Search results for: flutter suppression

Authors: Marta E. Hernandez-Caballero, Veronica Borgonio-Cuadra, Antonio Miranda-Duarte, Xochitl Rojas-Toledo, Normand Garcia-Hernandez, Maura Cardenas-Garcia, Teresa Abad-Camacho

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Breast cancer (BC) is the most common tumor in women over the world. DNA methylation is an epigenetic modification critical in CpG sites, aberrant methylation of CpG islands in promoters is a hallmark of cancer. So, gene expression can be regulated by alterations in DNA methylation. In cell lines DACT2 gene reduces the growth and migration of tumor cells by its participation in the suppression of TGFb/SMAD2/3. PHF20L1 is involved in histone acetylation therefore, it regulates transcription. Our aim was to analyze the methylation status of the DACT2 and PHF20L1 promoter regions in tumoral and healthy mammary tissue from women with BC in different progression states. The study included 77 patients from Centro Medico Nacional La Raza in Mexico City. After identifying a CpG island in DACT2 and PHF20L1 promoters, DNA methylation status was analyzed through sodium bisulfite with subsequent amplification using methylation-specific PCR. Results revealed no changes in methylation status of PHF20L1 and cancer stages (II y III) or in comparison to healthy tissues, it was demethylated. DACT2 promoter methylation was no significant between tumoral stages (II, P = 0.37; III, P = 0.17) or with healthy tissue. Previous data reported DACT2 methylated in nasopharyngeal carcinoma but in this study promoter methylation was not observed. PHF20L1 protein contains N-terminal Tudor and C-terminal plant homeodomain domains, it has been suggested that can stabilize DNMT1 regulating DNA methylation, therefore, was associated with poor prognostic in BC. We found no evidence of methylation in patients and controls in PHF20L1 promoter, so its association with BC may have no direct relation with promoter methylation. More studies including other methylation sites in these genes in BC are necessary.

Keywords: bisulfite conversion, breast cancer, DACT2, DNA methylation, PHF20L1, tumoral status

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Authors: Malihe Moeinin, Robert Hill, Ferranti Wong

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Background: A white spot lesion (WSL) is defined as subsurface enamel porosity from carious demineralisation on the smooth surfaces of the tooth. It appears as a milky white opacity. Lesions shown an apparently intact surface layer, followed underneath by the more porous lesion body. The small pores within the body of the lesion act as diffusion pathway for both acids and minerals, so allowing the demineralisation of enamel to occur at the advancing front of the lesion. Objectives: The objective is to mapthe porosity and its size on WSL with Focused Ion Bean- Scanning Electron Microscopy (FIB-SEM) Method: The basic method used for FIB-SEM consisted of depositing a one micron thick layer of platinum over 25μmx 25μm of the interest region of enamel. Then, making a rough cut (25μmx 5μmx 20μm) with 3nA current and 30Kv was applied with the help of drift suppression (DS), using a standard “cross-sectional” cutting pattern, which ended at the front of the deposited platinum layer. Two adjacent areas (25μmx 5μmx 20μm) on the both sides of the platinum layer were milled under the same conditions. Subsequent, cleaning cross-sections were applied to polish the sub-surface edge of interest running perpendicular to the surface. The "slice and view" was carried out overnight for milling almost 700 slices with 2Kv and 4nA and taking backscattered (BS) images. Then, images were imported into imageJ and analysed. Results: The prism structure is clearly apparent on FIB-SEM slices of WSL with the dissolution of prism boundaries as well as internal porosity within the prism itself. Porosity scales roughly 100-400nm, which is comparable to the light wavelength (500nm). Conclusion: FIB-SEM is useful to characterize the porosity of WSL and it clearly shows the difference between WSL and normal enamel.

Keywords: white spot lesion, FIB-SEM, enamel porosity, porosity

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Authors: Fazil Hasan, M. Shafiq Ansari, Mohammad Muslim

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Zygogramma bicolorata Pallister (Coleoptera: Chrysomelidae) is an exotic insect and effective biocontrol agent of Parthenium hysterophorus L. (Asteraceae). Our study aimed to determine the induction and termination of diapause, in response to abiotic (temperature and moisture) and biotic factors (age and reproductive status) and the effect of diapause on adult longevity and female fecundity. The adults burrowed into the soil about 1–6 cm below the surface for diapause at any time from July to December with a peak of 70% in the 2nd week of December at Aligarh region, India. The termination of diapause took place in May and June with the commencement of monsoon rains. Non-diapausing adults were also capable of breeding during winter under laboratory conditions. There was a significantly increased in the percentage of diapaused adults in subsequent generation i.e. 4% in F1 generation and 90% in F7 generation. The percentage of diapause was also significantly increased with age of adults. It has a positive effect on female fecundity as compared to the fecundity in pre-diapaused duration. Experiments proved that soil moisture played an important role in providing the conditions for initiation and termination of diapause. The adults which undergone diapause in January and February were continuously exposed to 35º, 40º and 45º C for one week and a daily dose of 10 and 8 hours for 6 and 5 days, respectively resulting in termination of diapause. This method may be used to initiate mass multiplication for carrying out releases early in the season. Exposure of adults to extremely low temperatures i.e. 5º and 10º C induced 94.3% and 92.5% diapause, respectively with no adult mortality. Therefore, low temperatures can also be used as a medium for the storage of mass reared beetles for a long time without having negative effect on their longevity and fecundity. Thus, our findings are of great utility in the biological suppression of P. hysterophorus as it will enhance the effectiveness of this beetle through manipulation of diapause.

Keywords: Zygogramma bicolorata, environmental factors, age, sex, diapause, Parthenium hysterophorus, biocontrol

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Authors: Raj Raghupathy

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

Keywords: cytokines, dydrogesterone, progesterone, recurrent spontaneous miscarriage

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Authors: Hosein Maghsoudi

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Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

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Authors: Ahmad Almaududy Amri

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Southeast Asia is considered as an area which is important in terms of piratical studies. There are several reasons to this argument: firstly, it has the second highest figure of piracy attacks in the world from 2008 to 2012. Only the African Region transcends the number of piracies that were committed in Southeast Asia. Secondly, the geographical location of the region is very important to world trade. There are several sea lanes and straits which are normally used for international navigation mainly for trade purposes. In fact, there are six out of 25 busiest ports all over the world located in Southeast Asia. In ancient times, the main drivers of piracy were raiding for plunder and capture of slaves; however, in modern times, developments in politics, economics and even military technology have drastically altered the universal crime of piracy. There are a variety of motives behind modern day piracy including economic gains from receiving ransoms from government or ship companies, political and even terrorist reasons. However, it cannot be denied that piratical attacks persist and continue. States have taken measures both at the international and regional level in order to eradicate piratical attacks. The United Nations Convention on the Law of the Sea and the Convention on the Suppression of Unlawful Act against the Safety of Navigation served as the two main international legal frameworks in combating piracy. At the regional level, Regional Cooperation Agreement against Piracy and Armed Robbery and ASEAN measures are regard as prominent in addressing the piracy problem. This paper will elaborate the problems of piracy in Southeast Asia and examine the adequacy of legal frameworks at both the international and regional levels in order address the current legal measures in combating piracy. Furthermore, it will discuss current challenges in the implementation of anti-piracy measures at the international and regional levels as well as the way forward in addressing the issue.

Keywords: piracy, Southeast Asia, maritime security, legal frameworks

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Authors: Chitra Rajagopal, Indra Deo Kumar, Ruchi Joshi, Binoy Bhargavan

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Role of fighter planes in modern network centric military warfare scenarios has changed significantly in the recent past. New generation fighter planes have multirole capability of engaging both air and ground targets with high precision. Multirole aircraft undertakes missions such as Air to Air combat, Air defense, Air to Surface role (including Air interdiction, Close air support, Maritime attack, Suppression and Destruction of enemy air defense), Reconnaissance, Electronic warfare missions, etc. Designers have primarily focused on development of technologies to enhance the combat performance of the fighter planes and very little attention is given to human factor aspects of technologies. Unique physical and psychological challenges are imposed on the pilots to meet operational requirements during these missions. Newly evolved technologies have enhanced aircraft performance in terms of its speed, firepower, stealth, electronic warfare, situational awareness, and vulnerability reduction capabilities. This paper highlights the impact of emerging technologies on human factors for various military operations and missions. Technologies such as ‘cooperative knowledge-based systems’ to aid pilot’s decision making in military conflict scenarios as well as simulation technologies to enhance human performance is also studied as a part of research work. Current and emerging pilot protection technologies and systems which form part of the integrated life support systems in new generation fighter planes is discussed. System safety analysis application to quantify the human reliability in military operations is also studied.

Keywords: combat effectiveness, emerging technologies, human factors, systems safety analysis

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Authors: Abhaydeep Pandey, Shweta Shukla, Saptamita Goswami, Bhaswati Bandyopadhyay, Vishnampettai Ramachandran, Sudhanshu Vrati, Arup Banerjee

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Background: Long non-coding RNAs (lncRNAs) are the important regulators of gene expression and play important role in viral replication and disease progression. The role of lncRNA genes in the pathogenesis of Dengue virus-mediated pathogenesis is currently unknown. Methods: To gain additional insights, we utilized an unbiased RNA sequencing followed by in silico analysis approach to identify the differentially expressed lncRNA and genes that are associated with dengue disease progression. Further, we focused our study on lncRNAs NEAT1 (Nuclear Paraspeckle Assembly Transcript 1) as it was found to be differentially expressed in PBMC of dengue infected patients. Results: The expression of lncRNAs NEAT1, as compared to dengue infection (DI), was significantly down-regulated as the patients developed the complication. Moreover, pairwise analysis on follow up patients confirmed that suppression of NEAT1 expression was associated with rapid fall in platelet count in dengue infected patients. Severe dengue patients (DS) (n=18; platelet count < 20K) when recovered from infection showing high NEAT1 expression as it observed in healthy donors. By co-expression network analysis and subsequent validation, we revealed that coding gene; IFI27 expression was significantly up-regulated in severe dengue cases and negatively correlated with NEAT1 expression. To discriminate DI from dengue severe, receiver operating characteristic (ROC) curve was calculated. It revealed sensitivity and specificity of 100% (95%CI: 85.69 – 97.22) and area under the curve (AUC) = 0.97 for NEAT1. Conclusions: Altogether, our first observations demonstrate that monitoring NEAT1and IFI27 expression in dengue patients could be useful in understanding dengue virus-induced disease progression and may be involved in pathophysiological processes.

Keywords: dengue, lncRNA, NEAT1, transcriptome

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Authors: Rahbar Ali, Nitin Sharma, Dharmendra Singh, R. P. Singh, S. Muralithar, M. Afzal Ansari

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Heavy-ion-induced reactions on intermediate-mass targets are inherently complex, particularly at low energy levels. The study of these nuclear reactions, especially complete and incomplete fusion reactions, is of utmost importance to nuclear physicists. Researchers have demonstrated interest in exploring the mechanisms of nuclear reactions using heavy-ion beams at energies below 10 MeV/nucleon. In this study, the reaction mechanism of ¹⁶O⁷+ projectiles incident on a ¹⁵⁶Gd target at beam energies ranging from 4 to 7 MeV/nucleon was investigated. To gain a comprehensive understanding of the underlying processes, the excitation functions of evaporation residues produced via complete fusion (CF) and/or incomplete fusion (ICF) were measured. The evaporation residues were populated through xn/pxn and αxn/αpxn emission channels. The measured cross-sections of these residues were compared with the predictions of the statistical model codes PACE-4 and EMPIRE. The measured excitation functions of reaction residues populated through xn and pxn channels are in good agreement with the predictions of the statistical model code PACE4 and EMPIRE. This confirms that the production of these residues is solely due to the CF process. However, a significant enhancement was observed in the measured cross-sections of residues populated through α-emitting channels compared to theoretical predictions. This enhancement in the cross sections for α-emitting channels is ascribed to the ICF processes. The fusion cross-section data were also analyzed within the universal fusion function (UFF) and universal reaction function (URF) approach. The observed fusion suppression is primarily attributed to the breakup of the projectile. The ICF contribution in the reaction is dependent on projectile energy, mass asymmetry of the system and deformation of the target.

Keywords: nuclear reactions, above barrier reactions, evaporation residues, universal fusion function

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Authors: Dalia G. Aseel

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The potato (Solanum tubersum, L.) has become one of the major vegetable crops in Egypt and all over the world. Potato leafroll virus(PLRV) was observed on potato plants collected from different governorates in Egypt. Three cultivars, Spunta, Diamont, and Cara, infected with PLRV were collected; RNA was extracted and subjected to Real-Time PCR using the coat protein gene primers. The results showed that the expression of the coat protein was 39.6-fold, 12.45-fold, and 47.43-fold, respectively, for Spunta, Diamont, and Cara cultivars. Differential Display Polymerase Chain Reaction (DD-PCR) using pathogenesis-related protein 1 (PR-1), β-1,3-glucanases (PR-2), chitinase (PR-3), peroxidase (POD), and polyphenol oxidase (PPO) forward primers for pathogenesis-related proteins (PR). The obtained data revealed different banding patterns depending on the viral type and the region of infection. Regarding PLRV, 58 up-regulated and 19 down-regulated genes were detected. Sequence analysis of the up-and down-regulated genes revealed that infected plants were observed in comparison with the healthy control. Sequence analysis of the up-regulated gene was performed, and the encoding sequence analysis showed that the obtained genes include: induced stolen tip protein. On the other hand, two down-regulated genes were identified: disease resistance RPP-like protein and non-specific lipid-transfer protein. In this study, the expressions of PR-1, PR-2, PR-3, POD, and PPO genes in the infected leaves of three potato cultivars were estimated by quantitative real-time PCR. We can conclude that the PLRV-infection of potato plants inhibited the expression of the five PR genes. On the contrary, infected leaves by PLRV elevated the expression of some defense genes. This interaction may also induce and/or suppress the expression of some genes responsible for the plant's defense mechanisms.

Keywords: PLRV, pathogenesis-related proteins (PRs), DD-PCR, sequence, real-time PCR

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Authors: Seyede Sanaz Seyedebrahimi, Shima Rahimi, Shohreh Fakhari, Ali Jalili

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Background: CXCR4, as a chemokine receptor, plays well-known roles in various types of cancers. Several studies have been conducted to overcome CXCR4 axis acts in multiple myeloma (MM) pathogenesis and progression. Dexamethasone, a standard treatment for multiple myeloma, has been shown to increase CXCR4 levels in multiple myeloma cell lines. Herein, we focused on the effects of metformin and dexamethasone on CXCR4 at the cellular level and the migration rate of cell lines after exposure to a combination compared to single-agent models. Materials and Method: Multiple myeloma cell lines (U266 and RPMI8226) were cultured with different metformin and dexamethasone concentrations in single-agent and combination models. The simultaneous combination doses were calculated by CompuSyn software. Cell surface and mRNA expression of CXCR4 were determined using flow cytometry and the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay, respectively. The Transwell cell migration assay evaluated the migration ability. Results: In concurred with previous studies, our results showed a dexamethasone up-regulation effect on CXCR4 in a dose-dependent manner. Although, the metformin single-agent model could reduce CXCR4 expression of U266 and RPMI8226 in cell surface and mRNA expression level. Moreover, the administration of metformin and dexamethasone simultaneously exerted a higher suppression effect on CXCR4 expression than the metformin single-agent model. The migration rate through the combination model's matrigel membrane was remarkably lower than the metformin and dexamethasone single-agent model. Discussion: According to our findings, the combination of metformin and dexamethasone effectively inhibited dexamethasone-induced CXCR4 expression in multiple myeloma cell lines. As a result, metformin may be counted as an alternative medicine combined with other chemotherapies to combat multiple myeloma. However, more research is required.

Keywords: CXCR4, dexamethasone, metformin, migration, multiple myeloma

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Authors: Hany M. Fayed, Rehab F. Abdel-Rahman, Alyaa F. Hessin, Hanan A. Ogaly, Gihan F. Asaad, Abeer A. A. Salama, Sahar Abdelrahman, Mahmoud S. Arbid, Marwan Abd Elbaset Mohamed

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Liver fibrosis is a serious global health problem that occurs as a result of a variety of chronic liver disorders. Apigenin, a flavonoid found in many plants, has several pharmacological properties. The aim of this study was to evaluate the antifibrotic efficacy of apigenin (APG) against experimentally induced hepatic fibrosis in rats via using thioacetamide (TAA) and to explore the possible underlying mechanisms. TAA (100 mg/kg, i.p.) was given three times each week for two weeks to induce liver fibrosis. After TAA injections, APG was given orally (5 and 10 mg/kg) daily for two weeks. Biochemical, molecular, histological and immunohistochemical analyses were performed on blood and liver tissue samples. The functioning of the liver, oxidative stress, inflammation, and liver fibrosis indicators were all evaluated. The findings showed that TAA markedly increased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as the levels of malondialdehyde (MDA), focal adhesion kinase (FAK), hypoxia-inducible factor-1 (HIF-1), nuclear factor-κB (NF-κB), transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) with a reduction in albumin, total protein, A/G ratio, GSH content and interleukin-10 (IL-10). Moreover, TAA elevated the content of collagen I, α -smooth muscle actin (α-SMA), and hydroxyproline in the liver. The treatment with APG in a dose-dependent manner has obviously prevented these alterations and amended the harmful effects induced by TAA. The histopathological and immunohistochemical observations supported this biochemical evidence. The higher dose of APG produced the most significant antifibrotic effect. As a result of these data, APG appears to be a promising antifibrotic drug and could be used as a new herbal medication or dietary supplement in the future for the treatment of liver fibrosis. This effect might be related to the inhibition of the HIF-1/FAK signaling pathway.

Keywords: apigenin, FAK, HIF-1, liver fibrosis, rat, thioacetamide

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Authors: Balakrishna Shetty

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Introduction: Stem Cell Imaging is a challenging field since the advent of Stem Cell treatment in humans. Series of research on tagging and tracking the stem cells has not been very effective. The present study is an effort by the authors to track the stem cells injected into calf muscles by Magnetic Resonance Diffusion Weighted Imaging. Materials and methods: Stem Cell injection deep into the calf muscles of patients with peripheral vascular disease is one of the recent treatment modalities followed in our institution. 5 patients who underwent deep intramuscular injection of stem cells as treatment were included for this study. Pre and two hours Post injection MRI of bilateral calf regions was done using 1.5 T Philips Achieva, 16 channel system using 16 channel torso coils. Axial STIR, Axial Diffusion weighted images with b=0 and b=1000 values with back ground suppression (DWIBS sequence of Philips MR Imaging Systems) were obtained at 5 mm interval covering the entire calf. The invert images were obtained for better visualization. 120ml of autologous bone marrow derived stem cells were processed and enriched under c-GMP conditions and reduced to 40ml solution containing mixture of above stem cells. Approximately 40 to 50 injections, each containing 0.75ml of processed stem cells, was injected with marked grids over the calf region. Around 40 injections, each of 1ml normal saline, is injected into contralateral leg as control. Results: Significant Diffusion hyper intensity is noted at the site of injected stem cells. No hyper intensity noted before the injection and also in the control side where saline was injected conclusion: This is one of the earliest studies in literature showing diffusion hyper intensity in intramuscularly injected stem cells. The advantages and deficiencies in this study will be discussed during the presentation.

Keywords: stem cells, imaging, DWI, peripheral vascular disease

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Authors: Xinxiu Li, Chuqian Zheng, Yanyan Qian, Hong Fan

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Objectives: In hepatocellular carcinoma (HCC), oncogenes are continuously and robustly transcribed due to aberrant expression of essential components of the trans-acting super-enhancers (SE) complex. Preclinical and clinical trials are now being conducted on small-molecule inhibitors that target core-transcriptional components, including as transcriptional bromodomain protein 4 (BRD4) and cyclin-dependent kinase 7 (CDK7), in a number of malignant tumors. This study aims to explore whether co-overexpression of BRD4 and CDK7 is a potential marker of worse prognosis and a combined therapeutic target in HCC. Methods: The expression pattern of BRD4 and CDK7 and their correlation with prognosis in HCC were analyzed by RNA sequencing data and survival data of HCC patients from TCGA and GEO datasets. The protein levels of BRD4 and CDK7 were determined by immunohistochemistry (IHC), and survival data of patients were analyzed using the Kaplan-Meier method. The mRNA expression levels of genes in HCC cell lines were evaluated by quantitative PCR (q-PCR). CCK-8 and colony formation assays were conducted to assess cell proliferation of HCC upon treatment with BRD4 inhibitor JQ1 or/and CDK7 inhibitor THZ1. Results: It was shown that BRD4 and CDK7 were often overexpressed in HCCs and were associated with poor prognosis of HCC by analyzing the TCGA and GEO datasets. BRD4 or CDK7 overexpression was related to a lower survival rate. It's interesting to note that co-overexpression of CDK7 and BRD4 was a worse prognostic factor in HCC. Treatment with JQ1 or THZ1 alone had an inhibitory effect on cell proliferation; however, when JQ1 and THZ1 were combined, there was a more notable suppression of cell growth. At the same time, the combined use of JQ1 and THZ1 synergistically suppresses the expression of HCC driver genes. Conclusion: Our research revealed that BRD4 and CDK7 coupled can be a useful biomarker in HCC prognosis and the combination of JQ1 and THZ1 can be a promising therapeutic therapy against HCC.

Keywords: BRD4, CDK7, cell proliferation, combined inhibition

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Authors: Rakan Hassan M. Alzahrani, Ziyad Alzahrani, Bader Bashrahil, Abdulrahman Elyasi, Abdullah a Ghaddaf, Rayan Alzahrani, Mohammed Alkathlan, Nawaf Alghamdi, Dakheelallah Almutairi

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Background: Corticosteroid irrigations, which regularly involve the off-label use of budesonide mixed with normal saline in high volume Sino-nasal irrigations, have been more commonly used in the management of post-operative chronic rhinosinusitis (CRS). Objective: This article attempted to measure the efficacy of post-operative budesonide nasal irrigation compared to normal saline-alone nasal irrigation in the management of chronic rhinosinusitis (CRS) through a systematic review and meta-analysis of randomized controlled trials (RCTs). Methods: The databases PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched by two independent authors. Only RCTs comparing budesonide irrigation to normal saline alone irrigation for CRS with or without polyposis after functional endoscopic sinus surgery (FESS) were eligible. A random effect analysis model of the reported CRS-related quality of life (QOL) measures and the objective endoscopic assessment scales of the disease was done. Results: Only 6 RCTs met the eligibility criteria, with a total number of participants of 356. Compared to normal saline irrigation, budesonide nasal irrigation showed statically significant improvements in both the CRS-related quality of life (QOL) and the endoscopic findings (MD= -4.22 confidence interval [CI]: -5.63, -2.82 [P < 0.00001]), (SMD= -0.50 confidence interval [CI]: -0.93, -0.06 [P < 0.03]) respectively. Conclusion: Both intervention arms showed improvements in CRS-related QOL and endoscopic findings in post-FESS chronic rhinosinusitis with or without polyposis. However, budesonide irrigation seems to have a slight edge over conventional normal saline irrigation with no reported serious side effects, including hypothalamic-pituitary-adrenal (HPA) axis suppression.

Keywords: Budesonide, chronic rhinosinusitis, corticosteroids, nasal irrigation, normal saline

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Authors: Fatemeh Benakashani, Hossein Tavakoli, Elias Soltani

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To ensure the sustainability of crop cultivation and rural economies, it is imperative that we focus on cultivating resilient crops capable of withstanding salt stress. However, the effective management of weeds in salt-affected soils remains a significant challenge. This study investigates the impact of living mulches, specifically Berseem clover (Trifolium alexandrinum) and Barley (Hordeum vulgare), on weed control, as well as the quality and yield of Black cumin (Nigella sativa) in salt-affected soil. In our research, we employed a two-fold mowing strategy for the living mulches: once following crop establishment and once before the flowering stage. Notably, the weed-free plots demonstrated Black cumin's seed yield, and oil content (31.1% to 34.3%), consistent with previous studies, highlighting its potential for the reclamation and utilization of salt-affected lands. However, Black cumin exhibited limited competitiveness against prevalent weeds in the field, such as Amaranthus retroflexus, Chenopodium album, and Portulaca oleracea, which significantly diminished both the 1000 grain mass in plots where weeds were present. Interestingly, the introduction of living mulches led to improvements in seed yield and seed oil content when compared to both weed-free and weed-infested plots. Notably, Berseem clover exhibited greater biomass than Barley, indicating its heightened competitiveness against weeds. Nevertheless, it's worth noting that in the long term, Berseem clover also competed with the main crop, thereby limiting overall productivity. Consequently, we recommend relocating the Berseem clover living mulch following the establishment of Black cumin as a strategy for weed management in Black cumin fields situated in salt-affected soils.

Keywords: weed management, competition, clover, barley, medicinal plant

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Authors: Dawit Chankaye

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Background: Azadirachta indica is the most versatile medicinal plant known as “the village pharmacy”. The plant is known for its broad spectrum of biological activity in India and various countries throughout history by many different human cultures. The present study was undertaken to determine the antimalarial and antidiabetic properties of the leaf extracts of A. indica grown in Ethiopia when treated in vivo. This work has also been concerned with determining essential oil composition and the antimicrobial activity of the plant in vitro. Methods: Leaf extracts were prepared using three different selected solvents. Standard and clinical isolates were treated with extracts of the leaves of A. indica using the agar well diffusion method. The antimalarial and antidiabetic tests were conducted in vivo in mice. Phytochemical screening was done using various chemical tests, and the volatile oil constituents were determined using gas chromatography-mass spectrometry (GC/MS). Results: In vivo antimalarial activity studies showed 85.23%, 69.01%, and 81.54% suppression of parasitemia for 70% ethanol, acetone, and water extracts, respectively. The extracts collected from the leaves also showed reduced blood sugar levels in alloxan-induced diabetic mice. In addition, the solvent extracts were shown to have an inhibitory effect on the growth of microorganisms under the study. The minimum inhibitory concentration (MIC) ranged from 850 to 1050 µg/ml. Notably, the phytochemical investigation of the ethanol extracts showed the presence of secondary metabolites. Seventeen compounds (mainly sesquiterpenes) that represent 75.45% of the essential oil were characterized by GC/MS analysis. Conclusion: Extracts examined in this study indicated that the leaf of A. indica grown in Ethiopia retained the biological activities demonstrating the extent equivalent to when it was grown in its natural habitat. In addition, phytochemical investigation and GC/MS analysis of volatile oil constituents showed comparable results to those presented in India and elsewhere.

Keywords: Azadirachta indica, vivo, antimalarial activity, antidiabetic activity, alloxan, mice, phytochemical

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Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee

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There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.

Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor

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Authors: Bandana Saikia, Ashok Bhattacharyya

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Endophytic microbes and their metabolites positively impact overall plant health, which may have a potential implication in agriculture. In the present study, 177 bacterial endophytes and 57 fungal endophytes were isolated, with the highest recovery rate from tomato roots. A maximum of 112 endophytes were isolated during monsoon, followed by 64 isolates and 58 isolates isolated during pre-monsoon and post-monsoon periods, respectively, indicating the rich diversity in bacterial and fungal endophytes of tomato crops from different locations of Assam, India. Further, the endophytes were evaluated for their antagonistic potential against Fusarium oxysporum f. sp. lycopersici. Fungal endophytic isolate AAUTLF (Endophytic Fungi of Tomato Leaf from Assam Agricultural University, Assam, India area) and bacterial endophyte D1B (Endophytic bacteria of tomato from Dhemiji, India district) showed the highest antifungal activity against the pathogen both in vitro and in vivo. Based on 5.8 rDNA sequence analysis of fungal and 16S rDNA sequence of bacteria endophytes, the most effective fungal and bacterial isolates against FOL were identified as Trichoderma asperellum AAUTLF and Stenotrophomonas maltophilia D1B, respectively. The isolates showed an antagonistic effect against Fusarium oxysporum f.sp. lycopersici in-vitro and reduced the disease index of Fusarium wilt in tomatoes by 64.4% under pot conditions. Trichoderma asperellum AAUTLF produced an antifungal compound viz., 6-pentyl-2H-pyran-2-one, which also possesses growth-promoting characteristics. The bacteria Stenotrophomonas maltophilia D1B produced antifungal compounds, including benzothiazole, oleic acid, phenylacetic acid, and 3-(Hydroxy-phenyl-methyl)-2,3-dimethyl-octan-4-one. This would be of high importance for the source of antagonistic strains and biocontrol of tomato Fusarium wilt, as well as other plant fungal diseases.

Keywords: root endophytes, Stemotrophomonas, Trichoderma, benzothiazole, 6-pentyl-2H-pyran-2-one

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Authors: Nhan N. T. Ton, Anh T. N. Dao, Kouichirou Katou, Toshiaki Taniike

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Facile electron-hole recombination and the broad band gap are two major drawbacks of titanium dioxide (TiO₂) when applied in visible-light photocatalysis. Hybridization of TiO₂ with graphene is a promising strategy to lessen these pitfalls. Recently, there have been many reports on the synthesis of TiO₂/graphene nanocomposites, in most of which graphene oxide (GO) was used as a starting material. However, the reduction of GO introduced a large number of defects on the graphene framework. In addition, the sensitivity of titanium alkoxide to water (GO usually contains) significantly obstructs the uniform and controlled growth of TiO₂ on graphene. Here, we demonstrate a novel technique to synthesize TiO₂/graphene nanocomposites without the use of GO. Graphene dispersion was obtained through the chemical exfoliation of graphite in titanium tetra-n-butoxide with the aid of ultrasonication. The dispersion was directly used for the sol-gel reaction in the presence of different catalysts. A TiO₂/reduced graphene oxide (TiO₂/rGO) nanocomposite, which was prepared by a solvothermal method from GO, and the commercial TiO₂-P25 were used as references. It was found that titanium alkoxide afforded the graphene dispersion of a high quality in terms of a trace amount of defects and a few layers of dispersed graphene. Moreover, the sol-gel reaction from this dispersion led to TiO₂/graphene nanocomposites featured with promising characteristics for visible-light photocatalysts including: (I) the formation of a TiO₂ nano layer (thickness ranging from 1 nm to 5 nm) that uniformly and thinly covered graphene sheets, (II) a trace amount of defects on the graphene framework (low ID/IG ratio: 0.21), (III) a significant extension of the absorption edge into the visible light region (a remarkable extension of the absorption edge to 578 nm beside the usual edge at 360 nm), and (IV) a dramatic suppression of electron-hole recombination (the lowest photoluminescence intensity compared to reference samples). These advantages were successfully demonstrated in the photocatalytic decomposition of methylene blue under visible light irradiation. The TiO₂/graphene nanocomposites exhibited 15 and 5 times higher activity than TiO₂-P25 and the TiO₂/rGO nanocomposite, respectively.

Keywords: chemical exfoliation, photocatalyst, TiO₂/graphene, sol-gel reaction

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Authors: Junaid Jibran Jawed, Prasanta Saini, Subrata Majumdar

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Background: Leishmania donovani infection causes severe host immune-suppression through the modulation of pathogen recognition receptors. Apart from TLRs (Toll Like Receptor), recent studies focus on the important contribution of NLR (NOD-Like Receptor) family member NOD1 and NOD2 as these receptors are capable of triggering host innate immunity. The aim of this study was to decipher the role of NOD1/NOD2 receptors during experimental visceral leishmaniasis (VL) and the important link between host failure and parasite evasion strategy. Method: The status of NOD1 and NOD2 receptors were analysed in uninfected and infected cells through western blotting and RT-PCR. The active contributions of these receptors in reducing parasite burden were confirmed by siRNA mediated silencing, and over-expression studies and the parasite numbers were calculated through microscopic examination of the Giemsa-stained slides. In-vivo studies were done by using non-toxic dose of Mw (Mycobacterium indicus pranii), Ara-LAM(Arabinoasylated lipoarabinomannan) along with MDP (Muramyl dipeptide) administration. Result: Leishmania donovani infection of the macrophages reduced the expression of NOD2 receptors whereas NOD1 remain unaffected. MDP, a NOD2-ligand, treatment during over-expression of NOD2, reduced the parasite burden effectively which was associated with increased pro-inflammatory cytokine generation and NO production. In experimental mouse model, Ara-LAM treatment increased the expression of NOD2 and in combination with MDP it showed active therapeutic potential against VL and found to be more effective than Mw which was already reported to be involved in NOD2 modulation. Conclusion: This work explores the essential contribution of NOD2 during experimental VL and mechanistic understanding of Ara-LAM + MDP combination therapy to work against this disease and highlighted NOD2 as an essential therapeutic target.

Keywords: Ara-LAM (Arabinoacylated Lipoarabinomannan), NOD2 (nucleotide binding oligomerization receptor 2), MDP (muramyl di peptide), visceral Leishmaniasis

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Authors: S. Ben-Shabat, T. Turgeman, O. Leubinski, N. Roth-Bejerano, V. Kagan-Zur, Y. Sitrit

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The ectomycorrhizal (ECM) desert truffle Terfezia boudieri produces edible fruit bodies and forms symbiosis with its host plant Helianthemum sessiliflorum (Cistaceae) in the Negev desert of Israel. The symbiosis is vital for both partners' survival under desert conditions. Under desert habitat conditions, ECMs must form symbiosis before entering the dry season. To secure a successful encounter, in the course of evolution, both partners have responded by evolving special signals exchange that facilitates recognition. Members of the Cistaceae family serve as host plants for many important truffles. Conceivably, during evolution a common molecule present in Cistaceae plants was recruited to facilitate successful encounter with ectomycorrhizas. Arbuscular vesicular fungi (AM) are promiscuous in host preferences, in contrast, ECM fungi show specificity to host plants. Accordingly, we hypothesize that H. sessiliflorum secretes a chemotrophic-signaling, which is common to plants hosting ECM fungi belonging to the Pezizales. However, thus far no signaling molecules have been identified in ECM fungi. We developed a bioassay for chemotrophic activity. Fractionation of root exudates revealed a substance with chemotrophic activity and molecular mass of 534. Following the above concept, screening the transcriptome of Terfezia, grown under chemoattraction, discovered genes showing high homology to G proteins-coupled receptors of plant pathogens involved in positive chemotaxis and chemotaxis suppression. This study aimed to identify the active molecule using analytical methods (LC-MS, NMR etc.). This should contribute to our understanding of how ECM fungi communicate with their hosts in the rhizosphere. In line with the ability of Terfezia to form also endomycorrhizal symbiosis like AM fungi, analysis of the mechanisms may likewise be applicable to AM fungi. Developing methods to manipulate fungal growth by the chemoattractant can open new ways to improve inoculation of plants.

Keywords: chemotrophic signal, Helianthemum sessiliflorum, Terfezia boudieri, ECM

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Authors: Ji-Young Choi, Jungjin Kim, Sang-Sun Yun, Sangmee Ahn Jo

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Intracellular adhesion molecule1 (ICAM1) is a mediator of inflammation and involved in adhesion and transmigration of leukocytes to endothelial cells, resulting in enhancement of brain inflammation. We hypothesized that increase of ICAM1 expression in endothelial cells is an early step in the pathogenesis of brain diseases such as Alzheimer’s disease. Here, we report that ICAM1 expression is regulated by pro-inflammatory cytokine TNFa in human microvascular endothelial cell (HBMVEC). TNFa significantly increased ICAM1 mRNA and protein levels at the concentrations showing no cell toxicity. This increase was also shown in micro vessels of mouse brain 24 hours after treatment with TNFa (8 mg/kg, i.v). We then investigated the epigenetic mechanism involved in the induction of ICAM1 expression. Chromatin immunoprecipitation assay revealed that TNFa reduced methylation of histone3K9 (H3K9-2me) and histone3K27 (H3K27-3me), well-known modification as gene suppression, with in the ICAM1 promoter region. However, acetylation of H3K9 and H3K14, well-known modification as gene activation, was not changed by TNFa. Treatment of BIX01294, a specific inhibitor of histone methyltransferase G9a responsible for H3K9-2me, dramatically increased in ICAM1 mRNA and protein levels and overexpression of G9a gene suppressed TNFa-induced ICAM1 expression. In contrast, GSK126, an inhibitor of histone methyltransferase EZH2 responsible for H3K27-3me and valproic acid, an inhibitor of histone deacetylase (HDAC) did not affect ICAM1 expression. These results suggested that histone3 methylation is involved in ICAM1 repression. Moreover, TNFa or BIX01294-induced ICAM induction resulted in both enhancements in adhesion and transmigration of leukocyte on endothelial cell. This study demonstrates that TNFa upregulates ICAM1 expression through H3K9-2me and H3K27-3me within the ICAM1 promoter region, in which G9a is likely to play a pivotal role in ICAM1 transcription. Our study provides a novel mechanism for ICAM1 transcription regulation in HBMVEC.

Keywords: ICAM1, TNFa, HBMVEC, H3K9-2me

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Authors: Angeli Marie P. Lagman, Nephtali M. Gorgonio

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Catamenial pneumothorax is defined as a recurrent accumulation of air in the pleural cavity, which occurs in the period of 72 hours before or after menses. In a menstruating woman presenting with the difficulty of breathing and chest pain with concomitant radiographic evidence of pneumothorax, a diagnosis of catamenial pneumothorax should be entertained. Two cases of catamenial pneumothorax were reported in our local literature. This report added two more cases. The first case is 45 years old G1P1, while the second case is 46 years old G2P2. These two patients had a history of pelvic endometriosis in the past. All other signs and symptoms were similar to the previously reported cases. All patients presented with difficulty of breathing associated with chest pain. Imaging studies showed right-sided pneumothorax in all patients. Intraoperatively, subpleural bleb, diaphragmatic fenestrations, and endometriotic implants were found. Three patients underwent video-assisted thoracosurgery (VATS), while one patient underwent open thoracotomy with pleurodesis. Histopathology revealed endometriosis in only two patients. All patients received postoperative hormonal therapy, and there were no recurrences noted in all patients. Endometriosis-related catamenial pneumothorax is a rare condition that needs early recognition of the symptoms. Several theories may be involved to explain the pathogenesis of catamenial pneumothorax. Two cases show a strong significant association between a history of pelvic endometriosis and the development of catamenial pneumothorax, while one case can be explained by the hormonal theory. The difficulty of breathing and chest pain in relation to menses may prompt early diagnosis. One case has shown that pneumothorax may occur even after menstruation. A biopsy of the endometrial implants may not always show endometrial glands and stroma, nor will immunostaining, which will not always show estrogen and progesterone receptors. Video-assisted thoracoscopic surgery is the gold standard in the diagnosis and treatment of catamenial pneumothorax. Postoperative hormonal suppression will further reduce the disease recurrence and facilitate the effectiveness of the surgical treatment.

Keywords: catamenial pneumothorax, endometriosis, menstruation, video assisted thoracosurgery

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Authors: Danielle A. Walker, Kyle L. Johnson, Tara B. Thomas, Sandor Dorgo, Jacen S. Moore

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Approximately 37 million people worldwide are infected with the Human Immunodeficiency Virus (HIV), with the majority located in sub-Saharan Africa. The relationship existing between HIV incidence and socioeconomic inequity confirms the critical need for programs promoting HIV education, prevention and treatment access. This literature review analyzed 36 sources with a specific focus on the Democratic Republic of Congo, whose critically low socioeconomic status and education rate have resulted in a drastically high HIV rates. Relationships between HIV testing and treatment and barriers to care were explored. Cultural and religious considerations were found to be vital when creating and implementing HIV education and testing programs. Partnerships encouraging active support from community-based spiritual leaders to implement HIV educational programs were also key mechanisms to reach communities and individuals. Gender roles were highlighted as a key component for implementation of effective community trust-building and successful HIV education programs. The efficacy of added support by hospitals and clinics in rural areas to facilitate access to HIV testing and care for people living with HIV/AIDS (PLWHA) was discussed. This review highlighted the need for healthcare providers to provide a network of continued education for PLWHA in clinical settings during disclosure and throughout the course of treatment to increase retention in care and promote medication adherence for viral load suppression. Implementation of culturally sensitive models that rely on community familiarity with HIV educators such as ‘train-the-trainer’ were also proposed as efficacious tools for educating rural communities about HIV. Further research is needed to promote community partnerships for HIV education, understand the cultural context of gender roles as barriers to care, and empower local health care providers to be successful within the HIV Continuum of Care.

Keywords: cultural sensitivity, Democratic Republic of the Congo, education, HIV

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Authors: Iyabode A. Kehinde, Joshua O. Oyekanmi, Jumoke T. Abimbola, Olajumoke E. Ayanda

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African yam bean (AYB), (Sphenostylis stenocarpa) is a leguminous crop that provides nutritionally rich seeds, tubers and leaves for human consumption. AYB potentials as an important food security crop is yet to be realized and thus classified as underutilized crop. Underutilization of the crop has been partly associated with scarce information on the incidence and characterization of fungal endophytes infecting vascular parts of AYB. Accurate and robust detection of these endophytic fungi is essential for diagnosis, modeling, surveillance and protection of germplasm (seed) health. This work aimed at isolating and identifying fungal endophytes associated with leaves, stems and roots of AYB in Ogun State, Nigeria. This study investigated both cultural and molecular properties of endophytic fungi in AYB for its characterization and diversity. Fungal endophytes were isolated and culturally identified. DNA extraction, PCR amplification using ITS primers and analyses of nucleotide sequences of ribosomal DNA fragments were conducted on selected isolates. BLAST analysis was conducted on consensus nucleotide sequences of 28 out of 30 isolates and results showed similar homology with genera of Rhizopus, Cunninghamella, Fusarium, Aspergillus, Penicillium, Alternaria, Diaporthe, Nigrospora, Purpureocillium, Corynespora, Magnaporthe, Macrophomina, Curvularia, Acrocalymma, Talaromyces and Simplicillium. Slight similarity was found with endophytes associated with soybean. Phylogenetic analysis by maximum likelihood method showed high diversity among the general. These organisms have high economic importance in crop improvement. For an instance, Purpureocillium lilacinum showed high potential in control of root rot caused by nematodes in tomatoes. Though some can be pathogens, but many of the fungal endophytes have beneficial attributes to plant in host health, uptake of nutrients, disease suppression, and host immunity.

Keywords: molecular characterization, African Yam Bean, fungal endophyte, plant parts

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Authors: Fadia Gafri, Kathryn Mckintosh, Louise Young, Alan Harvey, Simon Mackay, Andrew Paul, Robin Plevin

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Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor found originally to play a key role in regulating inflammation. However considerable evidence links this pathway to the suppression of apoptosis, cellular transformation, proliferation and invasion (Aggarwal et al., 2006). Moreover, recent studies have also linked inflammation to cancer progression making NF-κB overall a promising therapeutic target for drug discovery (Dobrovolskaia & Kozlov, 2005). In this study we examined the effect of the natural product canthin-6-one (SU182) as part of a CRUK small molecule drug discovery programme for effects upon the NF-κB pathway. Initial studies demonstrated that SU182 was found to have good potency against the inhibitory kappa B kinases (IKKs) at 30M in vitro. However, at concentrations up to 30M, SU182 had no effect upon TNFα stimulated loss in cellular IκBα or p65 phosphorylation in the keratinocyte cell line NCTC2544. Nevertheless, 30M SU182 reduced TNF-α / PMA-induced NF-κB-linked luciferase reporter activity to (22.9 ± 5%) and (34.6± 3 %, P<0.001) respectively, suggesting an action downstream of IKK signalling. Indeed, SU182 neither decreased NF-κB-DNA binding as assayed by EMSA nor prevented the translocation of p65 (NF-κB) to the nucleus assessed by immunofluorescence and subcellular fractionation. In addition to the inhibition of transcriptional activity of TNFα-induced NF-κB reporter activity SU182 significantly reduced PMA-induced AP-1-linked luciferase reporter activity to about (48± 9% at 30M, P<0.001) . This mode of inhibition was not sufficient to prevent the activation of NF-κB dependent induction of other proteins such as COX-2 and iNOS, or activated MAP kinases (p38, JNK and ERK1/2) in LPS stimulated RAW 264.7 macrophages. Taken together these data indicate the potential for SU182 to interfere with the transcription factors NF-κB and AP-1 at transcriptional level. However, no potential anti-inflammatory effect was indicated, further investigation for other NF-κB dependent proteins linked to survival are also required to identify the exact mechanism of action.

Keywords: Canthin-6-one, NF-κB, AP-1, phosphorylation, Nuclear translocation, DNA-binding activity, inflammatory proteins.

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Authors: Fang Liu, JunShuai Xue, JiaJia Yao, GuanLin Wu, ZuMaoLi, XueYan Yang, HePeng Zhang, ZhiPeng Sun

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Terahertz spectra is in great demand since last two decades for many photonic and electronic applications. III-Nitride resonant tunneling diode is one of the promising candidates for portable and compact THz sources. Room temperature microwave oscillator based on GaN/AlN resonant tunneling diode was reported in this work. The devices, grown by plasma-assisted molecular-beam epitaxy on free-standing c-plane GaN substrates, exhibit highly repeatable and robust negative differential resistance (NDR) characteristics at room temperature. To improve the interface quality at the active region in RTD, indium surfactant assisted growth is adopted to enhance the surface mobility of metal atoms on growing film front. Thanks to the lowered valley current associated with the suppression of threading dislocation scattering on low dislocation GaN substrate, a positive peak current density of record-high 2.1 MA/cm2 in conjunction with a peak-to-valley current ratio (PVCR) of 1.2 are obtained, which is the best results reported in nitride-based RTDs up to now considering the peak current density and PVCR values simultaneously. When biased within the NDR region, microwave oscillations are measured with a fundamental frequency of 0.31 GHz, yielding an output power of 5.37 µW. Impedance mismatch results in the limited output power and oscillation frequency described above. The actual measured intrinsic capacitance is only 30fF. Using a small-signal equivalent circuit model, the maximum intrinsic frequency of oscillation for these diodes is estimated to be ~260GHz. This work demonstrates a microwave oscillator based on resonant tunneling effect, which can meet the demands of terahertz spectral devices, more importantly providing guidance for the fabrication of the complex nitride terahertz and quantum effect devices.

Keywords: GaN resonant tunneling diode, peak current density, microwave oscillation, intrinsic capacitance

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Authors: Mahdokht Sadeghvishkaei, Azizah Abdul-Hamid, Amin Ismail, Nazamid Saari

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Hypertension is a common and serious chronic health problem and known as the most important risk factor for development of many diseases such as stroke. Since angiotensin I-converting enzyme (ACE) is the key enzyme involved in blood pressure, one of the well accepted mechanisms to control hypertension is through ACE inhibition. The ACE inhibitory effect of Actinopyga lecanora (stone fish) proteolysate in vitro had been reported. Hence, this study aimed to evaluate the ACE inhibitory potential of Actinopyga lecanora proteolysate in vivo in normotensive rats. Therefore the ACE inhibitory capability of the proteolysate to prevent increasing systolic blood pressure, after inducing hypertension by angiotensin I was examined. The pre-fed rats with the proteolysates at various doses (200, 400, 800 mg/kg body weight) revealed the significant (p ≤ 0.05) suppression effect compared with control groups. Furthermore, different doses of the proteolysate (200, 400, 800 mg/kg body weight) were examined to find its optimum effective dose. Results depicted that 800 mg proteolysate/kg body weight significantly reduced systolic blood pressure without negative effect on normal blood pressure (p ≤ 0.05). Furthermore, Sub-acute toxicity study based on OECD guideline demonstrated the safety of the proteolysate in vivo. The present study indicated that the proteolysate at a dose of 1000 mg/kg daily for 14 days did not cause toxicity signs such as death, changes in activity, or piloerection. Since there are no significant differences between treated groups and control groups, hematological and biochemical analysis confirmed safety of the proteolysate (p > 0.05). In addition, there were no significant differences between organs weights of the treated groups and the control groups. Morphologically, neither histopathological changes, nor gross abnormalities were observed. However, the proteolysate caused significant decrease in body weight in relation to the control groups (p ≤ 0.05) probably due to appetite stimulation by the proteolysate, leading to decreased food consumption in sub-acute group. It is concluded that the proteolysate generated from Actinopyga lecanora possess a significant anti-hypertensive effect and would be potentially used as natural alternative of ACE inhibitors.

Keywords: ACE inhibition, Actinopyga lecanora, anti-hypertensive activity, bioactive peptides, normotensive rats

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Authors: Esabelle Lo Yan Yam, Pheak Chhoun, Sovannary Tuot, Emily Lancsar, Siyan Yi

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Persons living with HIV (PLHIV) need lifelong antiretroviral treatment (ART) to keep their viral load suppressed to an undetectable level, maintain a healthy immune system, and reduce the risk of transmitting HIV to others. However, many factors affect PLHIV's adherence to ART, including access to antiretrovirals (ARV), stigma, lack of social support, and the burden of seeking lifelong care. Community-based care has been shown to be instrumental in the experience of PLHIV in many countries, including Cambodia. In this study based in Cambodia, a community-based ART delivery (CAD) intervention involving community action workers (CAWs) who are PLHIVs was introduced. These workers collect pre-packaged ARVs from the ART clinics and dispense them to PLHIVs in the communities. The quasi-experimental study involved approximately 2000 stable PLHIV in the intervention arm and another 2000 PLHIV in the control arm (receiving usual care). A cost-effectiveness analysis is currently conducted to complement the clinical effectiveness of the CAD intervention on the care continuum and treatment outcomes for stable PLHIV, as well as the operational effectiveness in increasing the efficiency of the ART clinics and the health system. The analysis will consider health system and societal perspectives based on primary outcomes, including retention in care, viral load suppression, and adherence to ART. Additionally, a consultation with the National Centre for HIV/AIDS, Dermatology, and STD under the Cambodia Ministry of Health will be done to discuss the conduct of a budget impact analysis that can quantify the financial impact on the government's budget when adopting the CAD intervention at the provincial and national levels. The budget impact analysis will take into consideration various scaling-up scenarios for the interventions in the country. The research will assess the cost-effectiveness of the CAD intervention to support national stakeholders in Cambodia to make an informed decision on the adoption and scaling up of the intervention in Cambodia. The results are currently being analyzed and will be available at the time of the conference.

Keywords: Cambodia, community intervention, economic evaluation, global health, HIV/AIDs, implementation research

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