Search results for: induced mood

Authors: Manal M. Kame, Zeinab A. Demerdash, Hanan G. El-Baz, Salwa M. Hassan, Faten M. Salah, Wafaa Mansour, Olfat Hammam

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Cord blood (CB) derived Unrestricted Somatic Stem Cells (USSCs) with their multipotentiality hold great promise in liver regeneration. This work aims at evaluation of the therapeutic potentiality of USSCs in two experimental models of chronic liver injury induced either by S. mansoni infection in balb/c mice or CCL4 injection in hamsters. Isolation, propagation, and characterization of USSCs from CB samples were performed. USSCs were induced to differentiate into osteoblasts, adipocytes and hepatocyte-like cells. Cells of the third passage were transplanted in two models of liver fibrosis: (1) Twenty hamsters were induced to liver fibrosis by repeated i. p. injection of 100 μl CCl4 /hamster for 8 weeks. This model was designed as; 10 hamsters with liver fibrosis and treated with i.h. injection of 3x106 USSCs (USSCs transplanted group), 10 hamsters with liver fibrosis (pathological control group), and 10 hamsters with healthy livers (normal control group). (2) Murine chronics S.mansoni model: twenty mice were induced to liver fibrosis with S. mansoni ceracariae (60 cercariae/ mouse) using the tail immersion method and left for 12 weeks. This model was designed as; 10 mice with liver fibrosis were transplanted with i. v. injection of 1×106 USCCs (USSCs transplanted group). Other 2 groups were designed as in hamsters model. Animals were sacrificed 12 weeks after USSCs transplantation, and their liver sections were examined for detection of human hepatocyte-like cells by immunohistochemistry staining. Moreover, liver sections were examined for fibrosis level, and fibrotic indices were calculated. Sera of sacrificed animals were tested for liver functions. CB USSCs, with fibroblast-like morphology, expressed high levels of CD44, CD90, CD73 and CD105 and were negative for CD34, CD45, and HLA-DR. USSCs showed high expression of transcripts for Oct4 and Sox2 and were in vitro differentiated into osteoblasts, adipocytes. In both animal models, in vitro induced hepatocyte-like cells were confirmed by cytoplasmic expression of glycogen, alpha-fetoprotein, and cytokeratin18. Livers of USSCs transplanted group showed engraftment with human hepatocyte-like cells as proved by cytoplasmic expression of human alpha-fetoprotein, cytokeratin18, and OV6. In addition, livers of this group showed less fibrosis than the pathological control group. Liver functions in the form of serum AST & ALT level and serum total bilirubin level were significantly lowered in USSCs transplanted group than pathological control group (p < 0.001). Moreover, the fibrotic index was significantly lower (p< 0.001) in USSCs transplanted group than pathological control group. In addition liver sections, of i. v. injection of 1×106 USCCs of mice, stained with either H&E or sirius red showed diminished granuloma size and a relative decrease in hepatic fibrosis. Our experimental liver fibrosis models transplanted with CB-USSCs showed liver engraftment with human hepatocyte-like cells as well as signs of liver regeneration in the form of improvement in liver function assays and fibrosis level. These data provide hope that human CB- derived USSCs are introduced as multipotent stem cells with great potentiality in regenerative medicine & strengthens the concept of cellular therapy for the treatment of liver fibrosis.

Keywords: cord blood, liver fibrosis, stem cells, transplantation

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Authors: Surendra Bodakhe

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In this investigation, anticataract activity was determined using cataract formation in developing chick embryo by hydrocortisone. Lenses were evaluated firstly for the extent of opacity and secondly, for lens glutathione (GSH) levels. Betulinic acid was isolated from the chloroform fraction of the crude ethanolic extract of Bauhinia variegata bark (SBE). Fourteen days old Australorp fertilized eggs were divided into different groups of six eggs each. After 24 hrs incubation in a humidified incubator (37οC), at 15 days of age; hydrocortisone (0.25µM/0.2ml/egg) was administered to the chorioallantoic membrane of chick embryos through a small hole in the egg shell on the air sack. Ascorbic acid (standard) or Betulinic acid (test) were administered at 3, 10 and 20 hr after hydrocortisone administration at a specified dose. The puncture was sealed with a cellophane tape and eggs were incubated for 48 hrs in a humidified incubator at 37οC. After 48 hrs, the lenses were isolated for the determination of the extent of opacity and Glutathione level. The betulinic acid prevented the opacification of the chick embryo lenses induced by hydrocortisone. The betulinic acid also prevented the decline of GSH content caused by hydrocortisone. The results indicate that betulinic acid protect the cataract formation in chick embryo lenses induced by hydrocortisone.

Keywords: betulinic acid, cataract, cloudiness, ovine

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Authors: Maha E. Ibrahim, Mona Abdel Aziz

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Background: Chronic low back pain (CLBP) in urban communities represents a challenge to healthcare systems worldwide. The traditional biomedical approach to back pain has been particularly inadequate. Failure of the biomedical model to explain the poor correlation between pain and disability on the one hand, and biological and physical factors that explain those symptoms on the other has led to the adoption of the biopsychosocial model, to recognize the reciprocal influence of physical, social and psychological factors implicated in CLBP, a condition that shows higher prevalence among women residing in urban areas. Urban design of the built community has been shown to exert a significant influence on physical and psychological health. However, little research has investigated the relationship between elements of the built environment, and the level of pain and disability of women with CLBP. As Egypt embarks on building a new capital city, and new settlements proliferate, better understanding of this relationship could greatly reduce the economic and human costs of this widespread medical problem for women. Methods: This study was designed as an exploratory mixed qualitative and quantitative study. Twenty-Six women with CLBP living in two neighborhoods in Cairo, different in their urban structure, but adjacent in their locations (Old Maadi and New Maadi) were interviewed using semi-structured interviews (8 from Old Maadi and 18 from New Maadi). Located in the South of Cairo, New Maadi is a neighborhood with the characteristic modern urban style (narrow streets and tall, adjacent buildings), while Old Maadi is known for being greener, quieter and more relaxed than the usual urban districts of Cairo. The interviews examined their perceptions of the built environment, including building shapes and colors and street light, as well as their sense of safety and comfort, and how it affects their physical and psychological health in general, and their back condition in particular. In addition, they were asked to rate their level of pain and to fill the Oswestry Disability Index (ODI), and the General Health Questionnaire (GHQ-12) to rate their level of disability and psychological status, respectively. Results: Women in both districts had moderate to severe pain and moderate disability with no significant differences between the two districts. However, those living in New Maadi had significantly worse scores on the GHQ-12 than those living in Old Maadi. Most women did not feel that specific elements of the built environment affected their back pain, however, they expressed distress of the elements that were ugly, distorted or damaged, especially where there were no ways of avoiding or fixing them. Furthermore, most women affirmed that the unsightly and uncomfortable elements of their neighborhoods affected their mood states and were a constant source of stress. Conclusion: This exploratory study concludes that elements of the urban built environment do not exert a direct effect on CLBP. However, the perception of women regarding these elements does affect their mood states, and their levels of stress, making them a possible indirect cause of increased suffering in these women.

Keywords: built environment, chronic back pain, disability, urban Cairo

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Authors: Daniel Osorio, Janneth Gonzalez, Andres Pinzon

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In this work, proteins and metabolic pathways associated with the neuroprotective response mediated by the synthetic neurosteroid tibolone under a palmitate-induced inflammatory model were identified by flux balance analysis (FBA). Three different metabolic scenarios (‘healthy’, ‘inflamed’ and ‘medicated’) were modeled over a gene expression data-driven constructed tissue-specific metabolic reconstruction of mature astrocytes. Astrocyte reconstruction was built, validated and constrained using three open source software packages (‘minval’, ‘g2f’ and ‘exp2flux’) released through the Comprehensive R Archive Network repositories during the development of this work. From our analysis, we predict that tibolone executes their neuroprotective effects through a reduction of neurotoxicity mediated by L-glutamate in astrocytes, inducing the activation several metabolic pathways with neuroprotective actions associated such as taurine metabolism, gluconeogenesis, calcium and the Peroxisome Proliferator Activated Receptor signaling pathways. Also, we found a tibolone associated increase in growth rate probably in concordance with previously reported side effects of steroid compounds in other human cell types.

Keywords: astrocytes, flux balance analysis, genome scale metabolic reconstruction, inflammation, neuroprotection, tibolone

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Authors: Mohamad Muqtada Ali Khan, Nor Ashikin Shaari, Donny Adriansyah bin Nazaruddin, Hafzan Eva Bt Mansoor

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Floods play a key role in landform evolution of an area. This process is likely to alter the topography of the earth’s surface. The present study area, Kota Bharu is very prone to floods extends from upstream of Kelantan River near Kemubu to the downstream area near Kuala Besar. These flood events which occur every year in the study area exhibit a strong bearing on river morphological set-up. In the present study, three satellite imageries of different time periods have been used to manifest the post-flood landform changes. The pre-processing of the images such as subset, geometric corrections and atmospheric corrections were carried-out using ENVI 4.5 followed by the analysis processes. Twenty sets of cross sections were plotted using software Erdas 9.2, ERDAS and ArcGis 10 for the all three images. The results show a significant change in the length of the cross section which suggest that the geomorphological processes play a key role in carving and shaping the river banks during the floods.

Keywords: flood induced, geomorphic imprints, Kelantan river, Malaysia

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Authors: Azza A. Ali, Mona G. Khalil, Hemat A. Elariny, Shereen S. El Shaer

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Background: Aluminium (Al) is very abundant metal in the earth’s crust. It is a constituent of cooking utensils, medicines, cosmetics, some foods and food additives. Salts of Al are widely used in the treatment of drinking water for purification purposes. Excessive and prolonged exposure to Al causes oxidative stress and impairment of many physiological functions. Its accumulation in liver and kidney causes hepatotoxicity and nephrotoxicity. Social isolation (SI) or Protein malnutrition (PM) also increases oxidative stress and may enhance the toxicity of Al as well as the degeneration in liver and kidney. Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea and has strong antioxidant as well as anti-inflammatory activities and can protect against oxidative stress-induced degenerations. Objective: To study the influence of stress or PM on Al-induced nephrotoxicity and hepatotoxicity in rats, as well as on the potential role of EGCG in providing protection. Methods: Rats received daily AlCl3 (70 mg/kg, IP) for three weeks (Al-toxicity groups) except one normal control group received saline. Al-toxicity groups were divided into four treated and four untreated groups; treated rats received EGCG (10 mg/kg, IP) together with AlCl3. One group of both treated and untreated rats served as control for each of them, and the others were subjected to either stress (mild using isolation or high using electric shock) or to PM (10% casein diet). Specimens of liver and kidney were used for assessment of levels of inflammatory mediators as TNF-α, IL6β, nuclear factor kappa B (NF-κB), oxidative stress (MDA, SOD, TAC, NO), Caspase-3 and for DNA fragmentation as well as for histopathological examinations. Biochemical changes were also measured in the serum as total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea as well as the level of Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate deshydrogenase (LDH). Results: Nephrotoxicity and hepatotoxicity induced by Al were enhanced in rats exposed to stress and to PM. The influence of stress was more pronounced than PM. Al-toxicity was indicated by the increase in liver and kidney MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3, DNA fragmentation and in ALT, AST, ALP, LDH and total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea levels, together with the decrease in total proteins, SOD, TAC. EGCG provided protection against hazards of Al as indicated by the decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation as well as in levels of ALT, AST, ALP, LDH and total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea in liver and kidney, together with the increase in total proteins, SOD, TAC and confirmed by histopathological examinations. It provided more pronounced protection in high stressful conditions than in mild one than in PM. Conclusion: Stress have a bad impact on Al-induced nephrotoxicity and hepatotoxicity more than PM. Thus it can clarify and maximize the role of EGCG in providing protection. Consequently, administration of EGCG is advised with excessive Al-exposure to avoid nephrotoxicity and hepatotoxicity especially in populations more subjected to stress or PM.

Keywords: aluminum, stress, protein malnutrition, nephrotoxicity, hepatotoxicity, epigallocatechin-3-gallate, rats

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Authors: Prerna Kalra, Surender Singh

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Cisplatin is the most common chemotherapeutic agent used in different solid tumors, but its main limiting factor is dose-dependent nephrotoxicity by generating reactive oxygen species, by stimulating inflammatory and apoptotic pathways. Additional adjuvant therapies to decrease the toxicity of this chemotherapeutic drug are essential. This study was designed to evaluate the protective role of Emblica officinalis Geartn (Indian gooseberry) against cisplatin induced nephrotoxicity. Emblica officinalis was orally administered to Wistar rats (n=6) for 10 days in 50, 100 and 200mg/kg body weight. On day 7, 8mg/kg of cisplatin was administered intra-peritoneally to rats in all groups. Serum creatinine, blood urea nitrogen and antioxidant levels were measured on day10. The renal damage was evaluated by histopathological and transmission electron microscopy. We found that 200mg/kg dose of Emblica officinalis significantly inhibited the elevation of biochemical parameters i.e. serum creatinine, blood urea nitrogen, oxidant stress marker (malondialdehyde) and increased the reduced levels of antioxidant marker (endogenous glutathione and superoxide dismutase). Cisplatin treated rats have shown acute tubular necrosis and infiltration of inflammatory cells in rat kidney which was reversed after treating the animals with Emblica officinalis in the treatment group. In ultrastructural changes cisplatin treated group showed the damaged mitochondria (M) with dissolved cristae and large number of lysosomes (L) and vacuole (V) formation in tubular epithelial cells. EOE administered group showed visible cristae formation and sign of autophagy vacuoles at a dose of 200mg/kg. Further in-silico studies revealed that ellagic acid is responsible for its nephroprotective effect. The above findings conclude that the Emblica officinalis may be used as an adjuvant therapy in cisplatin induced nephrotoxicity.

Keywords: antioxidant, cisplatin, Emblica officinalis, in silico, nephrotoxicity

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Authors: Chittapon Jantararussamee, Malai Taweechotipatr, Udomsri Showpittapornchai, Wisuit Pradidarcheep

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Hepatic fibrosis is characterized by collagen accumulation in hepatic lobules following wound healing process. If lefts untreated, it could progress into hepatic cirrhosis, portal hypertension, and liver failure. Probiotics comprise of lactic acid bacteria which are crucial components of the intestinal microflora and possess many beneficial properties. The objective of this study is to investigate the hepatoprotective effects of probiotic lactic acid bacteria (mixture of Lactobacillus paracasei, Lactobacillus casei, and Lactobacillus confusus at a ratio of 1: 1: 1) on thioacetamide-induced liver fibrotic rats in term of histomorphology study. Twenty-four male Wistar rats were randomly divided into four groups with 6 rats each: (A) control, (B) fibrotic, (C) fibrotic+probiotic, and (D) probiotic. Group (A) received daily oral administration of distilled water. Group (B and C) were induced by intraperitoneal injection of thioacetamide (TAA) (200 mg/kg BW) 3 times per week for consecutive 8 weeks. In probiotic-treated group (C and D), the number of a mixture of the viable microbial cells at 10⁹ CFU/ml was administered orally daily. After sacrifice, liver tissues were collected and processed for routine histological technique and stained with Sirius red. It was found that the fibrotic rats showed hepatic injury marked by area of inflammation, hydropic degeneration of hepatocytes, and accumulation of myofibroblast-like cells. The collagen fibers were substantially accumulated in the hepatic lobules. Moreover, probiotic-treated group significantly reduced the accumulation of collagen in rats treated by TAA. The liver damage was found to be lesser in the probiotic-treated group. It was noted that the liver tissues of control and probiotics groups were shown to be normal. Administration with probiotic lactic acid bacteria could improve the histomorphology in fibrotic liver and be useful for prevention of hepatic disorders.

Keywords: liver fibrosis, probiotics, lactic acid bacteria, thioacetamide

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Authors: Ramin Hosseinnezhad, Iurii Vozniak, Andrzej Galeski

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Shear-induced crystallization, originated from orientation of chains along the flow direction, is an inevitable part of most polymer processing technologies. It plays a dominant role in determining the final product properties and is affected by many factors such as shear rate, cooling rate, total strain, etc. Investigation of the shear-induced crystallization process become of great importance for preparation of nanocomposite, which requires crystallization of nanofibrous sheared inclusions at higher temperatures. Thus, the effects of shear time, shear rate, and also thermal condition of cooling on crystallization of two aliphatic-aromatic copolyesters have been investigated. This was performed using Linkam optical shearing system (CSS450) for both Ecoflex® F Blend C1200 produced by BASF and synthesized copolyester of butylene terephthalate and a mixture of butylene esters: adipate, succinate, and glutarate, (PBASGT), containing 60% of aromatic comonomer. Crystallization kinetics of these biodegradable copolyesters was studied at two different conditions of shearing. First, sample with a thickness of 60µm was heated to 60˚C above its melting point and subsequently subjected to different shear rates (100–800 sec-1) while cooling with specific rates. Second, the same type of sample was cooled down when shearing at constant temperature was finished. The intensity of transmitted depolarized light, recorded by a camera attached to the optical microscope, was used as a measure to follow the crystallization. Temperature dependencies of conversion degree of samples during cooling were collected and used to determine the half-temperature (Th), at which 50% conversion degree was reached. Shearing ecoflex films for 45 seconds with a shear rate of 100 sec-1 resulted in significant increase of Th from 56˚C to 70˚C. Moreover, the temperature range for the transition of molten samples to crystallized state decreased from 42˚C to 20˚C. Comparatively low shift of 10˚C in Th towards higher temperature was observed for PBASGT films at shear rate of 600 sec-1 for 45 seconds. However, insufficient melt flow strength and non-laminar flow due to Taylor vortices was a hindrance to reach more elevated Th at very high shear rates (600–800 sec-1). The shift in Th was smaller for the samples sheared at a constant temperature and subsequently cooled down. This may be attributed to the longer time gap between cessation of shearing and the onset of crystallization. The longer this time gap, the more possibility for crystal nucleus to re-melt at temperatures above Tm and for polymer chains to recoil and relax. It is found that the crystallization temperature, crystallization induction time and spherulite growth of aliphatic-aromatic copolyesters are dramatically influenced by both the cooling rate and the shear imposed during the process.

Keywords: induced crystallization, shear rate, aliphatic-aromatic copolyester, ecoflex

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Authors: Geraldine Landon, Enora Clero, Jean-Rene Jourdain

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In 2005, the Institut de Radioprotection et de Sûreté Nucléaire (IRSN, France) launched a research program named EPICE (acronym for 'Evaluation of Pathologies potentially Induced by CaEsium') to collect scientific information on non-cancer effects possibly induced by chronic exposures to low doses of ionizing radiation with the view of addressing a question raised by several French NGOs related to health consequences of the Chernobyl nuclear accident in children. The implementation of the program was preceded by a pilot phase to ensure that the project would be feasible and determine the conditions for implementing an epidemiological study on a population of several thousand children. The EPICE program focused on childhood cardiac arrhythmias started in May 2009 for 4 years, in partnership with the Russian Bryansk Diagnostic Center. The purpose of this cross-sectional study was to determine the prevalence of cardiac arrhythmias in the Bryansk oblast (depending on the contamination of the territory and the caesium-137 whole-body burden) and to assess whether caesium-137 was or not a factor associated with the onset of cardiac arrhythmias. To address these questions, a study bringing together 18 152 children aged 2 to 18 years was initiated; each child received three medical examinations (ECG, echocardiography, and caesium-137 whole-body activity measurement) and some of them were given with a 24-hour Holter monitoring and blood tests. The findings of the study, currently submitted to an international journal justifying that no results can be given at this step, allow us to answer clearly to the issue of radiation-induced childhood arrhythmia, a subject that has been debated for many years. Our results will be certainly helpful for health professionals responsible for the monitoring of population exposed to the releases from the Fukushima Dai-ichi nuclear power plant and also useful for future comparative study in children exposed to ionizing radiation in other contexts, such as cancer radiation therapies.

Keywords: Caesium-137, cardiac arrhythmia, Chernobyl, children

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Authors: Jyh-Cheng Chen, Tai-Jing Wang, Yun-Wei Lin

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Astaxanthin has been demonstrated to exhibit a wide range of beneficial effects including anti-inflammatory and anti-cancer properties. However, the molecular mechanism of astaxanthin-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination and high levels of Rad51 expression are observed in chemo- or radioresistant carcinomas. In this study, astaxanthin treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1703. Treatment with astaxanthin decreased Rad51 expression and phospho-AKT protein level in a time and dose-dependent manner. Furthermore, expression of constitutively active AKT (AKT-CA) vector significantly rescued the decreased Rad51 protein and mRNA levels in astaxanthin-treated NSCLC cells. Combined treatment with PI3K inhibitors (LY294002 or wortmannin) and astaxanthin further decreased the Rad51 expression in NSCLC cells. Knockdown of Rad51 enhanced astaxanthin-induced cytotoxicity and growth inhibition in NSCLC cells. These findings may have implications for the rational design of future drug regimens incorporating astaxanthin for the treatment of NSCLC.

Keywords: astaxanthin, cytotoxicity, AKT, non-small cell lung cancer, PI3K

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Authors: Yogendar Singh, Parasmani Rajput, Pawan Kumar Kulriya

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Understanding the radiation response of the pyrochlore structured ceramics in the nuclear reactor core-like environment is of quite an interest for their utilization as host matrices. Electronic excitation (100 MeV I7+) induced crystalline to amorphous phase transition in Nd2Zr2O7 pyrochlore synthesized through three steps solid-state sintering method was investigated. The x-ray diffraction, along with Raman spectroscopy and x-ray absorption spectroscopy experiments conducted on pristine and irradiated pyrochlore, showed an increase in the rate of amorphization with ion fluence. XRD results indicate that specimen is completely amorphized on irradiation at the highest fluence of 5×1013 ions/cm2. The EXAFS spectra of the K-Zr edge and the Nd LIII edge confirmed a significant change in the chemical environment of Nd upon swift heavy ion irradiation. Observation of a large change in the intensity of K-Zr pre-edge spectra is also a good indicator of the phase transition from pyrochlore to the amorphous phase, which is supported by the FT modulus of the LIII-Nd edge. However, the chemical environment of Zr is less affected by irradiation, but it clearly exhibits an increase in the degree of disorder.

Keywords: nuclear host matrices, swift heavy ion irradiation, x-ray absorption spectroscopy, pyrochlore oxides

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Authors: Lijun Wang, Zhen-Yu Chen

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A high-fat diet induces the accumulation of lipid hydroperoxides, accelerates the ageing process and causes a greater mortality in Drosophila melanogaster. The purple sweet potato is rich in antioxidant anthocyanin. The present study was to examine if supplementation of purple sweet potato anthocyanin (PSPA) could reduce the mortality of fruit flies fed a high-fat diet. Results showed that the mean lifespan of fruit fly was shortened from 56 to 35 days in a dose-dependent manner when lard in the diet increased from 0% to 20%. PSPA supplementation attenuated partially the lard-induced mortality. The maximum lifespan and 50% survival time were 49 and 27 days for the 10% lard control flies, in contrast, they increased to 57 and 30 days in the PSPA-supplemented fruit flies. PSPA-supplemented diet significantly up-regulated the mRNA of superoxide dismutase, catalase and Rpn11, compared with those in the control lard diet. In addition, PSPA supplementation could restore the climbing ability of fruit flies fed a 10% lard diet. It was concluded that the lifespan-prolonging activity of PSPA was most likely mediated by modulating the genes of SOD, CAT and Rpn11.

Keywords: purple sweet potato, anthocyanin, high-fat diet, oxidative stress

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Authors: Jaomai Tungsiripat, Patompong Satapornpong

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Allopurinol have been used to treat diseases that relating with the reduction of uric acid and be a treatment preventing the severity of, including gout, chronic kidney disease, chronic heart failure, and diabetes mellitus (type 2). However, allopurinol metabolites can cause a severe cutaneous adverse reaction (SCARs) consist of Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) and Stevens-Johnson Syndrome(SJS)/Toxic Epidermal Necrolysis (TEN). Previous studies, we found only HLA-B*58:01 allele has a strongly association with allopurinol-induced SCARs in many populations: Han Chinese [P value = 4.7 x 10−24], European [P value <10−6], and Thai [P value <0.001].However, there was no update the frequency of HLA-B alleles and pharmacogenetics markers distribution in healthy Thais and support for screening before the initiation of treatment. The aim of this study was to investigate the prevalence of HLA-B*58:01 allele associated with allopurinol-induced SCARs in healthy Thai population. A retrospective study of 260 individual healthy subjects who living in Thailand. HLA-B were genotyped using sequence-specific oligonucleotides (PCR-SSOs).In this study, we identified the prevalence of HLA-B alleles consist ofHLA-B*46:01 (12.69%), HLA-B*15:02 (8.85%), HLA-B*13:01 (6.35%), HLA-B*40:01 (6.35%), HLA-B*38:02 (5.00%), HLA-B*51:01 (5.00%), HLA-B*58:01 (4.81%), HLA-B*44:03 (4.62%), HLA-B*18:01 (3.85%) and HLA-B*15:25 (3.08%). Therefore, the distribution of HLA-B*58:01 will support the clinical implementation and screening usage of allopurinol in Thai population.

Keywords: allopurinol, HLA-B*58: 01, Thai population, SCARs

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Authors: Suprabha Islam, Sifat Ullah Tanzil

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During past few decades, being amazed by the excellent silent flight of owl, scientists have been trying to demystify the unique features of its wing feathers. Our present study is dedicated to taking our understanding further on this phenomenon. In this present study, a numerical investigation was performed to analyze how the shape of the leading-edge serration at owl wing feathers effects the flow-induced noise generation. For the analysis, an owl inspired single feather wing model was prepared for both with and without serrations at the leading edge. The serration profiles were taken at different positions of the vane length for a single feather. The broadband noise was studied to quantify the local contribution to the total acoustic power generated by the flow, where the results clearly showed the effect of serrations in reducing the noise generation. It was also clearly visible that the shape of the serration has a very strong influence on noise generation. The frequency spectrum of noise was also analyzed and a strong relation was found between the shape of the serration and the noise generation. It showed that the noise suppression is strongly influenced by the height to length ratio of the serration. With the increase in height to length ratio, the noise suppression is enhanced further.

Keywords: aeroacoustics, aerodynamic, biomimetics, serrations

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Authors: Kemal Efe Eseller, Göktuğ Yazici

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Laser-induced breakdown spectroscopy (LIBS) is a rapid optical atomic emission spectroscopy which is used for material identification and analysis with the advantages of in-situ analysis, elimination of intensive sample preparation, and micro-destructive properties for the material to be tested. LIBS delivers short pulses of laser beams onto the material in order to create plasma by excitation of the material to a certain threshold. The plasma characteristics, which consist of wavelength value and intensity amplitude, depends on the material and the experiment’s environment. In the present work, medicine samples’ spectrum profiles were obtained via LIBS. Medicine samples’ datasets include two different concentrations for both paracetamol based medicines, namely Aferin and Parafon. The spectrum data of the samples were preprocessed via filling outliers based on quartiles, smoothing spectra to eliminate noise and normalizing both wavelength and intensity axis. Statistical information was obtained and principal component analysis (PCA) was incorporated to both the preprocessed and raw datasets. The machine learning models were set based on two different train-test splits, which were 70% training – 30% test and 80% training – 20% test. Cross-validation was preferred to protect the models against overfitting; thus the sample amount is small. The machine learning results of preprocessed and raw datasets were subjected to comparison for both splits. This is the first time that all supervised machine learning classification algorithms; consisting of Decision Trees, Discriminant, naïve Bayes, Support Vector Machines (SVM), k-NN(k-Nearest Neighbor) Ensemble Learning and Neural Network algorithms; were incorporated to LIBS data of paracetamol based pharmaceutical samples, and their different concentrations on preprocessed and raw dataset in order to observe the effect of preprocessing.

Keywords: machine learning, laser-induced breakdown spectroscopy, medicines, principal component analysis, preprocessing

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Authors: Minhal Abidi, Moinuddin

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Diabetes mellitus (DM) induced metabolic abnormalities causes oxidative stress which leads to the pathogenesis of complications associated with diabetes like retinopathy, nephropathy periodontitis etc. Combination of glycation and oxidation 'glycoxidation' occurs when oxidative reactions affect the early state of glycation products. Low density lipoprotein (LDL) is prone to glycoxidative attack by sugars and methylglyoxal (MGO) being a strong glycating agent may have severe impact on its structure and consequent role in diabetes. Pro-inflammatory cytokines like IL1β and TNFα produced by the action of gram negative bacteria in periodontits (PD) can in turn lead to insulin resistance. This work discusses modifications to LDL as a result of glycoxidation. The changes in the protein molecule have been characterized by various physicochemical techniques and the immunogenicity of the modified molecules was also evaluated as they presented neo-epitopes. Binding of antibodies present in diabetes patients to the native and glycated LDL has been evaluated. Role of modified epitopes in the generation of antibodies in diabetes and periodontitis has been discussed. The structural perturbations induced in LDL were analyzed by UV–Vis, fluorescence, circular dichroism and FTIR spectroscopy, molecular docking studies, thermal denaturation studies, Thioflavin T assay, isothermal titration calorimetry, comet assay. MALDI-TOF, ketoamine moieties, carbonyl content and HMF content were also quantitated in native and glycated LDL. IL1β and TNFα levels were also measured in the type 2 DM and PD patients. We report increased carbonyl content, ketoamine moieties and HMF content in glycated LDL as compared to native analogue. The results substantiate that in hyperglycemic state MGO modification of LDL causes structural perturbations making the protein antigenic which could obstruct normal physiological functions and might contribute in the development of secondary complications in diabetic patients like periodontitis.

Keywords: advanced glycation end products, diabetes mellitus, glycation, glycoxidation, low density lipoprotein, periodontitis

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Authors: Ginpreet Kaur, Mohammad Yasir Usmani, Mohammed Kamil Khan

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Diabetes mellitus is a disease with a high global burden and results in significant morbidity and mortality. In India, the number of people suffering with diabetes is expected to rise from 19 to 57 million in 2025. At present, interest in herbal remedies is growing to reduce the side effects associated with conventional dosage form like oral hypoglycemic agents and insulin for the treatment of diabetes mellitus. Our aim was to investigate the antidiabetic activities of combinatorial extract of N. sativa & C. cassia in Streptozotocin induced type-I Diabetic Rats. Thus, the present study was undertaken to screen postprandial glucose excursion potential through α- glucosidase inhibitory activity (In Vitro) and effect of combinatorial extract of N. sativa & C. cassia in Streptozotocin induced type-I Diabetic Rats (In Vivo). In addition changes in body weight, plasma glucose, lipid profile and kidney profile were also determined. The IC50 values for both extract and Acarbose was calculated by extrapolation method. Combinatorial extract of N. sativa & C. cassia at different dosages (100 and 200 mg/kg orally) and Metformin (50 mg/kg orally) as the standard drug was administered for 28 days and then biochemical estimation, body weights and OGTT (Oral glucose tolerance test) were determined. Histopathological studies were also performed on kidney and pancreatic tissue. In In-Vitro the combinatorial extract shows much more inhibiting effect than the individual extracts. The results reveals that combinatorial extract of N. sativa & C. cassia has shown significant decrease in plasma glucose (p<0.0001), total cholesterol and LDL levels when compared with the STZ group The decreasing level of BUN and creatinine revealed the protection of N. sativa & C. cassia extracts against nephropathy associated with diabetes. Combination of N. sativa & C. cassia significantly improved glucose tolerance to exogenously administered glucose (2 g/kg) after 60, 90 and 120 min interval on OGTT in high dose streptozotocin induced diabetic rats compared with the untreated control group. Histopathological studies shown that treatment with N. sativa & C. cassia extract alone and in combination restored pancreatic tissue integrity and was able to regenerate the STZ damaged pancreatic β cells. Thus, the present study reveals that combination of N. sativa & C. cassia extract has significant α- glucosidase inhibitory activity and thus has great potential as a new source for diabetes treatment.

Keywords: lipid levels, OGTT, diabetes, herbs, glucosidase

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Authors: Hae Jeong Park, Joo-Ho Chung

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In this study, the effect of essential oil from Chamaecyparis obtuse (EOCO) on early life stress using maternal separation (MS) rats was investigated. Anxiety-related behaviors were examined in MS rats using the elevated plus-maze (EPM) test. The changes of gene expressions by EOCO in the hippocampus of MS rats were analyzed using a microarray method. Rats in the MS groups were separated from their respective mothers from postnatal day (pnd) 14 to 28. Rats in the EOCO-treated groups were exposed to EOCO for 1 h or 2 h by inhalation from pnd 21 to 28. The EOCO-treated MS rats showed decreased anxiety-related behaviors compared to the MS rats in the EPM test. In the microarray analysis, EOCO downregulated the expressions of cytokine genes such as Ccl2, Il6, Cxcl10, Ccl19, and Il1rl in the hippocampus of MS rats, and it was also confirmed through RT-PCR. In particular, the expressions of Ccl2 and Il6 were predominantly decreased by EOCO in the hippocampus of MS rats. Interestingly, their protein expressions were also reduced by EOCO in MS rats. These results indicate that EOCO decreases MS-induced anxiety-related behaviors, and modulate cytokines, particularly Ccl2 and Il6, in the hippocampus of MS rats.

Keywords: anxiety-related behavior, Chamaecyparis obtuse, cytokine gene, early-life stress, maternal separation

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Authors: Joana Portia Sakyi

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The uniqueness of auxiliary verbs and their contribution to grammar as constituents, which act as preverbs to supply additional grammatical or functional meanings to clauses, are well established. Functionally, they relate clauses to tense, aspect, mood, voice, emphasis, and modality, along with the main verbs conveying the appropriate lexical content. There has been an issue in Akan grammar vis-à-vis the status of auxiliary verbs, in terms of whether Akan has auxiliaries or not and even which forms are to be regarded as auxiliaries. We investigate the syntactic, semantic, and pragmatic components of expressions and claim that Akan has auxiliary verbs that contribute the functional or grammatical meaning of modality, tense/aspect, etc., to clauses they occur in. Essentially, we use a self-created corpus data to consider the affix bέ- ‘may’, ‘must’, ‘should’; the form tùmí ‘can’, ‘be able to’; mà ‘to let’, ‘to allow’, ‘to permit’, ‘to make’, or ‘to cause’ someone to do something; the multi-word forms ὲsὲ sέ ‘must’, ‘should’ or ‘have to’ and ètwà sέ ‘must’, ‘should’ or ‘have to’, and assert that they are legitimate modal auxiliaries conveying epistemic, deontic, and dynamic modalities, as well as other meanings in the language.

Keywords: Akan, modality, modal auxiliaries, semantics

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Authors: Manju Lata Sharma

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Damage to cells caused by free radicals is believed to play a central role in the ageing process and in disease progression. Withania somnifera is widely used in ayurvedic medicine, and it is one of the ingredients in many formulations to increase energy, improve overall health and longevity and prevent disease. Withania somnifera possesses antioxidative properties. The antioxdant activity of Withania somnifera consisting of an equimolar concentration of active principles of sitoindoside VII-X and withaferin A. The antioxidant effect of Withania somnifera extract was investigated on lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) activity in mice. Aim: To study the antioxidant activity of an extract of Withania somnifera leaf against a mice model of chronic stress. Healthy swiss albino mice (3-4 months old) selected from an inbred colony were divided in to 6 groups. Biochemical estimation revealed that stress induced a significant change in SOD, LPO, CAT AND GPX. These stress induced perturbations were attenuated Withania somnifera (50 and 100 mg/kg BW). Result: Withania somnifera tended to normalize the augmented SOD and LPO activities and enhanced the activities of CAT and GPX. The result indicates that treatment with an alcoholic extract of Withania somnifera produced a significant decrease in LPO ,and an increase in both SOD and CAT in brain mice. This indicates that Withania somnifera extract possesses free radical scavenging activity .

Keywords: Withania somnifera, antioxidant, lipid peroxidation, brain

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Authors: Nuzsep Almigo, Md Amin Md Taff, Yusop Ahmad, Norkhalid Salimin, Gunathevan Elumalai

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This research aimed to determine the level of self-efficacy in obese trainees before and after the Healthy Lifestyle Program. Self-efficacy is defined as the feeling, belief, perception, belief in the ability to cope with a particular situation that will influence the way individuals cope with the situation. Research instrument used was self efficacy questionnaire consisting of four main factors: (i) cognitive (abilities in a positive and realistic attitudes to the potential of to perform the duties, restrictions, or social desire), (ii) effective (mental management ability, feeling and mood), (iii) motivation (determination and the level of ability to achieve the purpose or goal), and (iv) selective (ability to choose the social conditions confronting and adapting to situations). The study sample consisted of 118 trainees from Healthy Lifestyle Program. The analysis showed there was a significant difference in self-efficacy before and after the Healthy Lifestyle Program (p = 0.00) indicated by increasing self-efficacy in the program.

Keywords: self efficacy, self-confidence, affective, motivation, selective

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

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To investigate the chemoprotective potential of NBRIQU16 chemotype isolated from Argyreia speciosa (Family: Convolvulaceae) on N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and NaCl-induced gastric carcinomas in Wistar rats. Forty-six male 6-week-old Wistar rats were divided into two groups. Thirty rats in group A were fed with a diet supplemented with 8 % NaCl for 20 weeks and simultaneously given N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) in drinking water at a concentration of 100 ug/ml for the first 17 weeks. After administration of the carcinogen, 200 and 400 mg/kg of NBRIQU16 were administered orally once a day throughout the study. From week 18, these rats were given normal water. From week 21, these rats were fed with a normal diet for 15 weeks. Group B containing 16 rats was fed standard diet for thirty-five days. It served as control. Ten rats from group A were sacrificed after 20 weeks. Scarification of remaining animals was conducted after 35 weeks. Entire stomach and some part of the duodenum were incised parallel to the greater curvature, and the samples were collected. After opening the stomach location and size of tumors were recorded. The number of tumors with their locations and sizes were recorded. Expression of survivin was examined by recording the Immunohistochemistry of the specimens. The treatment with NBRIQU16 significantly reduced the nodule incidence and nodule multiplicity in the rats after MNNG administration. Surviving expression in glandular stomachs of normal rats, of rats in middle induction period, in adenocarcinomas and NBRIQU16 treated tissues adjacent to tumor were 0, 42.0 %, 79.3%, and 36.4 %, respectively. Expression of survivin was significantly different as compared to the normal rats. Histological observations of stomach tissues too correlated with the biochemical observations.These finding powerfully supports that NBRIQU16 chemopreventive effect by suppressing the tumor burden and restoring the activities of gastric cancer marker enzymes on MNNG and NaCl-induced gastric carcinomas in Wistar rats.

Keywords: Argyreia speciosa, gastric carcinoma, immunochemistry, NBRIQU16

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Authors: Rei-Tang Tsai, Chih-Yang Wu, Chia-Yuan Chang, Ming-Ying Kuo

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This study aims to investigate the mixing behaviors of deionized (DI) water and carboxymethyl cellulose (CMC) solutions in C-shaped serpentine micromixers over a wide range of flow conditions. The flow of CMC solutions exhibits shear-thinning behaviors. Numerical simulations are performed to investigate the effects of the mean flow speed, fluid properties and geometry parameters on flow and mixing in the micromixers with serpentine channel of the same overall channel length. From the results, we can find the following trends. When fluid mixing is dominated by convection, the curvature-induced vortices enhance fluid mixing effectively. The mixing efficiency of a micromixer consisting of semicircular C-shaped repeating units with a smaller center-line radius is better than that of a micromixer consisting of major-segment repeating units with a larger center-line radius. The viscosity of DI water is less than the overall average apparent viscosity of CMC solutions, and so the effect of curvature-induced vortices on fluid mixing in DI water is larger than that in CMC solutions for the cases with the same mean flow speed.

Keywords: curved channel, microfluidics, mixing, non-newtonian fluids, vortex

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Authors: Tanvi P. Medshinge, Prasad Vaidya, Monisha E. Royan

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In India, cooling loads in residential sector is a major contributor to its total energy consumption. Due to the increasing cooling need, the market penetration of air-conditioners is further expected to rise. Natural Ventilation (NV), however, possesses great potential to save significant energy consumption especially for residential buildings in moderate climates. As multifamily residential apartment buildings are designed by repetitive use of prototype designs, deriving individual NV based design prototype solutions for a combination of different wind incidence angles and orientations would provide significant opportunity to address the rise in cooling loads by residential sector. This paper presents the results of NV performance of a selected prototype apartment design with a cluster of four units in Pune, India, and an attempt to improve the NV performance through design modifications. The water table apparatus, a physical modelling tool, is used to study the flow patterns and simulate wind-induced NV performance. Quantification of NV performance is done by post processing images captured from video recordings in terms of percentage of area with good and poor access to ventilation. NV performance of the existing design for eight wind incidence angles showed that of the cluster of four units, the windward units showed good access to ventilation for all rooms, and the leeward units had lower access to ventilation with the bedrooms in the leeward units having the least access. The results showed improved performance in all the units for all wind incidence angles to more than 80% good access to ventilation. Some units showed an additional improvement to more than 90% good access to ventilation. This process of design and performance evaluation improved some individual units from 0% to 100% for good access to ventilation. The results demonstrate the ease of use and the power of the water table apparatus for performance-based design to simulate wind induced NV.  

Keywords: fluid dynamics, prototype design, natural ventilation, simulations, water table apparatus, wind incidence angles

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Authors: Mabroka Omar Sherehe

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Despite the great efficacy of isoniazid (INH) and rifampicine (RIF) combination in the treatment of tuberculosis, hepatotoxicity is the most common serious complication. The potential protective effect of simvastatin (sim) against combination-induced hepatotoxicity was investigated in the present study. The administration of INH-RIF combination (50mg/kg each for 14 days) resulted in a significant increased activities of serum alanine and aspartate aminotransferases, such effects were further supported by histopathological studies. INH-RIF combination produced a significant increase in liver lipid, decreased SOD and CAT, and a significant depletion of GSH level. Additionally, treatment with INH-RIF combination resulted in a significant increase in liver MPO activity. The lipid-lowering drug, Sim demonstrated in the current study an evident antioxidant action, such effect was mediated via decreasing the elevated MDA, MPO, and restoring liver CAT activity. Additionally, Sim restored liver NO level to near basal value Furthermore, one cannot rule out the lipid-lowering effect of Sim that would probably add to its beneficial hepatoprotective antioxidant activity, where Sim decreased the elevated cholesterol, TGs and LDL cholesterol level and increased the serum HDL cholesterol level.

Keywords: isoniazid, rifampicine, oxidative stress, nitric oxide

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Authors: Francisco J. Arias

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Consideration is given to a mechanism of heat and mass transport in solutions similar than that of natural convection but with one important difference. Here the mechanism is not promoted by density differences in the fluid occurring due to temperature gradients (coefficient of thermal expansion) but rather by solubility differences due to the thermal dependence of the solubility (coefficient of thermal solubility). Utilizing a simplified physical model, it is shown that by the proper choice of the concentration of a given solution, convection might be induced by the alternating precipitation of the solute -when the solution becomes supersaturated, and its posterior recombination when changes in temperature occurs. The spontaneous change in the Gibbs free energy during the mixing is the driven force for the mechanism. The maximum extractable energy from this new type of thermal convection was derived. Experimental data from a closed-loop circuit was obtained demonstrating the feasibility for continuous separation and recombination of the solution. This type of heat and mass transport -which doesn’t depend on gravity, might potentially be interesting for heat and mass transport downwards (as in solar-roof collectors to inside homes), horizontal (e.g., microelectronic applications), and in microgravity (space technology). Also, because the coefficient of thermal solubility could be positive or negative, the investigated thermo-osmosis convection can be used either for heating or cooling.

Keywords: natural convection, thermal gradient, solubility, osmotic pressure

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Authors: Eric Beyegue, Boris Azantza, Judith Laure Ngondi, Julius E. Oben

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Background: Insulin resistance (IR) and oxidative stress are associated with obesity, diabetes mellitus, and other cardio metabolic disorders. The aim of this study was to investigate the effect of Coula edulis extracts (CEE) on insulin resistance and oxidative stress markers in high-fat/high sucrose diet-induced insulin resistance in rats. Materials and Methods: Thirty male rats were divided into 6 groups of 5 rats each fed, received daily oral administration of CE extracts for 8 weeks as follows: Group 1 or negative control group, fed with standard diet (SD); Group 2 fed with high-fat/high sucrose diet (HFHS) only; Group3 fed with HFHS + CEAq 200; Group 4 fed with HFHS + CEAq 400; Group 5 fed with HFHS + CEEt 200; Group 6 fed with HFHS + CEEt 400. At the end of the experiment (8 weeks), animals were sacrificed plasma lipid profile, glucose, insulin, oxidative marker and digestive enzyme activities were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) was determined. Results: Feedings with HFHS significantly (p < 0.01) induced plasma hyperglycaemia, hyperinsulinaemia, increased triglyceride, total cholesterol, and low-density lipoprotein levels, decreased high-density lipoprotein levels, alterations of α amylase, and glucose-6-phosphatase activities, and oxidative stress. Daily oral administration with CEE for eight weeks after insulin resistance induction had a hypolipidaemic action, antioxidative activities and modulated metabolic markers. Ethanolic extract at the higher dose had the best effect on body weight gain and insulin resistance, whereas aqueous extract showed the better activity on hyperlipidemia. Conclusion: These results suggest that CEAq and CEEt at 400mg/kg are promising complementary supplements that can be used to protect better from metabolic disorders associated with HFHS.

Keywords: Coula edulis Baill, high-fat / high sucrose diet, insulin resistance, oxidative stress

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Authors: Darya O. Prima, Elena V. Vorontsova, Yuri G. Slizhov, Andrey V. Zibarev

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A broad family of carbocycle-fluorinated aza-heterocycles including 1,3-benzodiazoles (benzimidazoles), 1,2,3-benzotriazoles, 2,1,3-benzothia/selenadiazoles and 1,4-benzodiazines (quinoxalines) was synthesized in the unified way and assessed for cytotoxicity towards the Hep2 (laryngeal epidermoid carcinoma, a kind of oral cancer) cells. The diazoles, triazoles and selenadiazoles revealed low medium inhibitory concentrations IC50 = 2.2-26.4 µМ and induced the cells’ apoptosis at low concentrations C = 1-25 µМ. For selenadiazoles, cell death dynamics was observed already in the first hours after the treatment. Replacement of one atom F by group Me2N in some cases enlarged apoptotic activity of the compounds towards the Hep2 cells. In contrast, the archetypal (i.e. non-fluorinated) 1,3-benzodiazole, 1,2,3-benzotriazole and 2,1,3-benzoselenadiazole were low toxic (IC50 > 100 µM) and induced apoptosis only at high concentrations. The chlorinated congeners of the heterocycles under discussion were highly toxic towards the Hep2 cells but revealed insignificant ability to induce their apoptosis. Overall, the findings above suggest that fluorinated 1,3-benzodiazole, 1,2,3-benzotriazole and 2,1,3-benzoselenadiazole derivatives can be considered as potential anticancer drugs. For the laryngeal epidermoid carcinoma (for which, according to available statistics, the five-year survival rate remained ~50% during the past 30 years), it is especially important since surgical treatment is seriously complicated here thus encouraging medicament one.

Keywords: Apoptosis, aza-heterocycles, cytotoxicity, fluorinated, Hep2 cells, synthesis

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Authors: K. Biswas, U. H. Armin, S. M. J. Prodhan, J. A. Prithul, S. Sarker, F. Afrin

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Alzheimer’s disease (AD) (a progressive neurodegenerative disorder) is mostly predominant cause of dementia in the elderly. Prolonging the function of acetylcholine by inhibiting both acetylcholinesterase and butyrylcholinesterase is most effective treatment therapy of AD. Traditionally Pterocarpus santalinus L. is widely known for its medicinal use. In this study, in vitro acetylcholinesterase inhibitory activity was investigated and methanolic extract of the plant showed significant activity. To confirm this activity (in vivo), learning and memory enhancing effects were tested in mice. For the test, memory impairment was induced by scopolamine (cholinergic muscarinic receptor antagonist). Anti-amnesic effect of the extract was investigated by the passive avoidance task in mice. The study also includes brain acetylcholinesterase activity. Results proved that scopolamine induced cognitive dysfunction was significantly decreased by administration of the extract solution, in the passive avoidance task and inhibited brain acetylcholinesterase activity. These results suggest that bark extract of Pterocarpus santalinus can be better option for further studies on AD via their acetylcholinesterase inhibitory actions.

Keywords: Pterocarpus santalinus, cholinesterase inhibitor, passive avoidance, Alzheimer’s disease

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