Search results for: anti hypercholesterolemic effects

Authors: Seunghwan Seo, Woo-Seok Lee, Ji-Sun Shin, Young Kyoung Rhee, Chang-Won Cho, Hee-Do Hong, Kyung-Tae Lee

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Doenjang, known as traditional Korean food, is product of a natural mixed fermentation process carried out by lactic acid bacteria (LAB). Lactobacillus sakei K040706 (K040706) has been accepted as the most populous LAB in over ripened doenjang. Recently, we reported the immunostimulatory effects of K040706 in RAW 264.7 macrophages and in a cyclophosphamide-induced mouse model. In this study, we investigated the ameliorative effects of K040706 in a dextran sulfate sodium (DSS)-induced colitis mouse model. We induced colitis using DSS in 5-week-ICR mice over 14 days with or without 0.1, 1 g/kg/day K040706 orally. The body weight, stool consistency, and gross bleeding were recorded for determination of the disease activity index (DAI). At the end of treatment, animals were sacrificed and colonic tissues were collected and subjected to histological experiments and myeloperoxidase (MPO) accumulation, cytokine determination, qRT-PCR and Western blot analysis. Results showed that K040706 significantly attenuated DSS-induced DAI score, shortening of colon length, enlargement of spleen and immune cell infiltrations into colonic tissues. Histological examinations indicated that K040706 suppressed edema, mucosal damage, and the loss of crypts induced by DSS. These results were correlated with the restoration of tight junction protein expression, such as, ZO-1 and occludin in K040706-treated mice. Moreover, K040706 reduced the abnormal secretions and mRNA expressions of pro-inflammatory mediators, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). DSS-induced mRNA expression of intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in colonic tissues was also downregulated by K040706 treatment. Furthermore, K040706 suppressed the protein and mRNA expression of toll-like receptor 4 (TLR4) and phosphorylation of NF-κB and signal transducer and activator of transcription 3 (STAT3). These results suggest that K040706 has an anti-colitic effect by inhibition of intestinal inflammatory responses in DSS-induced colitic mice.

Keywords: Lactobacillus sakei, NF-κB, STAT3, ulcerative colitis

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Authors: Zsofia Nagy

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A sharp increase in the number of refugees crossing Hungary during 2015, coupled with the Hungarian government’s agenda-setting strategy led to a powerful anti-migrant campaign in public, framing asylum-seekers as external threats to the country. While this campaign was, by and large, unchallenged by the Hungarian parliamentary opposition, Two-Tailed Dog Party, a Hungarian mock-party launched a counter-billboard campaign attacking the governmental discourse. Taking the latter as a case of digitally supported civic action, the paper first discusses two theoretical problems related to contemporary social movements: the problem of voice and the problem of participation. Afterward the paper presents the case of the Hungarian anti-migrant billboard campaign led by the government and the counter-billboard campaign and examines their action repertoires. It argues that a number of strategic differences are noteworthy: contrasts between traditional and digital methods, the reliance on the ’spirals of silence’ on the one hand and the breaking of this very silence on the other, where people are holding a minority opinion were given a platform and visibility in public. On a deeper level, the counter-campaign challenged the hegemonic views about public discourse. It effectively contrasted the government’s one-to-many, top-bottom approach to political communication with a campaign that relied on many-to-many communication and a bottom-up approach. While it is true that through memetic engineering, the original governmental messages were altered and the outcomes were brought back to the streets of Hungary; the effects of the two campaigns nevertheless reinforced the original anti-migrant focus of the political agenda.

Keywords: counterpublics, migration, refugees, social movements

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Authors: Beata Skibska, Andrzej Stanczak, Agnieszka Skibska

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Nanodiamond (ND) is a carbon nanomaterial that has high biocompatibility, and it has a very positive effect on a number of biochemical processes. NDs have great potential in treating multiple inflammation-associated diseases. The purpose of this study was to investigate the anti-inflammatory effect of nanodiamonds and lipoic acid (LA) (as antioxidants) on rats' cardiovascular systems after lipopolysaccharide (LPS) administration. Animal experiments enabled the determination of how nanodiamonds act when applied independently or in combination with lipoic acid. The effect of NDs and LA on C-reactive protein (CRP) levels and heart edema was evaluated. NDs and LA administered after LPS administration attenuated heart edema and significantly decreased the CRP level. The results suggest that NDs and LA play an important role in LPS-induced inflammation in the heart. NDs find new applications in modern biomedical science and biotechnologies.

Keywords: nanodiamonds, lipoic acid, inflammation, cardiovascular system

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Authors: Haile F. Darge, Hsieh C. Tsai

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The tumor microenvironment affects the therapeutic outcomes of cancer disease. In a malignant tumor, overexpression of vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks. This results in a hostile tumor environment that hinders anti-cancer drug activities and profoundly fuels tumor progression. In this study, we develop a strategy of sequential sustain release of the anti-angiogenic drug: Bevacizumab(BVZ), and anti-cancer drug: Doxorubicin(DOX) which had a synergistic effect on cancer treatment. Poly (D, L-Lactide)- Poly (ethylene glycol) –Poly (D, L-Lactide) (PDLLA-PEG-PDLLA) thermo-sensitive hydrogel was used as a vehicle for local delivery of drugs in a single platform. The in vitro release profiles of the drugs were investigated and confirmed a relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) for a prolonged period. The cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. The in vivo study on Hela xenograft nude mice verified that hydrogel co-loaded with BVZ and DOX displayed the highest tumor suppression efficacy for up to 36 days with pronounce anti-angiogenic effect of BVZ and with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drugs by the hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Keywords: anti-angiogenesis, chemotherapy, controlled release, thermo-sensitive hydrogel

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Authors: Monika Malik, Pooja Arora, Ruchi Sachdeva, Vishnampettai G. Ramachandran, Rahul Pal

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Apoptotic debris is believed to be the antigenic trigger in lupus. Whether such debris and autoantibodies induced in lupus-prone mice which specifically recognize its constituents can mediate differential effects on innate and humoral responses in such mice was assessed. The influence of apoptotic blebs and apoptotic cell-reactive monoclonal antibodies on phenotypic markers expressed on bone marrow-derived dendritic cells (BMDCs) and secreted cytokines were evaluated. Sera from lupus-prone and healthy mice immunized with the antibodies were analyzed for anti-self reactivity. Apoptotic blebs, as well as somatically-mutated IgG and non-mutated IgM apoptotic-cell reactive monoclonal antibodies, induced the preferential maturation of BMDCs derived from lupus-prone mice relative to BMDCs derived from healthy mice; antibody specificity and cell genotype both influenced the secretion of inflammatory cytokines. Immunization of lupus-prone mice with IgM and IgG antibodies led to hypergammaglobulinemia; elicited antibodies were self-reactive, and exhibited enhanced recognition of lupus-associated autoantigens (dsDNA, Ro60, RNP68, and Sm) in comparison with adjuvant-induced sera. While ‘natural’ IgM antibodies are believed to contribute to immune homeostasis, this study reveals that apoptotic cell-reactive IgM antibodies can promote inflammation and drive anti-self responses in lupus. Only in lupus-prone mice did immunization with IgG auto-antibodies enhance the kinetics of humoral anti-self responses, resulting in advanced-onset glomerulosclerosis. This study reveals that preferential innate and humoral recognition of the products of cell death in an autoimmune milieu influences the indices associated with lupus pathology.

Keywords: antigen spreading, apoptotic cell-reactive pathogenic IgG, and IgM autoantibodies, glomerulosclerosis, lupus

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Authors: Harukuni Tokuda, Takanari Arai, Xu FengHao, Nobutaka Suzuki

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In our continuous search for anti-tumor promoting, chemopreventive active potency from natural source material, a kind of healthy tea, Gromwell seed (Coix lachryma-jobi) ext., and including compounds Monoolein and Trilinolein have been screened using the in vitro synergistic assay indicated by inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by TPA. In assay, Gromwell seed aqueous extract and hot aqueous extract exhibited the potential inhibitory effects on EBV-EA activation without strong cytotoxicity on Raji cells. In our experimental system, the inhibitory effects of both Gromwell extracts and compounds were greater than that of beta-carotene, which is known anti-tumor promoting agent and/or chemopreventive agent. These compounds were evaluated for their in vitro inhibitory effect on EBV-EA activation induced by TPA. The percentages of the inhibition of TPA-induced EBV-EA activation for these materials were 60% and 30% at concentration 100 μg. Based on the results obtained in vitro, we studied the inhibitory effect of compounds, in an in vivo two-stage carcinogenesis test of mouse skin papilloma using DMBA as an initiator and TPA as a potential promoter. The control animals showed a 100% incidence of papilloma at 20 weeks after DMBA-TPA tumor promotion, while treatment with compounds reduced the percentage of number of tumor to 60 % after 20 weeks. Results from in vitro and in vivo studies showing chemopreventive activity against TPA promoting stage and these data support the effective potency of carcinogenic stage in clinical evaluation of integrative oncology.

Keywords: gromwell seed, medicinal plant, chemoprevention, pharmaceutical medicine

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Authors: Faraj M. Elkhatri, Hana Ellafi

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

Keywords: formation damage, porosity loses, pore throat, quartz cement

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Authors: M. Kosandi, V. Susanti, N. I. Subono, E. Kartini

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This paper discusses the risk of glorification trap in combating human trafficking, as it is shown in the case of Indonesia. Based on a research on Indonesian combat against trafficking in 2017-2018, this paper shows the tendency of misinterpretation and misapplication of the Indonesian anti-trafficking law into misusing the law for glorification, to create an image of certain extent of achievement in combating human trafficking. The objective of this paper is to explain the persistent occurrence of human trafficking crimes despite the significant progress of anti-trafficking efforts of Indonesian government. The research was conducted in 2017-2018 by qualitative approach through observation, depth interviews, discourse analysis, and document study, applying the three-dimensional model for analyzing human trafficking in the source country. This paper argues that the drive for glorification of achievement in the combat against trafficking has trapped Indonesian government in the loop of misinterpretation, misapplication, and misuse of the anti-trafficking law. In return, the so-called crime against humanity remains high and tends to increase in Indonesia.

Keywords: human trafficking, anti-trafficking policy, transnational crime, source country, glorification trap

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Authors: Edy Wahyu Susilo

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This research discusses a comparative analysis of various anti-corruption responses of three Indonesian City Governments (Jakarta, Surabaya, and Medan) and completes previous findings on the effectiveness of the city anti-corruption program. Some factors (transparency, accountability, leadership, law enforcement, and bureaucratic reform) have been chosen in this study to diagnose the main role in the success and the failure of anti-corruption programs in these cities. These factors diagnose the relationship between factors and their dominancy, which is then utilized to create the city’s strategic anti-corruption programs. Although this study found leadership had a dominant influence both in encouraging and discouraging the performance of city transformation drastically, however, it is not the only factor that determined the performance of the city in the fight against corruption. It needs other factors as an ideal balancing element to achieve an anti-corruption program, namely KPK’s intervention and public engagement. Based on the dominance factors found, this research then develops an appropriate strategy using a policy evaluation approach to create a real practical guide regardless of the existence of good or bad leadership in the city. This research is expected to be a useful reference for stakeholders, especially the government, as a blueprint to prevent corruption by considering several important steps and guidance in efforts to eradicate corruption in the city, especially in Indonesia.

Keywords: intervention, KPK (corruption eradication commission), law enforcements, leadership, policy evaluation

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Authors: M. Abdel-Hamid, P. Saporito, R. V. Mateiu, A. Osman, E. Romeih, H. Jenssen

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Camel milk whey (CMW) was hydrolyzed with papain from Carica papaya and fractionated by size exclusion chromatography (SEC). The antibacterial and anti-biofilm activity of the CMW, Camel milk whey hydrolysate (CMWH) and the obtained SEC-fractions was assessed against Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA). SEC-F2 (fraction 2) exhibited antibacterial effectiveness against MRSA and P. aeruginosa with the minimum inhibitory concentration of 0.31 and 0.156 mg/ml, respectively. Furthermore, SEC-F2 significantly decreased biofilm biomass by 71% and 83 % for MRSA and P. aeruginosa in a crystal violet microplate assay. Scanning electron microscopy showed that the SEC-F2 caused changes in the treated bacterial cells. Additionally, LC/MS analysis was used to characterize the peptides of SEC-F2. Two major peptides were detected in SEC-F2 having masses of 414.05 Da and 456.06 Da. In conclusion, this study has demonstrated that hydrolysis of CMW with papain generates small and extremely potent antibacterial and anti-biofilm peptides against both MRSA and P. aeruginosa.

Keywords: camel milk, whey proteins, antibacterial peptide, anti-biofilm

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Authors: Chanyuan Gu, Shouming Zhong

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Synchronization is a fundamental phenomenon that enables coherent behavior in networks as a result of interactions. The purpose of this research had been to investigate the problem of anti-phase synchronization for complex delayed dynamical networks with output coupling. The coupling configuration is general, with the coupling matrix not assumed to be symmetric or irreducible. The amount of the coupling variables between two connected nodes is flexible, the nodes in the drive and response systems need not to be identical and there is not any extra constraint on the coupling matrix. Some pinning controllers are designed to make the drive-response system achieve the anti-phase synchronization. For the convenience of description, we applied the matrix Kronecker product. Some new criteria are proposed based on the Lyapunov stability theory, linear matrix inequalities (LMI) and Schur complement. Lastly, some simulation examples are provided to illustrate the effectiveness of our proposed conditions.

Keywords: anti-phase synchronization, complex networks, output coupling, pinning control

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Authors: Farah Ali, Tehreem Fayyaz, Musadiq Idris

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The present work was undertaken to investigate effects of various extracts of W. somniferafor anti-diabetic activity in alloxan induced diabetic rabbits. Rabbits were acclimatized for a week to standard laboratory temperature. Animals were fed according to a strict schedule (8 am, 3 pm and 10 pm) with green fodder (Medicago sativa) and tap water ad libitum. Animals were divided into nine groups of six rabbits each in a random manner. Body weights and physical activities of all rabbits were recorded before start of experiments. The animals of group 1 and 2 were given lactose (250 mg/kg,p.o) and Withaniasomniferaroot powder (100 mg/kg, p.o) respectively daily from day 1-20. Animals of group 3 were given alloxan (100 mg/kg,i.v) as a single dose on day 1. Powdered root of Withaniasomnifera in the doses of 100, 150, 200 mg/kg and its aqueous and ethanol extracts (equivalent to 200 mg/kg of crude drug) were given to the treated animals (groups 4-8), respectively by oral route for three weeks (day 1-20o.d), along with alloxan (100 mg/kg, i.v) as a single dose on day 1. Group 9 was treated with metformin (200 mg/kg, p.o) daily from day 1-20, along with a single dose of alloxan (100 mg/ kg, i.v) on day 1. Fasting serum glucose concentration in groups 3-9 was increased significantly (p<0.05) on day 3, with a maximum increase (215.3 mg/dl) in animals of toxic control (TC) group (3) on day 21 of the experiment as compared to normal control (NC) group (1). Effects of different doses (100, 150, 200 mg/kg, p.o) of W. somnifera root powder (WS) decreased the fasting serum glucose concentration as compared to toxic control group, with a maximum decrease (88.3 mg/dl) in group 2 (treated control) on day 21 of the experiment. Metformin (200 mg/kg, p.o) (reference control), aqueous extract (AWS) and ethanol extract (EWS) of W. somnifera (equivalent to 100 mg/kg W.somnifera root, p.o) antagonized the effects of alloxan as compared to toxic control group. These results indicate that the W. somnifera possess significant anti –diabetic activity.

Keywords: diabetes, serum, glucose, blood, sugar, rabbits

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Authors: Sevgi Balkan-Sahin

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The Justice and Development Party (AKP) government has included nuclear power as a major component of Turkey’s new energy strategy by promoting it as the only alternative for Turkey to diversify energy resources, trigger economic growth, and boost competitiveness of the country. The effective promotion of such a framing has created a hegemonic discourse around nuclear energy in Turkey. However, fiercely opposing the nuclear initiative of the government, the Turkish anti-nuclear platform (ANP) composed of more than 50 civil society groups has challenged the hegemonic discourse of the AKP government by presenting nuclear energy as dangerous for human health, human rights, and the protection of environment. Based on an engagement between Gramscian perspective and Laclau and Mouffe’s discourse theory, this paper considers the discourses of the Turkish anti-nuclear platform and its associated activities as a counter-hegemonic strategy to change the ‘common sense’ on nuclear energy in Turkey. Analyzing the data from interviews with the representatives of the anti-nuclear platform coupled with primary sources, such as Parliamentary Records and official statements by civil society organizations, the paper highlights how the anti-nuclear platform exercises power through counter-hegemonic discourses in terms of the delegitimization of nuclear energy in Turkey.

Keywords: counter-hegemony, discourse, nuclear energy, Turkey

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Authors: Sourav Ghosh, Antony Gomes

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Since 1894 anti-snake venom serum (ASVS) is the only available treatment against snake envenomation, although there are many side effects and limitations. The need for a supportive treatment was felt for a long time to overcome the side effects and limitations of ASVS. Andrographolide conjugated with gold nanoparticle (A-GNP) has been found to antagonize viper venom-induced local damages. The present study was aimed to study the protective efficacy of A-GNP against Viper venom-induced inflammatory response and organ toxicity in animal model. Ethical clearance was obtained from animal experiments. Physico-chemical characterization of A-GNP was done by DLS (diameter and zeta potential), FE-SEM and XRD. Swiss albino male mice were divided into 4 groups: Gr.1-Sham control, Gr.2- Russell’s Viper venom (RVV) control, Gr.3- andrographolide treated and Gr.4- A-GNP treated. The 1/5th minimum lethal dose of RVV (500µg/kg, s.c.) was induced in animals of group 2, 3 & 4 animals, followed by treatment with andrographolide (100mg/kg, i.p.) and A-GNP (100mg/kg, i.v.) in group 3 & 4 animals, respectively. Blood was collected after 18 h, serum was prepared, and inflammatory markers (IL 1β, 6, 17a, 10, TNF α) and biochemical markers (AST, ACP, LDH, urea, creatinine) were assessed. Values were expressed as mean±SEM (n=4), one way ANOVA was done, P<0.05 was considered as statistically significant. DLS size showed the hydrodynamic diameter of A-GNP to be 230-260nm with polydispersity index of 0.103 and zeta potential was -18.32mV. XRD data confirmed the presence of crystalline gold in A-GNP, and FESEM indicated the presence of nearly spherical particle with size18-24nm.Treatment with A-GNP significantly decreased viper venom-induced proinflammatory markers (IL 1β, 6, 17, TNF α) increased anti-inflammatory markers (IL 10) and decreased organ toxicity markers (AST, ACP, LDH, urea, creatinine) in animal model. Venom neutralization efficacy of A-GNP was > andrographolide, which confirmed the increased efficacy of andrographolide after gold nanoparticle conjugation. Venom neutralization by A-GNP was due to anti-oxidant/anti-inflammatory activity of andrographolide, which showed increased efficacy after gold nanoparticle tagging. Thus, A-GNP may serve as a supportive therapy in snake-bite (against inflammatory response and organ toxicity) subject to further detail studies.

Keywords: andrographolide, gold nanoparticle, inflammatory response, organ toxicity, snake venom, snake venom neutralization, viper venom

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Authors: Rachid Kacem

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Excessive recruitment of Neutrophils into the lungs is a hallmark of several chronic inflammatory disorders such as emphysema and COPD. The resulting of this recruitment is the pathogenesis of lungs which is characterized by an imbalance between leukocyte serine proteinases mainly neutrophil elastase and the physiological inhibitors. The development of emphysema and remodeling of airway tissue occurred when neutrophil migrate into the lungs with more release of elastase and other proteolytic enzymes. Many reports have demonstrated that the extracts from medicinal plants such as Nigella sativa (L.) seeds extracts have anti-elastase activity; this is mainly due to the enrichment of the extracts with many bioactive molecules mainly phenolic compounds. Neutrophil serine proteases including human neutrophil elastase are involved in many inflammatory diseases, such as chronic obstructive pulmonary disease and emphysema. Since the current therapies for these diseases are inadequate and have numerous adverse effects, there is an acute need of potential alternative therapies. The natural protease inhibitors have received increasing attention as useful tools for potential utilization in pharmacology. This work is elucidating the most important natural phenolic substances that have been reported recently for their effectiveness as natural anti-elastase molecules, and hence, to the possibility of their use in the field of pharmaceuticals.

Keywords: medicinal plants, phenols, elastase, anti-elastase, chronic obstructive pulmonary disease, COPD, emphysema

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Authors: Michio Kurosu

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Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

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Authors: Tauseef Ahmad, Muhammad Ishaq, Mathew Eapen, Ahyoung Park, Sam Karpiniec, Vanni Caruso, Rajaraman Eri

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Fucoidans are complex, fucose-rich sulfated polymers discovered in brown seaweeds. Fucoidans are popular around the world, particularly in the nutraceutical and pharmaceutical industries, due to their promising medicinal properties. Fucoidans have been shown to have a variety of biological activities, including anti-inflammatory effects. They are known to inhibit inflammatory processes through a variety of mechanisms, including enzyme inhibition and selectin blockade. Inflammation is a part of the complicated biological response of living systems to damaging stimuli, and it plays a role in the pathogenesis of a variety of disorders, including arthritis, inflammatory bowel disease, cancer, and allergies. In the current investigation, various fucoidan extracts from Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica were assessed for inhibition of pro-inflammatory cytokine production (TNF-α, IL-1β, and IL-6) in LPS induced human macrophage cell line (THP-1) and human peripheral blood mononuclear cells (PBMCs). Furthermore, we also sought to catalogue these extracts based on their anti-inflammatory effects in the current in-vitro cell model. Materials and Methods: To assess the cytotoxicity of fucoidan extracts, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5, -diphenyltetrazolium bromide) cell viability assay was performed. Furthermore, a dose-response for fucoidan extracts was performed in LPS induced THP-1 cells and PBMCs after pre-treatment for 24 hours, and levels of TNF-α, IL-1β, and IL-6 cytokines were measured using Enzyme-Linked Immunosorbent Assay (ELISA). Results: The MTT cell viability assay demonstrated that fucoidan extracts exhibited no evidence of cytotoxicity in THP-1 cells or PBMCs after 48 hours of incubation. The results of the sandwich ELISA revealed that all fucoidan extracts suppressed cytokine production in LPS-stimulated PBMCs and human THP-1 cells in a dose-dependent manner. Notably, at lower concentrations, the lower molecular fucoidan (5-30 kDa) extract from Macrocystis pyrifera was a highly efficient inhibitor of pro-inflammatory cytokines. Fucoidan extracts from all species including Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica exhibited significant anti-inflammatory effects. These findings on several fucoidan extracts provide insight into strategies for improving their efficacy against inflammation-related diseases. Conclusion: In the current research, we have successfully catalogued several fucoidan extracts based on their efficiency in LPS-induced macrophages and PBMCs in downregulating the key pro-inflammatory cytokines (TNF-, IL-1 and IL-6), which are prospective targets in human inflammatory illnesses. Further research would provide more information on the mechanism of action, allowing it to be tested for therapeutic purposes as an anti-inflammatory medication.

Keywords: fucoidan, PBMCs, THP-1, TNF-α, IL-1β, IL-6, inflammation

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Authors: Strahinja Kovačević, Sanja Podunavac-Kuzmanović, Lidija Jevrić, Milica Karadžić

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The present study is based on the quantitative structure-activity relationship (QSAR) analysis of eighteen compounds with anti-prion activity. The structures and anti-prion activities (expressed in response units, RU%) of the analyzed compounds are taken from CHEMBL database. In the first step of analysis 85 molecular descriptors were calculated and based on them the hierarchical cluster analysis (HCA) and principal component analysis (PCA) were carried out in order to detect potential significant similarities or dissimilarities among the studied compounds. The calculated molecular descriptors were physicochemical, lipophilicity and ADMET (absorption, distribution, metabolism, excretion and toxicity) descriptors. The first stage of the QSAR analysis was simple linear regression modeling. It resulted in one acceptable model that correlates Henry's law constant with RU% units. The obtained 2D-QSAR model was validated by cross-validation as an internal validation method. The validation procedure confirmed the model’s quality and therefore it can be used for prediction of anti-prion activity. The next stage of the analysis of anti-prion activity will include 3D-QSAR and molecular docking approaches in order to select the most promising compounds in treatment of prion diseases. These results are the part of the project No. 114-451-268/2016-02 financially supported by the Provincial Secretariat for Science and Technological Development of AP Vojvodina.

Keywords: anti-prion activity, chemometrics, molecular modeling, QSAR

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Authors: Angalabiri-Owei E. Bekekeme, Brambaifa Nelson

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In view of the peculiar environment of the Niger Delta, access to modern health care is limited, hence the inhabitants especially those in the swampy areas resorts to sourcing for alternatives cure for their ailments using plants commonly found in this area without scientific evaluation. Rhizophora racemosa, G. F. Meyer (Rhizophoraceae) is the most abundant mangrove plant in the Niger Delta Area of Nigeria. The plant has been observed to be used for relief of a toothache and dysmenorrhoea among some Ijaw communities in the region. This work has revealed the likely potential of the plant in drug discovery and development. The crude methanol extract at doses of 300 mg/kg and 600 mg/kg (intraperitoneal) were tested for analgesic effect using fresh egg albumin induced inflammatory pain and Randall–Sellito method to assess the pain threshold. The anti-inflammatory effect was also evaluated with the extract at doses of 300 mg/kg and 600 mg/kg (intraperitoneal) using acute inflammatory model; fresh egg albumin induced paw oedema and assessed using Plethysmometer in rats. The methanol extracts 300 mg/kg and 600 mg/kg exhibited a significant (P < 0.001) and dose-dependent analgesic activity compared with the negative control and a standard drug diclofenac using ANOVA with Least Significant Difference post hoc test as evidenced by increased pain threshold. Also, the extract significantly (P < 0.001) reduced the rat paw oedema induced by the sub plantar injection of fresh egg albumin when compared with the negative control and a standard diclofenac using above statistical methods. This study revealed that the plant possesses analgesic and anti-inflammatory activities hence provide scientific bases for use as medicine.

Keywords: analgesic, anti-inflammatory, plethysmometer, Rhizophora racemosa

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Authors: Muhammad Al Rizqi Dharma Fauzi, Dwi Yulian Fahruddin Shah, Andre Pratama, Ari Hasna Widyapuspa, Ganden Supriyanto

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Diabetes mellitus is still known as one of diseases which give a big amount of death in the world. From 2012 to 2014, diabetes is estimated to have resulted in 1.5 to 4.9 million deaths each year. In this paper, we present our research in the analysis and dose determination of Tenebrio molitor (Mealworm) extract as an anti-diabetic agent which is believed by Indonesian people as a traditional treatment to prevent and treat diabetes. We found that Tenebrio molitor extract has a potential as an anti-diabetic agent by in vitro test to Mus musculus which were divided into six group of treatment. Our dose determination analysis gave a conclusion that at 2,5 g/mL of concentration of the extract would give the optimal result in healing a wound given to Mus musculus which were induced by aloxane monohydrate. These results show that Tenebrio molitor extract is potential to be used as an Anti-Diabetic agent.

Keywords: diabetes, extraction, Tenebrio molitor, traditional medicine

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Authors: Lubna Azmi, Ila Shukla, Shyam Sundar Gupta, Padam Kant, C. V. Rao

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Elvitegravir is the mainstay of anti-HIV combination therapy in most endemic countries presently. However, it cannot be used alone owing to its long onset time of action. 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one (Quercetin: QU) is a polyphenolic compound obtained from Argeria speciosa Linn (Family: Convolvulaceae), an anti-HIV candidate. In the present study, a sensitive, simple and rapid high-performance liquid chromatography coupled with positive ion electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the simultaneous determination elvitegravir and Quercetin, in rat plasma. The method was linear over a range of 0.2–500 ng/ml. All validation parameters met the acceptance criteria according to regulatory guidelines. LC–MS/MS method for determination of Elvitegravir and Quercetin was developed and validated. Results show the potential of drug–drug interaction upon co-administration this marketed drugs and plant derived secondary metabolite.

Keywords: anti-HIV resistance, extraction, HPLC-ESI-MS-MS, validation

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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: Ikram Mohamed Eltayeb, Ustina Saeed Barsoumbolice

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Cinnamomum zeylanicum belong to the family Lauraceae and Artemisia absinthium belong to the family Asteraceae. Both were traditionally used as antiemetic, anti-inflammatory and antidiabetic. In Sudan, the mixtures of the two plants were traditionally used for the treatment of diabetes. Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia. It is mainly classified into two major groups, type-1 and type-2. Type-2 is a combination of resistance to insulin action and an inadequate compensatory insulin secretory response. The treatment of type-2 diabetes mellitus (DM) with synthetic drugs have many side effects so many researches were conducted to overcome or reduce this side effects by using alternative medicine. The objective of this study is to investigate and compare the anti-diabetic activity of C. zeylanicum and A. absinthium and their combination with difference ratio. C. zeylanicum and A. absinthium were extracted by 96% ethanol using Soxhlet apparatus. Thirty-two rats were divided into eight groups; each group contains four rats. 1st group was administered with distilled water at dose of 10ml/kg, 2nd group had received glucose only at dose of 2g/kg intraperitoneal, the standard group (3rd group) had received Glibenclamide orally at dose of 0.45mg/kg, 4th group received 100 mg C. zeylanicum + 300 mg A. absinthium with a ratio of (25:75), 5th group received 300 mg C. zeylanicum + 100 mg A. absinthium with a ratio of (75:25), 6th group received 200 mg C. zeylanicum + 200 mg A. absinthiumwith a ratio of (50:50), 7th group received 400 mg of A. absinthium, 8th group received 400 mg of C. zeylanicum. Then the blood samples were taken Retro-orbitally at 0, 1, 2 and 4 hours and the glucose level was measured. Each plant alone and their combination with different ratios shows antidiabetic effect. The significant activity was shown by A. absinthium extract (400 mg/kg), combination of ratio of (75:25) A. absinthium: C. zeylanicum(400mg/kg) and then C. zeylanicum(400mg/kg) with p-value 0.001, 0.022, 0.030 respectively, the activity was found to be increased with time. The other combinations showed less activity with p-value > 0.05. The result concludes that the good antidiabetic activity was performed by A. absinthium alone and its activity decreased by increase combination ratio with C. zeylanicum. Which maybe explains by the antagonistic effect between the compounds of C. zeylanicum and A. absinthium.

Keywords: antidiabetic, Artemisia absinthium , cinnamomum zeylanicum, combination

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Authors: Farah Ali, Tehreem Fayyaz, Musadiq Idris

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The present work was undertaken to investigate effects of various extracts of withania somnifera for anti-diabetic activity in alloxan induced diabetic rabbits. Rabbits were acclimatized for a week to standard laboratory temperature. Animals were fed according to a strict schedule (8 am, 3 pm and 10 pm) with green fodder (Medicago sativa) and tap water ad libitum. Animals were divided into nine groups of six rabbits each in a random manner. Body weights and physical activities of all rabbits were recorded before start of experiments. The animals of group 1 and 2 were given lactose (250 mg/kg, p.o) and Withania somniferaroot powder (100 mg/kg, p.o) respectively daily from day 1-20. Animals of group 3 were given alloxan (100 mg/kg, i.v) as a single dose on day 1. Powdered root of Withania somnifera in the doses of 100, 150, 200 mg/kg and its aqueous and ethanol extracts (equivalent to 200 mg/kg of crude drug) were given to the treated animals (groups 4-8), respectively by oral route for three weeks (day 1-20o.d), along with alloxan (100 mg/kg, i.v) as a single dose on day 1. Group 9 was treated with metformin (200 mg/kg, p.o) daily from day 1-20, along with a single dose of alloxan (100 mg/ kg, i.v) on day 1. Fasting serum glucose concentration in groups 3-9 was increased significantly (p<0.05) on day 3, with a maximum increase (215.3 mg/dl) in animals of toxic control (TC) group (3) on day 21 of the experiment as compared to normal control (NC) group (1). Effects of different doses (100, 150, 200 mg/kg, p.o) of W. somnifera root powder (WS) decreased the fasting serum glucose concentration as compared to toxic control group, with a maximum decrease (88.3 mg/dl) in group 2 (treated control) on day 21 of the experiment. Metformin (200 mg/kg, p.o) (reference control), aqueous extract (AWS) and ethanol extract (EWS) of W. somnifera (equivalent to 100 mg/kg W.somnifera root, p.o) antagonized the effects of alloxan as compared to toxic control group. These results indicate that the W. somnifera possess significant anti–diabetic activity.

Keywords: diabetes, serum, glucose, blood, sugar, rabbits

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Authors: Salieg L. Munestri

Abstract:

War on Terror became a principal war after the 9/11 attacks on U.S. homeland. Instead of helping to build up worldwide efforts to condemn terror and suicide bombings, the U.S.-led war on terror has given opportunities for the vast spread of terror. In much of Muslim world recently, the Bush’s Doctrine pushing all nations to choose sides in a war that is not truly a war has resulted worse effects. In the world’s most populous Muslim nation, Indonesia, more terror occurred since then. Instead of reinforcing the well-trained anti-terror military forces, Indonesian government established US-funded Special Detachment 88 to guarantee the accomplishment of war on terror in Indonesia and significantly to bring impact on regional security atmosphere. Indonesia is a potential power in Asia but it lacked off sophisticated military equipments. Consequently, Indonesia agrees to become a U.S. mutual partner in combating terrorism managed by Defense Security Cooperation Agency. The formation of elite anti-terror forces and U.S. partnerships perform Indonesia’s commitment to take a position beside the U.S. in coping with terrorism issue. However, this undeniably brings consequences on Indonesian political athmosphere, which encourages the writer to dig deep the consequences on the domestic environment of Indonesian political system. The establishment of the elite forces has aroused fluctuations within government, chiefly Indonesian House, concerning the establishment urgency, the large amount of funding, and the unpleasant performances, particularly the treatment toward suspected terrorists. Hence, evaluation process upon the Detachment 88 is highly demanding.

Keywords: anti-terror forces, Indonesia, political system, war on terror

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Authors: Shishen Xie, Yingda L. Xie

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Tuberculosis (TB) is a potentially serious infectious disease that remains a health concern. The Interferon Gamma Release Assay (IGRA) is a blood test to find out if an individual is tuberculous positive or negative. This study applies statistical analysis to the clinical data of interferon-gamma levels of seventy-three subjects who diagnosed pulmonary TB in an anti-tuberculous treatment. Data analysis is performed to determine if there is a significant decline in interferon-gamma levels for the subjects during a period of six months, and to infer if the anti-tuberculous treatment is effective.

Keywords: data analysis, interferon gamma release assay, statistical methods, tuberculosis infection

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Authors: Oluyomi Stephen Adeyemi, Kentaro Kato

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Toxoplasma gondii is the etiological agent of toxoplasmosis, a common parasitic disease capable of infecting a range of hosts, including nearly one-third of the human population. Current treatment options for toxoplasmosis patients are limited. In consequence, toxoplasmosis represents a large global burden that is further enhanced by the shortcomings of the current therapeutic options. These factors underscore the need for better anti-T. gondii agents and/or new treatment approach. In the present study, we sought to find out whether preparing and capping nanoparticles (NPs) in amino acids, would enhance specificity toward the parasite versus the host cell. The selection of amino acids was premised on the fact that T. gondii is auxotrophic for some amino acids. The amino acid-nanoparticles (amino-NPs) were synthesized, purified and characterized following established protocols. Next, we tested to determine the anti-T. gondii activity of the amino-NPs using in vitro experimental model of infection. Overall, our data show evidence that supports enhanced and excellent selective action against the parasite versus the host cells by amino-NPs. The findings are promising and provide additional support that warrants exploring the prospects of NPs as alternative anti-parasite agents. In addition, the anti-parasite action by amino-NPs indicates that nutritional requirement of parasite may represent a viable target in the development of better alternative anti-parasite agents. Furthermore, data suggest the anti-parasite mechanism of the amino-NPs involves multiple cellular processes including the production of reactive oxygen species (ROS), modulation of hypoxia-inducing factor-1 alpha (HIF-1α) as well as the activation of kynurenine pathway. Taken together, findings highlight further, the prospects of NPs as alternative source of anti-parasite agents.

Keywords: drug discovery, infectious diseases, mode of action, nanomedicine

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Authors: Adnan M. Al Assaf

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This research project aims to assess the methods of enhancing tolerant thinking and behavior among Muslim societies. This is in addition to spreading the anti-terrorist approach in their communities. The critical assessment for the Islamic major texts in question is the selected way for convincing, as Muslims adopt these sources as the authentic references for their lives and cultures. Moreover, this research devotes a special room to the analysis of the royal ‘Amman Message’ as a contemporary Islamic approach for enhancing tolerance and anti-terrorism from an Islamic perspective. The paper includes the study of the related concepts, texts, practical applications, with some reference to the history of Islam in human interaction, accepting the others, mercy with minorities, protecting human rights. Furthermore, it assesses the methods of enhancing tolerance and minimizing the terrorist thinking and behavior practically, in the view of Amman message, as well.

Keywords: Islam, tolerance, anti-terrorism, coexistence, Amman Message

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Authors: Yousry El-Sayed Elbolkiny, Mohamed Labib Salem

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Background: Rosemary (ROLE) and costus (SLRE) have been established to show antioxidant effects. Aim: This study aimed to evaluate the ameliorating effects of ROLE and SLRE on the side effects induced by cisplatin (CIS) in tumor-bearing mice. Materials and Methods: Extracts of ROLE and SLRE were examined for their phytochemical activities. To evaluate their anti-tumor effects, mice were inoculated intraperitoneally (i.p.) with 2.5x105 Ehrlich ascites carcinoma (EAC) and then treated i.p. with CIS at days 3-7 and with ROLE (dose) or SLRE (dose) at days 3-14. Mice were sacrificed on day 14 for CBC and T-cell analyses. Results: Phytochemical analysis revealed that both ROLE and SLRE showed similar antioxidant activities. Treatment of EAC-bearing mice with CIS-induced antitumor efficacy of about 90%. Treatment with CIS in combination with ROLE or SLRE did not further enhance the antitumor activity of CIS. However, co-administration of ROLE or SLRE with CIS significantly increased the antitumor efficacy of CIS. Flow cytometric analysis showed that the numbers of CD4+ and CD8+ T cells were decreased in EAC-bearing mice after treatment with CIS. Treatment with both ROLE and SLRE improved the number of these cells. Conclusion: Combinatorial treatment with rosemary and costus can enhance the antitumor activity of CIS

Keywords: CBC, cisplantin, costus, rosemary

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Authors: Sam Yurdakul, Nick Baverstock, Jim Mills

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TDT 064 (FLEXISEQ®) is a drug-free gel used to treat osteoarthritis (OA)-associated pain and joint stiffness. It contains ultra-deformable phospholipid Sequessome™ vesicles, which can pass through the skin barrier intact. In six randomized OA studies, topical TDT 064 was well tolerated and improved joint pain, physical function and stiffness. In the largest study, these TDT 064-mediated effects were statistically significantly greater than oral placebo and equivalent to celecoxib. To understand the therapeutic effects of TDT 064, we investigated the localisation of the drug-free vesicles within rat synovial joints. TDT 064 containing DiO-labelled Sequessome™ vesicles was applied to the knees of four 6-week-old CD® hairless rats (10 mg/kg/ joint), 2–3 times/day, for 3 days (representing the recommended clinical dose). Eighteen hours later, the animals and one untreated control were sacrificed, and the knee joints isolated, flash frozen and embedded in Acrytol Mounting Media™. Approximately 15 sections (10 µm) from each joint were analysed by fluorescence microscopy. To investigate whether the localisation of DiO fluorescence was associated with intact vesicles, an anti-PEG monoclonal antibody (mAb) was used to detect Tween, a constituent of Sequessome™ vesicles. Sections were visualized at 484 nm (DiO) and 647 nm (anti-PEG mAb) and analysed using inForm 1.4 (Perkin Elmer, Inc.). Significant fluorescence was observed at 484 nm in sections from TDT 064-treated animals. No non-specific fluorescence was observed in control sections. Fluorescence was detected as discrete vesicles on the cartilage surfaces, inside the cartilaginous matrix and within the synovial space. The number of DiO-labelled vesicles in multiple fields of view was consistent and >100 in sections from four different treated knees. DiO and anti-PEG mAb co-localised within the collagenous tissues in four different joint sections. Under higher magnification (40x), vesicles were seen in the intercellular spaces of the synovial joint tissue, but no fluorescence was seen inside cells. These data suggest that the phospholipid vesicles in TDT 064 localize at the surface of the joint cartilage; these vesicles may therefore be supplementing the phospholipid deficiency reported in OA and acting as a biolubricant within the synovial joint.

Keywords: joint pain, osteoarthritis, phospholipid vesicles, TDT 064

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