Blood samples were extracted from 3 different healthy donors and incubated with the different samples of barrier membranes for 24 hours. After the incubation time, serum samples were obtained and analyzed by means of biocompatibility assays taking into account 42 markers. Results: In an early stage of the inflammatory response, the Acellular dermal matrix, porcine peritoneum and porcine cross-linked collagen expressed similar patterns of cytokine expression with a great manifestation of ENA 78. Porcine pericardium and d-PTFE presented similar cytokine activation, especially for MMP-3 and MMP-9, although other cytokines were highlighted with lower expression. For the later immune response, Porcine peritoneum and acellular dermal matrix MCP-1 and IL-15 were evident. Porcine pericardium, porcine cross-linked collagen and d-PTFE presented a high expression of IL-16 and lower manifestation of other cytokines. Different behaviors depending on an earlier or later stage of the inflammation process were observed. Barrier membrane inflammatory expression does not only differ depending on the origin, variables such as treatment of the collagen and polymers may also have a great impact on the cytokine expression of the studied barrier membranes during inflammation. Conclusions: Surface treatment and modifications might affect the biocompatibility of the membranes, as different cytokine expressions were evidently depending on the origin of the biomaterial. This study is only a brushstroke regarding the biocompatibility of materials, as it is one of the pioneer studies for ex vivo barrier membranes assays. Studies regarding surface modification are needed in order to clarify mystifications of barrier membrane science.

Keywords: biomaterials, bone regeneration, biocompatibility, inflammation

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Authors: M. Samsami, A. Hekmatdoost, N. Ebrahimi Daryani, P. Rezanejad Asl

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Ulcerative colitis (UC) is an inflammatory bowel disease in which immune and inflammatory factors are thought to be effective in this disease. Resveratrol is an antioxidant and anti-inflammatory compound. This study determined the effects of resveratrol compound on inflammatory factors in patients with ulcerative colitis. This study was a double-blind randomized clinical trial conducted on 50 patients with UC. Subjects received one capsule daily for 6 wk of either resveratrol (500 mg) or a placebo. Inflammatory factors, anthropometric measures, and IBDQ-9 (Inflammatory Bowel Disease Questionnaire-9) scores were assessed at baseline and at the end of the study. STATA12 software was used for data analysis. No significant differences were found in the background variables between the two groups at baseline. The results indicated that resveratrol supplementation for 6 week significantly decreased plasma levels of TNF-a and hs-CRP and the activity of NF-κB over the placebo group (p<0.001). Significant differences remained after adjustment for vitamin C (p<0.0001). The IBDQ-9 scores increased significantly in the resveratrol group over the placebo group (p<0.001). The findings of this study showed that resveratrol supplementation can be useful in patients with ulcerative colitis.

Keywords: IBD, inflammation, resveratrol, ulcerative colitis

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Authors: Mansi Srivastava, Uzma Saqib, Adnan Naim, Anjali Roy, Dongfang Liu, Deepak Bhatnagar, Ravinder Ravinder, Mirza S. Baig

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Macrophages polarize to proinflammatory M1 or anti-inflammatory M2 states with distinct physiological functions. This transition within the M1 to M2 phenotypes decides the nature, duration, and severity of an inflammatory response. However, inspite of a substantial understanding of the fate of these phenotypes, the underlying molecular mechanisms are not well understood. We have investigated the role of Neuronal nitric oxide synthase (NOS1) mediated regulation of Activator protein 1 (AP-1) transcription factor in macrophages as a critical effector of macrophage phenotypic change. Activator protein 1 (AP-1) is a group of dimeric transcription factors composed of jun, Fos, and ATF family proteins. We determined that NOS1-derived nitric oxide (NO) facilitate Fos and jun interaction which induces IL12 & IL23 expression. Pharmacological inhibition of NOS1 inhibits Fos and jun interaction but increases ATF2 and Fos dimerization. Switching of Fos and jun dimer to ATF2 and jun dimerization switches phenotype from IL–12high IL-23high IL-10low to IL–12low IL-23lowIL-10high phenotype, respectively. Together, these findings highlight a key role of the TLR4-NOS1-AP1 signaling axis in regulating macrophage polarization.

Keywords: inflammation, macrophage, lipopolysaccharide (LPS), proinflammatory cytokines, activator protein 1 (AP-1), neuronal nitric oxide synthase (NOS1)

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Authors: Saimir Heta, Ilma Robo, Nevila Alliu, Tea Meta

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Background: Plasma levels of inflammatory markers are the expression of the infectious wastes of existing periodontitis, as well as of existing inflammation everywhere in the body. Materials and Methods: The study consists of the clinical part of the measurement of inflammatory markers of 23 patients diagnosed with chronic periodontitis and the recording of parental periodontal parameters of patient periodontal status: hemorrhage index and probe values, before and 7-10 days after non-surgical periodontal treatment. Results: The level of fibrinogen drops according to the categorization of disease progression, active and passive, with the biggest % (18%-30%) at the fluctuation 10-20 mg/d. Fluctuations in fibrinogen level according to the age of patients in the range 0-10 mg/dL under 40 years and over 40 years was 13%-26%, in the range 10-20 mg/dL was 26%-22%, in the 20-40 mg/dL was 9%-4%. Conclusions: Non-surgical periodontal treatment significantly reduces the level of non-inflammatory markers in the blood. Oral health significantly reduces the potential source for periodontal bacteria, with the potential of promoting thromboembolism, through interaction between thrombocytes.

Keywords: chronic periodontitis, atherosclerosis, risk factor, inflammatory markers

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Authors: Maha Ali Al-Mohaya, Lubna Majed Al-Otaibi, Ebtissam Nassir Al-Bakr, Abdulrahman Al-Asmari

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Objectives: Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease. Cytokines play an important role in the pathogenesis and disease progression of OLP. The purpose of this study was to investigate the association of tumor necrosis factor (TNF)-α, TNF-β and interleukin (IL)-10 gene polymorphisms with the OLP risk. Material and Methods: Forty-two unrelated patients with OLP and 211 healthy volunteers were genotyped for TNF-α (-308 G/A), TNF-β (+252A/G), IL-10 (-1082G/A), IL-10 (-819C/T), and IL-10 (-592C/A) polymorphisms. Results: The frequencies of allele A and genotype GA of TNF-α (-308G/A) were significantly higher while allele G and GG genotypes were lower in OLP patients as compared to the controls (P < 0.001). The frequency of GA genotype of TNF-β (+252A/G) was significantly higher in patients than in controls while the AA genotype was completely absent in OLP patients. These results indicated that allele A and genotype GA of TNF-α (-308G/A) as well as the GA genotype of TNF-β (+252A/G) polymorphisms are associated with OLP risk. The frequencies of alleles and genotypes of -1082G/A, -819C/T and -592C/A polymorphisms in IL-10 gene did not differ significantly between OLP patients and controls (P > 0.05). However, haplotype ATA extracted from 1082G/A, -819C/T, -592C/A polymorphisms of IL-10 were more prevalent in OLP patients when compared to controls indicating its possible association with OLP susceptibility. Conclusion: It is concluded that TNF-α (-308G/A), TNF-β (+252A/G) and IL-10 (-1082G/A, -819C/T and -592C/A) polymorphisms are associated with the susceptibility of OLP, thus giving additional support for the genetic basis of this disease. Further studies are required using a larger sample size to confirm this association and determine the prognostic values of these findings.

Keywords: oral lichen planus, cytokines, polymorphism, genetic

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Authors: Anca Dinischiotu, Sorina Nicoleta Voicu

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Silica nanoparticles (SiO2-NPs) are widely used in consumer products such as paints, plastics, insulation materials, tires, concrete production, as well as in gene delivery systems and imaging procedures. Environmental human exposure to them occurs during utilization of these products, in a time-dependent manner, the uptake being by topic and inhalation route especially. SiO2-NPs enter cells and induce membrane damage, oxidative stress and inflammatory reactions in a concentration-dependent manner. In this study, MRC-5 cells (human fetal lung fibroblasts) were exposed to amorphous SiO2-NPs at a dose of 62.5 μg/ml for 24, 48 and 72 hours. The size distribution of NPs was a lognormal function, in the range 3-14 nm. A time-dependent decrease of total reduced glutathione concentration by 36%, 50%, and 78% and an increase of NO level by 62%, 32%, respectively 24% compared to control were noticed. An up-regulation of NF-kB expression by 20%, 50% respectively 10% and of Nrf-2 by 139%, 58%, and 16% compared to control after 24, 48 and 72 hours was noticed also. The expression of IL-1β, IL-6, IL-8, and COX-2 was up-regulated in a time-dependent manner. Also, the expression of MMP-2 and MMP-9 were down-regulated after 48 and 72 hours, whereas their activities raised in a time-dependent manner. Exposure of cells to NPs up-regulated the expression of inducible NO synthase, as previously was shown, and probably this is the reason for the increased level of NO, that can react with the thiol groups of reduced glutathione molecules, diminishing its concentration Nrf2 is a transcription factor translocated in nucleus, under oxidative stress, where downstream gene expression activates in order to modulate the adaptive intracellular response against oxidative stress. The cross-talk between Nrf2 and NF-kB activities regulates the inflammatory processes. The activation of NF-kB could activate up-regulation of IL-1β, IL-6, and IL-8. The increase of COX-2 expression could be correlated with IL-1β one. Also, probably in response to the pro-inflammatory cytokines, MMP-2 and MMP-9 were induced and activated. In conclusion, the exposure of MRC-5 cells to SiO2-NPs generated inflammation in a time-dependent manner.

Keywords: inflammation, MRC-5 cells, oxidative stress, silica nanoparticles

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Authors: Chao Hsing Yeh, Wei Chun Lin

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Background: Current management of aromatase inhibitor-induced arthralgia (AIA) in postmenopausal breast cancer survivors (PBCS) has limited effect. Method: In this prospective randomized clinical trial (RCT), a 4-week APA treatment was used to manage AIA. Twenty PBCS participated. After baseline data was collected, participants were waited for a month before they receive APA at a convenient time once a week for 4 weeks. Blood samples from participants in both groups were collected at baseline and after 4 weeks of treatment. The primary outcomes included: pain intensity, pain interference, stiffness, and physical function. Results: After the 4-week APA treatment, the pro-inflammatory cytokines and chemokines display a trend of mean percentage reduction (i.e., -22% in IL-1α, -4% in IL-1β, -1% in IL-2, -3% in IL-6, -19% in IL-12, -9% in Eotaxin, and -2% in MCP-1). The anti-inflammatory cytokine IL-10 and IL-13 (i.e., 5% in IL-10 and 29% in IL-13) increased from pre- to post-APA treatment. Significant positive correlation of percentage mean change was observed between symptom severity and eotaxin (ρ = 0.56; p < 0.01) & MCP-1 (ρ = 0.65; p < 0.01). Interference and chemokines (eotaxin & MIP-1) also shows positive correlation (ρ = 0.48; p < 0.01 & ρ = 0.39; p < 0.05). Another positive correlation was found between worst pain and chemokines (eotaxin, ρ = 0.48; p < 0.01 & MIP-1, ρ = 0.39; p < 0.05). Additionally, interference also shows positive correlation among IL-1α (ρ = 0.36; p < 0.05) and IL-β (ρ = 0.33; p < 0.05). Conclusion: These findings suggest that APA intervention may inhibit inflammation of AIA patients and chemokine could be one of the key factors of AIA symptom improvement.

Keywords: acupressure, cytokine, pain management, breast cancer survivors

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Authors: Hani M. Alothaid, Louise Robson, Richmond Muimo

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Cystic fibrosis (CF) is a disease that affects respiratory function and in EU it affects about 1 in 2,500 live births with an average 40-year life expectancy. This disease caused by mutations within the gene encoding the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) chloride channel leading to dysregulation of epithelial fluid transport and chronic lung inflammation, suggesting functional alterations of immune cells. In airways, CFTR been found to form a functional complex with S100A10 and AnxA2 in a cAMP/PKA dependent manner. The multiprotein complex of AnxA2-S100A10 and CFTR is also regulated by calcineurin. The aim of this study was i) to investigate whether chloride ion (Cl−) channels are activated by Pseudomonas aeruginosa lipopolysaccharide (LPS from PA), ii) if this activation is regulated by cAMP/PKA/calcineurin pathway and iii) to investigate the role of LPS-activated Cl− channels in the release of pro-inflammatory cytokines by immune cells. Human peripheral blood monocytes were used in the study. Whole-cell patch records showed that LPS from PA can activate Cl− channels, including CFTR and outwardly-rectifying Cl− channel (ORCC). This activation appears to require an intact PKA/calcineurin signalling pathway. The Gout in the presence of LPS was significantly inhibited by diisothiocyanatostilbene-disulfonic acid (DIDS), an ORCC blocker (p<0.001). The Gout was further suppressed by CFTR(inh)-172, a specific inhibitor for CFTR channels (p<0.001). Monocytes pre-incubated with PKA inhibitor or calcineurin inhibitor before stimulated with LPS from PA that were resulted in DIDS and CFTR(inh)-172 insensitive currents. Activation of both ORCC and CFTR was however, observed in response to monocytes exposure to LPS. Additionally, ELISA showed that the CFTR and ORCC play a role in mediating the release of pro-inflammatory cytokines such as IL-1β upon exposure of monocytes to LPS. However, this secretion was significantly inhibited due to CFTR and ORCC inhibition. However, Cl− may play a role in IL-1β release independent of cAMP/PKA/calcineurin signalling due to the enhancement of IL-1β secretion even when cAMP/PKA/calcineurin pathway was inhibited. In conclusion, our data confirmed that LPS from PA activates Cl− channels in human peripheral blood monocytes. Our data also confirmed that Cl− channels were involved in IL-1β release in monocytes upon exposure to LPS. However, it has been found that PKA and calcineurin does not seem to influence the Cl− dependent cytokine release.

Keywords: cystic fibrosis, CFTR, Annexin A2, S100A10, PP2B, PKA, outwardly-rectifying Cl− channel, Pseudomonas aeruginosa

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