• BMB Reports
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• 제51권6호
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• pp.308-313
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• 2018

Small-molecule inhibitors are widely used to treat a variety of inflammatory diseases. In this study, we found a novel anti-inflammatory compound, 1-[(2R,4S)-2-methyl-4-(phenylamino)-1,2,3,4-tetrahydroquinolin-1-yl]prop-2-en-1-one (MPQP). It showed strong anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. These effects were exerted through the inhibition of the production of NO and pro-inflammatory cytokines, such as interleukin (IL)-6, $IL-1{\beta}$, and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$). Furthermore, MPQP decreased the expression levels of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2). Additionally, it mediated the inhibition of the phosphorylation of p38, c-Jun N-terminal kinase (JNK), the inhibitor of ${\kappa}B{\alpha}$ ($I{\kappa}B{\alpha}$), and their upstream kinases, $I{\kappa}B$ kinase (IKK) ${\alpha}/{\beta}$, mitogen-activated protein kinase kinase (MKK) 3/6, and MKK4. Furthermore, the expression of IL-1 receptor-associated kinase 1 (IRAK1) that regulates $NF-{\kappa}B$, p38, and the JNK signaling pathways, was also increased by MPQP. These results indicate that MPQP regulates the IRAK1-mediated inflammatory signaling pathways by targeting IRAK1 or its upstream factors.

• 한국식품영양과학회지
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• 제32권3호
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• pp.428-436
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• 2003

Carotenoids는 항암 효과가 있는 것으로 알려져 있으나 각각의 carotenoids가 대장암에 미치는 영향에 대해서는 명확하게 밝혀진 바가 없다. 본 연구에서는 4가지 종류의 carotenoids가 인간의 대장에서 유래한 암세포인 HT-29 세포의 증식에 미치는 영향을 조사하였다. $\alpha$-carotene, $\beta$-carotene, lutein lycopene을 농도를 달리 하여 세포 배양액 에 첨가하여 살아있는 세포의 수를 측정한 결과 $\beta$-carotene는 세포의 증식을 다소 증가시키는 반면 $\alpha$-carotene, lutein, lcopene은 세포의 증식을 감소하였다. 세포의 증식을 억제한 carotenoids 중에서 lycopene이 그 효과가 가장 컸다. ErbB receptor family는 세포의 증식을 촉진하고 대장암에서 그 발현이 증가된 것으로 보고되었기 때문에 lycopene이 heregulin-ErbB3 signaling을 억제하는지를 조사하였다. Lycopene는 ErbB2 단백질을 감소하였고 ErbB3 단백질의 변화를 초래하였다. Heregulin을 첨가하여 인산화를 유도한 경우 ErbB3의 인산화, ErbB3와 p85의 결합, Akt 인산화가 lycopene에 의해 억제되었다. 이 결과들은 carotenoids 중 lycopene이 대장암 세포 증식 억제 효과가 가장 크고, 대장암 세포의 DNA 합성을 억제하고 apoptosis를 유도하는 lycopene효과의 일부는 Erb-B3와 Akt의 인산화 감소에 기인하는 것임을 나타낸다.

• Genomics & Informatics
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• 제16권1호
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• pp.2-9
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• 2018

Olfactory receptors (ORs) in mammals are generally considered to function as chemosensors in the olfactory organs of animals. They are membrane proteins that traverse the cytoplasmic membrane seven times and work generally by coupling to heterotrimeric G protein. The OR is a G protein-coupled receptor that binds the guanine nucleotide-binding $G{\alpha}_{olf}$ subunit and the $G{\beta}{\gamma}$ dimer to recognize a wide spectrum of organic compounds in accordance with its cognate ligand. Mammalian ORs were originally identified from the olfactory epithelium of rat. However, it has been recently reported that the expression of ORs is not limited to the olfactory organ. In recent decades, they have been found to be expressed in diverse organs or tissues and even tumors in mammals. In this review, the expression and expected function of olfactory receptors that exist throughout an organism's system are discussed.

• Journal of Interdisciplinary Genomics
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• 제5권2호
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• pp.32-34
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• 2023

Resistance to thyroid hormone syndrome (RTH) is a genetic disease caused by the mutation of either the thyroid hormone receptor-β (THRB) gene or the thyroid hormone receptor-α (THRA) gene. RTH caused by THRB mutations (RTH-β) is characterized by the target tissue's response to thyroid hormone, high levels of triiodothyronine and/or thyroxine, and inappropriate secretion of thyroid-stimulating hormone (TSH). THRA mutation is characterized by hypothyroidism that affects gastrointestinal, neurological, skeletal, and myocardial functions. Most patients do not require treatment, and some patients may benefit from medication therapy. These syndromes are characterized by decreased tissue sensitivity to thyroid hormones, generating various clinical manifestations. Thus, clinical changes of resistance to thyroid hormones must be recognized and differentiated, and an approach to the practice of personalized medicine through an interdisciplinary approach is needed.

• Archives of Pharmacal Research
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• 제17권3호
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• pp.194-198
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• 1994

The antitumor effects of the 2E4 and anti--Tac, monoclonal antibodies directed to Il-2 receptor (IL-2R) conjugated with .alpha.-particle emitting radionuclide bismuth-212., were compared. The $^{212}Bi-2E4$ demonstratedspecific cytotocicity to EL4J3, 4, a I$L-2R^+$ cell line, than to EL4J, a $IL-2R^-$ cell line in thymidine incorporation assy. TEX>$^{212}Bi-2E4$ exerted the maximal antitumor effect in that % T/C in C57BL/6 mice implanted with EL4J3.4 ascitic tumor was 331% at the concentration of $50{\;}{\mu}Ci$, while that of $^{212}Bi-anti-Tac$ was 258% at $100{\;}{\mu}Ci$.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6247-6251
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• 2014

Background: The aim of the present study was to investigate the involvement of emodin on the growth of human breast cancer MCF-7 and MDA-MB-231 cells and the estrogen (E2) signal pathway in vitro. Materials and Methods: MTT assays were used to detect the effects of emodin on E2 induced proliferation of MCF-7 and MDA-MB-231 cells. Flow cytometry (FCM) was applied to determine the effect of emodin on E2-induced apoptosis of MCF-7 cells. Western blotting allowed detection of the effects of emodin on the expression of estrogen receptor ${\alpha}$, cyclin D1 and B-cell lymphoma-2 (Bcl-2), mitogen-activated protein kinases (MAPK) and phosphatidylinostiol 3-kinases (PI3K). Luciferase assays were emplyed to assess transcriptional activity of $ER{\alpha}$. Results: Emodin could inhibit E2-induced MCF-7 cell proliferation and anti-apoptosis effects, and arrest the cell cycle in G0/G1 phase, further blocking the effect of E2 on expression and transcriptional activity of $ER{\alpha}$. Moreover, Emodin influenced the ER ${\alpha}$ genomic pathway via downregulation of cyclin D1 and Bcl-2 protein expression, and influenced the non-genomic pathway via decreased PI3K/Akt protein expression. Conclusions: These findings indicate that emodin exerts inhibitory effects on MCF-7 cell proliferation via inhibiting both non-genomic and genomic pathways.

• Asian-Australasian Journal of Animal Sciences
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• 제13권3호
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• pp.390-400
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• 2000

The corpus luteum (CL) is a temporary endocrine gland whose main function is to secrete progesterone to support pregnancy. On the other hand, the cyclic bovine CL has also been shown to be a site of prostaglandin $F_{2{\alpha}}$ ($PGF_{2{\alpha}}$) production. Although there is general agreement that endometrial $PGF_{2{\alpha}}$ is an essential luteolysin in cattle, luteal $PGF_{2{\alpha}}$ seems to play a luteotropic role as an autocrine and/or paracrine factor, especially for the development and maintenance of the CL. This supposition is based on evidence that some of the prerequisites for autocrine/paracrine mechanisms are present, including local production of $PGF_{2{\alpha}}$ and the existence of specific binding sites within the CL. The purpose of this paper is to review the regulation of luteal $PGF_{2{\alpha}}$ secretion, its action on CL as an autocrine and/or paracrine factor and the receptivity of bovine CL to. $PGF_{2{\alpha}}$.

• 동의생리병리학회지
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• 제17권1호
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• pp.241-246
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• 2003

Bambusae Caulis in Liquamen(BCL) has been used to relieve the cough and asthma, and remove the phlegm in traditional Oriental medicine. In recent years, it was studied for its antiinflammatory, antiallergenic, immune-modulating, and anticarcinogenic capabilities. This experiment was performed to evaluate the microarray profiles of CD genes in human mast cells before and after BCL treatment. The results are as follows: The expression of 51 of the genes studied was up-regulated in the Bel-treated group; they include the genes coding L apoferritin, beta-2-microglobulin, ferritin light polypeptide, CD63, monocyte chemotactic and activating fact, heme oxygenase 1, CD140a, integrin alpha M, colony stimulating factor 2 receptor, eukaryotic translation elongation factor, CD37, interleukin 18, NADH dehydrogenase 1 beta, CD48, 5-lipoxygenase activating protein, interleukin 4, ribosomal protein L5, GABA(A) receptor-associated protein, beta-tubulin, integrin beta 1, CD162, CD32, lymphotoxin beta, alpha-tublin, integrin alpha L, CD2, CD151, CD331, 90 kDa heat shock protein, CD59, CD3Z, microsomal glutathione S-transferase 2, CD33, CD162R, cyclophilinA, CD84, interleukin 9 receptor, interleukin 11, CD117, CD39-Like 2, and so forth. The expression of 7 of the genes studied was down-regulated in the BCL-treated group; they include the genes coding con, CD238, SCF, CD160, CD231, CD24, and CD130. Consequently, the treatment of BCL on the human mast cells increased the expression of 51 genes and decreased the expression of 7 genes. These data would provide a fundamental basis to the traditional applications of Bambusae Caulis in Liquamen.

• Archives of Pharmacal Research
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• 제27권2호
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• pp.225-231
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• 2004

This study was designed to investigate the effect of Trolox, a hydrophilic analogue of vitamin E, on the alteration of vasoregulatory gene expression during hepatic ischemia and reperfusion (I/R). Rats were subjected to 60 min of hepatic ischemia in vivo. The rats were treated intravenously with Trolox (2.5 mg/kg) or the vehicle as a control 5 min before reperfusion. Liver samples were obtained 5 h after reperfusion for a RT-PCR analysis on the mRNA for the genes of interest. These mRNA peptides are endothelin-1 (ET -1), potent vasoconstrictor peptide, its receptor $ET_A$ and $ET_B$, vasodilator endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), heme oxygenase-1 (HO-1), tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and cyclooxygenase-2 (COX-2). It was seen that serum alanine aminotransferase and lipid peroxi-dation levels were markedly increased after I/R and Trolox significantly suppressed this increase. In contrast, the glutathione concentration decreased in the I/R group, and this decrease was inhibited by Trolox. ET-1 mRNA expression was increased by I/R, an increase which was prevented by Trolox. The mRNA levels for $ET_A$ receptor was significantly decreased, whereas ET$_{B}$ receptor transcript increased in the I/R group. The increase in $ET_A$ was prevented by Trolox. The mRNA levels for iNOS and HO-1 significantly increased in the I/R group and Trolox attenuated this increase. There were no significant differences in eNOS mRNA expression among any of the experimental groups. The mRNA levels for COX-2 and TNF-$\alpha$ significantly increased in I/R group and Trolox also attenuated this increase. Our findings suggest that I/R induces an imbalanced hepatic vasoregulatory gene expression and Trolox ameliorates this change through its free radical scavenging activity.y.

• Asian Pacific Journal of Cancer Prevention
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• 제15권14호
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• pp.5667-5672
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• 2014

Folate receptor alpha ($FR{\alpha}$) mediates folate uptake by endocytosis, and while folate is essential to DNA methylation and synthesis and may have an important role in proliferating cells. $FR{\alpha}$ is known to be expressed in rapidly proliferating cells, including many cancer cell lines, but there has been no systematic assessment of expression in cervical cancer cell lines. The aim of the present study was to evaluate the effects of $FR{\alpha}$ on proliferation and apoptosis of cervical cells and correlation mechanism. In this study, we investigated the biological function of $FR{\alpha}$ in Hela cells using RNA interference. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK8) assay, while cell cycling and apoptosis were assessed by flow cytometry, mRNA levels by real time-PCR and protein levels of $FR{\alpha}$, c-Fos and c-Jun by Western blotting. The results revealed that $FR{\alpha}$ was highly expressed in Hela cells and its silencing with a small interfering RNA (siRNA) inhibited cell proliferation and induced cell apoptosis, arresting the cell cycle in G0/G1 stages while decreasing the proportion in S and G2/M stages, and suppressed the expression levels of c-Fos and c-Jun. In conclusion, the results of this study indicated that $FR{\alpha}$ down-regulation might be capable of suppressing cervical cancer cell proliferation and promoting apoptosis. It suggested that $FR{\alpha}$ might be a novel therapeutic target for cervical cancer.