• Title/Summary/Keyword: alpha toxin

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Lysophosphatidic acid increases mesangial cell proliferation in models of diabetic nephropathy via Rac1/MAPK/KLF5 signaling

  • Kim, Donghee;Li, Hui Ying;Lee, Jong Han;Oh, Yoon Sin;Jun, Hee-Sook
    • Experimental and Molecular Medicine
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    • v.51 no.2
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    • pp.9.1-9.10
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    • 2019
  • Mesangial cell proliferation has been identified as a major factor contributing to glomerulosclerosis, which is a typical symptom of diabetic nephropathy (DN). Lysophosphatidic acid (LPA) levels are increased in the glomerulus of the kidney in diabetic mice. LPA is a critical regulator that induces mesangial cell proliferation; however, its effect and molecular mechanisms remain unknown. The proportion of ${\alpha}-SMA^+/PCNA^+$ cells was increased in the kidney cortex of db/db mice compared with control mice. Treatment with LPA concomitantly increased the proliferation of mouse mesangial cells (SV40 MES13) and the expression of cyclin D1 and CDK4. On the other hand, the expression of $p27^{Kip1}$ was decreased. The expression of $Kr{\ddot{u}}ppel$-like factor 5 (KLF5) was upregulated in the kidney cortex of db/db mice and LPA-treated SV40 MES13 cells. RNAi-mediated silencing of KLF5 reversed these effects and inhibited the proliferation of LPA-treated cells. Mitogen-activated protein kinases (MAPKs) were activated, and the expression of early growth response 1 (Egr1) was subsequently increased in LPA-treated SV40 MES13 cells and the kidney cortex of db/db mice. Moreover, LPA significantly increased the activity of the Ras-related C3 botulinum toxin substrate (Rac1) GTPase in SV40 MES13 cells, and the dominant-negative form of Rac1 partially inhibited the phosphorylation of p38 and upregulation of Egr1 and KLF5 induced by LPA. LPA-induced hyperproliferation was attenuated by the inhibition of Rac1 activity. Based on these results, the Rac1/MAPK/KLF5 signaling pathway was one of the mechanisms by which LPA induced mesangial cell proliferation in DN models.

Effects of dietary arginine in ameliorating the deleterious effects induced by mycotoxins on growth, immune system, body organs in growing pigs

  • Joseph, Moturi;SeYoung, Yoon;Abdolreza, Hosseindoust;SangHun, Ha;Habeeb, Tajudeen;JunYoung, Mun;SooJin, Sa;JinSoo, Kim
    • Journal of Animal Science and Technology
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    • v.64 no.4
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    • pp.727-739
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    • 2022
  • Mycotoxin contamination in pig feeds has a negative impact on growth performance, the immune system, and major body organs. Arginine (Arg) plays an important role in animals' body biochemistry and physiology. This study aimed to determine the effect of dietary Arg supplementation on mitigating the negative effects of mycotoxins in growing pigs. A total of 72 growing pigs (Landrace × Large white) with initial mean body weight (BW) = 55 ± 2.5 kg were allotted to four treatment groups with three replicates per group of six pigs per replicate in a completely randomized design. The treatments included a non-toxin diet with 1.2% Arg (NT1.2) and mycotoxin-challenged treatments supplemented with 1.2% Arg (TX1.2), 1.3% Arg (TX1.3), and 1.4% Arg (TX1.4). Statistical analysis of data included the effects of dietary level of Arg. The results indicated a significantly higher BW (p < 0.05), average daily gain (p < 0.05), and gain-to-feed ratio (p < 0.05) in the NT1.2 group than in the TX1.2, TX1.3, and TX1.4 groups. The relative weight of the liver was higher (p < 0.05) in the TX1.2 compared to that of the NT1.2 group, although it was not different from that of TX1.3 and TX1.4. The level of tumor necrosis factor-alpha was significantly up-regulated (p < 0.05) in the liver tissue of the TX1.2 group compared to that of the other treatments. Overall, dietary Arg supplementation remedied liver injury and alleviated the compromised immune system caused by mycotoxin toxicity.

Bacillus thuringiensis Cry4A and Cry4B Mosquito-larvicidal Proteins: Homology-based 3D Model and Implications for Toxin Activity

  • Angsuthanasombat, Chanan;Uawithya, Panapat;Leetachewa, Somphob;Pornwiroon, Walairat;Ounjai, Puey;Kerdcharoen, Teerakiat;Katzenmeier, Gerd;Panyim, Sakol
    • BMB Reports
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    • v.37 no.3
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    • pp.304-313
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    • 2004
  • Three-dimensional (3D) models for the 65-kDa activated Cry4A and Cry4B $\delta$-endotoxins from Bacillus thuringiensis subsp. israelensis that are specifically toxic to mosquito-larvae were constructed by homology modeling, based on atomic coordinates of the Cry1Aa and Cry3Aa crystal structures. They were structurally similar to the known structures, both derived 3D models displayed a three-domain organization: the N-terminal domain (I) is a seven-helix bundle, while the middle and C-terminal domains are primarily comprise of anti-parallel $\beta$-sheets. Circular dichroism spectroscopy confirmed the secondary structural contents of the two homology-based Cry4 structures. A structural analysis of both Cry4 models revealed the following: (a) Residues Arg-235 and Arg-203 are located in the interhelical 5/6 loop within the domain I of Cry4A and Cry4B, respectively. Both are solvent exposed. This suggests that they are susceptible to tryptic cleavage. (b) The unique disulphide bond, together with a proline-rich region within the long loop connecting ${\alpha}4$ and ${\alpha}5$ of Cry4A, were identified. This implies their functional significance for membrane insertion. (c) Significant structural differences between both models were found within domain II that may reflect their different activity spectra. Structural insights from this molecular modeling study would therefore increase our understanding of the mechanic aspects of these two closely related mosquito-larvicidal proteins.

Effect of Bacillus Subtilis-based Direct-fed Microbials on Immune Status in Broiler Chickens Raised on Fresh or Used Litter

  • Lee, K.W.;Lillehoj, H.S.;Jang, S.I.;Lee, S.H.;Bautista, D.A.;Siragusa, G.R.
    • Asian-Australasian Journal of Animal Sciences
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    • v.26 no.11
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    • pp.1592-1597
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    • 2013
  • Type of dietary direct-fed microbials (DFMs) or poultry litter could directly influence the composition of gut microbiota. Gut microbiota plays an important role in shaping the developing immune system and maintaining the homeostasis of the mature immune system in mammal and chickens. The present study was carried out to investigate the interaction among litter, DFMs and immunity in broiler chickens exposed to a field-simulated environment. Immune status of broiler chickens was assessed by serum antibodies against Eimeria spp. and Clostridium spp. and intestinal cytokine mRNA expression. The current experimental design had a $3{\times}2$ factorial arrangement of treatments with three types of litter, i.e., fresh litter or used litter that was obtained from a farm with no disease outbreak (used litter) or a farm with history of a gangrenous dermatitis outbreak (GD litter), and two dietary treatments with or without DFMs. It was found that either DFM addition or type of litter significantly affected anticoccidial antibody levels of broiler chickens at d 42. In general, dietary DFMs increased the anticoccidial antibodies in the fresh-litter raised chickens, but lowered the levels in the GD-litter raised chickens. Serum antibodies against Clostridium perfringens ${\alpha}$-toxin were significantly (p<0.05) higher in chickens raised on GD litter compared with those raised on fresh litter. Cytokine mRNA expression was significantly (p<0.05) altered by either the type of litter or DFMs. Of interest, dietary DFMs lowered interferon-${\gamma}$, interleukin 1beta, and CXCLi2 cytokine mRNA expression in chickens raised on fresh litter but increased them in GD-litter raised chickens. In conclusion, dietary DFMs modulate various immune parameters of broiler chickens, but the DFM-mediated effects were dependent upon the type of litter on which chickens were raised.

Cyanobacterial Blooms and Water Quality of Major Recreational Park Ponds in the Capital Region (수도권 주요 공원 연못의 수질 특성과 남조류 대발생)

  • Park, Myung-Hwan;Suh, Mi-Yeon;Hwang, Soon-Jin;Kim, Yong-Jae;Han, Myung-Soo;Kim, Baik-Ho
    • Korean Journal of Ecology and Environment
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    • v.41 no.1
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    • pp.54-65
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    • 2008
  • The seasonal dynamics of phytoplankton and water quality were evaluated bimonthly at 7 park ponds in the capital region from October 2004 to August 2005. With out the change of water temperature $(0.4\sim26.0^{\circ}C)$, cyanobacteria dominated in park ponds such as Gyungbokgung Gyunghyaeru and Seokchon reservoir. The standing crops of phytoplankton was significant related with cell densities of cyanobacteria (r=0.993), while they did not significant correlation with environmental factors. Almost of all park ponds in the capital region were classified as eutrophic state with high TP concentrations and TN/TP ratios less than 10. Major dominant cyanobacteria were as followed; Anabaena sp., Aphanocapsa elachista, Lyngbya contorta, Merismopedia elegans, Microcystis aeruginosa, M. wesenbergii, Microcystis sp., Oscillatoria sp., Phormidium tenue, and Plectonema sp. To date, although the concentration of chlorophyll-${\alpha}$ and cyanobacterial densities in the capital region was below the 'danger' level of WHO guidelines value, the monitoring of cyanobacterial densities and its toxin (microcystin) in recreational/bath water should be continued.

Occurrence of Clostridium perfringens according to Raising Periods in Broilers (육계의 사육 일령별 Clostridium perfringens 발생 분석)

  • Choe, Changyong;Park, In-Jae;Kang, Min;Jang, Hyung-Kwan;Hur, Tai-Young;Jung, Young-Hoon;Cho, Yong-Il;Do, Yoon-Jung;Yoo, Jae-Gyu;Na, Jae-Cheon;Hwangbo, Jong
    • Korean Journal of Poultry Science
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    • v.40 no.4
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    • pp.305-313
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    • 2013
  • The objective of this study was to investigate occurrence patterns of Clostridium perfringens on different raising periods in broilers. In different raising periods, we investigated the change in the gross lesion and microscopic histological findings of the mucose of the small intestine, colony forming unit (CFU) and the types C. perfringens with PCR assay. According to the gross lesions on the mucose of small intestine with 10-days-old broilers, the non-antibiotic group showed a higher value (0.6) than the antibiotic group (0.0). Whereas 20-days-old broilers with, the antibiotic treatment had a slightly lower value (1.0) than the non-antibiotic group (1.3). In the histological examination on the villi of the small intestine, there was no damage of the villi of the small intestine with 1-day-old broilers in both groups; however, the non-antibiotic group showed a higher value (0.4) than the antibiotic group (0.0) with 10-days-old broilers. In the non-antibiotic group, the CFU of C. perfringens of the fecal samples from the small intestine increased from 10 days of raising broilers and rapidly increase after 20 and 30 days of raising broilers. There was no detection of C. perfringens types with PCR assy in 1-day-old broilers, but we found C. perfringens type A in 10-, 20- and 30-days-old broilers. Although it is possible to raise healthy broilers by using antibiotics, the addition of antibiotics to concentrate feed is prohibited for public health. The results of this study would contribute to proper feeding management through the careful use of antibiotics.