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Rapamycin and PF4 Induce Apoptosis by Upregulating Bax and Down-Regulating Survivin in MNU-Induced Breast Cancer

  • Al-Astani Tengku Din, Tengku Ahmad Damitri;Shamsuddin, Shazana Hilda;Idris, Fauziah Mohamad;Wan Mansor, Wan Nor Ariffin;Abdul Jalal, Muhammad Irfan;Jaafar, Hasnan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.9
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    • pp.3939-3944
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    • 2014
  • Background: To elucidate the role of rapamycin and PF4 on apoptosis regulation via Bax (pro-apoptosis), Bcl-2 (anti-apoptosis) and survivin activation on the growth in the 1-methyl-1-nitrosourea-induced invasive breast carcinoma model. Materials and Methods: Thirty five female Sprague Dawley rats at age 21-day old were divided into 4 groups; Group 1 (control, n=10), Group 2 (PF4, n=5), Group 3 (rapamycin, n=10) and Group 4 (rapamycin+PF4, n=10). MNU was administered intraperitionally, dosed at 70mg/kg body weight. The rats were treated when the tumors reached the size of $14.5{\pm}0.5mm$ and subsequently sacrificed after 5 days. Rapamycin and PF4 were administered as focal intralesional injections at the dose of $20{\mu}g$/lesion. The tumor tissue was then subjected to histopathological examinations for morphological appraisal and immunohistochemical assessment of the pro-apoptotic marker, Bax and anti-apoptotic markers, Bcl-2 and survivin. Results: The histopathological pattern of the untreated control cohort showed that the severity of the malignancy augments with mammary tumor growth. Tumors developing in untreated groups were more aggressive whilst those in treated groups demonstrated a transformation to a less aggressive subtype. Combined treatment resulted in a significant reduction of tumor size without phenotypic changes. Bax, the pro-apoptotic marker, was significantly expressed at higher levels in the rapamycin-treated and rapamycin+PF4-treated groups compared to controls (p<0.05). Consequently, survivin was also significantly downregulated in the rapamycin-treated and rapamycin+PF4-treated group and this was significantly different when compared to controls (p). Conclusions: In our rat model, it could be clearly shown that rapamycin specifically affects Bax and survivin signaling pathways in activation of apoptosis. We conclude that rapamycin plays a critical role in the induction of apoptosis in MNU-induced mammary carcinoma.

How Our Practice of Histopathology, Especially Tumour Pathology has Changed in the Last Two Decades: Reflections from a Major Referral Center in Pakistan

  • Ahmad, Zubair;Idrees, Romana;Fatima, Saira;Arshad, Huma;Din, Nasir-Ud;Memon, Aisha;Minhas, Khurram;Ahmed, Arsalan;Fatima, Syeda Samia;Arif, Muhammad;Ahmed, Rashida;Haroon, Saroona;Pervez, Shahid;Hassan, Sheema;Kayani, Naila
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.9
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    • pp.3829-3849
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    • 2014
  • Continued advances in the field of histo pathology (and cyto pathology) over the past two decades have resulted in dramatic changes in the manner in which these disciplines are now practiced. This is especially true in the setting of a large university hospital where the role of pathologists as clinicians (diagnosticians), undergraduate and postgraduate educators, and researchers has evolved considerably. The world around us has changed significantly during this period bringing about a considerable change in our lifestyles and the way we live. This is the world of the internet and the world-wide web, the world of Google and Wikipedia, of Youtube and Facebook where anyone can obtain any information one desires at the push of a button. The practice of histo (and cyto) pathology has also evolved in line with these changes. For those practicing this discipline in a poor, developing country these changes have been breathtaking. This is an attempt to document these changes as experienced by histo (and cyto) pathologists practicing in the biggest center for Histopathology in Pakistan, a developing country in South Asia with a large (180 million) and ever growing population. The Section of Histopathology, Department of Pathology and Microbiology at the Aga Khan University Hospital (AKUH) in Karachi, Pakistan's largest city has since its inception in the mid-1980s transformed the way histopathology is practiced in Pakistan by incorporating modern methods and rescuing histopathology in Pakistan from the primitive and outdated groove in which it was stuck for decades. It set histopathology in Pakistan firmly on the path of modernity and change which are essential for better patient management and care through accurate and complete diagnosis and more recently prognostic and predictive information as well.

Coastal Eutrophication caused by Effluent from Aquaculture Ponds in Jeju (제주연안 육상양식장 밀집지역 주변해역의 영양염 과잉 요인)

  • Koh, Hyuk-Joon;Park, Sung-Eun;Cha, Hyung-Kee;Chang, Dae-Soo;Koo, Jun-Ho
    • Journal of the Korean Society of Marine Environment & Safety
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    • v.19 no.4
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    • pp.315-326
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    • 2013
  • This study investigated the temporal-spatial distribution and variations in water quality parameters (temperature, salinity, pH, DO, COD, SPM, DIN, DIP, silicate, TN, TP, and chlorophyll-a) in the coastal area of Jeju, Korea, adjacent to aquaculture ponds (Aewol-ri, Haengwon-ri, Pyosun-ri, and Ilkwa-ri). Data were collected bimonthly from February 2010 to December 2011. A principal component analysis (PCA) identified three major factors controlling variations in water quality during the sampling period. Aquaculture effluent water led to large changes in nutrient levels. The highest nutrient values were observed during the investigation period. The relatively large increase in organic matter at the sampling stations coupled with sea area runoff events during the summer rainy period. Variation in chlorophyll-a concentration was mainly driven by meteorological factors such as air temperature and rainfall in the coastal areas of Aewol and Haengwon. In the coastal areas of Pyosun and Ilkwa, pollution was caused by anthropogenic factors such as discharge of aquaculture effluent water. High nutrient concentrations at the majority of the coastal stations indicate eutrophication of coastal waters, especially within a distance of 300 m and depth of 10m from drainage channels. Coastal eutrophication driven by aquaculture effluent may be harmful inshore. Events such as eutrophication may potentially influence water pollution in aquaculture ponds when seawater intake is detected because of aquaculture effluent water.

Geochemical Characteristics and Benthos Distribution in the Three Shellfish Farms in Suncheon Bay, Korea (순천만 패류 양식장 3개소의 지화학적 특성과 저서생물상 분포 -가리맛조개 양식장과 새꼬막 양식장-)

  • Suh, Jinsoo;Kim, Taehoon;Shin, Seyeon;Kahng, Hyung-Yeel;Ahn, Samyoung;Jung, Jae-Sung;Kim, Youngsung;Won, Nam-Il
    • Journal of Environmental Science International
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    • v.26 no.6
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    • pp.691-710
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    • 2017
  • This study was performed to investigate the geochemical and benthic environment of three shellfish farms in Suncheon Bay during the period of September 2014 ~ April 2015. Three sampling stations were selected; St.1 is the shellfish farm of razor clam near Jangsan area. St.2 is the shellfish farm of small ark shell near Hwapo area and St.3 is the shellfish farm of razor clam near Yongdu area. Razor clam was the dominant species at St.1, small ark shell and granulated ark shell were dominant at St.2 and St.3, respectively. Granulated ark shell inhabited St.3, although it is not cultured at that station. This station's exposure to air during the ebb tide and sediment composition likely provides the appropriate habitat for granulated ark shell species. Analysis of the number of different species showed that 8 benthos species were found to be distributed at St.1, 18 species at St.2, and 13 species at St.3. Among three stations, the highest Ignition Loss (IL), Chemical Oxygen Demand (COD) and Acid Volatile Sulfide (AVS) values were obtained from the sediment at St.2. The analysis of pore water from St.2 also showed the highest values of Total Organic Carbon (TOC), ammonia ($NH_4^+$), Dissolved Inorganic Nitrogen (DIN) and phosphate ($PO_4^{3-}$). These results are related to the fact that species dominance and richness is the highest in St.2.

Protective Effects of Milk Thistle (Silybum marianum) against Aflatoxin B1 in Broiler Chicks

  • Chand, N.;Muhammad, Din;Durrani, F.R.;Qureshi, M. Subhan;Ullah, Sahibzada S.
    • Asian-Australasian Journal of Animal Sciences
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    • v.24 no.7
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    • pp.1011-1018
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    • 2011
  • Aflatoxin-contaminated feed cause mortality, suppression of the immune system, reduced growth rates and losses in feed efficiency. This research study was planned to investigate the immunomodulatory and growth promoting effect of milk thistle as feed additive against aflatoxin $B_1$ in broiler chicks at NWFP Agricultural University Peshawar, Pakistan. Two hundred and forty (240) day old broilers chicks were randomly assigned into four major groups AfF, aflatoxin free feed; Aflatoxin $B_1$ was present in the feed at the levels of 80-520 ${\mu}g/kg$ of the feed in the remaining three groups. Aflatoxin contaminated feed was provided for 5 weeks. Group AfB was supplemented with toxin binder "Mycoad" at 3 g/kg of feed and group AfT was supplemented with milk thistle at10 g/kg of feed. Each group was further sub divided into two sub-groups, vaccinated against ND (Newcastle disease), IB (Infectious bronchitis) and IBD (Infectious bursal diseases) according to recommended schedule of vaccination or non vaccinated. Each sub group carried three replicates with 10 chicks per replicate. Chicks were reared in pens in an open sided house. Supplementary heat was provided to all the chicks during brooding period. Mean body weight gain and dressing percentage were significantly (p<0.05) higher in group AfF, followed by AfT, AfB and Af. Weight gain and dressing percentage was the same in group AfB and AfT, while it was significantly lower in group Af. Feed intake, breast, thigh and leg weight were found significantly (p<0.05) higher in group AfF, followed by AfB, AfT and Af. Significantly lower (better) FCR value was recorded in group AfT. Water intake was significantly (p<0.05) higher in group AfT and AfF as compared to other groups. Mortality was significantly (p<0.05) higher in group Af. Mean bursa and thymus weights were found significantly (p<0.05) higher in group AfF, AfB and AfT followed by Af, while higher spleen weight was recorded in group AfT. Mean antibody titer against ND, IB and IBD was significantly (p<0.05) higher in group AfT, as compared to other groups. It is concluded that milk thistle at 10 g/kg of feed could effectively be utilized as immunostimulant and growth promotant in the presence of immunosuppressant aflatoxin $B_1$ in the feed.

The Correlation between Environmental Factors and Phytoplankton Communities in Spring and Summer Stratified Water-column at Jinhae Bay, Korea (진해만에서 춘계와 하계 성층기간 동안 환경요인과 식물플랑크톤 군집구조의 관계)

  • Son, Moonho;Hyun, Bong-Gil;Kim, Dong Sun;Choi, Hyun Woo;Kim, Young Ok;Baek, Seung Ho
    • Korean Journal of Environmental Biology
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    • v.30 no.3
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    • pp.219-230
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    • 2012
  • We surveyed 23 sites of Jinhae Bay in spring and summer 2010 in order to study the correlation between the variation of environmental factors, including salinity, temperature, and nutrients and the characteristics of phytoplankton community structures in summer stratification. Phytoplankton biomass was high in the surface water in summer; however, it was very low in the bottom water. The results showed a negative correlation between chlorophyll a (chl. a) and nutrients (silicate, nitrate, nitrite, ammonium, and phosphate) or nutrients ratio in summer; however, there was mostly a positive correlation between chl. a and these nutrients in spring. This inconsistent correlation between spring and summer was attributed to the phytoplankton community, because a diverse phytoplankton community has different nutrient uptake abilities. In addition, the results of CCA (canonical correspondence analysis) showed a negative correlation between phosphate and dominant species, including Chaetoceros spp., Skeletonema costatum-like spp., and Pseudo-nitzschia delicatissima in summer, but a strong positive correlation between DIN (dissolved inorganic nitrogen) and the dominant species, including Cryptomonas spp. and Pseudo-nitzschia multistriata in spring. Consistently, the dominant algal species in summer showed a relatively smaller size cells compared with those in spring, suggested that it may have related with the low nutrient levels at surface layer due to strong stratified water column of summer.

Control of Cyanobacteria (Microcystis aeruginosa) Blooms by Floating Aquatic Plant (Iris pseudoacorus): an in situ Mesocosm Experiment Using Stable ($^{13}C$, $^{15}N$) Isotope Tracers ($^{13}C$, $^{15}N$ 추적자 실험을 통한 부유 수생식물(Iris pseudoacorus)의 Cyanobacteria (Microcystis aeruginosa) 성장억제능력 평가)

  • Kim, Min-Seob;Lee, Yeon-Jung;Kim, Baik-Ho;Hwang, Soon-Jin;An, Kwang-Guk;Park, Sun-Koo;Ume, Han-Yong;Shin, Kyung-Hoon
    • Korean Journal of Ecology and Environment
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    • v.44 no.3
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    • pp.280-291
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    • 2011
  • Bottom-up approaches to control of Microcystis aeruginosa blooms were comparatively investigated through an in situ mesocosm experiment using aquatic plants (Iris pseudoacorus). In the mesocosm experiments, floating I. pseudoacorus, seemed to be effective in controlling massive M. aeruginosa blooms in an agricultural reservoir, exhibiting a close coupling with temporal variations in Chl-a and DO concentration. Shading by floating I. pseudoacorus resulted in a reduced phytoplankton abundance inhibiting light energy availability. Moreover, I. pseudoacorus may suppress phytoplankton growth through the excretion of chemical substances, likes a allelopathy, that inhibit phytoplankton photosynthetic activity. The $^{15}N$ atom % of I. pseudoacorus showed higher values than POM, suggesting that I. pseudoacorus assimilates DIN predominantly compared to phytoplankton, which was mostly M. aeruginosa. This result strongly suggests that the M. aeruginosa bloom should be regulated by aquatic plants, like I. pseudoacorus, this approach can affect zooplankton composition. This is the first study that has used stable isotope tracers to evaluate the biomanipulation efficiency through floating I. pseudoacorus.

An Innovative Solution for the Power Quality Problems in Induction Motor by Using Silica and Alumina Nano Fillers Mixed Enamel for the Coatings of the Windings

  • Mohanadasse, K.;Sharmeela, C.;Selvaraj, D. Edison
    • Journal of Electrical Engineering and Technology
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    • v.10 no.4
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    • pp.1621-1625
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    • 2015
  • Power quality has always been a concern of power engineers. Certainly an argument can be successfully made that most parts of power engineering have the ultimate objective to improve power quality. AC motors were widely used in industrial and domestic applications. Generally, AC motors were of two types: Induction and Synchronous motors. In motor many parameters like different load cycling, switching, working in hot weather and unbalances creates harmonics which creates major reasons for temperature rise of the motors. Due to high peak value of voltage, harmonics can weaken insulation in cables, windings and capacitors and different electronic components. Higher value of harmonics increase the motor current and decrease the power factor which will reduce the life time of the motor and increase the overall rating of all electrical equipments. Harmonics reduction of all the motors in India will save more power. Coating of windings of the motor with nano fillers will reduce the amount of harmonics in the motor. Based on the previous project works, actions were taken to use the enamel filled with various nano fillers for the coating of the windings of the different AC motors. Ball mill method was used to convert the micro particles of Al2O3, SiO2, TiO2, ZrO2 and ZnO into nano particles. SEM, TEM and XRD were used to augment the particle size of the powder. The synthesized nano powders were mixed with the enamel by using ultrasonic vibrator. Then the enamel mixed with the nano fillers was coated to the windings of the several AC motors. Harmonics were measured in terms of various indices like THD, VHD, CHD and DIN by using Harmonic analyzer. There are many other measures and indices to describe power quality, but none is applicable in all cases and in many instances, these indices may hide more than they show. Sometimes power quality indices were used as a basis of comparison and standardization. The efficiency of the motors was increased by 5 – 10 %. The thermal withstanding capacity of the motor was increased by 5º to 15º C. The harmonics of the motors were reduced by 10 – 50%.

Effects of Water Temperature, Salinity and Irradiance on the Growth of the Toxic Dinoflagellate, Gymnodinium catenatum (Graham) Isolated from Yeosuhae Bay, Korea (여수해만에서 분리한 유독 와편모조류, Gymnodinium catenatum (Graham)의 성장에 미치는 수온, 염분과 광 조건)

  • Oh, Seok-Jin;Yoon, Yang-Ho
    • ALGAE
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    • v.19 no.4
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    • pp.293-301
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    • 2004
  • A chain-forming toxic din flagellate, Gymnodinium catenatum (Graham) was known as a paralytic toxin-producer among Gymnodinoid group. In the study, the effects of water temperature, salinity and irradiance on the growth of G. catenatum isolated from Yeosuhae Bay, Korea were investigated. Water temperature range in which G. catenatum showed specific growth rate higher than 0.3 day$^{-1}$ were above about 18${^{\circ}C}$. However, salinity did not have such an effect on growth of G. catenatum. The maximum growth rate (0.5 day$^{-1}$) was obtained at 25${^{\circ}C}$ and 30 psu. The specific growth rate (u) expressed as a polynomial equation as functions of temperature (T; ${^{\circ}C}$) and salinity (S; psu) was $\mu$ = 0.005·T$^2$ - 0.0001164 T$^3$ - 0.063-S + 0.005-S$^2$ - 0.00007608-S$^3$ - 0.003-T-S + 0.00005308-T$^2$-S. Thus, in aspects of water temperature and salinity, the species may be expected to survive in most Korean coastal waters from early summer to autumn. The irradiance-growth curve was described as = 0.16 (I - 10.4)/(1 + 21.8) at 18${^{\circ}C}$ and 30 psu, indicating a half-saturation (Ks) photon flux density (PFD) of 42.6$\mu$mol m$^{-2}s^{-1}$ and compensation PFD (I$_0$) of 10.4$\mu$mol m$^{-2}s^{-1}$. These characteristic responses to irradiance suggest that G. catenatum can reside at the sub-surface.

Temporal and Spatial Fluctuations of Coastal Water Quality and Effect of Small Tide Embankment in the Muan Peninsula of Korea (무안반도 연안수질의 시ㆍ공간적 변동과 소규모 방조제의 영향)

  • Lee Dae-In;Cho Hyeon-Seo;Lee Gyu-Hyung;Lee Moon-Ok
    • Journal of the Korean Society for Marine Environment & Energy
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    • v.6 no.4
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    • pp.24-36
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    • 2003
  • In this study, we estimated the seasonal fluctuations of water quality and effect of small tide embankment in coastal water around the Muan Peninsula, which is located in the northern part of Mokpo city, and layer farming ground is spread around there. Some physical and chemical factors were analyzed to characterize water quality from Jan. to Oct. in 1994. The results were as follows: Dissolved oxygen was slightly under saturation in the almost areas of July, and in some bottom layer at ebb tide of October. Distribution of COD showed high values that over 2㎎/L in October and flood tide of April by the discharge of freshwater and resuspension of benthic sediment, which exceeded water quality criteria II. Maximum values of dissolved inorganic nitrogen ware appeared in surface layer during the flood tide of October, while minimum of that showed in surface layer in April. Concentration of dissolved inorganic phosphorus was higher at July than the others, which ranged from 0.24 to 2.08㎍-at/L. Mostly mean values of N/P ratio were lower than 16, it mean that nitrogen is more limiting nutrient than phosphorus for the growth of phytoplankton. The values of eutrophication index were in the range of 0.07~0.81. However, very high values due to increase of COD were estimated near the tide embankment and southern part in relation to tidal current in October. Water quality around tide embankment was suddenly changed worse within a short period after opening the water gate during the rainfall.

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