Search results for: mismatch repair protein
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2938

Search results for: mismatch repair protein

868 QSAR, Docking and E-pharmacophore Approach on Novel Series of HDAC Inhibitors with Thiophene Linker as Anticancer Agents

Authors: Harish Rajak, Preeti Patel

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HDAC inhibitors can reactivate gene expression and inhibit the growth and survival of cancer cells. The 3D-QSAR and Pharmacophore modeling studies were performed to identify important pharmacophoric features and correlate 3D-chemical structure with biological activity. The pharmacophore hypotheses were developed using e-pharmacophore script and phase module. Pharmacophore hypothesis represents the 3D arrangement of molecular features necessary for activity. A series of 55 compounds with well-assigned HDAC inhibitory activity was used for 3D-QSAR model development. Best 3D-QSAR model, which is a five PLS factor model with good statistics and predictive ability, acquired Q2 (0.7293), R2 (0.9811) and standard deviation (0.0952). Molecular docking were performed using Histone Deacetylase protein (PDB ID: 1t69) and prepared series of hydroxamic acid based HDAC inhibitors. Docking study of compound 43 show significant binding interactions Ser 276 and oxygen atom of dioxine cap region, Gly 151 and amino group and Asp 267 with carboxyl group of CONHOH, which are essential for anticancer activity. On docking, most of the compounds exhibited better glide score values between -8 to -10.5. We have established structure activity correlation using docking, energetic based pharmacophore modelling, pharmacophore and atom based 3D QSAR model. The results of these studies were further used for the design and testing of new HDAC analogs.

Keywords: Docking, e-pharmacophore, HDACIs, QSAR, Suberoylanilidehydroxamic acid.

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867 RACK1 Integrates Light and Brassinosteroid Signaling to Coordinate Cell Division During Root Soil Penetration

Authors: Liang Jiansheng, Zhu Wei

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Light and brassinosteroids are essential external and internal cues for plant survival. Although the coordination of light with phytohormone signals is crucial for plant growth and development, the molecular connection between light and brassinosteroid signaling during root soil penetration remains elusive. Here, we reveal that light-stabilized RACK1 couples a brassinosteroid signaling cascade to drive cell division in root meristems. RACK1 family scaffold proteins positively regulate light-induced the promotion of root elongation during soil penetration. Under the light condition, RACK1A interacts with both phyB and SPA1, then reinforces the phyB-SPA1 association to accumulate its abundance in roots. In response to brassinosteroid signals, RACK1A competes with BKI1 to attenuate the BRI1-BKI1 interaction, thereby leading to activating BRI1 actions in root development. Furthermore, RACK1A binds to BES1 to repress its DNA binding activity toward the target gene CYCD3;1. This ultimately allows to release the inhibition of CYCD3;1 transcription, and promotes cell division during root growth. Our study illustrates a new mechanistic model of how plants engage scaffold proteins in transducing light information to facilitate brassinosteroid signaling for root growth in the soil.

Keywords: root growth, cell division, light signaling, brassinosteroid signaling, soil penetration, scaffold protein, RACK1

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866 The Importance of Efficient and Sustainable Water Resources Management and the Role of Artificial Intelligence in Preventing Forced Migration

Authors: Fateme Aysin Anka, Farzad Kiani

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Forced migration is a situation in which people are forced to leave their homes against their will due to political conflicts, wars and conflicts, natural disasters, climate change, economic crises, or other emergencies. This type of migration takes place under conditions where people cannot lead a sustainable life due to reasons such as security, shelter and meeting their basic needs. This type of migration may occur in connection with different factors that affect people's living conditions. In addition to these general and widespread reasons, water security and resources will be one that is starting now and will be encountered more and more in the future. Forced migration may occur due to insufficient or depleted water resources in the areas where people live. In this case, people's living conditions become unsustainable, and they may have to go elsewhere, as they cannot obtain their basic needs, such as drinking water, water used for agriculture and industry. To cope with these situations, it is important to minimize the causes, as international organizations and societies must provide assistance (for example, humanitarian aid, shelter, medical support and education) and protection to address (or mitigate) this problem. From the international perspective, plans such as the Green New Deal (GND) and the European Green Deal (EGD) draw attention to the need for people to live equally in a cleaner and greener world. Especially recently, with the advancement of technology, science and methods have become more efficient. In this regard, in this article, a multidisciplinary case model is presented by reinforcing the water problem with an engineering approach within the framework of the social dimension. It is worth emphasizing that this problem is largely linked to climate change and the lack of a sustainable water management perspective. As a matter of fact, the United Nations Development Agency (UNDA) draws attention to this problem in its universally accepted sustainable development goals. Therefore, an artificial intelligence-based approach has been applied to solve this problem by focusing on the water management problem. The most general but also important aspect in the management of water resources is its correct consumption. In this context, the artificial intelligence-based system undertakes tasks such as water demand forecasting and distribution management, emergency and crisis management, water pollution detection and prevention, and maintenance and repair control and forecasting.

Keywords: water resource management, forced migration, multidisciplinary studies, artificial intelligence

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865 Sun Protection Factor (SPF) Determination of Sericin Cream and Niosomal Gel

Authors: Farzad Doostishoar, Abbas Pardakhty, Abdolreza Hassanzadeh, Sudeh salarpour, Elham Sharif

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Background: Sericin is a protein extracted from silk and has antioxidant, antimicrobial, antineoplastic, wound healing and moisturizing properties. Different cosmetic formulation of sericin is available in different countries such as Japan and the other south-eastern Asian countries. We formulated and evaluated the sunscreen properties of topical formulations of sericin by an in vitro method. Method: Niosomes composed of sorbitan palmitate (Span 40), polysorbate 40 (Tween 40) and cholesterol (300 µmol, 3.5:3.5:3 molar ratio) were prepared by film hydration technique. Sericin was dissolved in normal saline and the lipid hydration was carried out at 60°C and the niosomes were incorporated in a Carbomer gel base. A W/O cream was also prepared and the release of sericin was evaluated by using Franz diffusion cell. Particle size analysis, sericin encapsulation efficiency measurement, morphological studies and stability evaluation were done in niosomal formulations. SPF was calculated by using Transpore tape in vitro method for both formulations. Results: Niosomes had high stability during 6 months storage at 4-8°C. The mean volume diameter of niosomes was less than 7 µm which is ideal for sustained release of drugs in topical formulations. The SPF of niosomal gel was 25 and higher than sericin cream with a diffusion based release pattern of active material. Conclusion: Sericin can be successfully entrapped in niosomes with sustained release pattern and relatively high SPF.

Keywords: sericin, niosomes, sun protection factor, cream, gel

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864 Clustering of Natural and Nature Derived Compounds for Cardiovascular Disease: Pharmacophore Modeling

Authors: S. Roy, R. Rekha, K. Sriram, G. Subhadra, R. Johana

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Cardiovascular disease remains a leading cause of death in most industrialized countries. Many chemical drugs are available in the market which targets different receptor proteins related to cardiovascular diseases. Of late the traditional herbal drugs are safer when compared to chemical drugs because of its side effects. However, many herbal remedies used in treating cardiovascular diseases have not undergone scientific assessment to prove its pharmacological activities. There are many natural compounds, nature derived and Natural product mimic compounds are available which are in the market as approved drug. In the most of the cases drug activity at the molecular level are not known. Here we have categorized those compounds with our experimental compounds in different classes based on the structural similarity and physicochemical properties, using a tool, Chemmine and has attempted to understand the mechanism of the action of a experimental compound, which are clustered with Simvastatin, Lovastatin, Mevastatin and Pravastatin. Target protein molecule for Simvastatin, Lovastatin, Mevastatin and Pravastatin is HMG-CoA reductase, so we concluded that the experimental compound may be able to bind to the same target. Molecular docking and atomic interaction studies with simvastatin and our experimental compound were compared. A pharmacophore modeling was done based on the experimental compound and HMG-CoA reductase inhibitor.

Keywords: molecular docking, physicochemical properties, pharmacophore modeling structural similarity, pravastatin

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863 Identification and Characterization of Genes Expressed in Diseased Condition Silkworms (Bombyx mori): A Systematic Investigation

Authors: Siddharth Soni, Gourav Kumar Pandey, Sneha Kumari, Dev Mani Pandey, Koel Mukherjee

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The silkworm Bombyx mori is a commercially important insect, but a major roadblock in silk production are silkworm diseases. Flacherie is one of the diseases of the silkworm, that affects the midgut of the 4th and 5th instar larvae and eventually makes them lethargic, stop feeding and finally result in their death. The concerned disease is a result of bacterial and viral infection and in some instances a combination of both. The present study aims to identify and study the expression level of genes in the flacherie condition. For the said work, total RNA was isolated from the infected larvae at their most probable infectious instar and cDNA was synthesized using Reverse Transcriptase PCR (RT-PCR). This cDNA was then used to amplify disease relalted genes whose expression levels were checked using quantitaive PCR (qPCR) using the double delta Ct method. Cry toxin receptors like APN and BtR-175, ROS mediator Dual Oxidase are few proteins whose genes were overexpressed. Interestingly, pattern recognition receptors (PRRs) C-type lectins' genes were found to be downregulated. The results explain about the strong expression of genes that can distinguish the concerned protein in the midgut of diseased silkworm and thereby aiding knowledge in the field of inhibitor designing research.

Keywords: Bombyx mori, flacherie disease, inhibitor designing, up and down regulation

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862 Protective Effects of Sinapic Acid on Organophosphate Poisoning

Authors: Turker Yardan, Bahattin Avci, S. Sirri Bilge, Ayhan Bozkurt

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Sinapic acid (SA) is a phenylpropanoid compound with anti-inflammatory, antioxidant, and neuroprotective activities. The purpose of this study was to characterize the possible protective effect of sinapic acid on chlorpyrifos (CPF), a common organophosphorus pesticide used worldwide, induced toxicity in rats. Forty male and female rats (240-270 g) were used in this study. Each group was composed of 5 male and 5 female rats. Sinapic acid (20 mg/kg or 40 mg/kg) or vehicle (olive oil, 1 ml ⁄ rat) were given orally for 5 days. CPF (279 mg/kg) or vehicle (peanut oil, 2 ml ⁄ kg, s.c.) was administered on the sixth day, immediately after the recording of the body weight of the animals. Twenty four hours following CPF administration body weight, body temperature and locomotor activity values were recorded before decapitation of the animals. Trunk blood, brain, and liver samples were collected for biochemical examinations. Chlorpyrifos administration decreased butyrylcholinesterase activity in blood, brain, and liver, while it increased malondialdehyde (MDA) levels and advanced oxidation protein products (AOPPs) (p < 0.01 - 0.001). Additionally, CPF administration reduced the body weight, body temperature, and locomotor activity values of the animals (p < 0.01 - 0.001). All these physiological and biochemical changes induced by CPF were reduced with the 40 mg/kg dose of SA (p < 0.05 - 0.001). Our results suggest that SA administration ameliorates CPF induced toxicity in rats, possibly by supporting the antioxidant mechanism.

Keywords: antioxidant, Chlorpyrifos, poisoning, sinapic acid

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861 Sirt1 Promotes C2C12 Myoblast Cell Proliferation by Myostatin Signaling Pathway

Authors: Cuili Yang, Chengcao Sun, Ruilin Xue, Yongyong Xi, Liang Wang, Dejia Li

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Backgrounds: Previous studies showed that Sirt1 plays an important role in C2C12 myoblast cell proliferation, but the mechanism(s) involved in this process remains unclear. This work was undertaken to determine if Myostatin participates in the regulation of C2C12 proliferation by Sirt1. Methods: We administrated the Sirt1 activator resveratrol, inhibitor Nicotinamide (NAM) and Myostatin inhibitor SB431542 on C2C12 myoblast cells. Cell viability was evaluated by CCK8 assay. The expression of Sirt1 and MyoD were detected by qRT-PCR. Utilizing western blot to determinate the expression of myostatin, P107 and p-P107. Results: Our results showed that resveratrol promoted the proliferation of C2C12 myoblast cells, while NAM suppressed the proliferation of C2C12 myoblast cells; SB431542 promoted the proliferation of C2C12 myoblast cells and attenuated the inhibition effect of NAM on C2C12 myoblast cells proliferation; Resveratrol can significantly increase the expression of Sirt1 and MyoD, decrease the expression of Myostatin, while NAM can significantly down-regulate the expression of Sirt1, MyoD and the phosphorylation of P107(p-P107), but up-regulate the expression of Myostatin and the protein P107; SB431542 can significantly mitigate the effect of NAM on the expression of MyoD, P107, and p-P107. Conclusions: Taken together, these results indicate that Sirt1 promotes the proliferation of C2C12 myoblast cells via Myostatin signaling pathway.

Keywords: Sirt1, C2C12 cells, proliferation, myostatin signaling pathway

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860 Protective Efficacy of Curcuma Aromatica Leaf Extract on Liver of Arsenic Intoxicated Albino Rats

Authors: Priya Bajaj, Baby Tabassum

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Arsenic is a poisonous metalloid, naturally occurring in soil, air, rocks and ground water. This dreadful metalloid commonly exists as inorganic compound, arsenic trioxide. WHO permitted maximum limit for arsenic in water is 0.01 mg/L, but some affected areas show ground water level of arsenic up to 3 mg/L even. Ground water arsenic pollution has created a number of health problems, viz. keratosis, melanosis, lesions and even skin cancers. The key objective of our nested study was to characterize arsenic induced hepatotoxicity and to find out some herbal protection against it. For the purpose, we selected albino rat (Rattus norvegicus) as model for arsenic induced liver injury and wild turmeric (Curcuma aromatica) leaf extract as remedy for it. The study was performed at acute (1 day) and subacute (7, 14 & 21 days) levels. The LD50 estimated for arsenic trioxide was 14.98 mg/kg body weight. In our investigation, we observed a significant restoration of altered hepatic lipid, cholesterol, protein and glycogen contents as well as liver weight, body-weight and hepato-somatic index by Curcuma aromatica leaf extract before arsenic intoxication. The results reveal excellent protective efficacy of Curcuma aromatica leaf extract that further can be exploited in remediation programme in heavy metal affected areas.

Keywords: arsenic, Curcuma aromatica, glycogen, lipids

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859 Natural Honey and Effect on the Activity of the Cells

Authors: Abujnah Dukali

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Natural honey was assessed in cell culture system for its anticancer activity. Human leukemic cell line HL 60 was treated with honey and cultured for 5 days and cytotoxicity was calculated by MTT assay. Honey showed cytotoxicity with CC50 value of 174.20 µg/ml. Radical modulation activities was assessed by lipid peroxidation assay using egg lecithin. Honey showed antioxidant activity with EC50 value of 159.73 µg/ml. In addition, treatment with HL60 cells also resulted in nuclear DNA fragmentation, as seen in agarose gel electrophoresis. This is a hallmark of cells undergoing apoptosis. Confirmation of apoptosis was performed by staining the cells with Annexin V and FACS analysis. Apoptosis is an active, genetically regulated disassembly of the cell form within. Disassembly creates changes in the phospholipid content of the cytoplasmic membrane outer leaflet. Phosphatidylserine (PS) is translocated from the inner to the outer surface of the cell for phagocytic cell recognition. The human anticoagulant, annexin V, is a Ca2+-dependent phospholipid protein with a high affinity for PS. Annexin V labeled with fluorescein can identify apoptotic cells in the population It is a confirmatory test for apoptosis. Annexin V-positive cells were defined as apoptotic cells. Since honey shows both antioxidant activity and cytotoxicity at almost the same concentration, it can prevent the free radical induced cancer as prophylactic agent and kill the cancer cells by apoptotic process as a chemotherapeutic agent. Everyday intake of honey can prevent the cancer induction.

Keywords: anticancer, cells, DNA, honey

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858 Retrospective Analysis of 142 Cases of Incision Infection Complicated with Sternal Osteomyelitis after Cardiac Surgery Treated by Activated PRP Gel Filling

Authors: Daifeng Hao, Guang Feng, Jingfeng Zhao, Tao Li, Xiaoye Tuo

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Objective: To retrospectively analyze the clinical characteristics of incision infection with sternal osteomyelitis sinus tract after cardiac surgery and the operation method and therapeutic effect of filling and repairing with activated PRP gel. Methods: From March 2011 to October 2022, 142 cases of incision infection after cardiac surgery with sternal osteomyelitis sinus were retrospectively analyzed, and the causes of poor wound healing after surgery, wound characteristics, perioperative wound management were summarized. Treatment during operation, collection and storage process of autologous PRP before debridement surgery, PRP filling repair and activation method after debridement surgery, effect of anticoagulant drugs on surgery, postoperative complications and average wound healing time, etc.. Results: Among the cases in this group, 53.3% underwent coronary artery bypass grafting, 36.8% underwent artificial heart valve replacement, 8.2% underwent aortic artificial vessel replacement, and 1.7% underwent allogeneic heart transplantation. The main causes of poor incision healing were suture reaction, fat liquefaction, osteoporosis, diabetes, and metal allergy in sequence. The wound is characterized by an infected sinus tract. Before the operation, 100-150ml of PRP with 4 times the physiological concentration was collected separately with a blood component separation device. After sinus debridement, PRP was perfused to fill the bony defect in the middle of the sternum, activated with thrombin freeze-dried powder and calcium gluconate injection to form a gel, and the outer skin and subcutaneous tissue were sutured freely. 62.9% of patients discontinued warfarin during the perioperative period, and 37.1% of patients maintained warfarin treatment. There was no significant difference in the incidence of postoperative wound hematoma. The average postoperative wound healing time was 12.9±4.7 days, and there was no obvious postoperative complication. Conclusions: Application of activated PRP gel to fill incision infection with sternal osteomyelitis sinus after cardiac surgery has a less surgical injury and satisfactory and stable curative effect. It can completely replace the previously used pectoralis major muscle flap transplantation operation scheme.

Keywords: platelet-rich plasma, negative-pressure wound therapy, sternal osteomyelitis, cardiac surgery

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857 Physico-Chemical Characteristics of Terminalia arjuna Encapsulated Dairy Drink

Authors: Sawale Pravin Digambar, G. R. Patil, Shaik Abdul Hussain

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Terminalia arjuna (TA), an important medicinal plant in Indian System of Medicine, is specifically recognized for its recuperative effect on heart ailments. Alcoholic extract of TA (both free and encapsulated) was incorporated into milk to obtain functional dairy beverages. The respective beverages were appropriately flavored and optimized using response surface methodology to improve the sensory appeal. The beverages were evaluated for their compositional, anti-oxidative and various other physico-chemical aspects. Addition of herb (0.3%) extract to flavoured dairy drink (Drink 1) resulted in significantly lowered (p>0.05) HMF content and increased antioxidant activity, total phenol content as compared with control (Control 1). Subsequently, a significant (p>0.05) increase in acidity and sedimentation was also observed. Encapsulated herb (1.8%) incorporated drink (Drink 2) had significantly (P>0.05) enhanced HMF value and decreased antioxidant activity, phenol content as compared to herb added vanilla chocolate dairy drink (Drink 1). It can be concluded that addition of encapsulated TA extract and non-encapsulated TA extract to chocolate dairy drink at 0.3% concentration altered the functional properties vanilla chocolate dairy drink which could be related to the interaction of herb components such as polyphenol with milk protein or maltodextrin/ gum Arabic matrix.

Keywords: Terminalia arjuna, encapsulate, antioxidant activity, physicochemical study

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856 Downtime Estimation of Building Structures Using Fuzzy Logic

Authors: M. De Iuliis, O. Kammouh, G. P. Cimellaro, S. Tesfamariam

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Community Resilience has gained a significant attention due to the recent unexpected natural and man-made disasters. Resilience is the process of maintaining livable conditions in the event of interruptions in normally available services. Estimating the resilience of systems, ranging from individuals to communities, is a formidable task due to the complexity involved in the process. The most challenging parameter involved in the resilience assessment is the 'downtime'. Downtime is the time needed for a system to recover its services following a disaster event. Estimating the exact downtime of a system requires a lot of inputs and resources that are not always obtainable. The uncertainties in the downtime estimation are usually handled using probabilistic methods, which necessitates acquiring large historical data. The estimation process also involves ignorance, imprecision, vagueness, and subjective judgment. In this paper, a fuzzy-based approach to estimate the downtime of building structures following earthquake events is proposed. Fuzzy logic can integrate descriptive (linguistic) knowledge and numerical data into the fuzzy system. This ability allows the use of walk down surveys, which collect data in a linguistic or a numerical form. The use of fuzzy logic permits a fast and economical estimation of parameters that involve uncertainties. The first step of the method is to determine the building’s vulnerability. A rapid visual screening is designed to acquire information about the analyzed building (e.g. year of construction, structural system, site seismicity, etc.). Then, a fuzzy logic is implemented using a hierarchical scheme to determine the building damageability, which is the main ingredient to estimate the downtime. Generally, the downtime can be divided into three main components: downtime due to the actual damage (DT1); downtime caused by rational and irrational delays (DT2); and downtime due to utilities disruption (DT3). In this work, DT1 is computed by relating the building damageability results obtained from the visual screening to some already-defined components repair times available in the literature. DT2 and DT3 are estimated using the REDITM Guidelines. The Downtime of the building is finally obtained by combining the three components. The proposed method also allows identifying the downtime corresponding to each of the three recovery states: re-occupancy; functional recovery; and full recovery. Future work is aimed at improving the current methodology to pass from the downtime to the resilience of buildings. This will provide a simple tool that can be used by the authorities for decision making.

Keywords: resilience, restoration, downtime, community resilience, fuzzy logic, recovery, damage, built environment

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855 Production of Fish Hydrolyzates by Single and Multiple Protease Treatments under Medium High Pressure of 300 MPa

Authors: Namsoo Kim, So-Hee Son, Jin-Soo Maeng, Yong-Jin Cho, Chong-Tai Kim

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It has been reported that some enzymes such as trypsin and Alcalase 2.4L are tolerant to a medium high pressure of 300 MPa and preparation of protein hydrolyzates under 300 MPa was advantageous with regard to hydrolysis rate and thus production yield compared with the counterpart under ambient pressure.1,2) In this study, nine fish comprising halibut, soft shell clam and carp were hydrolyzed using Flavourzyme 500MG only, and the combination of Flavourzyme 500 mg, Alcalase 2.4 L, Marugoto E, and Protamex under 300 MPa. Then, the effects of single and multiple protease treatments were determined with respect to contents of soluble solid (SS) and soluble nitrogen, sensory attributes, electrophoretic profiles, and HPLC peak patterns of the fish hydrolyzates (FHs) from various species. The contents of SS of the FHs were quite species-specific and the hydrolyzates of halibut showed the highest SS contents. At this point, multiple protease treatment increased SS content conspicuously in all fish tested. The contents of total soluble nitrogen and TCA-soluble nitrogen were well correlated with those of SS irrespective of fish species and methods of enzyme treatment. Also, it was noticed that multiple protease treatment improved sensory attributes of the FHs considerably. Electropherograms of the FHs showed fast migrating peptide bands that had the molecular masses mostly lower than 1 kDa and this was confirmed by peptide patterns from HPLC analysis for some FHs that had good sensory quality.

Keywords: production, fish hydrolyzates, protease treatments, high pressure

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854 One Building at a Time for Tambak Lorok

Authors: Etika Sukma Adiyanti, H. N. Nurul Huda Putu Ekapraja, Gugun Gunawan

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Global warming causes climate change and sea level rise. This is a threat for coastal regions, especially for coastal settlements with activities that are influenced by this natural phenomenon. Consequences are damage of houses, humid house environment, sustainability of the houses, obstructed economic activities and domestic works, disruption of sanitation facilities, lack of electricity, failure of transport system, psychological issues and other. Icons Tambak Lorok as 'Fisherman Village' is not something familiar to residents of the city of Semarang. Especially for the housewife who every day have to buy the ingredients high in protein and omega fish auction which is adjacent to the main street market in the village of Tambak Lorok. However, there are major problems that are being experienced by this small neighborhood. In fact, this issue includes seven infrastructure that should spoil the fishermen in activity with marine life. With this research, we will investigate water urbanism and climate change resiliency in Semarang, specifically the traditional fisher community of Tambak Lorok. We intend to find out how the local people in the fisher settlement Tambak Lorok deal with water urbanism, proverty and living with floods. So, we have a good solution for this problem, Floating Stage. We think that Tambak Lorok needs a new design for the common future. With this, One Building at A Time for Tambak Lorok, will be a good solution.

Keywords: fisher community, environment, climate change, settlement

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853 Metabolic Syndrome and Its Effects on Cartilage Degeneration vs Regeneration: A Pilot Study Using Osteoarthritis Biomarkers

Authors: Neena Kanojia, R. K. Kanojia

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Background: Osteoarthritis OA of the knee is one of the leading causes of disability characterized by degeneration of hyaline cartilage combined with reparative processes. Its strong association with metabolic syndrome is postulated to be due to both mechanical and biochemical factors. Our study aims to study differential effect of metabolic risk factors on cartilage degeneration and regeneration at biomarker level. Design: After screening 281 patients presenting with knee pain, 41 patients who met the selection criteria were included and were divided into metabolic MetS OA and non-metabolic Non-MetS OA phenotypes using National Cholesterol Education Programme-Adult Treatment Panel-III NCEP ATP III criteria for metabolic syndrome. Serum Cartilage Oligomeric Matrix Protein COMP and Procollagen type IIA N terminal Propeptide PIIANP levels were used as tools to assess cartilage degeneration and regeneration, respectively. Results: 22 among 41 patients 53.66% had metabolic syndrome. Covariates like age, gender, Kellgren Lawrence KL grades were comparable in both groups. MetS OA group showed significant increase in serum COMP levels (p 0.03 with no significant effect on serum PIIANP levels (p 0.46. Hypertriglyceridemia showed independent association with both cartilage anabolism (p 0.03 and catabolism (p 0.03. Conclusion: Metabolic syndrome, though has no effect on cartilage regeneration tends to shift cartilage homeostasis towards degeneration with hypertriglyceridemia showing significant independent effect on cartilage metabolism.

Keywords: metabolic, syndrome, cartilage, degernation

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852 Sesamol Decreases Melanin Biosynthesis via Melanogenesis-Related Gene Expressions in Melan-a Cells

Authors: Seung-Hwa Baek, In-Jung Nam, Sang-Han Lee

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The development of anti-melanogenic agents is important for the prevention of serious esthetic problem like a melasma, freckle, age spots, and chloasma. The aim of this study was to investigate the anti-melanogenic effect of sesamol, an active lignan isolated from sesame seed, by mushroom and cellular tyrosinase assay, melanin content and the analysis of melanogensis-related mRNA expressions in melana cells. Sesamol showed strong inhibitory activity against the mushroom tyrosinase in a dose-dependent manner. Intracellular tyrosinase inhibition activity was also confirmed by zymography. At a concentration of 50 μM, sesamol inhibited melanin production in melan-a cells with no cytoxicity while those of phenylthiourea (PTU) as a positive control were the same condition. Sesamol significantly inhibited the expression of melanogensis-related genes, such as tyrosinase, tyrosinase-related protein-1 (TRP-1), dopachrome tautomerase (Dct), microphthalmia-associated transcription factor (MITF) and melanocortin 1 receptor (MC1R). These findings indicate that sesamol could reduce melanin biosynthesis via the downregulation of tyrosinase activity and melanin production via subsequent gene expression of melanogenesis-related proteins. Together, these results suggest that the sesamol have strong potential in inhibiting melanin biosynthesis, in that the substance may be used as a new skin-whitening agent of cosmetic materials.

Keywords: sesamol, sesame seed, melanin biosynthesis, melanogenesis-related gene, skin-whitening agent

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851 Akt: Isoform-Specific Regulation of Cellular Signaling in Cancer

Authors: Bhumika Wadhwa, Fayaz Malik

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The serine/threonine protein kinase B (PKB) also known as Akt, is one of the multifaceted kinase in human kinome, existing in three isoforms. Akt plays a vital role in phosphoinositide 3-kinase (PI3K) mediated oncogenesis in various malignancies and is one of the attractive targets for cancer drug discovery. The functional significance of an individual isoform of Akt is not redundant in cancer cell proliferation and metastasis instead Akt isoforms play distinct roles during metastasis; thereby regulating EMT. This study aims to determine isoform specific functions of Akt in cancer. The results obtained suggest that Akt1 restrict tumor invasion, whereas Akt2 promotes cell migration and invasion by various techniques like MTT, wound healing and invasion assay. Similarly, qRT-PCR also revealed that Akt3 has shown promising results in promoting cancer cell migration. Contrary to pro-oncogenic properties attributed to Akt, it is to be understood how various isoforms of Akt compensates each other in the regulation of common pathways during cancer progression and drug resistance. In conclusion, this study aims to target selective isoforms which is essential to inhibit cancer. However, the question now is whether, and how much, Akt inhibition will be tolerated in the clinic remains to be answered and the experiments will have to address the question of which combinations of newly devised Akt isoform specific inhibitors exert a favourable therapeutic effect in in vivo models of cancer to provide the therapeutic window with minimal toxicity.

Keywords: Akt isoforms, cancer, drug resistance, epithelial mesenchymal transition

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850 Identifying of Hybrid Lines for Lpx-B1 Gene in Durum Wheat

Authors: Özlem Ateş Sönmezoğlu, Begüm Terzi, Ahmet Yıldırım, Ramazan Özbey

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The basic criteria which determine durum wheat quality is its suitability for pasta processing that is pasta making quality. Bright yellow color is a desired property in pasta products. Durum wheat pasta making quality is affected by grain pigment content and oxidative enzymes which affect adversely bright yellow color. Of the oxidative enzymes, lipoxygenase LOX is the most effective one on oxidative bleaching of yellow pigments in durum wheat products. Thus, wheat cultivars that are high in yellow pigments but low in LOX enzyme activity should be preferred for the production of pasta with high color quality. The aim of this study was to reduce lipoxygenase activities of the backcross durum wheat lines that were previously improved for their protein quality. For this purpose, two advanced lines with different parents (TMB2 and TMB3) were used recurrent parents. Also, Gediz-75 wheat with low LOX enzyme activity was used as the gene source. In all of the generations, backcrossed plants carrying the targeted gene region (Lpx-B1.1) were selected using SSR markers by marker assisted selection method. As a result, the study will be completed in three years instead of six years required in a classical backcross breeding study, leading to the development of high-quality candidate varieties. This research has been financially supported by TÜBİTAK (Project No: 112T910).

Keywords: durum wheat, lipoxygenase, LOX, Lpx-B1.1, MAS, Triticum durum

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849 MARISTEM: A COST Action Focused on Stem Cells of Aquatic Invertebrates

Authors: Arzu Karahan, Loriano Ballarin, Baruch Rinkevich

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Marine invertebrates, the highly diverse phyla of multicellular organisms, represent phenomena that are either not found or highly restricted in the vertebrates. These include phenomena like budding, fission, a fusion of ramets, and high regeneration power, such as the ability to create whole new organisms from either tiny parental fragment, many of which are controlled by totipotent, pluripotent, and multipotent stem cells. Thus, there is very much that can be learned from these organisms on the practical and evolutionary levels, further resembling Darwin's words, “It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change”. The ‘stem cell’ notion highlights a cell that has the ability to continuously divide and differentiate into various progenitors and daughter cells. In vertebrates, adult stem cells are rare cells defined as lineage-restricted (multipotent at best) with tissue or organ-specific activities that are located in defined niches and further regulate the machinery of homeostasis, repair, and regeneration. They are usually categorized by their morphology, tissue of origin, plasticity, and potency. The above description not always holds when comparing the vertebrates with marine invertebrates’ stem cells that display wider ranges of plasticity and diversity at the taxonomic and the cellular levels. While marine/aquatic invertebrates stem cells (MISC) have recently raised more scientific interest, the know-how is still behind the attraction they deserve. MISC, not only are highly potent but, in many cases, are abundant (e.g., 1/3 of the entire animal cells), do not locate in permanent niches, participates in delayed-aging and whole-body regeneration phenomena, the knowledge of which can be clinically relevant. Moreover, they have massive hidden potential for the discovery of new bioactive molecules that can be used for human health (antitumor, antimicrobial) and biotechnology. The MARISTEM COST action (Stem Cells of Marine/Aquatic Invertebrates: From Basic Research to Innovative Applications) aims to connect the European fragmented MISC community. Under this scientific umbrella, the action conceptualizes the idea for adult stem cells that do not share many properties with the vertebrates’ stem cells, organizes meetings, summer schools, and workshops, stimulating young researchers, supplying technical and adviser support via short-term scientific studies, making new bridges between the MISC community and biomedical disciplines.

Keywords: aquatic/marine invertebrates, adult stem cell, regeneration, cell cultures, bioactive molecules

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848 Growth and Laying Performance of Commercial Hens Fed with Varying Levels of Trichanthera gigantea (Nees.) Leaf Meal

Authors: Carmel Khrisna Wong Moreno, Dinah M. Espina

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The increasing price of feed ingredients has prompted farmers to seek feasible feed alternatives like the utilization of locally-grown protein-rich feedstuff which is cheaper but gives a positive result in poultry production. Trichanthera gigantea, a fodder tree which is an excellent alternative as feed ingredient in the Philippines has now gained popularity as feed supplement. This study was conducted to determine the growth and laying performance of commercial hens fed with varying levels of Trichanthera gigantea leaf meal. The incorporation of Trichanthera gigantea leaf meal at 5%, 10%, and 15% into the diet of commercial hens did not affect the growth and laying performance. Results of the study revealed that the weight gain of the birds fed with Trichanthera gigantea supplemented diets was not significantly different with the control (100% commercial layer mash). The voluntary feed intake, feed conversion ratio, weekly average egg weight and egg production of the commercial hens fed with T. gigantea leaf meal supplemented diets were not significantly different from the control. Results of the study showed that the supplementation of Trichanthera gigantea leaf meal of up to 15% into the diets of commercial hens is highly acceptable since it does not affect the growth and laying performance of the birds. In addition, it would mean a 15% savings in production cost from commercial feeds.

Keywords: egg production, growth, laying performance, trichanthera gigantea (nees)

Procedia PDF Downloads 399
847 Antibacterial Evaluation, in Silico ADME and QSAR Studies of Some Benzimidazole Derivatives

Authors: Strahinja Kovačević, Lidija Jevrić, Miloš Kuzmanović, Sanja Podunavac-Kuzmanović

Abstract:

In this paper, various derivatives of benzimidazole have been evaluated against Gram-negative bacteria Escherichia coli. For all investigated compounds the minimum inhibitory concentration (MIC) was determined. Quantitative structure-activity relationships (QSAR) attempts to find consistent relationships between the variations in the values of molecular properties and the biological activity for a series of compounds so that these rules can be used to evaluate new chemical entities. The correlation between MIC and some absorption, distribution, metabolism and excretion (ADME) parameters was investigated, and the mathematical models for predicting the antibacterial activity of this class of compounds were developed. The quality of the multiple linear regression (MLR) models was validated by the leave-one-out (LOO) technique, as well as by the calculation of the statistical parameters for the developed models and the results are discussed on the basis of the statistical data. The results of this study indicate that ADME parameters have a significant effect on the antibacterial activity of this class of compounds. Principal component analysis (PCA) and agglomerative hierarchical clustering algorithms (HCA) confirmed that the investigated molecules can be classified into groups on the basis of the ADME parameters: Madin-Darby Canine Kidney cell permeability (MDCK), Plasma protein binding (PPB%), human intestinal absorption (HIA%) and human colon carcinoma cell permeability (Caco-2).

Keywords: benzimidazoles, QSAR, ADME, in silico

Procedia PDF Downloads 359
846 Effects of Certain Natural Food Additives (Pectin, Gelatin and Whey Proteins) on the Qualities of Fermented Milk

Authors: Abderrahim Cheriguene, Fatiha Arioui

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The experimental study focuses on the extraction of pectin, whey protein and gelatin, and the study of their functional properties. Microbiological, physicochemical and sensory approach integrated has been implanted to study the effect of the incorporation of these natural food additives in the matrix of a fermented milk type set yogurt, to study the stability of the product during the periods of fermentation and post-acidification over a period of 21 days at 4°C. Pectin was extracted in hot HCl solution. Thermo-precipitation was carried out to obtain the whey proteins while the gelatin was extracted by hydrolysis of the collagen from bovine ossein. The fermented milk was prepared by varying the concentration of the incorporated additives. The measures and controls carried performed periodically on fermented milk experimental tests were carried out: pH, acidity, viscosity, the enumeration of Streptococcus thermophilus, cohesiveness, adhesiveness, taste, aftertaste, whey exudation, and odor. It appears that the acidity, viscosity, and number of Streptococcus thermophilus increased with increasing concentration of additive added in the experimental tests. Indeed, it seems clear that the quality of fermented milk and storability is more improved than the incorporation rate is high. The products showed a better test and a firmer texture limiting the whey exudation.

Keywords: fermented milk, pectin, gelatin, whey proteins, functional properties, quality, conservation, valorization

Procedia PDF Downloads 124
845 Development of Lectin-Based Biosensor for Glycoprofiling of Clinical Samples: Focus on Prostate Cancer

Authors: Dominika Pihikova, Stefan Belicky, Tomas Bertok, Roman Sokol, Petra Kubanikova, Jan Tkac

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Since aberrant glycosylation is frequently accompanied by both physiological and pathological processes in a human body (cancer, AIDS, inflammatory diseases, etc.), the analysis of tumor-associated glycan patterns have a great potential for the development of novel diagnostic approaches. Moreover, altered glycoforms may assist as a suitable tool for the specificity and sensitivity enhancement in early-stage prostate cancer diagnosis. In this paper we discuss the construction and optimization of ultrasensitive sandwich biosensor platform employing lectin as glycan-binding protein. We focus on the immunoassay development, reduction of non-specific interactions and final glycoprofiling of human serum samples including both prostate cancer (PCa) patients and healthy controls. The fabricated biosensor was measured by label-free electrochemical impedance spectroscopy (EIS) with further lectin microarray verification. Furthermore, we analyzed different biosensor interfaces with atomic force microscopy (AFM) in nanomechanical mapping mode showing a significant differences in the altitude. These preliminary results revealing an elevated content of α-2,3 linked sialic acid in PCa patients comparing with healthy controls. All these experiments are important step towards development of point-of-care devices and discovery of novel glyco-biomarkers applicable in cancer diagnosis.

Keywords: biosensor, glycan, lectin, prostate cancer

Procedia PDF Downloads 354
844 Effects of Valproate on Vascular Endothelial Growth Factor in the Retina Associated with Choroidal Neovascularization

Authors: Zhang Zhenzhen

Abstract:

Valproate (VPA) is commonly used in the treatment of bipolar disorder and epilepsy. The mechanism is complicated, including its ability to inhibit histone deacetylases (HDACs). Here, we show that VPA attenuated VEGF gene expression and the morphological changes in choroidal neovascularization (CNV) induced by photocoagulation in retina. C57BL/6 mice were injected subcutaneously at 300mg/kg twice daily with VPA before insult. Vascular endothelial growth factor (VEGF)-A and VEGF-B were examined in the eyes of VPA-treated mice and in human retinal pigment epithelial cell lines (ARPE-19) exposed to VPA. In addition, CNV was induced by photocoagulation in mice injected with VPA, and the volume of CNV was compared by fluorescence-labeled choroidal flat mount. Morphological changes were analyzed on stained histological sections. Western blot analysis was used to determine protein levels of VEGF-A and VEGF-B, and acetylation of histone H3 in each group. VPA injected intraperitoneally attenuated the VEGF-A and VEGF-B expression in the retina, accompanied by the hyperacetylation of retina tissue, indicating that VPA acts directly on retina tissues through acetylation to reduce the expression of VEGF. VPA also attenuated the VEGF-A mRNA expression in the retinal pigment epithelium showed by immunohistochemistry. Moreover, the administration of VPA significantly attenuated photocoagulation-induced CNV in mice. These results demonstrate that VPA attenuated VEGF production in retina associated with choroidal neovascularization possibly via the HDAC inhibition.

Keywords: retina, acetylation, chorodial neovascularization, vascular endothelial growth factor

Procedia PDF Downloads 178
843 Evaluation of Storage Stability and Quality Parameters in Biscuit Made from Blends of Wheat, Cassava (Manihot esculenta) and Carrot (Daucus carota) Flour

Authors: Aminat. O Adelekan, Olawale T. Gbadebo

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Biscuit is one of the most consumed cereal foods in Nigeria and research has shown that locally available tropical crops like cassava, sweet potato can be made into flour and used in the production of biscuits and other pastries. This study investigates some quality parameters in biscuits made from blends of wheat, cassava and carrot flour. The values of result of samples increased with increasing percentage substitution of cassava and carrot flour in some quality parameter like fiber, ash, gluten content, and carbohydrate. The protein content reduced significantly (P < 0.05) with increasing percentage substitution of cassava and carrot flour which ranged from 14.80% to 11.80% compared with the control sample which had 15.60%. There was a recorded significant increase (P < 0.05) in some mineral composition such as calcium, magnesium, sodium, iron, phosphorus, and vitamin A and C composition as the percentage substitution of cassava and carrot flour increased. During storage stability test, samples stored in the fridge and freezer were found to be the best storage location to preserve the sensory attributes and inhibit microbial growth when compared with storage under the sun and on the shelf. Biscuit made with blends of wheat, cassava and carrot flour can therefore serve as an alternative to biscuits made from 100% wheat flour, as they are richer in vitamin A, vitamin C, carbohydrate, dietary fiber and some essential minerals.

Keywords: biscuit, carrot, flour blends, storage

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842 Evaluation of Botanical Plant Powders against Zabrotes subfasciatus (Boheman) (Coleoptera: Bruchidae) in Stored Local Common Bean Varieties

Authors: Fikadu Kifle Hailegeorgis

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Common bean is one of the most important sources of protein in Ethiopia and other developing countries. However, the Mexican bean weevil, Zabrotes subfasciatus (Boheman), is a major factor in the storage of common beans that causes losses. Studies were conducted to evaluate the efficacy of botanical powders of Jatropha curcas (L.), Neem/Azadrachta indica, and Parthenium hysterophorus (L) on local common bean varieties against Z subfasciatus at Melkassa Agriculture Research Center. Twenty local common bean varieties were evaluated twice against Z. Subfasciatus in a completely randomized design in three replications at the rate of 0.2g/250g of seed for each experiment. Malathion and untreated were used as standard checks. The result indicated that RAZ White and Round Yellow showed high resistance variety in experiments while Batu and Black showed high susceptible variety in experiments. Jatropha seed powder was the most effective against Z. subfasciatus. Parthenium seed powders and neem leaf powders also indicate promising results. Common beans treated with botanicals significantly (p<0.05) had a higher germination percentage than that of the untreated seed. In general, the results obtained indicated that using bean varieties (RAZ white and Round yellow) and botanicals (Jatropha) seed powder gave the best control of Z. subfasciatus.

Keywords: botanicals, malathion, resistant varieties, Z. subfasciatus

Procedia PDF Downloads 46
841 VHL, PBRM1, and SETD2 Genes in Kidney Cancer: A Molecular Investigation

Authors: Rozhgar A. Khailany, Mehri Igci, Emine Bayraktar, Sakip Erturhan, Metin Karakok, Ahmet Arslan

Abstract:

Kidney cancer is the most lethal urological cancer accounting for 3% of adult malignancies. VHL, a tumor-suppressor gene, is best known to be associated with renal cell carcinoma (RCC). The VHL functions as negative regulator of hypoxia inducible factors. Recent sequencing efforts have identified several novel frequent mutations of histone modifying and chromatin remodeling genes in ccRCC (clear cell RCC) including PBRM1 and SETD2. The PBRM1 gene encodes the BAF180 protein, which involved in transcriptional activation and repression of selected genes. SETD2 encodes a histone methyltransferase, which may play a role in suppressing tumor development. In this study, RNAs of 30 paired tumor and normal samples that were grouped according to the types of kidney cancer and clinical characteristics of patients, including gender and average age were examined by RT-PCR, SSCP and sequencing techniques. VHL, PBRM1 and SETD2 expressions were relatively down-regulated. However, statistically no significance was found (Wilcoxon signed rank test, p > 0.05). Interestingly, no mutation was observed on the contrary of previous studies. Understanding the molecular mechanisms involved in the pathogenesis of RCC has aided the development of molecular-targeted drugs for kidney cancer. Further analysis is required to identify the responsible genes rather than VHL, PBRM1 and SETD2 in kidney cancer.

Keywords: kidney cancer, molecular biomarker, expression analysis, mutation screening

Procedia PDF Downloads 437
840 The Coalescence Process of Droplet Pairs in Different Junctions

Authors: Xiang Wang, Yan Pang, Zhaomiao Liu

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Droplet-based microfluidics have been studied extensively with the development of the Micro-Electro-Mechanical System (MEMS) which bears the advantages of high throughput, high efficiency, low cost and low polydispersity. Droplets, worked as versatile carriers, could provide isolated chambers as the internal dispersed phase is protected from the outside continuous phase. Droplets are used to add reagents to start or end bio-chemical reactions, to generate concentration gradients, to realize hydrate crystallization or protein analyses, while droplets coalescence acts as an important control technology. In this paper, deionized water is used as the dispersed phase, and several kinds of oil are used as the continuous phase to investigate the influence of the viscosity ratio of the two phases on the coalescence process. The microchannels are fabricated by coating a polydimethylsiloxane (PDMS) layer onto another PDMS flat plate after corona treatment. All newly made microchannels are rinsed with the continuous oil phase for hours before experiments to ensure the swelling fully developed. High-speed microscope system is used to document the serial videos with a maximum speed of 2000 frames per second. The critical capillary numbers (Ca*) of droplet pairs in various junctions are studied and compared. Ca* varies with different junctions or different liquids within the range of 0.002 to 0.01. However, droplets without extra control would have the problem of synchronism which reduces the coalescence efficiency.

Keywords: coalescence, concentration, critical capillary number, droplet pair, split

Procedia PDF Downloads 227
839 Association of Hypoxia-Inducible Factor-1α in Patients with Chronic Obstructive Pulmonary Diseases

Authors: Kriti Upadhyay, Ashraf Ali, Puja Sohal, Randeep Guleria

Abstract:

Background: In Chronic Obstructive Pulmonary diseases (COPD) pathogenesis oxidative stress plays an important role. Hypoxia-Inducible factor (HIF-1α) is a dimeric protein complex which Functions as a master transcriptional regulator of the adaptive response to hypoxiaand is a risk factor that increases when oxidative stress triggers. The role ofHIF-1αin COPD due to smoking is lacking. Aim: This study aims to evaluate the role of HIF-1α in smoker COPD patients comparing its association with diseases severity. Method: In this cross-sectional study, we recruited 87 subjects, 57 were smokers with COPD,15 were smokers without COPD and other 15 were non-smoker healthy controls. The mean age was 54.6± 9.32 (cases 57.08±8.15; controls 50.0± 9.8). There were 62%smokers, 25% non-smokers,7% tobacco chewers and 6% ex-smokers. Enzyme-linked immune sorbent assay (ELISA) method was used for analyzing serum samples wherein HIF-1α was analyzed by Sandwich-ELISA. Results: In smoker COPD patients, a significantly higher HIF-1α level showed positive association with hypoxia, smoking status and severity of disease (p=0.03). The mean value of HIF-1α was not significantly different in smokers without COPD and healthy controls. Conclusion: It is found that HIF-1α level was increased in smoker COPD, but not in smokers without COPD. This suggests that development of COPD drive the HIF-1α pathway and it correlates with the severity of diseases.

Keywords: COPD, chronic obstructive pulmonary diseases, smokers, nonsmokers, hypoxia

Procedia PDF Downloads 123