• Archives of Pharmacal Research
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• v.26 no.5
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• pp.358-366
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• 2003

Some N-p-substituted phenyl uracil-5-sulphonamide derivatives have been synthesized to be evaluated as molluscicides against Biomphalaria alexandrina snails, the intermediate host of Schistosoma mansoni. Schistosoma mansoni infected mice were treated with hemolymph obtained from pre-treated Biomphalaria alexandrina snails with the products 4a, 10a, 10b and 4b or obtained from non-treated snails. The selection of the concentration based on the predetermined dose which caused mortality of less than 50% of snails/24 h. $LC_{50}$ of compounds 4a, 10a, 10b and 4b was 50, 100, 200 and 50 ppm respectively. The result showed that immuno-stimulatory effect of treated hemolymph with compounds 4a, 10a and 4b was related to significant protective effects (44.4, 34.6 and 50.4% reduction in worm burden respectively). In addition, mean total worm burdens were significantly reduced in non treated hemolymph by 33.8%. The effect of hemolymph obtained from treated or non treated snails on S. mansoni adult worms antigens was studied by indirect immunofluorescence technique using chronic mouse sera (CMS). The results indicated that there was a strong reaction with epitopes in gut epithelium, tubercles, teigument and subtegumental musculature of untreated and treated S. mansoni adult worms antigens. Therefore, treatment of hemolymph obtained from pre-treated snails with compounds 4a, 10a, and 4b can stimulate specific immune response and induce protective effects against S. mansoni infection.

• Journal of Microbiology and Biotechnology
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• v.30 no.9
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• pp.1395-1403
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• 2020

There is an increasing interest in using inactivated probiotics to modulate the host immune system and protect against pathogens. As the immunomodulatory function of heat-killed Lactobacillus brevis KCTC 12777BP (LBB) and its mechanism is unclear, we investigated the effect of LBB on immune response based on the hypothesis that LBB might exert stimulatory effects on immunity. In the current study, we demonstrate that administration of LBB can exert immune-stimulatory effects and promote clearance of foreign matters through enhancing phagocytosis. Treatment with LBB induced the production of TNF-α, IL-6, and nitric oxide in macrophages. Importantly, LBB directly increased the phagocytic activity of macrophages against bacterial particles. LBB was able to promote the production of TNF-α in bone marrow-derived macrophages and splenocytes and also increase the proliferation rate of splenocytes, suggesting that the immune-stimulating activity of LBB can be observed in primary immune cells. Investigation into the molecular mechanism responsible revealed that LBB upregulates TAK1 activity and its downstream ERK, p38, and JNK signaling pathways. To further confirm the immunomodulatory capability of LBB in vivo, we orally administered LBB to mice and assessed the effect on primary splenocytes. Splenocytes isolated from LBB-treated mice exhibited higher TNF-α expression and proliferative capacity. These results show that heat-killed L. brevis, a wildly consumed probiotic, may provide protection against pathogens through enhancing host immunity.

• The Korean Journal of Pharmacology
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• v.2 no.1 s.2
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• pp.71-82
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• 1966

The inhibitory effect of 5-hydroxytryptamine (5-HT) on the isolated intestinal strips of the tortoise (Amyda japonica), rat, rabbit and guinea pig was investigated. 1) The strips from the middle or lower part of the tortoise intestine responded with relaxation to 5-HT $(10^{-9}{\sim}10^{-5}g/ml)$, and the magnitude of the relaxation was proportional to the dose of 5-HT. The rectal part of the tortoise intestine, in contrast, showed contraction, the magnitude of which also was proportional to the dose of 5-HT. 2) Various blocking agents such as methysergide, morphine, tetracaine, nethalide, bretylium, hexamethonium, mecamylamine and chlorisondamine, showed no selective blocking activity on the relaxant effect of 5-HT on the tortoise intestine. The inhibitory effect of isoproterenol on the tortoise intestine, however, was selectively blocked by nethalide, and the stimulatory effect of 5-HT on the rectal part of the tortoise was blocked by methysergide. 3) In the presence of 5-HT, the stimulatory effect of DMPP on the tortoise intestine was remarkably attenuated, whereas that of acetylcholine and $BaCl_2$ was little affected. In the presence of isoproterenol, the stimulatory effect of acetylcholine and $BaCl_2$ were affected, but that of DMPP was little affected. 4) Large dose of 5-HT($10^{-4}$g/ml) produced inhibitory effect on the strips from the distal part of the isolated colon of the rat, rabbit and guinea pig, when the strips had been exposed to 5-HT($10^{-4}$g/ml), methysergide or phen`oxybenzamine. 5) Bretylium, as well as nethalide, abolished or remarkably reduced, in a few cases of the experiments, the inhibitory effect of the large dose of 5-HT on the distal part of the colon, whereas morphine did not affect it. 6) The ileal strips of the guinea pig also showed relaxation, as in the colonic strips, having been exposed to the large dose of 5-HT or phenoxybenzamine. This effect, however, was not obsered in the case of the rabbit ileum. 7) The property of the action-site of 5-HT in the tortoise intestine seemd to be different from the 5-HT receptors which have been revealed by several investigators. 8) Adrenergic component seemed to be participated in the inhibitory effect of 5-HT on the colon of the rat and rabbit.

• Journal of Microbiology
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• v.41 no.2
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• pp.161-164
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• 2003

Recombinant light chain of Clostridium botulinum neurotoxin type B stimulated transglutaminase activity in a dose dependent manner, Compared to native toxin, recombinant light chain showed av greater stimulatory effect on transglutaminase activity. Zn-chelating agents, inhibiting the proteolytic activity of the clostridial toxins, did not interfere with this stimulation. These results suggest that the light chain plays a major stimulatory role, which is not due to its metallopeptidase activity, but is possibly due to specific interaction with transglutaminase. More importantly, this report provides a new insight into the intracellular action of C. botulinum neurotoxins.

• The Korean Journal of Physiology
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• v.29 no.2
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• pp.191-202
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• 1995

The purpose of this study was to compare effects of insulin and IGFs on growth, apical membrane enzyme activities and membrane transport systems of primary cultured rabbit kidney proximal tubule cells. Results were as follows: 1. Insulin and IGF-I produced significant growth stimulatory effects at $5{\times}10^{-10}M.\;IGF-II(5×10^{-10}\;M)$ did not stimulate significant cell growth. 2. Insulin stimulated the phosphorylation of a 97 KD protein. It was difficult to determine whether this band represents insulin and/or the IGF-I receptor. 3. The activities of apical membrane enzymes (alkaline phosphatase, leucine aminopeptidase, and ${\gamma}-glutamyl \;transpeptidase)$ were observed to be diminished after the cells were placed in the culture environment. 4. The uptake of ${\alpha}-MG,$ Pi and Na was significantly increased in cells incubated with insulin or IGF-I, IGF-II had no effect on the uptake of these substrates. 5. Na-pump activity, as assayed by Rb uptake, was significantly increased in cells treated with insulin or IGFs. In conclusion, insulin and IGF-I exert stimulatory effects on growth and membrane transporter(glucose, Na, Pi, and Na-pump) activities in primary cultured rabbit kidney proximal tubule cells. IGF-II had no effect on cell growth and membrane transporter(glucose, Na and Pi) activities.

• Archives of Pharmacal Research
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• v.19 no.2
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• pp.112-115
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• 1996

Some antioxidant phenolic compounds exhibit prooxidant activity mainly due to their abilities to reduce $Fe^{3+}\; to\; Fe^{2+}.$ Reducing ability and prooxidant activity of maltol, an antioxidant component of Korean red ginseng, were compared with those of pyrogallol. Maltol at 2 mM did not appreciably reduce$ Fe^{3+}\; to\; Fe^{2+}$ and also failed to reduce nitroblue tetrazolium. Stimulation of hydroxyl radical mediated-deoxyribose degradation by pyrogallol was maximal at 60 .mu.M. Maltol stimulated the deoxyribose degradation to a much less extent, and a similar stimulatory effect was observed at a concentration of more than 100-fold higher than that of pyrogallol. The stimulatory effect of maltol reached a plateau over 1 mM, suggesting the removal of hydroxyl radicals by excess maltol. In bleomycin-$Fe^{3+}$-DNA assay, maltol at 2 mM produced a 2.5-fold increase of the iron-bleomycin-dependent DNA degradation over the basal value, whereas pyrogallol at 10 .mu.M accelerated DNA degradation by ca. 10-fold. Furthermore, maltol inhibited $Fe^{2+}$-stimulated DNA degradation by bleomycin. These results strongly suggested that maltol is an antioxidant with little prooxidant activity.

• IMMUNE NETWORK
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• v.16 no.5
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• pp.305-310
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• 2016

In this study, we compared two different tumor cell vaccines for their induction of anti-tumor immunity; one was a tumor cell clone expressing a membrane-bound form of IL-12 p35 subunit (mbIL-12 p35 tumor clone), and the other was a tumor clone expressing heterodimeric IL-12 as a single chain (mb-scIL-12 tumor clone). The stimulatory effect of mb-scIL-12 on the proliferation of ConA-activated splenocytes was higher than that of mbIL-12 p35 in vitro. However, the stimulatory effect of mbIL-12 p35 was equivalent to that of recombinant soluble IL-12 (3 ng/ml). Interestingly, both tumor clones (mbIL-12 p35 and mb-scIL-12) showed similar tumorigenicity and induction of systemic anti-tumor immunity in vivo, suggesting that tumor cell expression of the membrane-bound p35 subunit is sufficient to induce anti-tumor immunity in our tumor vaccine model.

• Journal of Plant Biology
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• v.35 no.4
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• pp.409-414
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• 1992

Effect of quercetin, a kind of natural plant flavonoids, on auxin-induced ethylene production in barley coleoptiles was studied. Auxin-induced ethylene production was apparently stimulated by quercetin. This stimulatory effect of quercetin appeared after 4 h of incubation period. Ethylene production was stimulated 200% over the control after 8 h of incubation by $3{\times}10^{-5}\;M$ quercetin. The quercetin effect was most prominent at $10^{-4}\;M$ of IAA. Ethylene production induced by the synthetic auxin, 2,4-D and NAA, was not significantly affected by quercetin. Also ACC-based ethylene production was unaffected by the flavonoid. In an effort to elucidate mechanisms of quercetin action on auxin-induced ethylene production, the effect of quercetin on 1M metabolism was studied. Data obtained from these experiments indicate that quercetin treatment resulted in about 90% inhibition of IAA oxidase activity. IAA ($3{\times}10^{-5}\;M$) conjugation was found to be not affected by quercetin. This results suggest that the stimulatory effect of quercetin on auxin-induced ethylene production may be due to the fact that quercetin inhibits 1M oxidase activity, thus increasing the free IAA level.

• Asian-Australasian Journal of Animal Sciences
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• v.17 no.11
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• pp.1496-1500
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• 2004

In the mammalian ovary the follicular fluid contains proteins and peptides which play an important role in growth, development and maturation of oocytes. The gonadotropins and some other factors work synergistically and regulate ovarian functions. In the present study the effect of follicular fluid proteins (FFP) and gonadotropins on progesterone secretion by granulosa cells (GC) from buffalo ovary, was investigated during culture. The follicular fluid was collected from small (<5 mm), and medium (5-8 mm) follicles obtained from buffalo ovaries. The follicular fluid from medium follicles was fractionated with ammonium sulphate at 80% saturation. The precipitated protein fraction was further resolved in to minor (peaks I, III) and major (peak II) proteins using gel filtration (Sephadex G-200). The FFP from small follicles and major FFP (peak II) at a dose of 200 $\mu$g/well, significantly stimulated progesterone secretion by pooled GC (3${\times}10^{5}$ cells/2 ml medium/well). The minor FFP did not show any stimulatory effect. There was a significant increase in progesterone secretion by pooled GC in presence of FFP and LH (10 ng/well), however, FSH (20 ng/well) with FFP exhibited an inhibitory effect. The major FFP and gonadotropins were also studied for their effect on progesterone production by GC isolated from medium and large size follicles. The GC from medium follicles were more responsive to FSH and FFP whereas GC from large follicles exhibited enhanced progesterone secretion with LH and FFP. These results indicated that FFP have their own stimulatory effect and also act synergistically with gonadotropins. The significantly different response shown by GC, for steroid hormone secretion, is based on their stage of growth and differentiation. The purification and characterization of such steroidogenic proteins may help in elucidating their role in growth and differentiation of granulosa cells.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.3
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• pp.255-261
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• 2014

Essential fatty acid (EFA) is known to be required for the body to function normally and healthily. However, the effect of EFA on glucose uptake in skeletal muscle has not yet been fully investigated. In this study, we examined the effect of two EFAs, linoleic acid (LA) and ${\alpha}$-linolenic acid (ALA), on glucose uptake of C2C12 skeletal muscle cells and investigated the mechanism underlying the stimulatory effect of polyunsaturated EFAs in comparison with monounsaturated oleic acid (OA). In palmitic acid (PA)-induced insulin resistant cells, the co-treatment of EFAs and OA with PA almost restored the PA-induced decrease in the basal and insulin-stimulated 2-NBDG (fluorescent D-glucose analogue) uptake, respectively. Two EFAs and OA significantly protected PA-induced suppression of insulin signaling, respectively, which was confirmed by the increased levels of Akt phosphorylation and serine/threonine kinases ($PKC{\theta}$ and JNK) dephosphorylation in the western blot analysis. In PA-untreated, control cells, the treatment of $500{\mu}M$ EFA significantly stimulated 2-NBDG uptake, whereas OA did not. Phosphorylation of AMP-activated protein kinase (AMPK) and one of its downstream molecules, acetyl-CoA carboxylase (ACC) was markedly induced by EFA, but not OA. In addition, EFA-stimulated 2-NBDG uptake was significantly inhibited by the pre-treatment of a specific AMPK inhibitor, adenine 9-${\beta}$-D-arabinofuranoside (araA). These data suggest that the restoration of suppressed insulin signaling at PA-induced insulin resistant condition and AMPK activation are involved at least in the stimulatory effect of EFA on glucose uptake in C2C12 skeletal muscle cells.