Search results for: immune and inflammatory response

Authors: Katerina Bakela, Ioanna Zerva, Irene Athanassakis

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Lipopolysaccharide (LPS) is commonly used in murine sepsis models, which are largely associated with immunosuppression (incretion of MDSCs cells and Tregs, imbalance of inflammatory/anti-inflammatory cytokines) and collapse of the immune system. After adapting the LPS treatment to the needs of locally bred BALB/c mice, the present study explored the protective role of Micrococcus luteus peptidoglycan (PG) pre-activated vaccine-on chip in endotoxemia. The established protocol consisted of five daily intraperitoneal injections of 0.2mg/g LPS. Such protocol allowed longer survival, necessary in the prospect of the therapeutic treatment application. The so-called vaccine-on-chip consists of a 3-dimensional laser micro-texture Si-scaffold loaded with BALB/c mouse macrophages and activated in vitro with 1μg/ml PG, which exert its action upon subcutaneous implantation. The LPS treatment significantly decreased CD4+, CD8+, CD3z+, and CD19+ cells, while increasing myeloid-derived suppressor cells (MDSCs), CD25+, and Foxp3+ cells. These results were accompanied by increased arginase-1 activity in spleen cell lysates and production of IL-6, TNF-a, and IL-18 while acquiring severe sepsis phenotype as defined by the murine sepsis scoring. The in vivo application of PG pre-activated vaccine-on chip significantly decreased the percent of CD11b+, Gr1+, CD25+, Foxp3+ cells, and arginase-1 activity in the spleen of LPS-treated animals, while decreasing IL-6 and TNF-a in the serum, allowing survival to all animals tested and rescuing the severity of sepsis phenotype. In conclusion, these results reveal a promising mode of action of PG pre-activated vaccine-on chip in LPS endotoxemia, strengthening; thus, the use of treatment is septic patients.

Keywords: myeloid-derived suppressor cells, peptidoglycan, sepsis, Si-scaffolds

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Authors: Bernice Lottering, Yi-Wen Lin

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Chronic pain and depression have an estimated 80% rate of comorbidity with unsatisfactory treatment interventions signifying the importance of developing effective therapeutic interventions for a serious chronic condition affecting a large majority of the global population. Chronic pain is defined as persistent pain presenting for over 3 months. This disease state increases the risk of developing depression in comparison to healthy individuals. In the current study, complete Freund’s adjuvant (CFA) was used to induce cell-mediated chronic inflammatory pain in a murine model. Significant mechanical and thermal hyperalgesia was induced, alongside observable depression-like behaviors. These conditions were attenuated through the use of electroacupuncture (EA). Similarly, these effects were also investigated with respect to the transient receptor potential vanilloid 1 (TRPV1), by analyzing the effects of TRPV1 gene deletion on the comorbidity of chronic pain and depression. The expression of the TRPV1 inflammatory response, and related downstream molecules, including protein kinases (PKs), mitogen-activated protein kinase (MAPKs), and transcriptional factors, were significantly reduced in the thalamus, prefrontal cortex (PFC), hippocampus, and periaqueductal gray (PAG) of CFA-treated mice. In addition, phosphorylated N-methyl-D-aspartate (NMDA) receptor 1 was also found to be reduced in the aforementioned areas, suggesting potential application and validity in a clinical setting. Our study determined the prospective therapeutic effects of EA in the treatment of chronic inflammatory pain and depression comorbidity and provides a novel and detailed mechanism underlying EA-mediated analgesia. These findings may be relevant in the utilization of clinical intervention approaches related to chronic pain and depression comorbidity.

Keywords: chronic pain, depression, NMDA, prefrontal cortex, TRPV1

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Authors: Christianah Adebimpe Dare, Nelson Oghenebrorhie Elvis

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This study was aimed at analysing the phytochemicals in Chrysophyllum albidum cotyledon extract and their in vitro antioxidant and anti-inflammatory effects. The star apple fruit was bought at Igbona market Osogbo, Osun State, Nigeria. The seed from the fruit was removed and defatted. The residue was exhaustively extracted with methanol. The Chrysophyllum albidum cotyledon methanol extract (CCME) was phytochemically screened, flavonoids and phenol contents, antioxidant and anti-inflammatory assays were carried out on the extract using standard procedures. Phytochemicals analysis revealed the presence of steroids, tannins, flavonoid, saponin, triterpenes, and xanthoproteins. The phenolic concentration, total flavonoids concentration, and total sugar concentration were found to be 26.72 ± 0.048 µgTAE/mg, 23.12 ± 1.92µg of Rutin equivalent (RTE)/mg (10.49 ± 1.12µg of Quercetin equivalent (QE/mg) and 778.38 ± 12.82 µg of glucose/ml, respectively. The extract demonstrated significant inhibitory effect compared with the standards as potent antioxidant with percentage inhibition of DPPH as 38.10 %-39.51 %, lipid peroxidation as 45.85 %-65.85 %; ferric reducing power showed linear correlation to the standard and the anti-inflammatory potential with 22.06 %-26.37 % protection of the human red blood membrane and the percentage inhibition of denaturation of albumin 3.42 %-7.32 %. The study showed that C. albidum cotyledon methanol extract is a potent antioxidant and anti-inflammatory agent to combat oxidative stress and pathological diseases caused by reactive species.

Keywords: albumin denaturation, free radicals, lipid peroxidation, reactive species

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Authors: Anca Maria Cimpean, Serban Comsa

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Chick embryo chorioallantoic membrane (CAM) is a well vascularised in vivo experimental model used as a platform for testing the behavior of different implants inserted on it from tumor fragments to therapeutic agents or various biomaterials. Five types of collagen-based biomaterials with 2D and 3D structure (MotifMesh, Optimaix2D, Optimaix3D, Dual Layer Collagen and Xenoderm) were implanted on CAM and continuously evaluated by stereomicroscope for up to 5 days post-implant with an emphasis of their ability to requisite and develop new blood vessels (BVs) followed by microscopic analysis. MotifMEsh did not induce any angiogenic response lacking to be invaded by BVs from the CAM, but it induced intense inflammatory response necrosis and fibroblastic reaction around the implant. Optimaix2D has good adherence. CAM with minimal or no inflammatory reaction, a good integration of the CAM between the collagen mesh’s fibers, consistent adhesion of the cells to the collagen fibers,and a good ability to form pseudo-vascular channels filled with cells. Optimaix3D induced the highest angiogenic effects on CAM. The material shows good integration on CAM. The collagen fibers of the material show the ability to organize themselves into linear and tubular structures. It is possible to see blood elements, especially at the periphery of the implant. Dual-layer collagen behaves similar to Optimaix 3D, while Xenoderm induced a moderate angiogenic effect on CAM. Based on these data, we may conclude that collagen-based materials have variable ability to requisite and develop new blood vessels. A proper selection of collagen-based biomaterial scaffolds may crucially influence the acquisition and development of blood vessels during angiogenesis assays.

Keywords: chick embryo chorioallantoic membrane, collagen scaffolds, blood vessels, vascular microenvironment

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Authors: Asma Naseer Cheema, Attya Bhatti, Jabar Ali, John Peter

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Background: High cholesterol levels, endothelial dysfunction, inefficient coagulation cascade and hyper inflammatory response all are the basis of coronary artery disease (CAD). Several studies are carried out to see the genetic influence of these factors on disease outcome. Objective: The objective of our study was to see the association of 10 putative loci with coronary artery disease in our population. Materials & Methods: We screened our population for 10 putative loci of CAD showing significant association (p < 5x10-8) with candidate genes (regulating the cholesterol metabolism, endothelial function, coagulation cascade and inflammatory response of body). Hardy-Weinberg equilibrium and linkage disequilibrium in cases and controls s were estimated separately. Approximately 5-10 ng of dried DNA in 384 well plate format was used to genotype each sample on the Sequenom iPLEX assay at University of Pittsburgh Genomics and Proteomics Core Laboratories. It was built on single-base primer extension with the MALDI-TOF MS detection possessing high sensitivity and specificity. The SNPs were genotyped through Taqman assay. Hardy Weinberg test was applied. The 10 SNPs were selected as genetic markers for this study (rs579459, rs1561198, rs2954029, rs1122608, rs17114036, rs9515203, rs10947789, rs7173743, rs2895811, rs2075650). Results: Mean age of the patient was 52 ± 11 years. Blood pressure and positive family history was found a significant risk factor for CAD. None of the selected SNPs showed significant association with coronary artery disease in our population (p>0.05). Conclusion: rs579459, rs1561198, rs2954029, rs1122608, rs17114036, rs9515203, rs10947789, rs7173743, rs2895811, rs2075650 are not significant genetic markers for CAD in our population.

Keywords: CAD, genetic markers, loci, risk factors

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Authors: Nisrine Chlif, Mohammed Diouri, Amar Bentayeb

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Background: The Leaves of Brocchia cinerea (Vis.) (Asteraceae) is used traditionally and ethnomedicinally to alleviate pain, fever, and inflammation conditions. Objective: The current study investigates the anti-inflammatory, analgesic, and antipyretic activities of aqueous extract of the leaves of Brocchia cinerea (LBC). Material and methods: The extract was screened for anti-inflammatory (carrageenan-induced paw edema) and analgesic (acetic acid-induced writhing) activities in Wistar rats. Before acetic acid or carrageenan injection, rats were orally fed LBC (200 and 400 mg/ kg), Indomethacin (10 mg/kg), or Aspirin (100 mg/kg). The antipyretic effect was studied in brewer’s yeast-induced pyrexia model in rats using Paracetamol (100 mg/kg) as a standard drug. Results: The crude extract tested significantly prevented the increase in paw volume as compared to the control at 200 mg/kg and 400 mg/kg. The LBC treatment significantly inhibited pain at 400 mg/kg with a percent inhibition of 55.82%, as well as showing a significant reduction in hyperpyrexia in rats at 400 mg/kg. LBC extract produced a comparable activity to paracetamol at 100 mg/kg (p <0.01). Conclusion: The results of the present study that the leaves of B. cinerea extract exhibited strongly anti-inflammatory, analgesic, and antipyretic properties and justify the traditional use of this plant in inflammation, pain, and fever.

Keywords: analgesic, anti-inflammation, antipyretic, brocchia cinerea

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Authors: Iulianna Taritsa, Kuldeep Neote, Eric Fossel

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Lysosome-induced immunogenic cell death (LIICD) is a powerful mechanism of targeting cancer cells that kills circulating malignant cells and primes the host’s immune cells against future remission. Current immunotherapies for cancer are limited in preventing recurrence – a gap that can be bridged by training the immune system to recognize cancer neoantigens. Lysosomal leakage can be induced therapeutically to traffic antigens from dying cells to dendritic cells, which can later present those tumorigenic antigens to T cells. Previous research has shown that oxidative agents administered in the tumor microenvironment can initiate LIICD. We generated a fusion protein between an oxidative agent known as xanthine oxidase (XO) and a mini-antibody specific for EGFR/HER2-sensitive breast tumor cells. The anti-EGFR single domain antibody fragment is uniquely sourced from llama, which is functional without the presence of a light chain. These llama micro-antibodies have been shown to be better able to penetrate tissues and have improved physicochemical stability as compared to traditional monoclonal antibodies. We demonstrate that the fusion protein created is stable and can induce early markers of immunogenic cell death in an in vitro human breast cancer cell line (SkBr3). Specifically, we measured overall cell death, as well as surface-expressed calreticulin, extracellular ATP release, and HMGB1 production. These markers are consensus indicators of ICD. Flow cytometry, luminescence assays, and ELISA were used respectively to quantify biomarker levels between treated versus untreated cells. We also included a positive control group of SkBr3 cells dosed with doxorubicin (a known inducer of LIICD) and a negative control dosed with cisplatin (a known inducer of cell death, but not of the immunogenic variety). We looked at each marker at various time points after cancer cells were treated with the XO/antibody fusion protein, doxorubicin, and cisplatin. Upregulated biomarkers after treatment with the fusion protein indicate an immunogenic response. We thus show the potential for this fusion protein to induce an anticancer effect paired with an adaptive immune response against EGFR/HER2+ cells. Our research in human cell lines here provides evidence for the success of the same therapeutic method for patients and serves as the gateway to developing a new treatment approach against breast cancer.

Keywords: apoptosis, breast cancer, immunogenic cell death, lysosome

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Authors: Esshili Awatef, Manitz Marie-Pierre, Eßlinger Manuela, Gerhardt Alexandra, Plümper Jennifer, Wachholz Simone, Friebe Astrid, Juckel Georg

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Maternal immune activation (MIA) resulting from maternal viral infection during pregnancy is a known risk factor for schizophrenia. The neural mechanisms by which maternal infections increase the risk for schizophrenia remain unknown, although the prevailing hypothesis argues that an activation of the maternal immune system induces changes in the maternal-fetal environment that might interact with fetal brain development. It may lead to an activation of fetal microglia inducing long-lasting functional changes of these cells. Based on post-mortem analysis showing an increased number of activated microglial cells in patients with schizophrenia, it can be hypothesized that these cells contribute to disease pathogenesis and may actively be involved in gray matter loss observed in such patients. In the present study, we hypothesize that prenatal treatment with the inflammatory agent Poly(I:C) during embryogenesis at contributes to microglial activation in the offspring, which may, therefore, represent a contributing factor to the pathogenesis of schizophrenia and underlines the need for new pharmacological treatment options. Pregnant rats were treated with intraperitoneal injections a single dose of Poly(I:C) or saline on gestation day 17. Brains of control and Poly(I:C) offspring, were removed and into 20-μm-thick coronal sections were cut by using a Cryostat. Brain slices were fixed and immunostained with ba1 antibody. Subsequently, Iba1-immunoreactivity was detected using a secondary antibody, goat anti-rabbit. The sections were viewed and photographed under microscope. The immunohistochemical analysis revealed increases in microglia cell number in the prefrontal cortex, in offspring of poly(I:C) treated-rats as compared to the controls injected with NaCl. However, no significant differences were observed in microglia activation in the cerebellum among the groups. Prenatal immune challenge with Poly(I:C) was able to induce long-lasting changes in the offspring brains. This lead to a higher activation of microglia cells in the prefrontal cortex, a brain region critical for many higher brain functions, including working memory and cognitive flexibility. which might be implicated in possible changes in cortical neuropil architecture in schizophrenia. Further studies will be needed to clarify the association between microglial cells activation and schizophrenia-related behavioral alterations.

Keywords: Microglia, neuroinflammation, PolyI:C, schizophrenia

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Authors: Mustafa M. Donma, Orkide Donma

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Obesity is defined as a severe chronic disease characterized by a low-grade inflammatory state. Therefore, inflammatory markers gained utmost importance during the evaluation of obesity and metabolic syndrome (MetS), a disease characterized by central obesity, elevated blood pressure, increased fasting blood glucose and elevated triglycerides or reduced high density lipoprotein cholesterol (HDL-C) values. Some inflammatory markers based upon complete blood cell count (CBC) are available. In this study, it was questioned which inflammatory marker was the best to evaluate the differences between various obesity groups. 514 pediatric individuals were recruited. 132 children with MetS, 155 morbid obese (MO), 90 obese (OB), 38 overweight (OW) and 99 children with normal BMI (N-BMI) were included into the scope of this study. Obesity groups were constituted using age- and sex-dependent body mass index (BMI) percentiles tabulated by World Health Organization. MetS components were determined to be able to specify children with MetS. CBC were determined using automated hematology analyzer. HDL-C analysis was performed. Using CBC parameters and HDL-C values, ratio markers of inflammation, which cover neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), monocyte-to-HDL-C ratio (MHR) were calculated. Statistical analyses were performed. The statistical significance degree was considered as p < 0.05. There was no statistically significant difference among the groups in terms of platelet count, neutrophil count, lymphocyte count, monocyte count, and NLR. PLR differed significantly between OW and N-BMI as well as MetS. Monocyte-to HDL-C value exhibited statistical significance between MetS and N-BMI, OB, and MO groups. HDL-C value differed between MetS and N-BMI, OW, OB, MO groups. MHR was the ratio, which exhibits the best performance among the other CBC-based inflammatory markers. On the other hand, when MHR was compared to HDL-C only, it was suggested that HDL-C has given much more valuable information. Therefore, this parameter still keeps its value from the diagnostic point of view. Our results suggest that MHR can be an inflammatory marker during the evaluation of pediatric MetS, but the predictive value of this parameter was not superior to HDL-C during the evaluation of obesity.

Keywords: children, complete blood cell count, high density lipoprotein cholesterol, metabolic syndrome, obesity

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Authors: Salam N. Abdo, Orien L. Tulp, George P. Einstein

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The purpose of this exploratory study was to gather the insights into psoriasis etiology, treatment, and patient experience, for developing psoriasis and psoriatic arthritis diagnostic test. Data collection methods consisted of a comprehensive meta-analysis of relevant studies and psoriasis patient survey. Established meta-analysis guidelines were used for the selection and qualitative comparative analysis of psoriasis and psoriatic arthritis research studies. Only studies that clearly discussed psoriasis etiology, treatment, and patient experience were reviewed and analyzed, to establish a qualitative data base for the study. Using the insights gained from meta-analysis, an existing psoriasis patient survey was modified and administered to collect additional data as well as triangulate the results. The hypothesis is that specific types of psoriatic disease have specific etiology and pathophysiologic pattern. The following etiology categories were identified: bacterial, environmental/microbial, genetic, immune, infectious, trauma/stress, and viral. Additional results, obtained from meta-analysis and confirmed by patient survey, were the common age of onset (early to mid-20s) and type of psoriasis (plaque; mild; symmetrical; scalp, chest, and extremities, specifically elbows and knees). Almost 70% of patients reported no prescription drug use due to severe side effects and prohibitive cost. These results will guide the development of psoriasis and psoriatic arthritis diagnostic test. The significant number of medical publications classified psoriatic arthritis disease as inflammatory of an unknown etiology. Thus numerous meta-analyses struggle to report any meaningful conclusions since no definitive results have been reported to date. Therefore, return to the basics is an essential step to any future meaningful results. To date, medical literature supports the fact that psoriatic disease in its current classification could be misidentifying subcategories, which in turn hinders the success of studies conducted to date. Moreover, there has been an enormous commercial support to pursue various immune-modulation therapies, thus following a narrow hypothesis/mechanism of action that is yet to yield resolution of disease state. Recurrence and complications may be considered unacceptable in a significant number of these studies. The aim of the ongoing study is to focus on a narrow subgroup of patient population, as identified by this exploratory study via meta-analysis and patient survey, and conduct an exhaustive work up, aiming at mechanism of action and causality before proposing a cure or therapeutic modality. Remission in psoriasis has been achieved and documented in medical literature, such as immune-modulation, phototherapy, various over-the-counter agents, including salts and tar. However, there is no psoriasis and psoriatic arthritis diagnostic test to date, to guide the diagnosis and treatment of this debilitating and, thus far, incurable disease. Because psoriasis affects approximately 2% of population, the results of this study may affect the treatment and improve the quality of life of a significant number of psoriasis patients, potentially millions of patients in the United States alone and many more millions worldwide.

Keywords: biologics, early diagnosis, etiology, immune disease, immune modulation therapy, inflammation skin disorder, phototherapy, plaque psoriasis, psoriasis, psoriasis classification, psoriasis disease marker, psoriasis diagnostic test, psoriasis marker, psoriasis mechanism of action, psoriasis treatment, psoriatic arthritis, psoriatic disease, psoriatic disease marker, psoriatic patient experience, psoriatic patient quality of life, remission, salt therapy, targeted immune therapy

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Authors: Asavasereerat K., Teacharsripaitoon T., Tungyingyong P., Charupongrat S., Noppiboon S. Hochareon L., Kitsuban P.

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Third generation of vaccines is based on gene therapy where DNA is introduced into patients. The antigenic or therapeutic proteins encoded from transgenes DNA triggers an immune-response to counteract various diseases. Moreover, DNA vaccine offers the customization of its ability on protection and treatment with high stability. The production of DNA vaccines become of interest. According to USFDA guidance for industry, the recommended limits for impurities from host cell are lower than 1%, and the active conformation homogeneity supercoiled DNA, is more than 80%. Thus, the purification strategy using two-steps chromatography has been established and verified for its robustness. Herein, pVax1/lacZ, a pre-approved USFDA DNA vaccine backbone, was used and transformed into E. coli strain DH5α. Three purification process parameters including sample-loading flow rate, the salt concentration in washing and eluting buffer, were studied and the experiment was designed using response surface method with central composite face-centered (CCF) as a model. The designed range of selected parameters was 10% variation from the optimized set point as a safety factor. The purity in the percentage of supercoiled conformation obtained from each chromatography step, AIEX and HIC, were analyzed by HPLC. The response data were used to establish regression model and statistically analyzed followed by Monte Carlo simulation using SAS JMP. The results on the purity of the product obtained from AIEX and HIC are between 89.4 to 92.5% and 88.3 to 100.0%, respectively. Monte Carlo simulation showed that the pVAX1/lacZ purification process is robust with confidence intervals of 0.90 in range of 90.18-91.00% and 95.88-100.00%, for AIEX and HIC respectively.

Keywords: AIEX, DNA vaccine, HIC, puification, response surface method, robustness

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Authors: Ishani Das, Avinash Padhi, Sitabja Mukherjee, Santosh Kar, Avinash Sonawane

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Activation of cell mediated and humoral immune responses to Mycobacterium tuberculosis (Mtb) are critical for protection. Herein, we show that mice immunized with Mtb lipid bound chitosan nanoparticles(NPs) induce secretion of prominent Th1 and Th2 cytokines in lymph node and spleen cells, and also induced significantly higher levels of IgG, IgG1, IgG2 and IgM in comparison to control mice measured by ELISA. Furthermore, significantly enhanced γδ-T cell activation was observed in lymph node cells isolated from mice immunized with Mtb lipid coated chitosan-NPs as compared to mice immunized with chitosan-NPs alone or Mtb lipid liposomes through flow cytometric analysis. Also, it was observed that in comparison to CD8+ cells, significantly higher CD4+ cells were present in both the lymph node and spleen cells isolated from mice immunized with Mtb lipid coated chitosan NP. In conclusion, this study represents a promising new strategy for efficient delivery of Mtb lipids using chitosan NPs to trigger enhanced cell mediated and antibody response against Mtb lipids.

Keywords: antibody response, chitosan nanoparticles, cytokines, mycobacterium tuberculosis lipids

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Authors: Tong-Chien Wu, Ching-Liang Hsieh, Yi-Wen Lin

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There are accumulating evidences surrounding the therapeutic effect of electroacupuncture (EA). Local EA can reliably attenuate inflammatory pain in mouse with unclear mechanisms. However, the effect of EA on distal and contralateral acupoint for pain control has been rarely studied and the result was controversial. Here in our study, we found that inflammatory hindpaw pain in mouth, which was induced by injecting the complete Freund’s adjuvant (CFA) 2 days ago can be alleviated immediately after 2Hz 15mins EA treatment at contralateral forefoot acupoint LI4 through both mechanic and thermal behavior test, while sham acupoint group is not. The efficacy was observed to be more obvious after the second round of EA treatment on the following day. This analgesic effect is produced by applying EA to a site remote from the painful area. The present study provides a powerful experimental animal model that can be used for investigating the unique physiological mechanisms involved in acupuncture analgesia.

Keywords: remote electroacupuncture, distal EA, pain control, anti-inflammation

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Authors: Surabhi Gautam, Uma Kumar, Rima Dada

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A sustained acute-phase response in Rheumatoid Arthritis (RA) is associated with increased joint damage and inflammation leading to progressive disability. It is induced continuously by consecutive stimuli of proinflammatory cytokines, following a wide range of pathophysiological reactions, leading to increased synthesis of acute phase proteins like C - reactive protein (CRP) and dysregulation in levels of immunomodulatory soluble Human Leukocyte Antigen-G (HLA-G) molecule. This study was designed to explore the effect of yoga and meditation based lifestyle intervention (YMLI) on inflammatory markers in RA patients. Blood samples of 50 patients were collected at baseline (day 0) and after 30 days of YMLI. Patients underwent a pretested YMLI under the supervision of a certified yoga instructor for 30 days including different Asanas (physical postures), Pranayama (breathing exercises), and Dhayna (meditation). Levels of CRP, IL-6, IL-17A, soluble HLA-G and erythrocyte sedimentation rate (ESR) were measured at day 0 and 30 interval. Parameters of disease activity, disability quotient, pain acuity and quality of life were also assessed by disease activity score (DAS28), health assessment questionnaire (HAQ), visual analogue scale (VAS), and World Health Organization Quality of Life (WHOQOL-BREF) respectively. There was reduction in mean levels of CRP (p < 0.05), IL-6 (interleukin-6) (p < 0.05), IL-17A (interleukin-17A) (p < 0.05) and ESR (p < 0.05) and elevation in soluble HLA-G (p < 0.05) at 30 days compared to baseline level (day 0). There was reduction seen in DAS28-ESR (p < 0.05), VAS (p < 0.05) and HAQ (p < 0.05) after 30 days with respect to the base line levels (day 0) and significant increase in WHOQOL-BREF scale (p < 0.05) in all 4 domains of physical health, psychological health, social relationships, and environmental health. The present study has demonstrated that yoga practices are associated with regression of inflammatory processes by reducing inflammatory parameters and regulating the levels of soluble HLA-G significantly in active RA patients. Short term YMLI has significantly improved pain perception, disability quotient, disease activity and quality of life. Thus this simple life style intervention can reduce disease severity and dose of drugs used in the treatment of RA.

Keywords: inflammation, quality of life, rheumatoid arthritis, yoga and meditation

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Authors: Tamphasana Wairokpam

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Inflammatory myopathies (IMs) have long been recognised as a heterogenous family of myopathies with acute, subacute, and sometimes chronic presentation and are potentially treatable. Necrotizing autoimmune myopathies (NAM) are a relatively new subset of myopathies. Patients generally present with subacute onset of proximal myopathy and significantly elevated creatinine kinase (CK) levels. It is being increasingly recognised that there are limitations to the independent diagnostic utility of muscle biopsy. Immunohistochemistry tests may reveal important information in these cases. The traditional classification of IMs failed to recognise NAM as a separate entity and did not adequately emphasize the diversity of IMs. This review and case report on NAM aims to highlight the heterogeneity of this entity and focus on the distinct clinical presentation, biopsy findings, specific auto-antibodies implicated, and available treatment options with prognosis. This article is a meta-analysis of literatures on NAM and a case report illustrating the clinical course, investigation and biopsy findings, antibodies implicated, and management of a patient with NAM. The main databases used for the search were Pubmed, Google Scholar, and Cochrane Library. Altogether, 67 publications have been taken as references. Two biomarkers, anti-signal recognition protein (SRP) and anti- hydroxyl methylglutaryl-coenzyme A reductase (HMGCR) Abs, have been found to have an association with NAM in about 2/3rd of cases. Interestingly, anti-SRP associated NAM appears to be more aggressive in its clinical course when compared to its anti-HMGCR associated counterpart. Biopsy shows muscle fibre necrosis without inflammation. There are reports of statin-induced NAM where progression of myopathy has been seen even after discontinuation of statins, pointing towards an underlying immune mechanism. Diagnosisng NAM is essential as it requires more aggressive immunotherapy than other types of IMs. Most cases are refractory to corticosteroid monotherapy. Immunosuppressive therapy with other immunotherapeutic agents such as IVIg, rituximab, mycophenolate mofetil, azathioprine has been explored and found to have a role in the treatment of NAM. In conclusion,given the heterogeneity of NAM, it appears that NAM is not just a single entity but consists of many different forms, despite the similarities in presentation and its classification remains an evolving field. A thorough understanding of underlying mechanism and the clinical correlation with antibodies associated with NAM is essential for efficacious management and disease prognostication.

Keywords: inflammatory myopathies, necrotising autoimmune myopathies, anti-SRP antibody, anti-HMGCR antibody, statin induced myopathy

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Authors: Corina Muscurel, Irina Stoian, Laura Gaman, Valeriu Atanasiu

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Chronic inflammation predisposes cells to neoplastic transformation and is associated with angiogenesis. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) give rise to anti-inflammatory metabolites and decrease some inflammatory cytokines. The aim of the study was to analyze the effect of n-3 PUFAs intake on patients with tumors in early-stage (without regional or distant metastasis). There were two groups of patients: one group with colon tumors and one group with lung tumors. All patients took for 60 days daily supplements from fish-oil containing 600 mg eicosapentaenoic acid and 400 mg docosahexaenoic acid. The plasma markers were evaluated before and after PUFAs intake: ceruloplasmin (using p-phenylenediamine oxidase method), plasma total thiol groups (using dithiobis-nitrobenzoic acid method) and CEA (carcinoembryonic antigen using electrochemiluminescent immunoassay). The results reflect ceruloplasmin decrease (p < 0.05), plasma total thiol groups increase (not statistically significant) and CEA decrease (p < 0.05) after n-3 PUFAs intake. Conclusions: n-3 PUFAs intake is favorable in premalignant lesions or in early tumor stage and dietary fish-oil has anti-inflammatory effects and can contribute to reduce cancer progression.

Keywords: cancer, fish-oil, inflammation, n-3 polyunsaturated fatty acids

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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: Jyoti Singh, Ranju Bansal

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Fighting pain and inflammation is a common problem faced by physicians while dealing with a wide variety of diseases. Since ancient time nonsteroidal anti-inflammatory agents (NSAIDs) and opioids have been the cornerstone of treatment therapy, however, the usefulness of both these classes is limited due to severe side effects. NSAIDs, which are mainly used to treat mild to moderate inflammatory pain, induce gastric irritation and nephrotoxicity whereas opioids show an array of adverse reactions such as respiratory depression, sedation, and constipation. Moreover, repeated administration of these drugs induces tolerance to the analgesic effects and physical dependence. Further discovery of selective COX-2 inhibitors (coxibs) suggested safety without any ulcerogenic side effects; however, long-term use of these drugs resulted in kidney and hepatic toxicity along with an increased risk of secondary cardiovascular effects. The basic approaches towards inflammation and pain treatment are constantly changing, and researchers are continuously trying to develop safer and effective anti-inflammatory drug candidates for the treatment of different inflammatory conditions such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, psoriasis and multiple sclerosis. Synthetic 3(2H)-pyridazinones constitute an important scaffold for drug discovery. Structure-activity relationship studies on pyridazinones have shown that attachment of a lactam at N-2 of the pyridazinone ring through a methylene spacer results in significantly increased anti-inflammatory and analgesic properties of the derivatives. Further introduction of the heterocyclic ring at lactam nitrogen results in improvement of biological activities. Keeping in mind these SAR studies, a new series of compounds were synthesized as shown in scheme 1 and investigated for anti-inflammatory, analgesic, anti-platelet activities and docking studies. The structures of newly synthesized compounds have been established by various spectroscopic techniques. All the synthesized pyridazinone derivatives exhibited potent anti-inflammatory and analgesic activity. Homoveratryl substituted derivative was found to possess highest anti-inflammatory and analgesic activity displaying 73.60 % inhibition of edema at 40 mg/kg with no ulcerogenic activity when compared to standard drugs indomethacin. Moreover, 2-substituted-4-benzo[d][1,3]dioxole-6-phenylpyridazin-3(2H)-ones derivatives did not produce significant changes in bleeding time and emerged as safe agents. Molecular docking studies also illustrated good binding interactions at the active site of the cyclooxygenase-2 (hCox-2) enzyme.

Keywords: anti-inflammatory, analgesic, pyridazin-3(2H)-one, selective COX-2 inhibitors

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Authors: Benedict Ofori, Kwabena Sarpong, Stephen Antwi

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Background: Medicinal plants are utilized all around the world and are becoming increasingly important economically. The WHO notes that ‘inappropriate use of traditional medicines or practices can have negative or dangerous effects and that future research is needed to ascertain the efficacy and safety of such practices and medicinal plants used by traditional medicine systems. The poor around the world have limited access to palliative care or pain relief. Pharmacologists have been focused on developing safe and effective anti-inflammatory drugs. Most of the issues related to their use have been linked to the fact that numerous traditional and herbal treatments are classified in different nations as meals or dietary supplements. As a result, there is no need for evidence of the quality, efficacy, or safety of these herbal formulations before they are marketed. The fact that access to drugs meant for pain relief is limited in low-income countries means advanced studies should be done on home drugs meant for inflammation to close the gap. Methods: The ethanolic extracts of the plant were screened for the presence of 10 phytochemicals. The Pierce BCA Protein Assay Kit was used for the determination of the protein concentration of the egg white. The rats were randomly selected and put in 6 groups. The egg white was sub-plantar injected into the right-hand paws of the rats to induce inflammation. The animals were treated with the three plant extracts obtained from the root bark, stem, and leaves of the plant. The control groups were treated with normal saline, while the standard groups were treated with standard drugs indomethacin and celecoxib. Plethysmometer was used to measure the change in paw volume of the animals over the course of the experiment. Results: The results of the phytochemical screening revealed the presence of reducing sugars and saponins. Alkaloids were present in only R.L.S (1:1:1), and phytosterols were found in R.L(1:1) and R.L.S (1:1:1). The estimated protein concentration was found to be 103.75 mg/ml. The control group had an observable increase in paw volume, which indicated that inflammation was induced during the 5 hours. The increase in paw volume for the control group peaked at the 1st hour and decreased gradually throughout the experiment, with minimal changes in the paw volumes. The 2nd and 3rd groups were treated with 20 mg/kg of indomethacin and celecoxib. The anti-inflammatory activities of indomethacin and celecoxib were calculated to be 21.4% and 4.28%, respectively. The remaining 3 groups were treated with 2 dose levels of 200mg/kg plant extracts. R.L.S, R.L, and S.R.L had anti-inflammatory activities of 22.3%, 8.2%, and 12.07%, respectively. Conclusions: Egg albumin-induced paw model in rats can be used to evaluate the anti-inflammatory activity of herbs that might have potential anti-inflammatory activity. Herbal medications have potential anti-inflammatory activities and can be used to manage various inflammatory conditions if their efficacy and side effects are well studied. The three extracts all possessed anti-inflammatory activity, with R.L.S having the highest anti-inflammatory activity.

Keywords: inflammation, capparis erythrocarpos, anti-inflammatory activity, herbal medicine, paw volume, egg albumin

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Authors: Valizadeh Gever Bita, Joel Caren, Louisa Huand, Yu-Cheng Zhu, Esmaeil Amiri

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Within a honey bee colony, queen is the sole reproducer of fertilized eggs, while queens are safeguarded by worker bees, trophallactic behavior and food sharing activities could expose them to agrochemicals. Here, we assessed the effects of three widely used pesticides—Acephate, Bifenthrin, and Chlorantraniliprole— on worker bees, to investigate indirect effects on the physiology and reproductive traits of queens as well as the eggs they produce. Using RT-qPCR we measured the expression of several detoxification and immune genes in adult worker bees, queens, and freshly laid eggs after pesticide exposure. These analyses aimed to elucidate the physiological changes in queens and potential transgenerational effects. While no significant changes in reproductive traits were observed following Chlorantraniliprole and Bifenthrin exposure, Acephate caused adverse effects on egg size, egg-laying activity, and queen weight. The expression of detoxification, immune and antioxidant-related genes in workers, queens and freshly laid eggs changed over time in response to these pesticides. The results of this investigation revealed that pesticides can cause negative impact on queen physiology and reproduction indirectly through their effects on exposed worker bees. These effects can potentially extend to the next generation of honey bees.

Keywords: apis mellifera, egg laying, detoxification enzymes, gene expression, honey bee queen

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Authors: Chris George, Adam Hamlin, Lily Pereg, Richard Charlesworth, Gal Winter

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Background: According to the ‘hygiene hypothesis’ the current rise in allergies and autoimmune diseases stems mainly from reduced microbial exposure due, amongst other factors, to urbanisation and distance from soil. However, this hypothesis is based on epidemiological and not biological data. Useful insights into the underlying mechanisms of this hypothesis can be gained by studying our interaction with soil. Soil microbiota may be directly ingested or inhaled by humans, enter the body through skin-soil contact or using plants as vectors. This study aims to examine the ability of soil microbiota to colonise the gut, study the interaction of soil microbes with the immune system and their potential protective activity. Method: The nutrition of the rats was supplemented daily with fresh or autoclaved soil for 21 days followed by 14 days of no supplementations. Faecal samples were collected throughout and analysed using 16S sequencing. At the end of the experiment rats were sacrificed and tissues and digesta were collected. Results/Conclusion: Results showed significantly higher richness and diversity following soil supplementation even after recovery. Specific soil microbial groups identified as able to colonise the gut. Of particular interest was the mucosal layer which emerged as a receptive host for soil microorganisms. Histological examination revealed innate and adaptive immune activation. Findings of this study reinforce the ‘hygiene hypothesis’ by demonstrating the ability of soil microbes to colonise the gut and activate the immune system. This paves the way for further studies aimed to examine the interaction of soil microorganisms with the immune system.

Keywords: gut microbiota, hygiene hypothesis, microbiome, soil

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Authors: Karolina Siejka, Monika Piekarska, Monika Zbroja, Weronika Cyranka, Maryla Kuczynska, Magdalena Grzegorczyk, Malgorzata Nowakowska, Agnieszka Brodzisz, Magdalena Maria Wozniak

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Crohn’s disease is one of chronic inflammatory bowel diseases. It is increasing in prevalence worldwide, especially with young people. The disease usually occurs in the second to the fourth decade of life. Traditionally is diagnosed by clinical indicates, endoscopic, and histological findings. Magnetic Resonance Enterography (MRE) can demonstrate mural and extramural inflammatory signs and complications, which make it a valuable diagnostic modality. The study included 76 adults and 36 children diagnosed with Crohn’s disease. Each patient underwent MRE with intravenous administration of a contrast agent. All the studies were performed using Siemens Aera 1.5T scanner according to a local study protocol. Whenever applicable, MR Enterography findings were verified with endoscopy. Forty adults and all 36 children had an active phase of Crohn’s disease; five adults had a chronic phase of the disease; one adult had both chronic and active inflammatory features. Thirty adults have no sings of pathology. In both adult and pediatric groups the most commonly observed manifestation of active disease was thickened edematous ileum wall (26 adults and 36 children). Adults had Bauhin’s valve edema in 58% cases (n=23) and mesenteric changes in 34% cases (n=9). To compare, 32 children had Bauhin’s valve edema (89%) and, in 23 cases, was found inflammatory infiltration of the peri-intestinal fat (64%). The involvement of the large intestine was more common among children (100%). Complications of Crohn’s disease were found commonly in adults (40% of adults, 22% of children). There were observed 18 fistulas (14 adults, four children) and six abscesses (2 adults, four children). MRE is a reliable method in the evaluation of Crohn’s disease activity, especially of its complications. The lack of radiations makes MRE well-tolerated modality, which can be often repeated, particularly in young patients. The disease had different medical sings depending on age – children often had a more active inflammatory process, but there were more complications in the adult group.

Keywords: Crohn's disease, diagnostics, inflammatory bowel disease, magnetic resonance enterography, MRE

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Authors: Jai Myung Yang, Na Young Kim, Sung Ho Shin

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The adverse reactions of current live smallpox vaccines and potential use of smallpox as a bioterror weapon have heightened the development of new effective vaccine for this infectious disease. In the present study, DNA vaccine vector was produced which was optimized for expression of the vaccinia virus L1 antigen in the mouse model. A plasmid IgM-tL1R, which contains codon-optimized L1R gene, was constructed and fused with an IgM signal sequence under the regulation of a SV40 enhancer. The expression and secretion of recombinant L1 protein was confirmed in vitro 293 T cell. Mice were administered the DNA vaccine by electroporation and challenged with vaccinia virus. We observed that immunization with IgM-tL1R induced potent neutralizing antibody responses and provided complete protection against lethal vaccinia virus challenge. Isotyping studies reveal that immunoglobulin G2 (IgG2) antibody predominated after the immunization, indicative of a T helper type 1 response. Our results suggest that an optimized DNA vaccine, IgM-tL1R, can be effective in stimulating anti-vaccinia virus immune response and provide protection against lethal orthopoxvirus challenge.

Keywords: DNA vaccine, electroporation, L1R, vaccinia virus

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Authors: Saha Saradindu, Das Payel, Somdeb BoseDasgupta

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Tuberculosis caused by Mycobacteria tuberculosis is a dreadful disease and more so with the advent of extreme and total drug-resistant species. Mycobacterial pathogenesis is an ever-changing paradigm from phagosome maturation block to phagosomal escape into macrophage cytosol and finally acid tolerance and survival inside the lysosome. Mycobacteria are adept at subverting the host immune response by highjacking host cell signaling and secreting virulence factors. One such virulence factor is a ser/thr kinase; Protein kinase G (PknG), which is known to prevent phagosome maturation. The host substrates of PknG, allowing successful pathogenesis still remain an enigma. Hence we carried out a comparative phosphoproteomic screen and identified a number of substrates phosphorylated by PknG. We characterized some of these substrates in vivo and in vitro and observed that PknG mediated phosphorylation of these substrates leads to reduced TNFa production as well as decreased response to TNFa induced macrophage necroptosis, thus enabling mycobacterial survival and proliferation.

Keywords: mycobacteria, Protein kinase G, phosphoproteomics, necroptosis

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Authors: Neşe Taşci, Soner Çubuk, Ece Kök Yetimoğlu, M. Vezir Kahraman

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Bisphenol-A (BPA), 2,2-bis(4-hydroxyphenly)propane, is one of the highest usage volume chemicals in the world. Studies showed that BPA maybe has negative effects on the central nervous system, immune and endocrine systems. Several of analytical methods for the analysis of BPA have been reported including electrochemical processes, chemical oxidation, ozonization, spectrophotometric, chromatographic techniques. Compared with other conventional analytical techniques, optic sensors are reliable, providing quick results, low cost, easy to use, stands out as a much more advantageous method because of the high precision and sensitivity. In this work, a new photocured polymeric fluorescence sensor was prepared and characterized for Bisphenol-A (BPA) analysis. Characterization of the membrane was carried out by Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and Scanning Electron Microscope (SEM) techniques. The response characteristics of the sensor including dynamic range, pH effect and response time were systematically investigated. Acknowledgment: This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) under Grant 115Y469.

Keywords: bisphenol-a, fluorescence, photopolymerization, polymeric sensor

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Authors: Valeria T. Dilcheva, Svetlozara L. Petkova, Ivelin Vladov

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Trichinellosis is a food-borne parasitic disease caused by nematodes of the genus Trichinella which are zoonotic parasites with cosmopolitan distribution and major socio-economic importance. Human infection is acquired through consumption of undercooked meat from domestic or wild animal. Penetration of Trichinella larvae into striated skeletal muscle cells results in ultrastructural and metabolic changes. Migration of larvae causes the typical symptoms and signs of the disease. The severity of the symptoms depends on the number of ingested Trichinella larvae and the immune response of the host. Eosinophilia is present, with few exceptions, in most cases of human trichinellosis, inasmuch as it is the earliest and most important host response. Even in human asymptomatic cases, increases in eosinophilia of up to 15% have been observed. Eosinophilia appears at an early stage of infection between the second and fifth weeks of infection. By 2005 it was considered that only two species of Trichinella genus were found in the country. After routine trichinelloscopy procedure disseminated single muscle larvae in samples of wild boars and badger were PCR-identified as T. pseudospiralis. The study aimed to observed hematological changes occurring during experimentally induced infection with Trichinella spiralis, T. britovi and T. pseudospiralis in mice. We performed hematological blood profile, tracking 15 blood indicators. In statistical analysis made by Two-way ANOVA, there were significant differences of HGB, MCHC, PLT, Lymph%, Gran% in all three types of trichinellosis compared to control animals. Capsule-forming T. spiralis showed statistically significant differences in HGB, MCHC, Lymph% and PLT compared to the other two species. Non capsule-forming T. pseudospiralis showed statistically significant differences in Lymph%, Gran% relative to the control and in Gran% relative to T. spiralis. It appears rather substantial the process of capsule formation for prolonged immune response and retention of high content of percentage of lymphocytes(Lymph%) and low of granulocyte(Gran%) in T. pseudospiralis, which is contrary to studies for T. spiralis and eosinophilia. Studies and analyzes of some specific blood profile parameters can provide additional data in favor of early diagnosis and adequate treatment as well as provide a better understanding of acute and chronic trichinosis.

Keywords: hematological test, T. britovi, T. spiralis, T. pseudospiralis

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Authors: Jeong-Hyun Hong, Wonsuk Choi, Hyungdal Park, Jinseok Kim, Junesun Kim

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Identifying the chronic functions of an implanted neural electrode is an important factor in acquiring neural signals through the electrode or restoring the nerve functions after peripheral nerve injury. The purpose of this study was to investigate the biocompatibility of the chronic implanted neural electrode into the sciatic nerve. To do this, a sieve-type neural electrode was implanted at proximal and distal ends of a transected sciatic nerve as an experimental group (Sieve group, n=6), and the end-to-end epineural repair was operated with the cut sciatic nerve as a control group (reconstruction group, n=6). All surgeries were performed on the sciatic nerve of the right leg in Sprague Dawley rats. Behavioral tests were performed before and 1, 4, 7, 10, 14, and weekly days until 5 months following surgery. Changes in sensory function were assessed by measuring paw withdrawal responses to mechanical and cold stimuli. Motor function was assessed by motion analysis using a Qualisys program, which showed a range of motion (ROM) related to the joints. Neurofilament-heavy chain and fibronectin expression were detected 5 months after surgery. In both groups, the paw withdrawal response to mechanical stimuli was slightly decreased from 3 weeks after surgery and then significantly decreased at 6 weeks after surgery. The paw withdrawal response to cold stimuli was increased from 4 days following surgery in both groups and began to decrease from 6 weeks after surgery. The ROM of the ankle joint was showed a similar pattern in both groups. There was significantly increased from 1 day after surgery and then decreased from 4 days after surgery. Neurofilament-heavy chain expression was observed throughout the entire sciatic nerve tissues in both groups. Especially, the sieve group was showed several neurofilaments that passed through the channels of the sieve-type neural electrode. In the reconstruction group, however, a suture line was seen through neurofilament-heavy chain expression up to 5 months following surgery. In the reconstruction group, fibronectin was detected throughout the sciatic nerve. However, in the sieve group, the fibronectin was observed only in the surrounding nervous tissues of an implanted neural electrode. The present results demonstrated that the implanted sieve-type neural electrode induced a focal inflammatory response. However, the chronic implanted sieve-type neural electrodes did not cause any further inflammatory response following peripheral nerve injury, suggesting the possibility of the chronic application of the sieve-type neural electrodes. This work was supported by the Basic Science Research Program funded by the Ministry of Science (2016R1D1A1B03933986), and by the convergence technology development program for bionic arm (2017M3C1B2085303).

Keywords: biocompatibility, motor functions, neural electrodes, peripheral nerve injury, sensory functions

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Authors: S. Nasri, G. H. Amin, A. Azimi

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The use of herbs to treat disease is accompanied with the history of human life. This research is aimed to study the anti-inflammatory and antinociceptive effects of hydroalcoholic extract of aerial parts of "Tanacetum balsamita balsamita". In the experimental studies 144 male mice are used. In the inflammatory test, animals were divided into six groups: Control, positive control (receiving Dexamethason at dose of 15mg/kg), and four experimental groups receiving Tanacetum balsamita balsamita hydroalcoholic extract at doses of 25, 50, 100 and 200mg/kg. Xylene was used to induce inflammation. Formalin was used to study the nociceptive effects. Animals were divided into six groups: control group, positive control group (receiving morphine) and four experimental groups receiving Tanacetum balsamita balsamita (Tb.) hydroalcoholic extract at doses of 25, 50, 100 and 200mg/kg. I.p. injection of drugs or normal saline was performed 30 minutes before test. The data were analyzed by using one way Variance analysis and Tukey post-test. Aerial parts of Tanacetum balsamita balsamita hydroalcoholic extract decreased significantly inflammatory at dose of 200mg/kg (P<0/001) and caused a significant decrease and alleviated the nociception in both first and second phases at doses of 200mg/kg (p<0/001) and 100mg/kg (P<0/05). Tanacetum balsamita balsamita extract has the anti-inflammatory and anti-nociceptive effects which seems to be related with flavonoids especially Quercetin.

Keywords: inflammation, nociception, hydroalcoholic extract, aerial parts of Tanacetum balsamita balsamita L.

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Authors: J. B. Minari, O. B. Oloyede

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Polymorphonuclear neutrophils (PMNs) play a crucial role in a variety of infections caused by bacteria, fungi, and parasites. Indeed, the involvement of PMNs in host defence against Plasmodium falciparum is well documented both in vitro and in vivo. Many of the antimalarial drugs such as chloroquine used in the treatment of human malaria significantly reduce the immune response of the host in vitro and in vivo. Myeloperoxidase is the most abundant enzyme found in the polymorphonuclear neutrophil which plays a crucial role in its function. This study was carried out to investigate the effect of chloroquine on the enzyme. In investigating the effects of the drug on myeloperoxidase, the influence of concentration, pH, partition ratio estimation and kinetics of inhibition were studied. This study showed that chloroquine is concentration-dependent inhibitor of myeloperoxidase with an IC50 of 0.03 mM. Partition ratio estimation showed that 40 enzymatic turnover cycles are required for complete inhibition of myeloperoxidase in the presence of chloroquine. The influence of pH on the effect of chloroquine on the enzyme showed significant inhibition of myeloperoxidase at physiological pH. The kinetic inhibition studies showed that chloroquine caused a non-competitive inhibition with an inhibition constant Ki of 0.27mM. The results obtained from this study shows that chloroquine is a potent inhibitor of myeloperoxidase and it is capable of inactivating the enzyme. It is therefore considered that the inhibition of myeloperoxidase in the presence of chloroquine as revealed in this study may partly explain the impairment of polymorphonuclear neutrophil and consequent immunosuppression of the host defence system against secondary infections.

Keywords: myeloperoxidase, chloroquine, inhibition, neutrophil, immune

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Authors: Shweta Sinha, Mukesh Doble, Manju S. L.

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Pyrazole scaffold is an important group of compound in heterocyclic chemistry and is found to possess numerous uses in chemistry. Pyrazole derivatives are also known to possess important biological activities including antitumor, antimicrobial, antiviral, antifungal, anticancer and anti-inflammatory. Inflammation is associated with pain, allergy and asthma. Leukotrienes are mediators of various inflammatory and allergic disorders. 5-Lipoxygenase (5-LOX) is an important enzyme involved in the biosynthesis of leukotrienes and metabolism of arachidonic acid (AA) and thus targeted for anti-inflammation. In vitro inhibitory activity of pyrazol-3-yl thiazole 4-carboxylic acid derivatives is tested against enzyme 5-LOX. Most of these compounds exhibit good inhibitory activity against this enzyme. Binding mode study of these compounds is determined by computational tool. Further experiments are being done to understand the mechanism of action of these compounds in inhibiting this enzyme. To conclude, these compounds appear to be a promising target in drug design against 5-LOX.

Keywords: inflammation, inhibition, 5-lipoxygenase, pyrazole

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