Search results for: expression omnibus (GEO)

Authors: Ajay Kumar, Satwinderjeet Kaur

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Onosma bracteata Wall. (Boraginaceae), is known to be a medicinal plant, useful in the treatment of body swellings, abdominal pain and urinary calculi, etc. The present study focused on the radical scavenging and cancer growth inhibitory properties of isolates from O. bracteata. Obea fraction demonstrated noticeable free radical scavenging ability along with antiproliferative activity in human osteosarcoma MG-63, human neuroblastoma IMR-32, and human lung cancer A549 cell lines using MTT assay with GI50 values of 88.56, 101.61 and 112.7 μg/ml, respectively. The scanning electron and confocal microscopy studies showed morphological alterations including nuclear condensation and formation of apoptotic bodies in osteosarcoma MG-63 cells. Obea fraction in osteosarcoma MG-63 cells augmented the reactive oxygen species (ROS) level and decreased the mitochondrial membrane potential. Flow cytometry analysis revealed the Obea treated cells to be arrested in the G0/G1 phase in a dose dependent manner supported by the observed increase in the early apoptotic cell population. Western blotting analysis showed that the expression of p-NF-kB, COX-2, p-Akt, and Bcl-xL decreased whereas, the expression of GSK-3β, p53, caspase-3 and caspase-9 proteins increased. The downregulation of Bcl-2, Cyclin E, CDK2 and mortalin gene expression and upregulation of p53 genes was unfolded in RT-qPCR studies. The presence of catechin, kaempferol, Onosmin A and epicatechin, as revealed in high-performance liquid chromatography (HPLC) studies, contributes towards the chemopreventive potential of O. bracteata which can be tapped for chemotherapeutic use.

Keywords: apoptosis, confocal microscopy, HPLC, mitochondria membrane potential, reactive oxygen species

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Authors: Enjie Xu, Zhen Huang, Kunpeng Zhu, Jianping Hu, Xiaolong Ma, Yongjie Wang, Jiazhuang Zhu, Chunlin Zhang

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Abstract: Hypoxia and dedifferentiation of osteosarcoma (OS) cells leads to poor prognosis. We plan to identify the role of hypoxia on dedifferentiation and the associated signaling pathways. We performed a sphere formation assay and determined spheroid cells as dedifferentiated cells by detecting stem cell-like markers. RNAi assay was used to explore the expression relationship between hypoxia inducible factor 1 subunit alpha (HIF1A) and platelet derived growth factor receptor beta (PDGFRB). We obtained PDGFRB knockdown and overexpression cells through lentiviral infection experiments and the effects of PDGFRB on cytoskeleton rearrangement and cell adhesion were explored by immunocytochemistry. Wound-healing experiments, transwell assays, and animal trials were employed to investigate the effect of PDGFRB on OS metastasis. Dedifferentiated OS cells were found to exhibit high expression of HIF1A and PDGFRB, and HIF1A promoted the expression of PDGFRB, subsequently activated ras homolog family member A (RhoA), and increased the phosphorylation of myosin light chain (MLC). PDGFRB also enhanced the phosphorylation of focal adhesion kinase (FAK). The OS cell morphology and vinculin distribution were altered by PDGFRB. PDGFRB also promoted cell dedifferentiation and had a significant impact on the metastasis of OS cells both in vitro and in vivo. Our results demonstrated that HIF1A up-regulated PDGFRB under hypoxic conditions, and PDGFRB regulated the actin cytoskeleton by activating RhoA and subsequently phosphorylating MLC, thereby promoting OS dedifferentiation and pulmonary metastasis.

Keywords: osteosarcoma, dedifferentiation, metastasis, cytoskeleton rearrangement, PDGFRB, hypoxia

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Authors: Wenjiang Deng, Tian Mou, Yudi Pawitan, Trung Nghia Vu

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Estimation of isoform-level gene expression from RNA-seq data depends on simplifying assumptions, such as uniform reads distribution, that are easily violated in real data. Such violations typically lead to biased estimates. Most existing methods provide a bias correction step(s), which is based on biological considerations, such as GC content–and applied in single samples separately. The main problem is that not all biases are known. For example, new technologies such as single-cell RNA-seq (scRNA-seq) may introduce new sources of bias not seen in bulk-cell data. This study introduces a method called XAEM based on a more flexible and robust statistical model. Existing methods are essentially based on a linear model Xβ, where the design matrix X is known and derived based on the simplifying assumptions. In contrast, XAEM considers Xβ as a bilinear model with both X and β unknown. Joint estimation of X and β is made possible by simultaneous analysis of multi-sample RNA-seq data. Compared to existing methods, XAEM automatically performs empirical correction of potentially unknown biases. XAEM implements an alternating expectation-maximization (AEM) algorithm, alternating between estimation of X and β. For speed XAEM utilizes quasi-mapping for read alignment, thus leading to a fast algorithm. Overall XAEM performs favorably compared to other recent advanced methods. For simulated datasets, XAEM obtains higher accuracy for multiple-isoform genes, particularly for paralogs. In a differential-expression analysis of a real scRNA-seq dataset, XAEM achieves substantially greater rediscovery rates in an independent validation set.

Keywords: alternating EM algorithm, bias correction, bilinear model, gene expression, RNA-seq

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Authors: Iliyasu Musa Omoyine, Musa Sunday Abraham, Oladele Sunday Blessing, Iliya Ibrahim Abdullahi, Ibegbu Augustine Oseloka, Nuhu Nana-Hawau, Animoku Abdulrazaq Amoto, Yusuf Abdullateef Onoruoiza, Sambo Sohnap James, Akpulu Steven Peter, Ajayi Abayomi

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The neuroprotective role of inflammation from detrimental intrinsic and extrinsic factors has been reported. However, the overactivation of astrocytes and microglia due to lead toxicity produce excessive pro-inflammatory cytokines, mediating neurodegenerative diseases. The present study investigated the mitigatory effects of quercetin on neuroinflammation, correlating with memory function in lead-exposed rats. In this study, Wistar rats were administered orally with Quercetin (Q: 60 mg/kg) and Succimer as a standard drug (S: 10 mg/kg) for 21 days after lead exposure (Pb: 125 mg/kg) of 21 days or in combination with Pb, once daily for 42 days. Working and reference memory was assessed using an Eight-arm radial water maze (8-ARWM). The changes in brain lead level, the neuronal nitric oxide synthase (nNOS) activity, and the level of neuroinflammatory markers such as tumour necrosis factor-alpha (TNF-α) and Interleukin 1 Beta (IL-1β) were determined. Immunohistochemically, astrocyte expression was evaluated. The results showed that the brain level of lead was increased significantly in lead-exposed rats. The expression of astrocytes increased in the CA3 and CA1 regions of the hippocampus, and the levels of brain TNF-α and IL-1β increased in lead-exposed rats. Lead impaired reference and working memory by increasing reference memory errors and working memory incorrect errors in lead-exposed rats. However, quercetin treatment effectively improved memory and inhibited neuroinflammation by reducing astrocytes’ expression and the levels of TNF-α and IL-1β. The expression of astrocytes and the levels of TNF-α and IL-1β correlated with memory function. The possible explanation for quercetin’s anti-neuroinflammatory effect is that it modulates the activity of cellular proteins involved in the inflammatory response; inhibits the transcription factor of nuclear factor-kappa B (NF-κB), which regulates the expression of proinflammatory molecules; inhibits kinases required for the synthesis of Glial fibrillary acidic protein (GFAP) and modifies the phosphorylation of some proteins, which affect the structure and function of intermediate filament proteins; and, lastly, induces Cyclic-AMP Response Element Binding (CREB) activation and neurogenesis as a compensatory mechanism for memory deficits and neuronal cell death. In conclusion, the levels of neuroinflammatory markers negatively correlated with memory function. Thus, quercetin may be a promising therapy in neuroinflammation and memory dysfunction in populations prone to lead exposure.

Keywords: lead, quercetin, neuroinflammation, memory

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Authors: Elham Shakerian, Reza Afarin

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The hepatic disease causes approximately 2 million deaths/year worldwide. Liver fibrosis is the last stage of numerous chronic liver diseases, and until now there is no definite cure or drug for it. Activation of hepatic stellate cells (HSCs) is the main reason for fibrosis. Transforming growth factor (TGF-β), as a main profibrogenic cytokine, if increased in these cells, leads to liver fibrosis through smad3 signaling pathways and increasing the expressions of Collagen type I and III, and actin-alpha smooth muscle (αSMA) genes. Curcumin (CUR) is a polyphenolic compound and an active ingredient derived from the rhizome of the turmeric plant that exerts effective antioxidant, anti-inflammatory, and antimicrobial activity. It has been shown that daily consumption of curcumin may have a protective effect on the liver against oxidative stress associated with alcohol consumption. In this study, we investigate the role of Curcumin in decreasing HSC activation and treating liver fibrosis. First, the human HSCs were treated with 2 ng/ml of (TGF-β) for 24 hours to become activated, then with Silibinin for 24 hours. Total RNAs were extracted, reversely transcribed into cDNA, Quantitative Real-time PCR, and western blot were performed. The mRNA expression levels of Collagen type I and III, αSMA genes, and the level of smad3 phosphorylation in TGF-β activated human HSCs treated with Curcumin were significantly reduced compared to human HSCs untreated with Curcumin. Curcumin is effective in reducing the expression of fibrogenic genes in the activated human HSCs treated with TGFB through downregulation of the TGF-β/smad3 signaling pathway. Therefore, Curcumin possesses significant antifibrotic properties in hepatic fibrosis

Keywords: hepatic fibrosis, human HSCs, curcumin, fibrogenic genes

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Authors: Kadeejah Alsolami, Zainab Alrefay, Husaam Awad

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Obesity and vitamin D deficiency have both been related to cardiovascular disease. The present work aimed to investigate the possible protective effect of vitamin D on cardiac apoptosis in a rat model of dietary-induced obesity. Methods: 30 male Wistar rats included in this study. They were allocated into 4 groups: Control (n=5), animal were fed standard diet for 3 months: Control + vitamin D (VD) (n=5),animals were fed a standard diet with 400IU VD/kg for 3 months: hypercaloric diets group (n=10), animals were fed a high fat diet for 3 months: hypercaloric diet with VD group (n=10), animals were fed a high fat diet with 400IU VD/kg for 3 months. At the beginning of the experiment, the weight and length were measured to assess body mass index (BMI) and repeated every 45 days. Food intake and body weight were monitored throughout the study period. Then rats were sacrificed and heart tissues collected for Quantitative Real-time polymerase chain reaction (qRT-PCR). qRT-PCR used to detect different genetic markers of apoptosis (anti-apoptotic gene (BCL2), a pro-apoptotic gene(BAX), pro-apoptotic genes (FAS, FAS-L), tumour necrosis factor (TNF), mitogen-activated protein kinases (MAPK). Results: FAS and FAS-L gene expression were significantly upregulated in rats fed with high fat diet. And FAS-L gene expression was significantly upregulated in all groups on comparison with control. Whereas Bax gene expression was significantly downregulated in rats fed with high-fat diet supplied with vitamin D. TNF was significantly upregulated in rats fed with high-fat diet treated with vitamin D. MAPK was significantly upregulated in rats fed with high fat diet group, and in rats fed with high-fat diet supplied with vitamin D. Conclusion: The cardiac apoptotic pathways were more activated in rats fed with high-fat than lean rats. And vitamin D protect the heart from the cardiac mitochondrial-dependent apoptotic pathway.

Keywords: apoptosis, heart, obesity, Vitamin D

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Authors: Pureun-Haneul Lee, Byeong-Gon Kim, Sun-Hye Lee, An-Soo Jang

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Background: Nanoparticles may pose adverse health effects due to particulate matter inhalation. Nanoparticle exposure induces cell and tissue damage, causing local and systemic inflammatory responses. The inflammasome is a major regulator of inflammation through its activation of pro-caspase-1, which cleaves pro-interleukin-1β (IL-1β) into its mature form and may signal acute and chronic immune responses to nanoparticles. Objective: The aim of the study was to identify whether nanoparticles exaggerates inflammasome pathway leading to airway inflammation and hyperresponsiveness in an allergic mice model of asthma. Methods: Mice were treated with saline (sham), OVA-sensitized and challenged (OVA), or titanium dioxide nanoparticles. Lung interleukin 1 beta (IL-1β), interleukin 18 (IL-18), NACHT, LRR and PYD domains-containing protein 3 (NLRP3) and caspase-1 levels were assessed with Western Blot. Caspase-1 was checked by immunohistochemical staining. Reactive oxygen species were measured for the marker 8-isoprostane and carbonyl by ELISA. Results: Airway inflammation and hyperresponsiveness increased in OVA-sensitized/challenged mice and these responses were exaggerated by TiO2 nanoparticles exposure. TiO2 nanoparticles treatment increased IL-1β and IL-18 protein expression in OVA-sensitized/challenged mice. TiO2 nanoparticles augmented the expression of NLRP3 and caspase-1 leading to the formation of an active caspase-1 in the lung. Lung caspase-1 expression was increased in OVA-sensitized/challenged mice and these responses were exaggerated by TiO2 nanoparticles exposure. Reactive oxygen species was increased in OVA-sensitized/challenged mice and in OVA-sensitized/challenged plus TiO2 exposed mice. Conclusion: Our data demonstrate that inflammasome pathway activates in asthmatic lungs following nanoparticles exposure, suggesting that targeting the inflammasome may help control nanoparticles-induced airway inflammation and responsiveness.

Keywords: bronchial asthma, inflammation, inflammasome, nanoparticles

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Authors: Israel Oguche

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Journalism practice has faced several challenges across the globe, particularly in developing countries such as Nigeria. While Nigeria has thrived under democratic experiment for twenty years since the return to democracy in 1999, there is still a great lacuna in freedom of expression, such that the presidents, though elected democratically, have had the tendencies to use military might in clamping down on journalism practices across the country. Under Muhammadu Buhari, it seems Nigeria has returned to the military era when powers were used against who says what, on a media, so today, in Nigeria, there are obvious cases of outright human rights violations and detention of journalists whose offenses were not spelled out. From Abiri Jones to Abba Jalingo and Omoyele Sowore, Nigeria journalists have been placed under the cocoon of the tyrannical administration of Muhammadu Buhari, the president, with subsequent clamping down on the instruments of freedoms such as access to justice and fair hearing. This paper gave vivid analytical and empirical perspectives of journalism practice under the dark days of Muhammadu Buhari as Nigeria’s president. The objectives include; examining the core cases of attacks on journalists since 2015 to date, determining the burden of practicing journalism in a tyrannical government, reeling out the effects of restrictive practices of journalism on freedom of expression among Nigerians and proffering solutions for improvement in the years ahead. Using the cognitive dissonance theory, the survey method was used for the study, with qualitative research analysis as a tool for data presentation. In the findings, the number of journalists in jail for publishing objectively under the Buhari administration remains high while the government has clamped down on freedom of expression among the people. The study concluded that there is a need for repelling of laws made by the Nigeria government in order to save the Nigerian journalism industry from total collapse.

Keywords: communication, developing democracy, press freedom, journalism practices

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Authors: Redvan Ghasemlounia, Elham Ansari, Hikmet Kerem Cigizoglu

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Hydrological modeling in arid and semi-arid regions is very important. Iran has many regions with these climate conditions such as Chaharmahal and Bakhtiari province that needs lots of attention with an appropriate management. Forecasting of hydrological parameters and estimation of hydrological events of catchments, provide important information that used for design, management and operation of water resources such as river systems, and dams, widely. Discharge in rivers is one of these parameters. This study presents the application and comparison of some estimation methods such as Feed-Forward Back Propagation Neural Network (FFBPNN), Multi Linear Regression (MLR), Gene Expression Programming (GEP) and Bayesian Network (BN) to predict the daily flow discharge of the Soolegan River, located at Chaharmahal and Bakhtiari province, in Iran. In this study, Soolegan, station was considered. This Station is located in Soolegan River at 51° 14՜ Latitude 31° 38՜ longitude at North Karoon basin. The Soolegan station is 2086 meters higher than sea level. The data used in this study are daily discharge and daily precipitation of Soolegan station. Feed Forward Back Propagation Neural Network(FFBPNN), Multi Linear Regression (MLR), Gene Expression Programming (GEP) and Bayesian Network (BN) models were developed using the same input parameters for Soolegan's daily discharge estimation. The results of estimation models were compared with observed discharge values to evaluate performance of the developed models. Results of all methods were compared and shown in tables and charts.

Keywords: ANN, multi linear regression, Bayesian network, forecasting, discharge, gene expression programming

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Authors: Benoît Leclercq, Ilse Depraetere

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The goal of this presentation is to shed new light on the semantics and pragmatics of be able to. It presents the results of a corpus analysis based on data from the BNC (British National Corpus), and discusses these results in light of a specific stance on the semantics-pragmatics interface taking into account recent developments. Be able to is often discussed in relation to can and could, all of which can be used to express ability. Such an onomasiological approach often results in the identification of usage constraints for each expression. In the case of be able to, it is the formal properties of the modal expression (unlike can and could, be able to has non-finite forms) that are in the foreground, and the modal expression is described as the verb that conveys future ability. Be able to is also argued to expressed actualised ability in the past (I was able/could to open the door). This presentation aims to provide a more accurate pragmatic-semantic profile of be able to, based on extensive data analysis and one that is embedded in a very explicit view on the semantics-pragmatics interface. A random sample of 3000 examples (1000 for each modal verb) extracted from the BNC was analysed to account for the following issues. First, the challenge is to identify the exact semantic range of be able to. The results show that, contrary to general assumption, be able to does not only express ability but it shares most of the root meanings usually associated with the possibility modals can and could. The data reveal that what is called opportunity is, in fact, the most frequent meaning of be able to. Second, attention will be given to the notion of actualisation. It is commonly argued that be able to is the preferred form when the residue actualises: (1) The only reason he was able to do that was because of the restriction (BNC, spoken) (2) It is only through my imaginative shuffling of the aces that we are able to stay ahead of the pack. (BNC, written) Although this notion has been studied in detail within formal semantic approaches, empirical data is crucially lacking and it is unclear whether actualisation constitutes a conventional (and distinguishing) property of be able to. The empirical analysis provides solid evidence that actualisation is indeed a conventional feature of the modal. Furthermore, the dataset reveals that be able to expresses actualised 'opportunities' and not actualised 'abilities'. In the final part of this paper, attention will be given to the theoretical implications of the empirical findings, and in particular to the following paradox: how can the same expression encode both modal meaning (non-factual) and actualisation (factual)? It will be argued that this largely depends on one's conception of the semantics-pragmatics interface, and that this need not be an issue when actualisation (unlike modality) is analysed as a generalised conversational implicature and thus is considered part of the conventional pragmatic layer of be able to.

Keywords: Actualisation, Modality, Pragmatics, Semantics

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Authors: Shayli Varasteh Moradi, Wayne A. Johnston, Dejan Gagoski, Kirill Alexandrov

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The demand for a rapid and more efficient technique to identify protein-protein interaction particularly in the areas of therapeutics and diagnostics development is growing. The method described here is a rapid in vitro protein-protein interaction analysis approach based on AlphaLISA technology combined with Leishmania tarentolae cell-free protein production (LTE) system. Cell-free protein synthesis allows the rapid production of recombinant proteins in a multiplexed format. Among available in vitro expression systems, LTE offers several advantages over other eukaryotic cell-free systems. It is based on a fast growing fermentable organism that is inexpensive in cultivation and lysate production. High integrity of proteins produced in this system and the ability to co-express multiple proteins makes it a desirable method for screening protein interactions. Following the translation of protein pairs in LTE system, the physical interaction between proteins of interests is analysed by AlphaLISA assay. The assay is performed using unpurified in vitro translation reaction and therefore can be readily multiplexed. This approach can be used in various research applications such as epitope mapping, antigen-antibody analysis and protein interaction network mapping. The intra-viral protein interaction network of Zika virus was studied using the developed technique. The viral proteins were co-expressed pair-wise in LTE and all possible interactions among viral proteins were tested using AlphaLISA. The assay resulted to the identification of 54 intra-viral protein-protein interactions from which 19 binary interactions were found to be novel. The presented technique provides a powerful tool for rapid analysis of protein-protein interaction with high sensitivity and throughput.

Keywords: AlphaLISA technology, cell-free protein expression, epitope mapping, Leishmania tarentolae, protein-protein interaction

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Authors: Manali Jain, Neeta Singh, Raunaq Fatima, Soniya Nityanand, Mandakini Pradhan, Chandra Prakash Chaturvedi

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Isolated Congenital Heart Defect (ICHD) is the major cause of neonatal death worldwide among all forms of CHDs. A significant proportion of fetuses with ICHD die in the neonatal period if no treatment is provided. Recently, stem cell therapies have emerged as a potential approach to ameliorate ICHD in children. ICHD is characterized by cardiac structural abnormalities during embryogenesis due to alterations in the cardiomyogenic properties of a pool of cardiac progenitors/ stem cells associated with fetal heart development. The stem cells present in the amniotic fluid (AF) are of fetal origin and may reflect the physiological and pathological changes in the fetus during embryogenesis. Therefore, in the present study, the cardiomyogenic potential of AF-MSCs derived from fetuses with ICHD (ICHD AF-MSCs) has been evaluated and compared with that of AF-MSCs of structurally normal fetuses (normal AF-MSCs). Normal and ICHD AF-MSC were analyzed for the expression of cardiac progenitor markers viz., stage-specific embryonic antigen-1 (SSEA-1), vascular endothelial growth factor 2 (VEGFR-2) and platelet-derived growth factor receptor-alpha (PDGFR-α) by flow cytometry. The immunophenotypic characterization revealed that ICHD AF-MSCs have significantly lower expression of cardiac progenitor markers VEGFR-2 (0.14% ± 0.6 vs.48.80% ± 0.9; p <0.01), SSEA-1 (70.86% ± 2.4 vs. 88.36% ±2.7; p <0.01), and PDGFR-α (3.92% ± 1.8 vs. 47.59% ± 3.09; p <0.01) in comparison to normal AF-MSCs. Upon induction with 5’-azacytidine for 21 days, ICHD AF-MSCs showed a significantly down-regulated expression of cardiac transcription factors such as GATA-4 (0.4 ± 0.1 vs. 6.8 ± 1.2; p<0.01), ISL-1 (2.3± 0.6 vs. 14.3 ± 1.12; p<0.01), NK-x 2-5 (1.1 ± 0.3 vs. 14.1 ±2.8; p<0.01), TBX-5 (0.4 ± 0.07 vs. 4.4 ± 0.3; p<0.001), and TBX-18 (1.3 ± 0.2 vs. 4.19 ± 0.3; p<0.01) when compared with the normal AF-MSCs. Furthermore, immunocytochemical staining revealed that both types of AF-MSCs could differentiate into cardiovascular lineages and express cardiomyogenic, endothelial, and smooth muscle actin markers, viz., cardiac troponin (cTNT), CD31, and alpha-smooth muscle actin (α-SMA). However, normal AF-MSCs showed an enhanced expression of cTNT (p<0.001), CD31 (p<0.01), and α-SMA (p<0.05), compared to ICHD AF-MSCs. Overall, these results suggest that the ICHD-AF-MSCs have a defective cardiomyogenic differentiation potential and that the defects in these stem cells may have a role in the pathogenesis of ICHD.

Keywords: amniotic fluid, cardiomyogenic potential, isolated congenital heart defect, mesenchymal stem cells

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Authors: Adam M. Yates, Julie E. Byles

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Hypertension has been identified as a prominent co-morbidity of obesity. To improve clinical intervention of hypertension, it is critical to identify metrics that most accurately reflect risk for increased morbidity. Two of the most relevant and accurate measures for increased risk of hypertension due to excess adipose tissue are Body Mass Index (BMI) and Waist-Height Ratio (WHtR). Previous research has examined these measures in cross-national and cross-ethnic studies, but has most often relied on secondary means such as meta-analysis to identify and evaluate the efficacy of individual body mass measures. In this study, we instead use cross-sectional analysis to assess the cross-ethnic discriminative power of BMI and WHtR to predict risk of hypertension. Using the WHO SAGE survey, which collected anthropometric and biometric data from respondents in six middle-income countries (China, Ghana, India, Mexico, Russia, South Africa), we implement logistic regression to examine the discriminative power of measured BMI and WHtR with a known population of hypertensive and non-hypertensive respondents. We control for gender and age to identify whether optimum cut-off points that are adequately sensitive as tests for risk of hypertension may be different between groups. We report results for OR, RR, and ROC curves for each of the six SAGE countries. As seen in existing literature, results demonstrate that both WHtR and BMI are significant predictors of hypertension (p < .01). For these six countries, we find that cut-off points for WHtR may be dependent upon gender, age and ethnicity. While an optimum omnibus cut-point for WHtR may be 0.55, results also suggest that the gender and age relationship with WHtR may warrant the development of individual cut-offs to optimize health outcomes. Trends through multiple countries show that the optimum cut-point for WHtR increases with age while the area under the curve (AUROC) decreases for both men and women. Comparison between BMI and WHtR indicate that BMI may remain more robust than WHtR. Implications for public health policy are discussed.

Keywords: hypertension, obesity, Waist-Height ratio, SAGE

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Authors: Sahar Nasr, Lin Li, Edwin Wang

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Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.

Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics

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Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis

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Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.

Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma

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Authors: Antonio Munar-Frau, Sascha Klismoch, Manfred Schmolz, Federico Hernandez-Alfaro, Jordi Caballe-Serrano

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Introduction: Biocompatibility of biomaterials has been proposed as one of the main criteria for treatment success. For guided bone regeneration (GBR), barrier membranes present a conflict given the number of origins and modifications of these materials. The biologic response to biomaterials is orchestrated by a series of events leading to the integration or rejection of the biomaterial, posing questions such as if a longer occlusive property may trigger an inflammatory reaction. Whole blood cultures are a solution to study the immune response to drugs or biomaterials during the first 24-48 hours. The aim of this study is to determine the early immune response of different origins and chemical modifications of barrier membranes. Materials & Methods: 5 different widely used barrier membranes were included in this study: Acellular dermal matrix (AlloDerm, LifeCell®), Porcine Peritoneum (BioGide, Geistlich Pharma®), Porcine Pericardium (Jason, Botiss Biomaterials GmbH®), Porcine Cross-linked collagen (Ossix Plus, Datum Dental®) and d-PTFE (Cytoplast TXT, Osteogenics Biomedical®). Blood samples were extracted from 3 different healthy donors and incubated with the different samples of barrier membranes for 24 hours. After the incubation time, serum samples were obtained and analyzed by means of biocompatibility assays taking into account 42 markers. Results: In an early stage of the inflammatory response, the Acellular dermal matrix, porcine peritoneum and porcine cross-linked collagen expressed similar patterns of cytokine expression with a great manifestation of ENA 78. Porcine pericardium and d-PTFE presented similar cytokine activation, especially for MMP-3 and MMP-9, although other cytokines were highlighted with lower expression. For the later immune response, Porcine peritoneum and acellular dermal matrix MCP-1 and IL-15 were evident. Porcine pericardium, porcine cross-linked collagen and d-PTFE presented a high expression of IL-16 and lower manifestation of other cytokines. Different behaviors depending on an earlier or later stage of the inflammation process were observed. Barrier membrane inflammatory expression does not only differ depending on the origin, variables such as treatment of the collagen and polymers may also have a great impact on the cytokine expression of the studied barrier membranes during inflammation. Conclusions: Surface treatment and modifications might affect the biocompatibility of the membranes, as different cytokine expressions were evidently depending on the origin of the biomaterial. This study is only a brushstroke regarding the biocompatibility of materials, as it is one of the pioneer studies for ex vivo barrier membranes assays. Studies regarding surface modification are needed in order to clarify mystifications of barrier membrane science.

Keywords: biomaterials, bone regeneration, biocompatibility, inflammation

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Authors: T. M. L. Hoang, G. Tan, S. D. Bhowmik, B. Williams, A. Johnson, M. R. Karbaschi, Y. Cheng, H. Long, S. G. Mundree

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Iron deficiency is a worldwide problem affecting both developed and developing countries. Currently, two major approaches namely iron supplementation and food fortification have been used to combat this issue. These measures, however, are limited by the economic status of the targeted demographics. Iron biofortification through genetic modification to enhance the inherent iron content and bioavailability of crops has been employed recently. Several important crops such as rice, wheat, and banana were reported successfully improved iron content via this method, but there is no known study in legumes. Chickpea (Cicer arietinum) is an important leguminous crop that is widely consumed, particularly in India where iron deficiency anaemia is prevalent. Chickpea is also an ideal pulse in the formulation of complementary food between pulses and cereals to improve micronutrient contents. This project aims at generating enhanced ion accumulation and bioavailability chickpea through the exogenous expression of genes related to iron transport and iron homeostasis in chickpea plants. Iron-Regulated Transport (IRT) and Ferritin genes in combination were transformed into chickpea half-embryonic axis by agrobacterium–mediated transformation. Transgenic independent event was confirmed by Southern Blot analysis. T3 leaves and seeds of transgenic chickpea were assessed for iron contents using LA-ICP-MS (Laser Ablation – Inductively Coupled Plasma Mass Spectrometry) and ICP-OES (Inductively Coupled Plasma Optical Emission Spectrometry). The correlation between transgene expression levels and iron content in T3 plants and seeds was assessed using qPCR. Results show that iron content in transgenic chickpea expressing the above genes significantly increased compared to that in non-transgenic controls.

Keywords: iron biofortification, chickpea, IRT, ferritin, Agrobacterium-mediated transformation, LA-ICP-MS, ICP-OES

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Authors: Henrik L. Funke, Lars Ulke-Winter, Sandra Gelbrich, Lothar Kroll

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This work reports about an approach for an automatic adaptation of concrete formulations based on genetic algorithms (GA) to optimize a wide range of different fit-functions. In order to achieve the goal, a method was developed which provides a numerical description of a fibre reinforced concrete (FRC) mixture regarding the production technology and the property spectrum of the concrete. In a first step, the FRC mixture with seven fixed components was characterized by varying amounts of the components. For that purpose, ten concrete mixtures were prepared and tested. The testing procedure comprised flow spread, compressive and bending tensile strength. The analysis and approximation of the determined data was carried out by GAs. The aim was to obtain a closed mathematical expression which best describes the given seven-point cloud of FRC by applying a Gene Expression Programming with Free Coefficients (GEP-FC) strategy. The seven-parametric FRC-mixtures model which is generated according to this method correlated well with the measured data. The developed procedure can be used for concrete mixtures finding closed mathematical expressions, which are based on the measured data.

Keywords: concrete design, fibre reinforced concrete, genetic algorithms, GEP-FC

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Authors: Denise F. Brown, Melina McConatha

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African Americans utilizing the art of vocal expressions, particularly for self-expression, has been a historical avenue of advocating for social justice and human rights. Vocal expressions can take many forms, such as singing, poetry, storytelling, and acting. Many well-known artists, politicians, leaders, and teachers used their voices to promote the causes and concerns of the African American community as well as the expression of their own experiences of being 'black' in America. The purpose of this project was to evaluate the perceptions of African American students in utilizing their voices for self-awareness, interview skills, and social change after attending a three-part workshop on vocal advocacy. This research utilized the framework of black feminism to understand empowerment in advocacy and self-expression. Students participated in learning about the power of their voices, and what purpose presence, and passion they discovered through the Immersive Voice workshop. There were three areas covered in the workshop. The first area was the power of the voice, the second area was the application of vocal passion, and the third area was applying the vocal power to express personal interest, interests of advocating for others, and confidence and speaking to others to further careers, i.e., using vocal power for job interviewing skills. The students were instructed to prepare for the workshops by completing a pre-workshop open-ended survey. There were a total of 15 students that participated. After the workshop ended, the students were instructed to complete a post-workshop survey. The surveys were assessed by evaluating both themes and codes from student's written feedback. From the pre-workshop survey, students were given a survey for them to provide feedback regarding the power of voice prior to participating in the workshops. From the student's responses, the theme (advocating for self and others) emerged as it related to student's feedback on what it means to advocate. There were three codes that led to the theme, having knowledge about advocating for self and others, gaining knowledge to advocate for self and others, and using that knowledge to advocate for self and others. After the students completed participation in the workshops, a post workshop- survey was given to the students. Students' feedback was assessed, and the same theme emerged, 'advocating for self and others.' The codes related to the theme, however, were different and included using vocal power (a term students learned during the workshop) to represent self, represent others, and obtain a job/career. In conclusion, the results of the survey showed that students still perceived advocating as speaking up for themselves and other people. After the workshop, students still continued to associate advocacy with helping themselves and helping others but were able to be more specific about how the sound of their voice could help in advocating, and how they could use their voice to represent themselves in getting a job or starting a career.

Keywords: advocacy, command, self-expression, voice

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Authors: Florian Billing, Soren Segan, Meike Jakobi, Elsa Arefaine, Aliki Jerch, Xin Xiong, Matthias Becker, Thomas Joos, Burkhard Schlosshauer, Ulrich Rothbauer, Nicole Schneiderhan-Marra, Hanna Hartmann, Christopher Shipp

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The immune response plays a major role in implant biocompatibility, but an understanding of how to design biomaterials for specific immune responses is yet to be achieved. We aimed to better understand how changing certain material properties can drive immune responses. To this end, we tested immune response to experimental implant coatings that vary in specific characteristics. A layer-by-layer approach was employed to vary surface charge and wettability. Human-based in vitro models (THP-1 macrophages and primary peripheral blood mononuclear cells (PBMCS)) were used to assess immune responses using multiplex cytokine analysis, flow cytometry (CD molecule expression) and microscopy (cell morphology). We observed dramatic differences in immune response due to specific alterations in coating properties. For example altering the surface charge of coating A from anionic to cationic resulted in the substantial elevation of the pro-inflammatory molecules IL-1beta, IL-6, TNF-alpha and MIP-1beta, while the pro-wound healing factor VEGF was significantly down-regulated. We also observed changes in cell surface marker expression in relation to altered coating properties, such as CD16 on NK Cells and HLA-DR on monocytes. We furthermore observed changes in the morphology of THP-1 macrophages following cultivation on different coatings. A correlation between these morphological changes and the cytokine expression profile is ongoing. Targeted changes in biomaterial properties can produce vast differences in immune response. The properties of the coatings examined here may, therefore, be a method to direct specific biological responses in order to improve implant biocompatibility.

Keywords: biomaterials, coatings, immune system, implants

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Authors: Dawood Al Chanti, Alice Caplier

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Sparse representations of signals have received a great deal of attention in recent years. In this paper, the interest of using sparse representation as a mean for performing sparse discriminative analysis between spontaneous facial expressions is demonstrated. An automatic facial expressions recognition system is presented. It uses a KSVD-SVM approach which is made of three main stages: A pre-processing and feature extraction stage, which solves the problem of shared subspace distribution based on the random projection theory, to obtain low dimensional discriminative and reconstructive features; A dictionary learning and sparse coding stage, which uses the KSVD model to learn discriminative under or over dictionaries for sparse coding; Finally a classification stage, which uses a SVM classifier for facial expressions recognition. Our main concern is to be able to recognize non-basic affective states and non-acted expressions. Extensive experiments on the JAFFE static acted facial expressions database but also on the DynEmo dynamic spontaneous facial expressions database exhibit very good recognition rates.

Keywords: dictionary learning, random projection, pose and spontaneous facial expression, sparse representation

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Authors: Saylav Ejder Bora, Arife Erdogan, Mumin Alper Erdogan, Oytun Erbas, Ismet Parlak

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Objective: The aim of this study was to evaluate histological, electrical and biochemical effects of metoprolol, lipid emulsion and magnesium sulphate as an alternative method to be used in preventing long QT emergence, that is among the lethal consequences of amitryptiline toxicity. Methods: Thirty Sprague- Dawley male rats were included. Rats were randomly separated into 5 groups. First group was administered saline only while the rest had received amitryptiline 100 mg/kg + saline, 5 mg/kg metoprolol, 20 ml/kg lipid emulsion and 75 mg/kg magnesium sulphate (MgSO4) intraperitoneally. ECG at DI lead, biochemical tests following euthanasia were performed in all groups after 1 hour of administration. Cardiac tissues were removed, sections were prepared and examined. Results: QTc values were significantly shorter in the rest when compared to amitryptiline+ saline group. While lipid emulsion did not affect proBNP and troponin values biochemically as compared to that of the control group, histologically, it was with reduced caspase 3 expression. Though statistically insignificant in the context of biochemical changes, pro-BNP and urea levels were lower in the metoprolol group when compared to controls. Similarly, metoprolol had no statistically significant effect on histological caspase 3 expression in the group that was treated with amitryptiline+metoprolol. On the other hand, there was a statistically significant decrease in Troponin, pro-BNP and urea levels as well as significant decline in histological caspase 3 expression within the MgSO4 group when compared to controls. Conclusion: As still a frequent cause of mortality in emergency units, administration of MgSO4, lipid emulsion and metoprolol might be beneficial in alternative treatment of cardiovascular toxicity caused by tricyclic antidepressant overdose, whether intake would be intentional or accidental.

Keywords: amitryptiline, cardiovascular toxicity, long QT, Rat Model

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Authors: Zhongyang Sun, Shu Zhang

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In osteoblasts, L-type voltage sensitive calcium channels (LTCCs), especially the Cav1.2 LTCCs, play fundamental roles in cellular responses to external stimuli including both mechanical forces and hormonal signals. Several lines of evidence have revealed that the density of bone is increased and the resorption of bone is decreased when these calcium channels in osteoblasts are activated. And numerous studies have shown that mechanical loading promotes bone formation in the modeling skeleton, whereas removal of this stimulus in microgravity results in a reduction in bone mass. However, the effect of microgravity on LTCCs in osteoblasts is still unknown. The aim of this study was to determine whether microgravity exerts influence on LTCCs in osteoblasts and the possible mechanisms underlying. In this study, we demonstrate that simulated microgravity substantially inhibits LTCCs in osteoblast by suppressing the expression of Cav1.2. Then we show that the up-regulation of miR-103 is involved in the down-regulation of Cav1.2 expression and inhibition of LTCCs by simulated microgravity in osteoblasts. Our study provides a novel mechanism of simulated microgravity-induced adverse effects on osteoblasts, offering a new avenue to further investigate the bone loss caused by microgravity.

Keywords: L-type voltage sensitive calcium channels, Cav1.2, osteoblasts, microgravity

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Authors: Seyhan Sahan-Firat, Meryem Temiz-Resitoglu, Demet Sinem Guden, Sefika Pinar Kucukkavruk, Bahar Tunctan, Ayse Nihal Sari, Zumrut Kocak

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We hypothesized that mTOR inhibition may prevent the multiple organ failures following severe multiple tissue injury associated with increased NADPH oxidase system activity occur in zymosan-induced systemic inflammation. Therefore, we investigated the role of mTOR in oxidative/nitrosative stress associated with increase in NADPH oxidase activity in zymosan-induced systemic inflammation model in rats. Male Wistar rats received saline (4 ml/kg, i.p.) and zymosan (500 mg/kg, i.p.) at time 0. Saline, or zymosan-treated rats were given rapamycin (1 mg/kg, i.p.) 1 h after saline or zymosan injections. Rats were sacrified 4 h after zymosan challenge and kidney, heart, thoracic aorta, and superior mesenteric artery were collected. NADPH oxidase activity, p22phox, gp91phox, and p47phox protein expression and nitrotyrosine levels were measured in tissue samples. Zymosan administration caused an increase in NADPH oxidase activity, p22phox, gp91phox, and p47phox protein expression and nitrotyrosine levels in kidney, heart, thoracic aorta, and superior mesenteric artery. These changes caused by zymosan reversed by rapamycin, a selective mTOR inhibitor. Rapamycin alone had no effect on the parameters measured. Our results demonstrated that zymosan-induced oxidative/nitrosative stress presumably due to enhanced activity of NADPH oxidase, expression of p22phox, gp91phox, and p47phox and production of peroxynitrite were mediated by mTOR. [This work was financially supported by Research Foundation of Mersin University (2016-2-AP3-1900)].

Keywords: oxidative stress, mTOR, nitrosative stress, zymosan

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Authors: Suliman A. I. Ali, Mory Mandiana Diakite, Saqib Ali, Man-Qun Wang

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Lesser grain borer, Rhyzopertha dominica, is a causing damages of stored grains all tropical and subtropical area in the global, according to the information of antenna cDNA library of R. dominica, three olfactory protein genes, including R.domica CSPs2, R.domica PBPs1, R.domica PBPs2 genes (GenBank accessions are KJ186798.1, KJ186830.1, KJ186831.1 separately.), were successfully cloned. For sequencing and phylogenetic analysis, R.domica CSPs1 and R.domica CSPs2 belonged to Minus-C CSPs showed that have 4 conserved cysteine residues, while R.domica PBPs1 and R.domica PBPs2 showed conserved amino acids in all PBPs six conserved cysteine residues. The results of transcription expression level of PBPs1 and PBPs2 of R. dominica showed that the expression level of R.domnica PBP2 is much higher than that of R.domnica PBP1. The variation transcription level at the different developmental time suggested the PBP1, and PBP2 had their particular job in searching food sources, mates and oviposition sites.

Keywords: Rhyzopertha dominica, CSPs, PBPs, molecular cloning

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Authors: Liliana Rytel, Jarosław Całka

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One of the diseases that are very common health problem of modern man is the stomach hyperacidity. It is well known that this pathological state, during which gastric glands secrete too much of hydrochloric acid can be caused due to various factors such as stress, eating habits, alcohol, smoking and some, especially anti-inflammatory drugs. Moreover, hyperacidity is recognized as one of factors leading to development of peptic ulcer disease. Therefore, we analyzed expression of substance P (SP) and neuronal isoform of nitric oxide synthase (nNOS) in the porcine nodose ganglion sensory neurons innervating prepyloric stomach region in physiological state and following intragastric infusion of hydrochloric acid. The study was performed on 8 immature gilts of the Large White Polish breed. All animals were injected retrograde marker Fast Blue (FB) into the anterior prepyloric stomach wall. After injections of FB, pigs were divided into two groups: control (group C; n = 4) and experimental (HCL group, n = 4) and after convalescence period of 23 days, animals of HCL group were subjected to renewed anaesthesia. Then, 0.25 M aqueous solution of hydrochloric acid with a dose of 5 ml/kg body weight was administered intragastrically with use of a stomach tube. On 28th day, all control and HCL pigs were euthanized and bilateral reght (rNG) and left (lNG) were collected. Cryostat sections were processed for double immunofluorescence using anibodies against SP and NOS. Immunofluorescence staining in the even-numbered ganglia nodes showed the presence of FB-positive cells expressing SP (45,9 ± 3,38% in rNG and 60,4 ± 1,71% in lNG), and nNOS (34,9 ± 6,83% in rNG and 49,9 ± 9,32% in lNG). In HCL group increased expression of both SP (54,8 ± 5,34% in rNG and 56,9 ± 3,28 % in lNG) as well as nNOS (54,9 ± 4,45% in rNG and 52,5 ± 2,17 % in lNG) in FB+ perikaria was found. The acquired results suggest that SP and nNOS are neurotransmitters and/ or neuromodulators participating in the sensory regulation of the prepyloric region of porcine stomach function as well as their potential role in development of the stomach inflamatory state.

Keywords: nNOS, nodose ganglion, pig, SP

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Authors: Mudasir Ahmad Syed, Raashid Ahmd Wani, Mashooq Ahmad Dar, Uneeb Urwat, Riaz Ahmad Shah, Nazir Ahmad Ganai

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Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) is a primary avian pathogen responsible for severe intestinal pathology in younger chickens and economic losses. However, the Salmonella Typhimurium is also able to cause infection in humans, described by typhoid fever and acute gastro-intestinal disease. A study was conducted at days to investigate pathological, histopathological, haemato-biochemical, immunological and expression kinetics of NRAMP (natural resistance associated macrophage protein) gene family (NRAMP1 and NRAMP2) in broiler chickens following experimental infection of Salmonella Typhimurium at 0,1,3,5,7,9,11,13 and 15 days respectively. Infection was developed in birds through oral route at 2×108 CFU/ml. Clinical symptoms appeared 4 days post infection (dpi) and after one-week birds showed progressive weakness, anorexia, diarrhea and lowering of head. On postmortem examination, liver showed congestion, hemorrhage and necrotic foci on surface, while as spleen, lungs and intestines revealed congestion and hemorrhages. Histopathological alterations were principally observed in liver in second week post infection. Changes in liver comprised of congestion, areas of necrosis, reticular endothelial hyperplasia in association with mononuclear cell and heterophilic infiltration. Hematological studies confirm a significant decrease (P<0.05) in RBC count, Hb concentration and PCV. White blood cell count showed significant increase throughout the experimental study. An increase in heterophils was found up to 7dpi and a decreased pattern was observed afterwards. Initial lymphopenia followed by lymphocytosis was found in infected chicks. Biochemical studies showed a significant increase in glucose, AST and ALT concentration and a significant decrease (P<0.05) in total protein and albumin level in the infected group. Immunological studies showed higher titers of IgG in infected group as compared to control group. The real time gene expression of NRAMPI and NRAMP2 genes increased significantly (P<0.05) in infected group as compared to controls. The peak expression of NRAMP1 gene was seen in liver, spleen and caecum of infected birds at 3dpi, 5dpi and 7dpi respectively, while as peak expression of NRAMP2 gene in liver, spleen and caecum of infected chicken was seen at 9dpi, 5dpi and 9dpi respectively. This study has role in diagnostics and prognostics in the poultry industry for the detection of salmonella infections at early stages of poultry development.

Keywords: biochemistry, histopathology, NRAMP, poultry, real time expression, Salmonella Typhimurium

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Authors: J. H. Bang, H. J. Baek, K. I. Kim, B. J. Lee, H. J. Jung, H. J. Jang, S. K. Jung

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Asthma is a chronic inflammatory lung disease characterized by airway hyper responsiveness (AHR), airway obstruction and airway wall remodeling responsible for significant morbidity and mortality worldwide. Genetic and environment factors may result in asthma, but there are no the exact causes of asthma. Chungpye-tang (CPT) has been prescribed as a representative aerosol agent for patients with dyspnea, cough and phlegm in the respiratory clinic at Kyung Hee Korean Medicine Hospital. This Korean herbal medicines have the effect of dispelling external pathogen and dampness pattern. CPT is composed of 4 species of herbal medicines. The 4 species of herbal medicines are Ephedrae herba, Pogostemonis(Agatachis) herba, Caryophylli flos and Zingiberis rhizoma crudus. CPT suppresses neutrophil infiltration and the production of pro-inflammatory cytokines in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. Moreover, the anti-inflammatory effects of CPT on a mouse model of Chronic Obstructive Pulmonary Disease (COPD) was proved. Activation of the NF-κB has been proven that it plays an important role in inflammation via inducing transcription of pro-inflammatory genes. Over-expression of NF-κB has been believed be related to many inflammatory diseases such as arthritis, gastritis, asthma and COPD. So we firstly hypothesize whether CPT has an anti-inflammatory effect on asthmatic human airway epithelial tissue via inhibiting NF-κB pathway. In this study, CPT was extracted with distilled water for 3 hours at 100°C. After process of filtration and evaporation, it was freeze dried. And asthmatic human lung tissues were provided by MatTek Corp. We investigated the precise mechanism of the anti-inflammatory effect of CPT by western blotting analysis. We observed whether the decoction extracts could reduce NF-κB activation, COX-2 protein expression and NF-κB-mediated pro-inflammatory cytokines such as TNF-α, eotaxin, IL-4, IL-9 and IL-13 in asthmatic human lung tissue. As results of this study, there was a trend toward decreased NF-κB expression in asthmatic human airway epithelial tissue. We found that the inhibition effects of CPT on COX-2 expression was not determined. IL-9 and IL-13 secretion was significantly reduced in the asthmatic human lung tissue treated with CPT. Overall, our results indicate that CPT has an anti-inflammatory effect through blocking the signaling pathway of NF-κB, thereby CPT may be a potential remedial agent for allergic asthma.

Keywords: Chungpye-tang, allergic asthma, asthmatic human airway epithelial tissue, nuclear factor kappa B (NF-κB) pathway, COX-2

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Authors: Amber Zahid, Fatima Naseer, Maham Atta, Fareeha Zafar

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Corporate social authority (CSR) talk, scholarly scrutinize, open arrangement and media editorials, which have thrived in the previous not many decades according to the craving to characterize the nexus between business and social order had a tendency to center primarily on expansive corporate associations which are required to act mindfully. The enormous organizations have for a long time pulled in huge volume of expositive expression on CSR. Almost no expositive expression is presently accessible to upgrade our comprehension about the engagement of little and medium-measured endeavors (SMEs) in CSR. The SMEs, regularly characterized differently regarding turnover terrible stake quality, proprietorship structure and the amount of workers, is a noteworthy part worldwide as far as monetary ecological and the social effect they make. This paper endeavoured to extend this obvious research bay, characterized the way of SMEs the total commitments of the area to economies of both advanced and advancing countries and their part engagement in CSR. The study embraced qualitative literary works review strategy. An audit of the negligible expositive expression furnished knowledge and characterized the course of examination in this significant and underexplored region of study. SMEs were discovered to perform parts connected with group improvement, representative activities, consumerism, natural movements, and production network necessities. To defeat the imperatives going up against SMEs engagement in CSR activities the paper prescribed expanded assets, preparing programs advancement of SMEs arranged instruments and guidelines to guide appropriation and execution and government mediation systems to make the fundamental motivating forces and underpin administrations for adequate engagement.

Keywords: corporate social responsibility, small and medium-sized enterprises, responsible practices, corporate citizenship

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Authors: R. Prinsloo

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Amniotic fluid stem cells (AFSC) have been shown to contribute towards the amelioration of Acute Renal Failure (ARF), but the mechanisms underlying the renoprotective effect are largely unknown. Therefore, the main goal of the current study was to evaluate the therapeutic efficacy of AFSC in a cisplatin-induced rat model of ARF and to investigate the underlying mechanisms responsible for its renoprotective effect. To study the therapeutic efficacy of AFSC, ARF was induced in Wistar rats by an intra-peritoneal injection of cisplatin, and five days after administration, the rats were randomized into two groups and injected with either AFSC or normal saline intravenously. On day 8 and 12 after cisplatin injection, i.e., day 3 and day7 post-therapy respectively, the blood biochemical parameters, histopathological changes, apoptosis, and expression of pro-apoptotic, anti-apoptotic and autophagy-related proteins in renal tissues were studied in both groups of rats. Administration of AFSC in ARF rats resulted in improvement of renal function and attenuation of renal damage as reflected by significant decrease in blood urea nitrogen, serum creatinine levels, tubular cell apoptosis as assessed by Bax/Bcl2 ratio, and expression of the pro-apoptotic proteins viz. PUMA, Bax, cleaved caspase-3 and cleaved caspase-9 as compared to saline-treated group. Furthermore, in the AFSC-treated group as compared to saline-treated group, there was a significant increase in the activation of autophagy as evident by increased expression of LC3-II, ATG5, ATG7, Beclin1 and phospho-AMPK levels with a concomitant decrease in phospho-p70S6K and p62 expression levels. To further confirm whether the protective effects of AFSC on cisplatin-induced apoptosis were dependent on autophagy, chloroquine, an autophagy inhibitor was administered by the intra-peritoneal route. Chloroquine administration led to significant reduction in the anti-apoptotic effects of the AFSC therapy and further deterioration in the renal structure and function caused by cisplatin. Collectively, our results put forth that AFSC ameliorates cisplatin-induced ARF through induction of autophagy and inhibition of apoptosis. Furthermore, the protective effects of AFSC were blunted by chloroquine, highlighting that activation of autophagy is an important mechanism of action for the protective role of AFSC in cisplatin-induced renal injury.

Keywords: best interest of the child, children's rights, parent and child relationship, parental responsibilities and rights

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