Search results for: inflammatory factors

Authors: Kun Chun, Jin-Chun Heo, Sang-Han Lee

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Asthma is a chronic airway inflammatory disease characterized by the infiltration of inflammatory cells and tissue remodeling. In this study, we examined the anti-asthmatic activity of a derivative of L-allo threonine by in vitro and in vivo anti-asthmatic assays. Ovalbumin (OVA)-induced C57BL/6 mice were used to analyze lung inflammation and cytokine expressions for exhibiting anti-atopic activity of the derivative. LX519290, a derivative of L-allo threonine, induced an increased IFN-γ and a decreased IL-10 mRNA level. This compound exhibited potent anti-asthmatic activity by decreasing immune cell infiltration in the lung, and IL-4 and IL-13 cytokine levels in the serum of OVA-induced mice. These results indicated that chronic airway injury was decreased by LX519290. We also assessed that LX519290 inhibits infiltration of immune cell, mucus release and cytokine expression in an in vivo model. Our results collectively suggest that the L-allo threonine is effective in alleviating asthmatic symptoms by treating inflammatory factors in the lung.

Keywords: asthma, L -allo threonine, LX519290, mice

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Authors: Parinaz Tavakoli Zaniani, Dimitrios Balomenos

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Mitochondrial reactive oxygen species (mROS) play a crucial role in macrophage pro-inflammatory activation, although a detailed understanding of the mechanism and kinetics by which mROS drive signaling molecules is still lacking. In general, it is thought that NF-κB activation drives mROS and general ROS production. Here, We performed a detailed kinetic analysis of mROS production during macrophage activation. We found early mROS generation after LPS (lipopolysaccharide) stimulation. Remarkably as early as 5 minutes, mROS signaling promoted initial NF-κB, MAPK activation and pro-inflammatory cytokine production, as established through inhibition or quenching of mROS. On the contrary, NF-κB inhibition had no effect on mROS production. Our findings point to a mechanism by which mROS increase TRAF-6 ubiquitination and, thus NF-κB activity. mROS inhibition reduced LPS-induced lethality in an in vivo septic shock model by controlling pro-inflammatory cytokine production. Overall, our research provides novel insights into the role of mROS as a primary messenger in the pathway of macrophage and as a regulator of inflammatory responses. We found that early mROS production promotes initial NF-κB, and MAPK activation by regulating TRAF-6 ubiquitination and that mROS inhibition can reduce LPS-induced inflammatory cytokines and lethality in a septic shock model. These findings might lead to novel immunotherapeutic strategies targeting early mROS production and control of extreme inflammation in the context of sepsis and other inflammatory diseases.

Keywords: mitochondria, reactive oxygen species, nuclear factor κB, lipopolysaccharide, macrophages

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Authors: Raj Raghupathy

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Recurrent Spontaneous Miscarriage (RSM) is a common form of pregnancy loss, 50% of which are due to ‘unexplained’ causes. Evidence exists to suggest that RSM may be caused by immunologic factors such as cytokines which are critical molecules of the immune system, with an impressive array of capabilities. An association appears to exist between Th2-type reactivity (mediated by Th2 or anti-inflammatory cytokines) and normal, successful pregnancy, and between unexplained RSM and Th1 cytokine dominance. If pro-inflammatory cytokines are indeed associated with pregnancy loss, the suppression of these cytokines, and thus the ‘redirection’ of maternal reactivity, may help prevent cytokine-mediated pregnancy loss. The objective of this study was to explore the possibility of modulating cytokine production using Dydrogesterone (Duphaston®), an orally-administered progestogen. Peripheral blood mononuclear cells from 34 women with a history of at least 3 unexplained recurrent miscarriages were stimulated in vitro with a mitogen (to elicit cytokine production) in the presence and absence of dydrogesterone. Levels of selected pro- and anti-inflammatory cytokines produced by peripheral blood mononuclear cells were measured after exposure to these progestogens. Dydrogesterone down-regulates the production of pro-inflammatory cytokines and up-regulates the production of anti-inflammatory cytokines. The ratios of Th2 to Th1 cytokines are markedly elevated in the presence of dydrogesterone, indicating a shift from potentially harmful maternal Th1 reactivity to a more pregnancy-conducive Th2 profile. We used a progesterone receptor antagonist to show that this cytokine-modulating effect of dydrogesterone is mediated via the progesterone receptor. Dydrogesterone also induces the production of the Progesterone-Induced Blocking Factor (PIBF); lymphocytes exposed to PIBF produce higher levels of Th2 cytokines, affecting a Th1 → Th2 cytokine shift which could be favourable to the success of pregnancy. We conclude that modulation of maternal cytokine production profiles is possible with dydrogesterone which has the merits that it can be administered orally and that it is safe.

Keywords: cytokines, dydrogesterone, progesterone, recurrent spontaneous miscarriage

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Authors: Gina Cecilia Pistol, Loredana Calin, Mariana Stancu, Veronica Chedea, Ionelia Taranu

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Inflammatory-associated diseases have an increased trend in the past decades. The pharmacological strategies aimed to treat these inflammatory diseases are very expensive and with non-beneficial results. The current trend is to find alternative strategies to counteract or to control inflammatory component of diseases. The grape by-products either seeds or pomace are rich in bioactive compounds (e.g. polyphenols) which may be beneficial in prevention of inflammation associated with cancer progression and other pathologies with inflammatory component. The in vivo models are very useful for studying the immune and inflammatory status. The domestic pig (Sus scrofa domesticus) is related to human from anatomic and physiologic point of view, representing a feasible model for studying the human inflammatory pathologies. Starting from these data, we evaluated the effect of a diet containing 5% grape seed cakes (GS) on piglets blood biochemical parameters and immune pro- and anti-inflammatory biomarkers (IL-1 beta, IL-8, TNF-alpha, IL-6, IFN-gamma, IL-10, IL-4) in spleen and lymph nodes. 12 weaned piglets were fed for 30 days with a control diet or an experimental diet containing 5% GS. At the end of trial, plasma and tissue samples (spleen and lymph nodes) were collected and the biochemical and inflammatory markers were analysed by using biochemistry analyser and ELISA techniques. Our results showed that diet included 5% GS did not influence the health status determined by plasma biochemical parameters. Only a tendency for a slight increase of the biochemical parameters associated with energetic profile (glucose, cholesterol, triglycerides) was observed. Also, GS diet had no effect on pro- and anti-inflammatory cytokines content in spleen and lymph nodes tissue. Further experiments are needed in order to investigate other rate of dietary inclusion which could provide more evidence about the effect of grape bioactive compounds on pigs used as animal model.

Keywords: animal model, inflammation, grape seed by-product, immune organs

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Authors: T. E. Tshikalange, B. C. Mophuting

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Traditional medicine often consists of complex ingredients prepared from a mixture of plant species. These herbal mixtures are used in the treatment of various ailments such as sexually transmitted diseases including HIV. The present study was carried out to determine the biological activities of the herbal mixture used traditionally in the treatment of sexually transmitted diseases. This herbal mixture consists of four plant species from families Asteraceae, Bignoniaceae, Fabaceae, and Myrtaceae. Five crude extracts (hexane, dichloromethane, methanol, water and boiled) of the herbal mixture were investigated for anti-gonococcal, anti-inflammatory, and reverse transcriptase activities. The anti-inflammatory activity of the plant extracts was determined by measuring the extract inhibitory effect on the pro-inflammatory enzyme lipoxygenase. The extracts were also tested for anti-HIV activity against recombinant HIV-1 enzyme using non-radioactive HIV-RT colorimetric assay. The boiled extract exhibited good anti-inflammatory activity with an IC₅₀ of 87 µg/ml compared to that of the positive control quercetin (IC₅₀= 92 µg/ml). All the other extracts showed little or no activity. Hexane extract was the only extract that showed reverse transcriptase extract inhibitory effect with an IC₅₀ of 74 µg/ml. Anti-gonococcal and cytotoxicity investigations are underway. The preliminary results support the use of herbal mixture by traditional healers.

Keywords: sexually transmitted diseases, lipoxygenase, anti-inflammatory, herbal mixture

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Authors: Khairy M. A. Zoheir

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One of the most severe complications of Rheumatoid arthritis is delayed recovery. lipoic acid possesses antioxidant, hypoglycemic, and anti-inflammatory activity. In the present study, the effects of lipoic acid was investigated on the key mediators of Rheumatoid arthritis, namely, CD4+CD25+ T cell subsets, GITR expressing cells, CD4+CD25+Foxp3+ regulatory T (Treg) cells, T-helper-17 (Th17) cells, and pro-inflammatory cytokines Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Tumor Necrosis Factor- α (TNF-α)] through flow-cytometry and qPCR analyses. Lipoic acid treated mice showed a significant decrease in the Rheumatoid arthritis, the frequency of GITR-expressing cells, and Th1 cytokines (IL-17A, TNF-αand Interferon- γ (IFN-γ) compared with positive and negative controlled mice. Lipoic acid treatment also down regulated the mRNA expression of the inflammatory mediators compared with the Rheumatoid arthritis mouse model and untreated mice. The number of Tregs also found to be significantly upregulated in lipoic acid treated mice. Our results were confirmed by the histopathological examination. This study showed the beneficial role of lipoic acid in promoting a well-balanced tool for therapy Rheumatoid arthritis.

Keywords: lipoic acid, chemokines, inflammatory, rheumatoid arthritis

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Authors: Zohreh Afsharmand, Sokhanguei Yahya

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A growing body of literature suggests that that low-grade systemic inflammation associated to obesity plays a key role in the pathogenic mechanism of several disorders. In this study, the effect of 6 weeks aerobic training on IL-6 and IL-1B as inflammatory cytokine were investigated in adult obese women. For this purpose, 26 sedentary adult obese women were divided into exercise and control groups (n=12). Pre and post training of mentioned cytokines were measured in two groups. Student’s t-tests for paired samples were performed to determine whether there were significant within-group changes in the outcomes. A p value less than 0.05 was considered statistically significant. There were no statistically significant differences between the exercise and control groups with regard to anthropometrical markers or inflammatory cytokines. Despite the significant decrease in all anthropometrical markers, no significant differences were found in serum IL-6 and IL-1B by aerobic training with compared to baseline. Our findings indicate that aerobic training intervention for a short time is not associated with the anti-inflammatory property in obese women.

Keywords: aerobic training, cytokine, inflammation, obesity

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Authors: Khairy Mohamed Abdalla Zoheir

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One of the most severe complications of Rheumatoid arthritis is delayed recovery. lipoic acid possesses antioxidant, hypoglycemic, and anti-inflammatory activity. In the present study, the effects of lipoic acid were investigated on the key mediators of Rheumatoid arthritis, namely, CD4+CD25+ T cell subsets, GITR expressing cells, CD4+CD25+Foxp3+ regulatory T (Treg) cells, T-helper-17 (Th17) cells and pro-inflammatory cytokines Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Tumor Necrosis Factor- α (TNF-α)] through flow-cytometry and qPCR analyses. Lipoic acid-treated mice showed a significant decrease in Rheumatoid arthritis, the frequency of GITR-expressing cells, and Th1 cytokines (IL-17A, TNF-αand Interferon- γ (IFN-γ) compared with positive and negative controlled mice. Lipoic acid treatment also downregulated the mRNA expression of the inflammatory mediators compared with the Rheumatoid arthritis mouse model and untreated mice. The number of Tregs was also found to be significantly upregulated in lipoic acid-treated mice. Our results were confirmed by the histopathological examination. This study showed the beneficial role of lipoic acid in promoting a well-balanced tool for the therapy of Rheumatoid arthritis.

Keywords: lipoic acid, inflammatory markers, rheumatoid arthritis, qPCR

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Authors: Anna Pick Kiong Ling, Jia May Chin, Rhun Yian Koh, Ying Pei Wong

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Background: Uncontrolled inflammation may cause serious inflammatory diseases if left untreated. Non-steroidal anti-inflammatory drug (NSAIDs) is commonly used to inhibit pro-inflammatory enzymes, thus, reduce inflammation. However, long term administration of NSAIDs leads to various complications. Medicinal plants are getting more attention as it is believed to be more compatible with human body. One of them is a flavonoid-containing medicinal plants, Strobilanthes crispus which has been traditionally claimed to possess anti-inflammatory and antioxidant activities. Nevertheless, its anti-inflammatory activities are yet to be scientifically documented. Objectives: This study aimed to examine the anti-inflammatory activity of S. crispus by investigating its effects on intracellular oxidative stress and prostaglandin E₂ (PGE₂) levels. Materials and Methods: In this study, the Maximum Non-toxic Dose (MNTD) of methanol extract of both leaves and stems of S. crispus was first determined using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenytetrazolium Bromide (MTT) assay. The effects of S. crispus extracts at MNTD and half MNTD (½MNTD) on intracellular ROS as well as PGE₂ levels in 1.0 µg/mL LPS-stimulated RAW 264.7 macrophages were then be measured using DCFH-DA and a competitive enzyme immunoassay kit, respectively. Results: The MNTD of leaf extract was determined as 700µg/mL while for stem was as low as 1.4µg/mL. When LPS-stimulated RAW 264.7 macrophages were subjected to the MNTD of S. crispus leaf extract, both intracellular ROS and PGE₂ levels were significantly reduced. In contrast, stem extract at both MNTD and ½MNTD did not significantly reduce the PGE₂ level, but significantly increased the intracellular ROS level. Conclusion: The methanol leaf extract of S. crispus may possess anti-inflammatory properties as it is able to significantly reduce the intracellular ROS and PGE₂ levels of LPS-stimulated cells. Nevertheless, further studies such as investigating the interleukin, nitric oxide and cytokine tumor necrosis factor-α (TNFα) levels has to be conducted to further confirm the anti-inflammatory properties of S. crispus.

Keywords: anti-inflammatory, natural products, prostaglandin E2, reactive oxygen species

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Authors: Sina Mahdavi

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Background and Objective: Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the central nervous system (CNS) that affects the myelination process in the CNS. Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially Epstein-Barr virus (EBV) and MS, is one potential cause that is not well understood. In this study, we aim to summarize the available data on EBV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis," "Epstein-Barr virus," and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched, and 14 articles were chosen, studied, and analyzed. Results: Demyelinated lesions isolated from MS patients contain EBNAs from EBV proteins. The EBNA1 domain contains a pentapeptide fragment identical to B-crystallin, a heat shock peptide, that is increased in peripheral B cells in response to B-crystallin infection, resulting in myelin-directed autoimmunity mediated by proinflammatory T cells. EBNA2, which is involved in the regulation of viral transcription, may enhance transcription from MS risk loci. A 7-fold increase in the risk of MS has been observed in EBV infection with HLA-DR15 synergy. Conclusion: EBV infection along with a variety of specific genetic risk alleles, cause inflammatory cascades in the CNS by infected B cells. There is a high expression of EBV during the course of MS, which indicates the relationship between EBV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of EBV may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, Epstein-Barr virus, central nervous system, EBNAs

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Authors: Ae Ra Han, Seoung Eun Huh, Ji Yeon Kim, Joanne Kwak-Kim, Sung Ki Lee

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Objective: Prevalence of osteoporosis, cardiovascular disorders, and Alzheimer's disease rapidly increase after menopause. Immune activation and inflammation are suggested as an important pathogenesis of these serious diseases. Several pro-inflammatory cytokines are increased in women with surgical or natural menopause. However, the little is known about IL-17 producing T cells and Foxp3+ regulatory T (Treg) cells in post-menopause. Methods: A total of 34 postmenopausal women, who had no active cardiovascular, endocrine and infectious disorders were recruited as study group and healthy premenopausal women participated as controls. Peripheral blood mononuclear cells were isolated. Immuno-morphologic (CD3, CD4, CD8, CD19, CD56/CD16), intracellular cytokine (TNF-alpha, IFN-gamma, IL-10, IL-17), and Treg cell (Foxp3) studies were carried out using flow cytometry. The proportion of peripheral lymphocytes, including IL-17 producing and Foxp3+ Treg cells immune cell in each group were statistically analyzed. Results: The proportion of NK cells was significantly increased in menopausal women as compared to that of controls (P=.005). The ratios of TNF-alpha/IL-10 producing CD3+CD4+ T cells were increased in postmenopausal women. CD3+IL-17+ T cell level was higher in postmenopausal women and CD4+ Foxp3+ Treg cells was lower than that of controls. The ratios of CD3+IL-17+ T cell to CD3+Foxp3+ and to CD4+Foxp3+ Treg cells were significantly increased in postmenopausal women (P=.001). Conclusions: We found enhanced innate immunity and Th1- and Th17-mediated adaptive immunity in postmenopausal women. This may explain increasing prevalence of chronic inflammatory diseases after menopause. Further studies are needed to elucidate what factors contribute to this inflammatory shift in the postmenopause.

Keywords: inflammation, immune cell, menopause, Th17, regulatory T cell

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Authors: Yonghwa Lee, Yoon Suk Kim, Yongsub Yi

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This study was to confirm the effects of anti-melanogenesis and anti-inflammatory effects from Opuntia humifusa fruit and stem extracts. A potent anti-oxidant activity was shown from the leaf extract at IC50 value of 38.33±1.07 μg/mL and fruit extract at IC50 value of 40.23±2.21 μg/mL by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Also, phenolic contents were confirmed total phenolic assay by high performance liquid chromatography (HPLC). Fraction of taxifolin from leaf extract was identified using HPLC and gas chromatography/mass spectrometry. The extracts of Opuntia humifusa fruit and stem were confirmed about toxicity effect in B16 F1 by cell viability. Melanin contents were decreased. Opuntia humifusa fruit and stem extracts had a positive effect of melanin synthesis inhibition for skin whitening. In investigating the anti-inflammatory activities of Opuntia humifusa, the results of cell viability indicated that taxifolin did not show cytotoxicity on RAW264.7 cells at 500 μM of concentration. The results show that taxifolin inhibited lipopolysaccharide (LPS)-induced production of Nitrite oxide (NO). In addition, taxifolin indicated the inhibition of lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) -α and interleukin (IL) -6 productions by cytokine assay and cyclooxygenase (COX)-2 expression by western blot analysis, meaning that taxifolin had a significant anti-inflammatory effect. Our results suggested that taxifolin from Opuntia humifusa has anti-melanogenesis and anti-inflammatory activities.

Keywords: anti-melanogenesis, anti-inflammatory, Opuntia humifusa, taxifolin

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Authors: Maria Del Carmen Millan-Linares, Ana Lemus Conejo, Rocio Toscano, Alvaro Villanueva, Francisco Millan, Justo Pedroche, Sergio Montserrat-De La Paz

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GPETAFLR (Glycine-Proline-Glutamine-Threonine-Alanine-Phenylalanine-Leucine-Arginine) is a peptide isolated from Lupinus angustifolius L. protein hydrolysate (LPH). Herein, the effect of this peptide was investigated in two different models of neuroinflammation: in the immortalized murine microglia cell line BV-2 and in a high-fat-diet-induced obesity mouse model. Methods and Results: Effects of GPETAFLR on neuroinflammation were evaluated by RT-qPCR, flow cytometry, and ELISA techniques. In BV-2 microglial cells, Lipopolysaccharides (LPS) enhanced the release of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) whereas GPETAFLR decreased pro-inflammatory cytokine levels and increased the release of the anti-inflammatory cytokine IL-10 in BV2 microglial cells. M1 (CCR7 and iNOS) and M2 (Arg-1 and Ym-1) polarization markers results showed how the GPETAFLR octapeptide was able to decrease M1 polarization marker expression and increase the M2 polarization marker expression compared to LPS. Animal model results indicate that GPETAFLR has an immunomodulatory capacity, both decreasing pro-inflammatory cytokine IL-6 and increasing the anti-inflammatory cytokine IL-10 in brain tissue. Polarization markers in the brain tissue were also modulated by GPETAFLR that decreased the pro-inflammatory expression (M1) and increased the anti-inflammatory expression (M2). Conclusion: Our results suggest that GPETAFLR isolated from LPH has significant potential for management of neuroinflammatory conditions and offer benefits derived from the consumption of Lupinus angustifolius L. in the prevention of neuroinflammatory-related diseases.

Keywords: GPETAFLR peptide, BV-2 cell line, neuroinflammation, cytokines, high-fat-diet

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Authors: Mahzad Yousefi, Azin Tavakoli

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Periodontal disease is an inflammatory reaction; therefore, it is predicted that changes may occur in some inflammatory parameters that can be detected in routine blood tests. The objective of this study was to evaluate the hematological and biochemistry changes that occur in dogs affected with advanced stages of periodontal disease. 87 dogs were diagnosed with periodontal disease (PD group), and 76 healthy dogs entered the study. The PD dogs had been affected with periodontitis stage 3 or 4 and were candidates for any dental extractions. The healthy dogs were either referred for annual checkups or for issuing health travel certificates that their owners asked for complete lab tests. Neither the diseased nor healthy subjects had a history of infectious, or other general health problems or surgery in the past 3 months. Age, as well as all hematologic including PCV, WBC and RBC count, Hb, MCV, MCH, MCHC, PLT, CBC, NLR, and biochemistry data, including total protein, albumin, glucose, BUN, Creatinine, ALT, AST, and ALP, were recorded and analyzed statistically. Results confirmed that aging has a significant direct relationship with the advanced stages of periodontal disease. Mild leukocytosis occurred in the diseased group; however, it was not significant. Also, the mean total protein of the PD group was lower than that of the healthy dogs, and serum levels of albumin were found to be lower significantly in the diseased group (P<0.05). Mean ±SD amount of Platelet, MCH, and ALT were significantly higher in the diseased group in comparison to the healthy dogs (P<0.05). No significant differences were reported in other evaluated parameters. It is concluded that CBC indices of PD dogs are not systemic inflammatory; however, only a decrease in albumin showed inflammatory responses. Some indices in routine laboratory tests can be changed significantly during advanced stages of the periodontal disease dogs.

Keywords: periodontal disease, dogs, hematological factors, advanced stages, blood tests

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Authors: Ashit Syngle, Inderjit Verma, Pawan Krishan

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Objective: Endothelial progenitor cells (EPCs) have reparative potential in overcoming the endothelial dysfunction and reducing cardiovascular risk. EPC depletion has been demonstrated in the setting of established atherosclerotic diseases. With this background, we evaluated whether reduced EPCs population are associated with endothelial dysfunction, subclinical atherosclerosis and inflammatory markers in ankylosing spondylitis (AS) patients without any known traditional cardiovascular risk factor in AS patients. Methods: Levels of circulating EPCs (CD34+/CD133+), brachial artery flow-mediated dilatation, carotid intima-media thickness (CIMT) and inflammatory markers i.e erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tissue necrosis factor (TNF)–α, interleukin (IL)-6, IL-1 were assessed in 30 AS patients (mean age33.41 ± 10.25; 11 female and 19 male) who fulfilled the modified New York diagnostic criteria with 25 healthy volunteers (mean age 29.36± 8.64; 9 female and 16 male) matched for age and sex. Results: EPCs (CD34+/CD133+) cells were significantly (0.020 ± 0.001% versus 0.040 ± 0.010%, p<0.001) reduced in patients with AS compared to healthy controls. Endothelial function (7.35 ± 2.54 versus 10.27 ±1.73, p=0.002), CIMT (0.63 ± 0.01 versus 0.35 ± 0.02, p < 0.001) and inflammatory markers were also significantly (p < 0.01) altered as compared to healthy controls. Specifically, CD34+CD133+cells were inversely multivariate correlated with CRP and TNF-α and endothelial dysfunction was positively correlated with reduced number of EPC. Conclusion: Depletion of EPCs population is an independent predictor of endothelial dysfunction and early atherosclerosis in AS patients and may provide additional information beyond conventional risk factors and inflammatory markers.

Keywords: endothelial progenitor cells, atherosclerosis, ankylosing spondylitis, cardiovascular

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Authors: Mohamed Majrashi, Patricia Connolly, Terry Gourlay

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Cardiopulmonary bypass is known to cause inflammatory response during open heart surgery. It includes the initiation of different cascades such as coagulation, complement system and cytokines. Although the immune system is body’s key defense mechanism against external assault, when overexpressed, it can be injurious to the patient, particularly in a cohort of patients in which there is a heightened and uncontrolled response. The inflammatory response develops in these patients to an exaggerated level resulting in an autoimmune injury and may lead to poor postoperative outcomes (systemic inflammatory response syndrome and multi-organs failure). Previous studies by this group have suggested a correlation between the level of IL6 measured in patient’s blood before surgery and after polymeric activation and the observed inflammatory response during surgery. Based upon these findings, the present work is aimed at using this response to develop a test which can be used prior to the open heart surgery to identify the high-risk patients before their operation. The work will be accomplished via three main clinical phases including some pilot in-vitro studies, device development and clinical investigation. Current findings from studies using animal blood, employing DEHP and DEHP plasticized PVC materials as the activator, support the earlier results in patient samples. Having established this relationship, ongoing work will focus on developing an activated lateral flow strip technology as a screening device for heightened inflammatory propensity.

Keywords: cardiopulmonary bypass, cytokines, inflammatory response, overexpression

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Authors: Abdullah Alyoussef

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Folliculitis decalvans is a rare inflammatory scalp disorder. This paper gives an update to patient management and treatment modalities. Folliculitis decalvans is classified as primary neutrophilic cicatricial alopecia and predominantly occurs in middle-aged adults. The cause of folliculitis decalvans (FD) remains unknown. Staphylococcus aureus and a deficient host immune response seem to play an important role in the development of this disfiguring scalp disease. Lesions occur mainly in the vertex and occipital area. Clinically, the lesions present with follicular pustules, lack of ostia, diffuse and perifollicular erythema, follicular tufting, and, oftentimes, hemorrhagic crusts and erosions. Histology displays a mainly neutrophilic inflammatory infiltrate in early lesions and additionally lymphocytes and plasma cells in advanced lesions. Treatment is focused on the eradication of S. aureus and anti-inflammatory agents. Although the etiology of FD is unclear, S. aureus is almost always isolated from affected areas, and eradication is an important part of therapeutic management, in combination with systemic and ⁄ or topical anti-inflammatory treatment.

Keywords: cicatricial alopecia, folliculitis decalvans, tufted folliculitis, erosion

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Authors: Linda Chularojmontri, Seewaboon Sireeratawong, Suvara Wattanapitayakul

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Terminalia arjuna Roxb. (family Combretaceae) is commonly known as ‘Sa maw thet’ in Thai. The fruit is used in traditional medicine as natural mild laxatives, carminative and expectorant. Aim of the study: This research aims to study the anti-inflammatory, analgesic and antipyretic activities of Terminalia arjuna extract by using animal models in comparison to the reference drugs. Materials and Methods: The anti-inflammatory study was conducted by two experimental animal models namely ethyl phenylpropionate (EPP)-induced ear edema and carrageenan-induced paw edema. The study of analgesic activity used two methods of pain induction including acetic acid and heat-induced pain. In addition, the antipyretic activity study was performed by induced hyperthermia with yeast. Results: The results showed that the oral administration of Terminalia arjuna extract possessed acute anti-inflammatory effect in carrageenan-induced paw edema. Terminalia arjuna extract showed the analgesic activity in acetic acid-induced writhing response and heat-induced pain. This indicates its peripheral effect by inhibiting the biosynthesis and/or release of some pain mediators and some mechanism through Central nervous system. Moreover, Terminalia arjuna extract at the dose of 1000 and 1500 mg/kg body weight showed the antipyretic activity, which might be because of the inhibition of prostaglandins. Conclusion: The findings of this study indicated that the Terminalia arjuna extract possesses the anti-inflammatory, analgesic and antipyretic activities in animals.

Keywords: analgesic activity, anti-inflammatory activity, antipyretic activity, Terminalia arjuna extract

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Authors: Ashit Syngle, Nidhi Garg, Pawan Krishan

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Objective: Bone marrow derived stem cells, endothelial progenitor cells (EPCs), protect against atherosclerotic vascular damage. However, EPCs are depleted in AS and contribute to the enhanced cardiovascular risk. Statins have a protective effect in CAD and diabetes by enhancing the proliferation, migration and survival of EPCs. Therapeutic potential of augmenting EPCs to treat the heightened cardiovascular risk of AS has not yet been exploited. We aimed to investigate the effect of rosuvastatin on EPCs population and inflammation in AS. Methods: 30 AS patients were randomized to receive 6 months of treatment with rosuvastatin (10 mg/day, n=15) and placebo (n=15) as an adjunct to existing stable anti-rheumatic drugs. EPCs (CD34+/CD133+) were quantified by Flow Cytometry. Inflammatory measures (BASDAI, BASFI, CRP and ESR), pro-inflammatory cytokines (TNF-α, IL-6 and IL-1) and lipids were measured at baseline and after treatment. Results: At baseline, inflammatory measures and pro-inflammatory cytokines were elevated and EPCs depleted among both groups. EPCs increased significantly (p < 0.01) after treatment with rosuvastatin. At 6 months, BASDAI, BASFI, ESR, CRP, TNF-α, and IL-6 improved significantly in rosuvastatin group. Significant negative correlation was observed between EPCs and BASDAI, CRP and IL-6 after rosuvastatin treatment. Conclusion: First study to show that rosuvastatin augments EPCs population in AS. This defines a novel mechanism of rosuvastatin treatment in AS: the augmentation of EPCs with improvement in proinflammatory cytokines and inflammatory disease activity. The augmentation of EPCs by rosuvastatin may provide a novel strategy to prevent cardiovascular events in AS.

Keywords: ankylosing spondylitis, Endothelial Progenitor Cells, inflammation, pro-inflammatory cytokines, rosuvastatin

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Authors: Malay K. Das, Bhupen Kalita

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The poor oral bioavailability of resveratrol (RSV) due to presystemic metabolism can be avoided via dermal route of administration. The hydrophilic-lipophilic nature of resveratrol-phospholipid complex (RSVPs) favors the delivery of resveratrol via the skin. The RSVPs embedded polymeric patch with moderate adhesiveness was developed for dermal application for sustained anti-inflammatory effect. The prepared patches were evaluated for various physicochemical properties, surface morphology by SEM, TEM, and compatibility of patch components by FT-IR and DSC studies. The dermal flux of the optimized patch formulation was found to be at 4.28 ± 0.48 mg/cm2/24 h. The analysis of skin extract after permeation study revealed the presence of resveratrol, which confirmed the localization of RSVPs in the skin. The stability of RSVPs in the polymeric patch and the physiologic environment was confirmed by FE-SEM studies on the patches after drug release and skin permeation studies. The RSVPs particles released from the polymer matrix maintaining the structural integrity and permeate the keratinized horney layer of skin. The optimized patch formulation showed sustained anti-inflammatory effect (84.10% inhibition of inflammation at 24 h) in carrageenan-induced rat paw edema model compared to marketed diclofenac sodium gel (39.58% inhibition of inflammation at 24 h). The CLSM study confirmed the localization of RSVPs for a longer period, thus enabling drug targeting to the dermis for sustained anti-inflammatory effect. Histological studies with phase contrast trinocular microscope suggested no alteration of skin integrity and no evidence of the presence of inflammatory cells after exposure to the permeants. The patch was found to be safe for skin application as evaluated by Draize method for skin irritation scoring in a rabbit model. These results suggest the therapeutic efficacy of the developed patch in both acute and chronic inflammatory diseases.

Keywords: resveratrol-phospholipid complex, skin delivery, sustained anti-inflammatory effect, inflammatory diseases, dermal patch

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Authors: Lamees A. Ben Saad, Kah Hwi Kim, Chin Chew Quah, Mustafa Shahimi

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Background: Punica granatum (pomegranate) was used as a traditional medicine in different parts of the world. It has been used in the treatment of pain and inflammatory conditions such as peptic ulcer. The numerous risks associated with nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of pain and inflammation give rise to using medicinal herbs as alternative therapies. This study aimed to evaluate the anti-inflammatory effect of the ethyl acetate pomegranate fraction (EtOAc) by determination of its inhibitory effects on lipopolysaccharide (LPS), stimulated nitric oxide (NO), prostaglandin E2 (PGE-2), interleukin-6 (IL-6) and cyclooxxgenase-2 (COX2) release from RAW264.7cells. Methods: The inhibitory effect of EtOAc was evaluated on (LPS) induced NO production, PGE2, and IL-6 quantified by immunoassay kit and prostaglandin E2 competitive ELISA kit. COX2 production is an in vitro indication of possible anti-inflammatory activity and was estimated by Western blotting. Results: EtOAc potentially inhibited LPS-induced nitric oxide, prostaglandin, and IL-6 production. With these findings, it was evident that the EtOAc could reduce the LPS-induced cyclooxygenase-2 (COX-2) at the protein level in a dose-dependent manner as determined by Western blotting. Conclusion: The results emphasize potential therapeutic applications of Punica granatum in the treatment of inflammation.

Keywords: inflammation, Punica granatum, cytotoxicity, cytokines

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Authors: Margarita Ivanova, Julia Dao, Andrew Friedman, Neil Kasaci, Rekha Gopal, Ozlem Goker-Alpan

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In Fabry disease (FD), α-galactosidase A (α-Gal A) deficiency leads to the accumulation of globotriaosylceramide (Lyso-Gb3 and Gb3), triggering a pathologic cascade that causes the severity of organs damage. The heart is one of the several organs with high sensitivity to the α-Gal A deficiency. A subgroup of patients with significant residual of α-Gal A activity with primary cardiac involvement is occasionally referred to as “cardiac variant.” The cardiovascular complications are most frequently encountered, contributing substantially to morbidity, and are the leading cause of premature death in male and female patients with FD. The deposition of Lyso-Gb-3 and Gb-3 within the myocardium affects cardiac function with resultant progressive cardiovascular pathology. Gb-3 and Lyso-Gb-3 accumulation at the cellular level trigger a cascade of events leading to end-stage fibrosis. In the cardiac tissue, Lyso-Gb-3 deposition is associated with the increased release of inflammatory factors and transforming growth factors. Infiltration of lymphocytes and macrophages into endomyocardial tissue indicates that inflammation plays a significant role in cardiac damage. Moreover, accumulated data suggest that chronic inflammation leads to multisystemic FD pathology even under enzyme replacement therapy (ERT). NF-κB activation plays a subsequent role in the inflammatory response to cardiac dysfunction and advanced heart failure in the general population. TNFalpha/NF-κB signaling protects the myocardial evoking by ischemic preconditioning; however, this protective effect depends on the concentration of TNF-α. Thus, we hypothesize that TNF-α is a critical factor in determining the grade of cardio-pathology. Cardiac hypertrophy corresponds to the expansion of the coronary vasculature to maintain a sufficient supply of nutrients and oxygen. Coronary activation of angiogenesis and fibrosis plays a vital role in cardiac vascularization, hypertrophy, and tissue remodeling. We suggest that the interaction between the inflammatory pathways and cardiac vascularization is a bi-directional process controlled by secreted cytokines and growth factors. The co-coordination of these two processes has never been explored in FD. In a cohort of 40 patients with FD, biomarkers associated with inflammation and cardio hypertrophic remodeling were studied. FD patients were categorized into three groups based on LVmass/DSA, LVEF, and ECG abnormalities: FD with no cardio complication, FD with moderate cardio complication, and severe cardio complication. Serum levels of NF-kB, TNFalpha, Il-6, Il-2, MCP1, ING-gamma, VEGF, IGF-1, TGFβ, and FGF2 were quantified by enzyme-linked immunosorbent assays (ELISA). Among the biomarkers, MCP-1, INF-gamma, VEGF, TNF-alpha, and TGF-beta were elevated in FD patients. Some of these biomarkers also have the potential to correlate with cardio pathology in FD. Conclusion: The study provides information about the role of inflammatory pathways and biomarkers of cardio hypertrophic remodeling in FD patients. This study will also reveal the mechanisms that link intracellular accumulation of Lyso-GB-3 and Gb3 to the development of cardiomyopathy with myocardial thickening and resultant fibrosis.

Keywords: biomarkers, Fabry disease, inflammation, growth factors

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Authors: I-Han Hsiao, Chun-Ping Huang, Ching-Liang Hsieh, Yi-Wen Lin

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Epilepsy is chronic brain disorder that results in the sporadic occurrence of spontaneous seizures in the temporal lobe, cerebral cortex, and hippocampus. Clinical antiepileptic medicines are often ineffective or little benefits in the small amount of patients and usually initiate severe side effects. This inflammation contributes to enhanced neuronal excitability and the onset of epilepsy. Auricular electric-stimulation (AES) can increase parasympathetic activity and stimulate the solitary tract nucleus to induce the cholinergic anti-inflammatory pathway. Furthermore, it may be a therapeutic strategy for the treatment of epilepsy. In the present study, we want to investigate the effects of AES on inflammatory mediators in kainic acid (KA)-induced epileptic seizure rats. Experimental KA injection increased expression of TLR-2 pathway associated inflammatory mediators, were further reduced by either 2Hz or 15 Hz AES in the prefrontal cortex, hippocampus, and somatosensory cortex. We suggest that AES can successfully control the epileptic seizure by down-regulation of inflammation signaling pathway.

Keywords: auricular electric-stimulation, epileptic seizures, anti-inflammation

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Authors: Mohamed Hendawy Mousa, Warda Youssef Mohamed Morsy

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Background: Sepsis is a major cause of mortality and morbidity in trauma patients. Body mass index as an indicator of nutritional status was reported as a predictor of injury pattern and complications among critically ill injured patients. Aim: The aim of this study is to investigate the relationship between body mass index and the development of sepsis, systemic inflammatory response syndrome among adult trauma patients at emergency hospital - Cairo University. Research design: Descriptive correlational research design was utilized in the current study. Research questions: Q1. What is the body mass index profile of adult trauma patients admitted to the emergency hospital at Cairo University over a period of 6 months?, Q2. What is the frequency of systemic inflammatory response syndrome and sepsis among adult trauma patients admitted to the emergency hospital at Cairo University over a period of 6 months?, and Q3. What is the relationship between the development of sepsis, systemic inflammatory response syndrome and body mass index among adult trauma patients admitted to the emergency hospital at Cairo University over a period of 6 months?. Sample: A purposive sample of 52 adult male and female trauma patients with revised trauma score 10 to 12. Setting: The Emergency Hospital affiliated to Cairo University. Tools: Four tools were utilized to collect data pertinent to the study: Socio demographic and medical data tool, Systemic inflammatory response syndrome assessment tool, Revised Trauma Score tool, and Sequential organ failure assessment tool. Results: The current study revealed that, (61.5 %) of the studied subjects had normal body mass index, (25 %) were overweight, and (13.5 %) were underweight. 84.6% of the studied subjects had systemic inflammatory response syndrome and 92.3% were suffering from mild sepsis. No significant statistical relationship was found between body mass index and occurrence of Systemic inflammatory response syndrome (2= 2.89 & P = 0.23). However, Sequential organ failure assessment scores were affected significantly by body mass index was found mean of initial and last Sequential organ failure assessment score for underweight, normal and obese where t= 7.24 at p = 0.000, t= 16.49 at p = 0.000 and t= 9.80 at p = 0.000 respectively. Conclusion: Underweight trauma patients showed significantly higher rate of developing sepsis as compared to patients with normal body weight and obese. Recommendations: based on finding of this study the following are recommended: replication of the study on a larger probability sample from different geographical locations in Egypt; Carrying out of further studies in order to assess the other risk factors influencing trauma outcome and incidence of its complications; Establishment of standardized guidelines for managing underweight traumatized patients with sepsis.

Keywords: body mass index, sepsis, systemic inflammatory response syndrome, adult trauma

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Authors: Palwinder Singh

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Beyond the conventional mode of working with anti-inflammatory agents through enzyme inhibition, herein, an alternate substrate of cyclooxygenase-2 was developed. Proline centered pentapeptide iso-conformational to arachidonic acid exhibited appreciable selectivity for COX-2 overcoming acetic acid and formalin induced pain in rats to almost 80% and was treated as a substrate by the enzyme. Remarkably, COX-2 metabolized the pentapeptide into small fragments consisting mainly of di- and tri-peptides that ensured the safe breakdown of the peptide under in-vivo conditions. The kinetic parameter Kcat/Km for COX-2 mediated metabolism of peptide 6.3 x 105 M-1 s-1 was quite similar to 9.5 x 105 M-1 s-1 for arachidonic acid. Evidenced by the dynamic molecular studies and the use of Y385F COX-2, it was observed that the breakage of the pentapeptide has probably taken place through H-bond activation of the peptide bond by the side chains of Y385 and S530.

Keywords: small peptides, anti-inflammatory agents, cyclooxygenase-2, unnatural substrates

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Authors: Mahshid Rezaei, Zahra Tajari, Zahra Esmaeily, Atefeh Eyvazkhani, Shahrzad Daei, Marjan Mansouri Dara, Mohaddesh Rezaei, Abolghassem Djazayeri, Ahmadreza Dorosti Motlagh

Abstract:

Background: Musculoskeletal pain is one of the most prevalent symptoms in elderly age. Nutrition and diet are considered important underlying factors that could affect chronic musculoskeletal pain. The purpose of this study was to identify the relationship between empirical dietary inflammatory patterns (EDII) and musculoskeletal pain. Method: In this cross-sectional study, 213 elderly individuals were selected from several health centers. The usual dietary intake was evaluated by a valid and reliable 147-items food frequency questionnaire (FFQ). To measure the intensity of pain, Visual Analogue Scale (VAS) was used. Multiple Linear Regression was applied to assess the association between EDII and musculoskeletal pain. Results: The results of multiple linear regression analysis indicate that a higher EDII score was associated with higher musculoskeletal pain (β= 0.21: 95% CI: 0.24-1.87: P= 0.003). These results stayed significant even after adjusting for covariates such as sex, marital status, height, family number, sleep, BMI, physical activity duration, waist circumference, protector, and medication use (β= 0.16: 95% CI: 0.11-1.04: P= 0.02). Conclusion: Study findings indicated that higher inflammation of diet might have a direct association with musculoskeletal pains in elderlies. However, further investigations are required to confirm these findings.

Keywords: musculoskeletal pain, empirical dietary inflammatory pattern, elderlies, dietary pattern

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Authors: Jeremy J. Johnson

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Mediterranean herbs including rosemary (Rosmarinus officinalis) contain a variety of phytochemicals including diterpenes that possess extensive biological activity. Applications of diterpenes, including the more abundant forms carnosol and carnosic acid, have been shown to possess anti-cancer, anti-inflammatory, anti-oxidant, and anti-proliferation properties. To confirm these properties, we have evaluated rosemary extract and selected diterpenes for biological activity in cancer and inflammatory models. Our preliminary data have revealed that select diterpenes can disrupt androgen receptor functionality in prostate and breast cancer cells. This property is unique among natural products for hormone-responsive cancers. The second area of interest has been evaluating rosemary extract and selected diterpenes for activation of sestrin-2, an antioxidant protein, in colon cancer cells. A combination of in vitro and in vivo approaches have been utilized to characterize the activity of rosemary diterpenes in rosemary. Taken together, these results suggest that phytochemicals found in rosemary have distinct pharmacological actions for disrupting cell-signaling pathways in cancer and inflammatory bowel disease.

Keywords: rosemary, diterpene, cancer, inflammation

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Authors: Kamyar Moradi

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Background: Acute mesenteric ischemia is known as a life-threatening condition. Re-establishment of blood flow in this condition can lead to mesenteric ischemia reperfusion (MIR) injury, which is accompanied by inflammatory response. Still, clear blueprint of inflammatory mechanism underlying MIR injury has not been provided. Interestingly, Albendazole has exhibited notable effects on inflammation and cytokine production. In this study, we aimed to evaluate outcomes of MIR injury following pretreatment with Albendazole with respect to assessment of mesenteric inflammation and ischemia threshold. Methods: Male rats were randomly divided into sham operated, vehicle treated, Albendazole 100 mg/kg, and Albendazole 200 mg/kg groups. MIR injury was induced by occlusion of superior mesenteric artery for 30 minutes followed by 120 minutes of reperfusion. Samples were utilized for assessment of epithelial survival and villous height. Immunohistochemistry study revealed intestinal expression of TNF-α and HIF-1-α. Gene expression of NF-κB/TLR4/TNF-α/IL-6 was measured using RTPCR. Also, protein levels of inflammatory cytokines in serum and intestine were assessed by ELISA method. Results: Histopathological study demonstrated that pretreatment with Albendazole could ameliorate decline in villous height and epithelial survival following MIR injury. Also, systemic inflammation was suppressed after administration of Albendazole. Analysis of possible participating inflammatory pathway could demonstrate that intestinal expression of NF-κB/TLR4/TNF-α/IL-6 is significantly attenuated in treated groups. Eventually, IHC study illustrated concordant decline in mesenteric expression of HIF-1-α/TNF-α. Conclusion: Single dose pretreatment with Albendazole could ameliorate inflammatory response and enhance ischemia threshold following induction of MIR injury. Still, more studies would clarify existing causality in this phenomenon.

Keywords: albendazole, ischemia reperfusion injury, inflammation, mesenteric ischemia

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Authors: Wessam H. Abd-Elsalam, Mona M. Saber, Samar M. Abouelatta

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Non-steroidal anti-inflammatory drugs (NSAIDs) are considered a double edged sword in inflammatory bowel diseases (IBDs). Some studies reported their advantageous effect in decreasing inflammation, and other studies reported that their use is associated with colitis aggravation. This study aimed to use specifically formulated trehalose-based nano-carriers that targets the colon in an attempt to alleviate inflammation caused by NSAIDs. L-α-phosphatidylcholine (PL), trehalose, and transcutol were used to prepare the trehalosomes (THs), which were also loaded with Tenoxicam(TXM) as a model NSAID. To optimize the formulation variables, a full 23 factorial design, using Design-Expert® software, was performed. The optimized formulation composed of trehalose: PL at a weight ratio of 1:1, 377.72 mg transcutol, and sonicated for 4 min, possessed a spherical shape with a size of 268.61 nm and EE% of 97.83% and released 70.22% of its drug content over 24 h. The superior protective action of TXM loaded THs compared to TXM suspension and drug-free THs was shown by the inhibition of the inflammatory biomarkers, namely; IL-1ß, IL-6, and TNF-alpha levels, as well as oxidative stress markers, measured as GSH and MDA. Improved histopathology of the colonic tissue in male New Zealand rabbits also confirmed the superiority of the TXM loaded THs compared to the unformulated drug or the drug free nano-carriers. Our findings highlight the prosperous role of THs in colon targeting and its anti-inflammatory characteristics in guarding against possible NSAIDs-driven exacerbation of colitis.

Keywords: inflammatory bowel disease, trehalose, trehalosomes, colon targeting

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Authors: Arsalan Ghaderi

Abstract:

Introduction: Inactivity is one of the most important risk factors for cardiovascular disease. According to the study prevalence of inactivity in Iran, about 67.5% and in the staff, and especially nurses, are similar. The inflammatory index (HS-CRP) is highly predictive of the progression of these diseases. Physical activity education is very important in preventing these diseases. One of the modern educational methods is web-based theory-based education. Methods: This is a semi-experimental interventional study which was conducted in Isfahan and Kurdistan universities of medical sciences in two stages. A cross-sectional study was done to determine the status of physical activity and its predictive factors. Then, intervention was performed, and six months later the data were retrieved. The data was collected using a demographic questionnaire, an integrative model of behavior prediction constructs, a standard physical activity questionnaire and (HS-CRP) test. Data were analyzed by SPSS software. Results: Physical activity was low in 66.6% of nurses, 25.4% were moderate and 8% severe. According to Pearson correlation matrix, the highest correlation was found between behavioral intention and skill structures (0.553**), subjective norms (0.222**) and self-efficacy (0.198**). The relationship between age and physical activity in the first study was reverse and significant. After intervention, there was a significant change in attitudes, self-efficacy, skill and behavioral intention in the intervention group. This change was significant in attitudes, self-efficacy and environmental conditions of the control group. HS-CRP index decreased significantly after intervention in both groups, but there was not a significant relationship between inflammatory index and physical activity score. The change in physical activity level was significant only in the control group. Conclusion: Despite the effect of educational intervention on attitude, self-efficacy, skill, and behavioral intention, the results showed that if factors such as environmental factors are not corrected, training and changing structures cannot lead to physical activity behavior. On the other hand, no correlation between physical activity and HS-CRP showed that this index can be influenced by other factors, and this should be considered in any intervention to reduce the HS-CRP index.

Keywords: HS-CRP, integrative model of behavior prediction, physical activity, nurses, web-based education

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