Search results for: interferon signaling

Authors: Wael M. El-Deeb

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The aim of this study was to assess the pathophysiological importance of lipid profile, acute phase proteins, proinflammatory cytokines and oxidative stress markers in sheep with pneumonic pasteurellosis. Blood samples were collected from 36 Pasteurellamultocida-infected sheep, together with 20 healthy controls. Samples for bacteriological examination (nasal swabs, bronchoalveolar lavage) were collected from all animals and subjected to bacteriological examinations. Moreover, heart blood and lung samples were collected from the dead pneumonic sheep and subjected also to bacteriological examinations. A lipid profile was determined, along with a blood picture and other biochemical parameters. The acute phase proteins (fibrinogen, haptoglobin, serum amyloid A), the proinflammatory cytokine tumour necrosis factor-alpha, interleukins (IL-1α, IL-1β, IL-6), interferon-gamma and the oxidative stress markers malondialdehyde, super oxide dismutase, glutathione and catalase were also measured. The examined biochemical parameters were increased in the pneumonic sheep, except for cholesterol and high-density lipoprotein cholesterol (HDL-c), which were significantly lower than control group. Acute phase proteins and cytokines were significantly higher in the pneumonic sheep when compared to the healthy sheep. There was a significant increase in the levels of malondialdehyde; however, a significant decrease in the levels of super oxide dismutase, glutathione and catalase was observed. The present study shed the light on the possible pathphysiological role of lipid profile, acute phase proteins (APPs), proinflammatory cytokines and oxidative stress markers in pneumonic pasteurelosis in sheep.

Keywords: acute phase proteins, sheep, pasteurella, interleukins, stress

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Authors: Mohammed Benlemlih

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Using a sample of 22,839 US firm-year observations over the 1991-2012 period, we find that high CSR firms pay more dividends than low CSR firms. The analysis of individual components of CSR provides strong support for this main finding: five of the six individual dimensions are also associated with high dividend payout. When analyzing the stability of dividend payout, our results show that socially irresponsible firms adjust dividends more rapidly than socially responsible firms do: dividend payout is more stable in high CSR firms. Additional results suggest that firms involved in two controversial activities -the military and alcohol - are associated with low dividend payouts. These findings are robust to alternative assumptions and model specifications, alternative measures of dividend, additional control, and several approaches to address endogeneity. Overall, our results are consistent with the expectation that high CSR firms may use dividend policy to manage the agency problems related to overinvestment in CSR.

Keywords: corporate social responsibility, dividend policy, Lintner model, agency theory, signaling theory, dividend stability

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Authors: Mark Berry

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A number of studies have identified several factors involved in the malignant progression of cancer cells. The Primary modulator in driving inflammation to these transformed cells has been identified as the transcription factor known as nuclear factor-κB. This essential regulator of inflammation and the development of cancer, combined with a microenvironment of inflammation and signaling molecules, plays a major role in the malignant progression of cancer, and this progression is the result of the mutagenic predisposition of persistent substances that combat infection at tumor sites and other areas of chronic inflammation. Inflammation-induced tumors, and their inflammatory cells and regulators may be the primary source of metastasis of tumor cells through angiogenesis. Previous research on cytokines and chemokines, including their downstream targets, has been the focus of the cancer/inflammation connection. The identification of the biological mechanisms of other proteins vital to the inflammation cascade and their interactions are crucial to novel and effective therapeutic protocols for the treatment of inflammation-induced cancers. The Ancelim HSRP Protocol is just such a therapeutic intervention.

Keywords: ancelim, cancer, inflammation, tumor

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Authors: Arjmand Khaliq, Pemra Sohaib

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There is increasing trend of use of smart devices in the present age. The growth of computing techniques and advancement in hardware has also brought the use of sensors and smart devices to a high degree during the course of time. So use of smart devices for control, management communication and optimization has become very popular. This paper gives proposed methodology which involves sensing and switching unite for load, two way communications between utility company and smart phones of consumers using cellular techniques and price signaling resulting active participation of user in energy management .The goal of this proposed control methodology is active participation of user in energy management with accommodation of renewable energy resource. This will provide load adjustment according to consumer’s choice, increased security and reliability for consumer, switching of load according to consumer need and monitoring and management of energy.

Keywords: cellular networks, energy management, renewable energy source, smart grid technology

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Authors: Khayriniso Bakhtiyarovna Ganiyeva

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The article explores the significance of punctuation in achieving communicative competence. It underscores that effective communication goes beyond simply using punctuation correctly. In the successful completion of a communicative activity, it is important not that the writer correctly uses punctuation marks but that he was able to achieve a goal aimed at expressing a certain meaning. The unanimity of the writer and the reader in the mutual understanding of the text is of primary importance. It should also be taken into account that situational communication provides special informative content and expressiveness of speech. Also, the norms of the situation are determined by the nature of the information in the text, and the punctuation marks expressed in accordance with the norm perform logical-semantic, highlighting expressive-emotional and signaling functions. It is a mistake to classify the signs subject to the norm of the situation as created by the author because they functionally reflect the general stylistic features of different texts. Such signs are among the common signs that are codified only by the semantics and structure of the created text.

Keywords: communicative-pragmatic approach, expressiveness of speech, stylistic features, comparative analysis

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Authors: Naomi Seidu, Edward Poluyi, Chibuikem Ikwuegbuenyi, Eghosa Morgan

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The current poor prognosis of glioblastoma has called for the need for an improvement in treatment methods in order to improve its survival rate. Despite the different interventions currently available for this tumor, the average survival is still only a few months. (12-15). The aim is to create a more favorable prognosis and have a reduction in the resistance to treatment currently being experienced, even with surgical interventions and chemotherapy. From the available literature, there is a relationship between the presence of HOX genes (Homeobox genes) and glioblastoma, which could be attributable to the increasing treatment resistance. Hence silencing these genes can be a key to improving survival rates of glioblastoma. A series of studies have highlighted the role that HOX genes play in glioblastoma prognosis. Promotion of human glioblastoma initiation, aggressiveness, and resistance to Temozolomide has been associated with HOXA9. The role of HOX gene expression in cancer stem cells should be studied as it could provide a means of designing CSC-targeted therapies, as CSCs play a part in the initiation and progression of solid tumors.

Keywords: GBM- glioblastoma, HOXA gene- homeobox genes cluster, signaling pathways, temozolomide

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Authors: Natalia V. Naryzhnaya, Alexandr V. Mukhomedzyanov, Ivan A. Derkachev, Boris K. Kurbatov, Leonid N. Maslov

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Background: Techniques of adaptation to hypoxia and remote postconditioning (RPost) have great prospects for use in the clinic. However, recent studies have shown low efficacy of remote postconditioning in patients with AMI. We hypothesize that the reasons for this inefficiency may be metabolic disorders, which are very common, especially in patients with cardiovascular disease, and age of patients. The purpose of the study was to reveal the effectiveness of adaptation to chronic hypoxia and RPost. To determine the possible relationship between the decrease in the effectiveness of projective impacts and disorders of carbohydrate and lipid metabolism. Design: The study was carried out on Wistar rats 60 day old. MetS was induced by high-carbohydrate, high-fat diet (HСHFD). Modeling MS led to the formation of obesity, hypertension, impaired lipid and carbohydrate metabolism, hyperleptinemia, and moderate stress. Groups with adaptation to chronic hypoxia were subjected to hypoxia for 21 days at 12% O2 and 0.3% CO2 after complete of HСHFD. All animals were subjected to 45 min coronary occlusion and 120 min reperfusion. Groups with RPost, immediately after the end of ischemia, tourniquets were applied to the hind limbs in the area of the hip joint (3 times in the mode of 5 min ischemia, 5 min reperfusion). Results: RPost led to a twofold reduction of infarct size in rats with intact metabolism (р < 0.0001), while in rats with MetS, a decrease in infarct size during RPost was 25 % (p = 0.00003). A direct correlation was found between of infarct size during RPost and the serum leptin level of rats with MetC (r = 0.85). The presented data suggested that a decrease in the efficiency of remote postconditioning in rats with diet-induced metabolic syndrome depends on serum leptin. Chronic hypoxia resulted in a 38% reduced in infarct size in metabolically intact rats. The decrease of cardioprotection was observed in rats with chronic hypoxia and MetS. Infarct size showed a direct correlation with impaired glucose tolerance (AUC, glucose tolerance test, r = 0.034) and serum triglyceride levels (r = 0.39). Our study showed the dependence of cardioprotection in rats with metabolic syndrome during chronic hypoxia and DPost on opioids in the blood serum and myocardium, protein kinase C and NO synthase activity. Conclusion: The results obtained showed that the infarct-limiting efficiency of adaptation to hypoxia and remote postconditioning is reduced or completely absent in animals with metabolic syndrome. The increase in the infarction, in this case, directly depends on the disturbances in carbohydrate. lipid metabolism and opioids signaling. Funding: Investigation of effectiveness of chronic hypoxia at the metabolic syndrome was carried out within the support of Russian Science Foundation Grant 22-15-00048. Studies of the mechanisms of arterial hypertension in induced metabolic syndrome were carried out within the framework of the state assignment (122020300042-4). The work was performed using the Center for Collective Use "Medical Genomics".

Keywords: chronic hypoxia, opioids, remote postconditioning, metabolic syndrome

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Authors: Cheng-Cao Sun, Shu-Jun Li, De-Jia Li

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Determinants of growth and metastasis in cancer remain of great interest to define. MicroRNAs (miRNAs) have frequently emerged as tumor metastatic regulator by acting on multiple signaling pathways. Here, we report the definition of miR-346 as an oncogenic microRNA that facilitates non-small cell lung cancer (NSCLC) cell growth and metastasis. XPC, an important DNA damage recognition factor in nucleotide excision repair was defined as a target for down-regulation by miR-346, functioning through direct interaction with the 3'-UTR of XPC mRNA. Blocking miR-346 by an antagomiR was sufficient to inhibit NSCLC cell growth and metastasis, an effect that could be phenol-copied by RNAi-mediated silencing of XPC. In vivo studies established that miR-346 overexpression was sufficient to promote tumor growth by A549 cells in xenografts mice, relative to control cells. Overall, our results defined miR-346 as an oncogenic miRNA in NSCLC, the levels of which contributed to tumor growth and invasive aggressiveness.

Keywords: microRNA-346, miR-346, XPC, non-small cell lung cancer, oncogenesis

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Authors: A. Watson, G. Telford, D. I. Pritchard

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Objective: We investigated the immunomodulatory ability of licorice (Glycyrrhiza glabra). Such activities could have value for the management of common immunological diseases in dogs, such as environmental allergy. This study investigated the potential of a Licorice root extract (LRE) to influence the relative expression of Th-1, Th-2, and Th-17 cytokines in canine peripheral blood mononuclear cells (PBMC). Methods: A LRE was prepared using an alcoholic-aqueous-based solvent method. The extract was tested in three in vitro assays using canine leukocytes to determine its toxicity and immunoregulatory profile. Extract toxicity was assessed using the human T-lymphocyte cell line, Jurkat E6.1. The impact of the extract on the proliferation of concanavalin-activated canine PBMC was also determined. Finally, the extract was assessed for its ability to influence cytokine release in activated PBMC, measuring culture medium concentrations of interleukin-17, interferon gamma, and interleukin-4. One-way ANOVA followed by Dunnett’s post-test was used for statistics using concanavalin positive control as reference (p ≤ 0.05). Results: There was evidence that the LRE had specific immunomodulatory properties, causing significant inhibition of IL4 expression over a non-toxic/non-cytostatic concentration range (p < 0.001). In the same cell incubations, there was no significant impact on IL17 nor IFNg over the same non-toxic/non-cytostatic concentration range. Conclusion: The study provides in vitro evidence that LRE preferentially reduces the expression of a Th-2-type cytokine, IL4. The dog population, as with humans, is prone to conditions associated with a Th-2 bias of the immune system, such as environmental allergy. Based on these results, licorice merits further evaluation as a useful immune modulator for such allergic diseases.

Keywords: cytokine, Glycyrrhiza glabra, peripheral blood mononuclear cells, T-cell activation

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Authors: Anne Kariuki, Kellen Kiambati

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The broad objective of this study was to establish the mediating effect of media visibility on the relationship between corporate Social Responsibility (CSR) and the corporate performance of firms listed on the Nairobi Securities Exchange. The review of the literature provided conceptual and empirical gaps that formed the basis of the conceptual hypotheses. A survey questionnaire was distributed to the 50 heads of human resource departments in the different firms. A survey was conducted on fifty (50) companies listed on the Nairobi Securities Exchange. The study findings reported a significant relationship between CSR and non-financial performance and the mediating role of media visibility on the relationship between CSR and performance. The findings of the study support the signaling theory and stakeholder’s theory. Conclusively, CSR activities have an effect on media visibility, which in turn affects performance.

Keywords: corporate social responsibility, media visibility, corporate performance, non-financial performance

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Authors: Ryeong-Hyeon Kim, Ah-Reum Lee, Seong-Soo Roh, Gyo-Nam Kim

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Appropriate regulation of melanogenesis is important for the management of skin pigmentation-related disease. Although several beneficial effects of fisetin (3,7,3’,4’-tetrahydroxyflavone) have been reported, the precise role and molecular mechanisms of fisetin in skin health both remain unclear. Here, we induced melanogenesis of HRM2 mice (n=7/group) by UVB irradiation for 20 days. UVB-induced HRM2 mice showed that the significantly increased melanin accumulation, however, fisetin treatment (25mg and 50mg/kg of body weight) dose-dependently and significantly inhibits UVB-induced melanogenesis. In line with this, fisetin treatment effectively down-regulated m RNA and expression levels of tyrosinase, TRP2, and MITF. In addition, our inhibitor assay revealed the down-regulated melanogenic marker genes by fisetin treatment were mediated with connective tissue growth factor (CCN2)/TGF-β signaling pathway. Useful information is provided for development of functional foods using fisetin for skin health.

Keywords: connective tissue growth factor, fisetin, melanogenesis, skin, TGF-beta

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Authors: Jer-Yuh Liu, Je-Chiuan Ye, Jin-Ming Hwang

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Protein kinase C alpha (PKCα) is a key signaling molecule in human cancer development. As a therapeutic strategy, targeting PKCα is difficult because the molecule is ubiquitously expressed in non-malignant cells. PKCα is regulated by the cooperative interaction of the transcription factors myeloid zinc finger 1 (MZF-1) and Ets-like protein-1 (Elk-1) in human cancer cells. By conducting tissue array analysis, herein, we determined the protein expression of MZF-1/Elk-1/PKCα in various cancers. The data show that the expression of MZF-1/Elk-1 is correlated with that of PKCα in hepatocellular carcinoma (HCC), but not in bladder and lung cancers. In addition, the PKCα down-regulation by shRNA Elk-1 was only observed in the HCC SK-Hep-1 cells. Blocking the interaction between MZF-1 and Elk-1 through the transfection of their binding domain MZF-160–72 decreased PKCα expression. This step ultimately depressed the epithelial-mesenchymal transition potential of the HCC cells. These findings could be used to develop an alternative therapeutic strategy for patients with the PKCα-derived HCC.

Keywords: protein kinase C alpha, myeloid zinc finger 1, ets-like protein-1, hepatocellular carcinoma

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Authors: Yuping Liu, Li Tao, Yin Lu

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Accumulating evidence has been shown that diallyl trisulfide (DATS) from garlic may reduce the risk of developing several types of cancer. In view of the dynamic crosstalk interplayed by tumor cells and platelets in hematogenous metastasis, we demonstrate the effectiveness of DATS on the metastatic behaviors of MDA-MB-435s human breast cancer cell line co-incubated with activated platelets. Indeed, our data identified that DATS significantly blocked platelets fouction induced by PAF, followed by the decreased production of TXB2. DATS was found to dose-dependently suppressed MDA-MB-435s cell migration and invasion in presence of activated platelets by PAF in vitro. Furthermore, the expression, secretion and enzymatic activity of matrix metalloproteinase (MMP)-2/9, as well as the luciferase activity of upstream regulator NF-κB in MDA-MB-435s, were obviously diminished by DATS. In parallel, DATS blocked upstream NF-κB activation signaling complexes composed of extracellular signal-related kinase (ERK) as assessed by measuring the levels of the phosphorylated forms.

Keywords: DATS, ERK, metastasis, MMPs, NF-κB, platelet

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Authors: Yusra Tariq

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The Grass 37 gene is presently known in tomatoes, which are the source of healthy substances such as ascorbic acid, polyphenols, carotenoids and nutrients. It has a significant impact on the growth and development of humans. The GRASS 37 gene is a plant Transcription factor group assuming significant parts in various reactions of different Abiotic stresses such as (drought, salinity, thermal stresses, temperature, and bright waves) which could highly affect the growth. Tomatoes are very sensitive to temperature, and their growth or production occurs optimally in a temperature range from 21 C to 29.5 C during the daytime and from 18.5 C to 21 C during the night. This protein acts as a positive regulator of salt stress response and abscisic acid signaling. This study summarizes the structure characterized by molecular formula and protein-binding domains by different bioinformatics tools such as Expasy translate tool, Expasy Portparam, Swiss Prot and Inter Pro Scan, Clustal W tool regulatory procedure of GRASS gene components, also their reactions to both biotic and Abiotic stresses.

Keywords: GRAS37, gene, bioinformatics, tool

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Authors: Hechmi Saidi, Noureddine Hamdi

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The performance of Decode and Forward (DF) multihop Free Space Optical ( FSO) scheme deploying Multiple Input Multiple Output (MIMO) configuration under Gamma-Gamma (GG) statistical distribution, that adopts M-ary Pulse Position Modulation (MPPM) coding, is investigated. We have extracted exact and estimated values of Symbol-Error Rates (SERs) respectively. A closed form formula related to the Probability Density Function (PDF) is expressed for our designed system. Thanks to the use of DF multihop MIMO FSO configuration and MPPM signaling, atmospheric turbulence is combatted; hence the transmitted signal quality is improved.

Keywords: free space optical, multiple input multiple output, M-ary pulse position modulation, multihop, decode and forward, symbol error rate, gamma-gamma channel

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Authors: Rafia S. Al-lamki, Jun Wang, Simon Pacey, Jordan Pober, John R. Bradley

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Tumor necrosis factor alpha (TNF), signaling through TNFR2, may act an autocrine growth factor for renal tubular epithelial cells. Clear cell renal carcinomas (ccRCC) contain cancer stem cells (CSCs) that give rise to progeny which form the bulk of the tumor. CSCs are rarely in cell cycle and, as non-proliferating cells, resist most chemotherapeutic agents. Thus, recurrence after chemotherapy may result from the survival of CSCs. Therapeutic targeting of both CSCs and the more differentiated bulk tumor populations may provide a more effective strategy for treatment of RCC. In this study, we hypothesized that TNFR2 signaling will induce CSCs in ccRCC to enter cell cycle so that treatment with ligands that engage TNFR2 will render CSCs susceptible to chemotherapy. To test this hypothesis, we have utilized wild-type TNF (wtTNF) or specific muteins selective for TNFR1 (R1TNF) or TNFR2 (R2TNF) to treat either short-term organ cultures of ccRCC and adjacent normal kidney (NK) tissue or cultures of CD133+ cells isolated from ccRCC and adjacent NK, hereafter referred to as stem cell-like cells (SCLCs). The effect of cyclophosphamide (CP), currently an effective anticancer agent, was tested on CD133+SCLCs from ccRCC and NK before and after R2TNF treatment. Responses to TNF were assessed by flow cytometry (FACS), immunofluorescence, and quantitative real-time PCR, TUNEL, and cell viability assays. Cytotoxic effect of CP was analyzed by Annexin V and propidium iodide staining with FACS. In addition, we assessed the effect of TNF on isolated SCLCs differentiation using a three-dimensional (3D) culture system. Clinical samples of ccRCC contain a greater number SCLCs compared to NK and the number of SCSC increases with higher tumor grade. Isolated SCLCs show expression of stemness markers (oct4, Nanog, Sox2, Lin28) but not differentiation markers (cytokeratin, CD31, CD45, and EpCAM). In ccRCC organ cultures, wtTNF and R2TNF increase CD133 and TNFR2 expression and promote cell cycle entry whereas wtTNF and R1TNF increase TNFR1 expression and promote cell death of SCLCs. Similar findings are observed in SCLCs isolated from NK but the effect was greater in SCLCs isolated from ccRCC. Application of CP distinctly triggered apoptotic and necrotic cell death in SLCSs pre-treatment with R2TNF as compared to CP treatment alone, with SCLCs from ccRCC more sensitive to CP compared to SLCS from NK. Furthermore, TNF promotes differentiation of SCLCs to an epithelial phenotype in 3D cultures, confirmed by cytokeratin expression and loss of stemness markers Nanog and Sox2. The differentiated cells show positive expression of TNF and TNFR2. These findings provide evidence that selective engagement of TNFR2 drive CSCs to cell proliferation/differentiation, and targeting of cycling cells with TNFR2 agonist in combination with anti-cancer agents may be a potential therapy for RCC.

Keywords: cancer stem cells, ccRCC, cell cycle, cell death, TNF, TNFR1, TNFR2, CD133

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Authors: Fazilet Özlem Çekiç, Seyda Yılmaz

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Salinity and drought are important environmental problems in the world and have negative effects on plant metabolism. Gamma-aminobutyric acid (GABA), four-carbon non-protein amino acid, is a significant component of the free amino acid pool. GABA is widely distributed in prokaryotic and eukaryotic organisms. Environmental stress factors increase GABA accumulation in plants. Our aim was to evaluate the effect of gibberellic acid (GA) on GABA metabolism system during drought and salt stress factors in Phaseolus vulgaris L. plants. GABA, Glutamate dehydrogenase (GDH) activity, chlorophyll, and lipid peroxidation (MDA) analyses were determined. According to our results we can suggest that GA play a role in GABA metabolism during salt and drought stresses in bean plants. Also GABA shunt is an important metabolic pathway and key signaling allowing to adapt to drought and salt stresses.

Keywords: gibberellic acid, GABA, Phaseolus vulgaris L., salinity, drought

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Authors: Vishwesh Kulkarni, Nikhil Bellarykar

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Cellular complexity stems from the interactions among thousands of different molecular species. Thanks to the emerging fields of systems and synthetic biology, scientists are beginning to unravel these regulatory, signaling, and metabolic interactions and to understand their coordinated action. Reverse engineering of biological networks has has several benefits but a poor quality of data combined with the difficulty in reproducing it limits the applicability of these methods. A few years back, many of the commonly used predictive algorithms were tested on a network constructed in the yeast Saccharomyces cerevisiae (S. cerevisiae) to resolve this issue. The network was a synthetic network of five genes regulating each other for the so-called in vivo reverse-engineering and modeling assessment (IRMA). The network was constructed in S. cereviase since it is a simple and well characterized organism. The synthetic network included a variety of regulatory interactions, thus capturing the behaviour of larger eukaryotic gene networks on a smaller scale. We derive a new set of algorithms by solving a nonlinear optimization problem and show how these algorithms outperform other algorithms on these datasets.

Keywords: synthetic gene network, network identification, optimization, nonlinear modeling

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Authors: Saha Saradindu, Das Payel, Somdeb BoseDasgupta

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

Keywords: mycobacteria, Protein kinase G, phosphoproteomics, necroptosis

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Authors: Soheil Zorofchian Moghadamtousi, Habsah Abdul Kadir, Mohammadjavad Paydar, Elham Rouhollahi, Hamed Karimian

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The present study was designed to evaluate the molecular mechanisms of Annona muricata leaves ethyl acetate extract (AMEAE) against lung cancer A549 cells. Cell viability analysis revealed the selective cytotoxic effect of AMEAE towards A549 cells. Treatment of A549 cells with AMEAE significantly elevated the reactive oxygen species formation, followed by attenuation of mitochondrial membrane potential via upregulation of Bax and downregulation of Bcl-2, accompanied by cytochrome c release to the cytosol. The released cytochrome c triggered the activation of caspase-9 followed by caspase-3. In addition, AMEAE-induced apoptosis was accompanied by cell cycle arrest at G1 phase. Our data showed for the first time that AMEAE inhibited the proliferation of A549 cells, leading to cell cycle arrest and programmed cell death through activation of the mitochondrial-mediated signaling pathway.

Keywords: Annona muricata, lung cancer, apoptosis, mitochondria

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Authors: Jasminka Mujic, Karin Milde-Langosch, Volkmar Mueller, Mirza Suljagic, Tea Becirevic, Jozo Coric, Daria Ler

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MACC1 (metastasis associated in colon cancer-1) is a prognostic biomarker for tumor progression, metastasis, and survival of a variety of solid cancers. MACC1 also causes tumor growth in xenograft models and acts as a master regulator of the HGF/MET signaling pathway. In breast cancer, the expression of MACC1 determined by immunohistochemistry was significantly associated with positive lymph node status and advanced clinical stage. The aim of the present study was to further investigate the prognostic or predictive value of MACC1 expression in breast cancer using western blot analysis and immunohistochemistry. The results of our study have shown that high MACC1 expression in breast cancer is associated with shorter disease-free survival, especially in node-negative tumors. The MACC1 might be a suitable biomarker to select patients with a higher probability of recurrence which might benefit from adjuvant chemotherapy. Our results support a biologic role and potentially open the perspective for the use of MACC1 as predictive biomarker for treatment decision in breast cancer patients.

Keywords: breast cancer, biomarker, HGF/MET, MACC1

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Authors: Rijnbout-St.James Willem, Lindner Volkhard, Scholand Mary Beth, Ashton M. Tillett, Di Gennaro Michael Jude, Smith Silvia Enrica

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Introduction: Fibrosing lung diseases are characterized by changes in the lung interstitium and are classified based on etiology: 1) environmental/exposure-related, 2) autoimmune-related, 3) sarcoidosis, 4) interstitial pneumonia, and 4) idiopathic. Among interstitial lung diseases (ILD) idiopathic forms, idiopathic pulmonary fibrosis (IPF) is the most severe. Pathogenesis of IPF is characterized by an increased presence of proinflammatory mediators, resulting in alveolar injury, where injury to alveolar epithelium precipitates an increase in collagen deposition, subsequently thickening the alveolar septum and decreasing gas exchange. Identifying biomarkers implicated in the pathogenesis of lung fibrosis is key to developing new therapies and improving the efficacy of existing therapies. The transforming growth factor-beta (TGF-B1), a mediator of tissue repair associated with WNT5A signaling, is partially responsible for fibroblast proliferation in ILD and is the target of Pirfenidone, one of the antifibrotic therapies used for patients with IPF. Canonical TGF-B signaling is mediated by the proteins SMAD 2/3, which are, in turn, indirectly regulated by Collagen Triple Helix Repeat Containing 1 (CTHRC1). In this study, we tested the following hypotheses: 1) CTHRC1 is more elevated in the ILD cohort compared to unaffected controls, and 2) CTHRC1 is differently expressed among ILD types. Material and Methods: CTHRC1 levels were measured by ELISA in 171 plasma samples from the deidentified University of Utah ILD cohort. Data represent a cohort of 131 ILD-affected participants and 40 unaffected controls. CTHRC1 samples were categorized by a pulmonologist based on affectation status and disease subtypes: IPF (n = 45), sarcoidosis (4), nonspecific interstitial pneumonia (16), hypersensitivity pneumonitis (n = 7), interstitial pneumonia (n=13), autoimmune (n = 15), other ILD - a category that includes undifferentiated ILD diagnoses (n = 31), and unaffected controls (n = 40). We conducted a single-factor ANOVA of plasma CTHRC1 levels to test whether CTHRC1 variance among affected and non-affected participants is statistically significantly different. In-silico analysis was performed with Ingenuity Pathway Analysis® to characterize the role of CTHRC1 in the pathway of lung fibrosis. Results: Statistical analyses of CTHRC1 in plasma samples indicate that the average CTHRC1 level is significantly higher in ILD-affected participants than controls, with the autoimmune ILD being higher than other ILD types, thus supporting our hypotheses. In-silico analyses show that CTHRC1 indirectly activates and phosphorylates SMAD3, which in turn cross-regulates TGF-B1. CTHRC1 also may regulate the expression and transcription of TGFB-1 via WNT5A and its regulatory relationship with CTNNB1. Conclusion: In-silico pathway analyses demonstrate that CTHRC1 may be an important biomarker in ILD. Analysis of plasma samples indicates that CTHRC1 expression is positively associated with ILD affectation, with autoimmune ILD having the highest average CTHRC1 values. While characterizing CTHRC1 levels in plasma can help to differentiate among ILD types and predict response to Pirfenidone, the extent to which plasma CTHRC1 level is a function of ILD severity or chronicity is unknown.

Keywords: interstitial lung disease, CTHRC1, idiopathic pulmonary fibrosis, pathway analyses

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Authors: Michal Štros, Eva Polanská, Šárka Pospíšilová

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HMGB1 is an architectural protein in chromatin, acting also as a signaling molecule outside the cell. Recent reports from several laboratories provided evidence that a number of both the intracellular and extracellular functions of HMGB1 may depend on redox-sensitive cysteine residues of the protein. MALDI-TOF analysis revealed that mild oxidization of HMGB1 resulted in a conformational change of the protein due to formation of an intramolecular disulphide bond by opposing Cys23 and Cys45 residues. We have demonstrated that redox state of HMGB1 could significantly modulate the ability of the protein to bind and bend DNA. We have also shown that reduced HMGB1 could easily displace histone H1 from DNA, while oxidized HMGB1 had limited capacity for H1 displacement. Using microscale thermophoresis (MST) we have further studied mechanism of HMGB1 interaction with histone H1 in free solution or when histone H1 was bound to DNA. Our MST analysis indicated that reduced HMGB1 exhibited in free solution > 1000 higher affinity of for H1 (KD ~ 4.5 nM) than oxidized HMGB1 (KD <10 M). Finally, we present a novel mechanism for the HMGB1-mediated modulation of histone H1 binding to DNA.

Keywords: HMGB1, histone H1, redox state, interaction, cross-linking, DNA bending, DNA end-joining, microscale thermophoresis

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Authors: Mohammad Reza Hossein Zadeh

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Plants have different layers of defense responses against biotic and abiotic stresses. One of the well-defined defense mechanism in plants is systemic acquired resistance (SAR) against a broad-range of pathogens. Salicylic acid (SA) plays a crucial role in regulation of the SAR pathway. It has been proved that Chemically SA-like compounds can mimic the SA signaling role. Imidocloprid is an insecticide being used to control whiteflies on crop plants. In order to study the possible role of Imidocloprid as an elicitor of SAR in plants, experiments were conducted in a completely randomized design frame with three treatments and duplicates on the detached leaves and whole Nicotiana tabacum var. Samsun NN. plants inoculated with Tobacco mild green mosaic virus (TMGMV). Compared with the effect of other SAR-inducers such as SA, Imidoclorid conferred a robust SAR induction in the infected plants. The results suggested that Imidocloprid even more powerful than SA can be considered as strong SAR inducer in the infected plants with viruses, which develop the local lesion symptoms.

Keywords: imidocloprid, Nicotiana tabacum var. Samsun NN, SAR, tobacco mild green, mosaic virus

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Authors: S. Bayona, J. Nunez, D. Paez, C. Diaz

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The application of Lean manufacturing tools continues to be an effective solution for increasing productivity, reducing costs and eliminating waste in the manufacture of goods and services. This article analyzes the production process of a hot asphalt manufacturing company from an administrative and technical perspective. Three main phases were analyzed, the first phase was related to the determination of the risk priority number of the main operations in asphalt mix production process by an FMEA (Failure Mode Effects Analysis), in the second phase the Value Stream Mapping (VSM) of the production line was performed and in the third phase a SWOT (Strengths, Weaknesses Opportunities, Threats) matrix was constructed. Among the most valued failure modes were the lack training of workers in occupational safety and health issues, the lack of signaling and classification of granulated material, and the overweight of vehicles loaded. The analysis of the results in the three phases agree on the importance of training operational workers, improve communication with external actors in order to minimize delays in material orders and strengthen control suppliers.

Keywords: asphalt, lean manufacturing, productivity, process

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Authors: Seyyed Mohammad Amin Mousavi Sagharchi, Elham Javanroudi

Abstract:

Introduction: Tuberculosis (TB) is a known disease with hidden features caused by Mycobacterium tuberculosis (MTB). This disease, which is one of the 10 deadliest in the world, has caused millions of deaths in recent decades. Furthermore, TB is responsible for infecting about 30% population of world. Like any infection, TB can activate the immune system by locating and colonization in the human body, especially in the alveoli. TB is granulomatosis, so MTB can absorb the host’s immune cells and other cells to form granuloma. Method: Different databases (e.g., PubMed) were recruited to prepare this paper and fulfill our goals to search and find effective papers and investigations. Results: Immune response to MTB is related to T cell killers and contains CD1, CD4, and CD8 T lymphocytes. CD1 lymphocytes can recognize glycolipids, which highly exist in the Mycobacterial fatty cell wall. CD4 lymphocytes and macrophages form granuloma, and it is the main line of immune response to Mycobacteria. On the other hand, CD8 cells have cytolytic function for directly killing MTB by secretion of granulysin. Other functions and secretion to the deal are interleukin-12 (IL-12) by induction of expression interferon-γ (INF-γ) for macrophages activation and creating a granuloma, and tumor necrosis factor (TNF) by promoting macrophage phagolysosomal fusion. Conclusion: Immune cells in battle with MTB are macrophages, dendritic cells (DCs), neutrophils, and natural killer (NK) cells. These immune cells can recognize the Mycobacterium by various receptors, including Toll-like receptors (TLRs), Nod-like receptors (NLRs), and C-type lectin receptors (CLRs) located in the cell surface. In human alveoli exist about 50 dendritic macrophages, which have close communication with other immune cells in the circulating system and epithelial cells to deal with Mycobacteria. Against immune cells, MTB handles some factors (e.g., cordfactor, O-Ag, lipoarabinomannan, sulfatides, and adenylate cyclase) and practical functions (e.g., inhibition of macrophages).

Keywords: mycobacterium tuberculosis, immune responses, immunological mechanisms, respiratory tuberculosis

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Authors: Ghulam Hassan Abbasi, Moazzam Jamil, Ghazala Akhtar, M.Anwar-ul-Haq

Abstract:

Heavy metals are significant pollutants in environment and their toxicity is a problem for survival of living things while salicylic acid (SA) is signaling and ubiquitous bioactive molecule that regulates cellular mechanism in plants under stress condition. Therefore, exogenous application of salicylic acid (SA) under chromium stress in two chickpea varieties were investigated in hydroponic experiment with five treatments comprising of control, 5 µM Cr + 5 mM SA, 5µM Cr + 10 mM SA, 10µM Cr + 5 mM SA, and 10µM Cr + 10 mM SA. Results revealed that treatments of plants with 10 mM SA application under both 5 µM Cr and 10 µM Cr stress resulted in maximum improvement in plant morphological attributes (root and shoot length, root and shoot fresh and dry weight, membrane stability index and relative water contents) relative to 5 mM SA application in both chickpea varieties. Results regarding Cr concentration showed that Cr was more retained in roots followed by shoots and maximum reduction in Cr uptake was observed at 10 mM SA application. Chickpea variety BRC-61 showed maximum growth and least concentration of Cr in root and shoot relative to BRC-390 variety.

Keywords: chromium, Chickpea, salicylic acid, growth

Procedia PDF Downloads 482

Authors: Tianyu Chen

Abstract:

China's school district education policy has encouraged parents to purchase properties in school districts with high-quality education resources. Shanghai has implemented "Simultaneous Admission to Public and Private Schools" (SAPPS) since 2018, which has covered all nine-year compulsory education by 2020. This study examines the impact of SAPPS on the housing market, specifically the premium effect of houses located in dual-school districts. Based on the Hedonic Pricing Model and the Signaling Theory, data is collected from 585 second-hand house transactions in Pudong New Area, Shanghai, and it is analyzed with the Difference-in-Differences (DID) model. The results indicate that the implementation of SAPPS has exacerbated the premium of dual school district housing and weakened the effect of the policy to a certain degree. To ensure equal access to education for all students, the government should work both on the supply and demand sides of the education resource equation.

Keywords: simultaneous admission to public and private schools, housing prices, education policy, education equity

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

Abstract:

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

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

Procedia PDF Downloads 152

Authors: Nan Hu, Wujun Wang

Abstract:

In the ever-changing digital arena, augmented reality (AR) applications have transitioned from technological enthusiasm into business endeavors, signaling a near future in which AR applications are integrated into daily life. While practitioners in the design industry continue to explore AR’s potential for innovative communication, educators have taken steps to incorporate AR into the curricula for design, explore its creative potential, and realize early initiatives for teaching AR in design-related disciplines. In alignment with recent advancements, this paper presents a pedagogical model for a hybrid studio course in which students collaborate with AR alongside 3D modeling and graphic design. The course extended students’ digital capacity, fostered their design thinking skills, and immersed them in a multidisciplinary design process. This paper outlines the course and evaluates its effectiveness by discussing challenges encountered and outcomes generated in this particular pedagogical context. By sharing insights from the teaching experience, we aim to empower the community of design educators and offer institutions a valuable reference for advancing their curricular approaches. This paper is a testament to the ever-evolving landscape of design education and its response to the digital age.

Keywords: 3D, AR, augmented reality, design thinking, graphic design

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