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Sedum middendorffianum Maxim (SMM) is a Korean endemic plant belonging to the Crassulaceae family. This study aimed to investigate the antitumor effects of the SMM extract on human ovarian cancer cells. Among five endemic plants grown in Korea, the SMM extract showed the most potent cytotoxicity in ovarian cancer cells and had little effect on normal ovarian surface epithelial cells. Furthermore, we revealed that the SMM extract dose-dependently induced apoptosis in human ovarian cancer A2780 and SKOV3 cells. The SMM extract markedly stimulated the activation of caspase-3/8, while the broad-spectrum caspase inhibitor and caspase-8 selective inhibitor significantly reversed SMM extract-induced apoptosis. In addition, the SMM extract significantly inhibited cell invasion and the expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 in ovarian cancer cells. Notably, the SMM extract increased the generation of intracellular ROS, and pretreatment with antioxidant N-acetyl-L-cysteine (NAC) significantly suppressed SMM-induced cytotoxicity and anti-invasive activity. Moreover, NAC treatment reversed the SMM-induced inhibition of MMP-2/9 expression. Taken together, these data suggest that the SMM extract induces caspase-dependent apoptotic cell death and inhibits MMP-dependent invasion via ROS regulation.

Simple Summary Ovarian cancer is the most lethal of gynecological malignancies. Although metastasis leads to a bleak prognosis and high mortality, the molecular and cellular processes of ovarian cancer metastasis remain largely unclear. Non-malignant cells including macrophages constitute a unique microenvironment that can completely change the nature of malignant cells at various levels. In this study, we found that the expression of chemokine (C-C motif) ligand 7 (CCL7), a soluble inflammatory factor, was enhanced in macrophages stimulated by human ovarian cancer cells as well as peritoneal macrophages from patients with ovarian cancer; CCL7 promoted the invasion of ovarian cancer cells. Our study elucidates the crosstalk between macrophages and ovarian cancer cells that contributes to ovarian cancer metastasis. Abstract In the tumor microenvironment, macrophages have been suggested to be stimulated by tumor cells, becoming tumor-associated macrophages that promote cancer development and progression. We examined the effect of these macrophages on human ovarian cancer cell invasion and found that conditioned medium of macrophages stimulated by ovarian cancer cells (OC-MQs) significantly increased cell invasion. CC chemokine ligand 7 (CCL7) expression and production were significantly higher in OC-MQs than in the control macrophages. Peritoneal macrophages from patients with ovarian cancer showed higher CCL7 expression levels than those from healthy controls. Inhibition of CCL7 using siRNA and neutralizing antibodies reduced the OC-MQ-CM-induced ovarian cancer cell invasion. CC chemokine receptor 3 (CCR3) was highly expressed in human ovarian cancer cells, and a specific inhibitor of this receptor reduced the OC-MQ-CM-induced invasion. Specific signaling and transcription factors were associated with enhanced CCL7 expression in OC-MQs. CCL7-induced invasion required the expression of matrix metalloproteinase 9 via activation of extracellular signal-related kinase signaling in human ovarian cancer cells. These data suggest that tumor-associated macrophages can affect human ovarian cancer metastasis via the CCL7/CCR3 axis.

Intestinal neuropeptides and neurotrophins as endocrine messengers play a key role in the bidirectional gut-brain interaction both in health and disease status. Their alterations in several neurological disorders have been reported, but whether a remarkable change occurs in Parkinson disease (PD) remains unexplored. In this study, we aimed to investigate the levels of 13 neuropeptides and 4 neurotrophins in the intestine of neurotoxin-induced PD mice. The PD mice were obtained by chronic injection of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) or MPTP/probenecid (MPTP/p). The levels of mRNA and protein expression in mouse intestines were measured by using real-time reverse transcription polymerase chain reaction and Western blotting, respectively. We found that the mRNA expression of 2 neuropeptides (cholecystokinin [CCK] and dynorphin A [Dyn A]) and 2 neurotrophins (brain-derived neurotrophic factor [BDNF] and neurotrophin-5) was significantly decreased in the colon of MPTP group compared to the vehicle-treated group. The protein levels of CCK, Dyn A, and BDNF were reduced in the colon of MPTP- or MPTP/p-treated mice compared to those of the vehicle-treated group. These data suggest that the intestinal expression of CCK, Dyn A, and BDNF was significantly reduced in PD animal models, and may play a role in the gut-brain axis in PD.

Two new aryltetralin lactone lignans, petasitesins A and B were isolated from the hot water extract of the leaves of butterbur (Petasites japonicus) along with six known compounds. The chemical structures of lignans 1 and 2 were elucidated on the basis of 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data, electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) spectra. Petasitesin A and cimicifugic acid D showed significant inhibitory effects on the production of both prostaglandin E2 (PGE2) and NO in RAW264.7 macrophages. The expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were inhibited by compound 1 in RAW264.7 cells. Furthermore, compounds 1 and 3 exhibited strong affinities with both iNOS and COX-2 enzymes in molecular docking studies.

The stem bark of Ailanthus altissima is used in traditional medicine in Asia to treat a variety of diseases, including cancer. The aim of this study was to identify compounds with tumoricidal activity from A. altissima stem bark and to investigate their mechanisms of action. Among the 13 compounds isolated from the ethyl acetate fraction of A. altissima stem bark, the β-carboline alkaloid 9-hydroxycanthin-6-one had potent cytotoxicity in all three ovarian cancer cell types examined. 9-Hydroxycanthin-6-one induced apoptosis through the activation of caspases-3, -8, and -9. 9-Hydroxycanthin-6-one increased the intracellular levels of reactive oxygen species (ROS), and pre-treatment with the antioxidant N-acetyl-l-cysteine (NAC) attenuated the pro-apoptotic activity of 9-hydroxycanthin-6-one. Additionally, 9-hydroxycanthin-6-one was found to decrease the expressions of MCP-1 and RANTES, major determinants of macrophage recruitment at tumor sites, in ovarian cancer cells. Treatment with 9-hydroxycanthin-6-one inhibited the levels of M2 phenotype markers and some cancer-promoting factors, such as MMP-2, MMP-9, and VEGF, in macrophages educated in ovarian cancer conditioned medium. Taken together, these data suggest that 9-hydroxycanthin-6-one isolated from A. altissima stem bark induces apoptosis in human ovarian cancer cells through the caspase- and ROS-dependent pathways and inhibits the activation of tumor-associated macrophages.

Canthin-6-one (CO) alkaloids possess various biological activities, including antibacterial, antitumor, antifungal, and antiviral activities. However, their anti-inflammatory effects and underlying molecular mechanisms are poorly characterized. This study aimed to investigate the anti-inflammatory effects of CO and its derivative 5-(1-hydroxyethyl)-canthin-6-one (5-HCO), isolated from the stem barks of Ailanthus altissima in lipopolysaccharide (LPS)-stimulated macrophages. CO (1 and 5 µM) and 5-HCO (7.5 and 15 µM) significantly inhibited the LPS-induced expression of inducible nitric oxide synthase. In addition, CO (1 and 5 µM) and 5-HCO (15 µM) markedly suppressed the production of prostaglandin E2 (PGE2) and expression of cyclooxygenase-2, a key enzyme in PGE2 synthesis, in LPS-stimulated macrophages. Moreover, CO treatment significantly reduced monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) expression, whereas 5-HCO inhibited MCP-1, but not TNF-α expression. Both CO and 5-HCO inhibited the phosphorylation of inhibitor kappa B and transcriptional activation of nuclear factor kappa B (NF-κB) in LPS-stimulated macrophages. In addition, CO, but not 5-HCO, markedly reduced Akt phosphorylation. Taken together, these data suggest that CO, but not 5-HCO with a hydroxyethyl moiety on the D ring, has potent anti-inflammatory activity in LPS-stimulated macrophages through the downregulation of both the NF-κB and the Akt pathway.

A phytochemical study on the fruits of Schisandra chinensis led to the isolation and characterization of nineteen compounds. The structures of the isolates were determined to be schizandrin, deoxyschizandrin, angeloylgomisin H, gomisin A, gomisin J, (−)-gomisin L1, (−)-gomisin L2, wuweizisu C, gomisin N, meso-dihydroguaiaretic acid, kadsuphilactone B, α-ylangenol, α-ylangenyl acetate, β-chamigrenal, β-chamigrenic acid, 4-hydroxybenzoic acid, protocatechuic acid, p-methylcarvacrol, and indole-3-acetic acid. Of these, some lignans and a nortriterpene showed cytotoxic activity in human ovarian and endometrial cancer cells. In particular, a nortriterpenoid kadsuphilactone B exhibited significant cytotoxic activity with IC50 values below 25 μM in both A2780 and Ishikawa cells. Kadsuphilactone B induced apoptotic cell death and stimulated the activation of caspase-3, -8, and -9 and the cleavages of poly (ADP-ribose) polymerase. Caspase inhibitors attenuated the pro-apoptotic activity of kudsuphilactone B. In addition, kadsuphilactone B altered the expression levels of B cell lymphoma 2 (Bcl-2) family proteins. Moreover, activation of MAPKs was modulated by kadsuphilactone B in a dose-dependent manner. Taken together, these results show that kadsuphilactone B induces caspase-dependent apoptosis in human cancer cells via the regulation of Bcl-2 family protein and MAPK signaling.

The antibiotic susceptibilities and characteristics of 94 Bacillus licheniformis strains isolated from traditional Korean fermented soybean foods were assessed. The minimum inhibitory concentration tests revealed that all strains were susceptible to gentamicin, kanamycin, tetracycline, and vancomycin, and that antibiotic resistances were expressed in a strain-specific manner. The resistances of B. licheniformis to chloramphenicol and streptomycin were established as intrinsic characteristics. The advent of erythromycin-resistant strains was attributed to the acquisition of a plasmid-mediated erythromycin resistance determinant. All strains sustained growth on tryptic soy agar (TSA) containing 14% NaCl (w/v), but 51.1% of strains did not grow at 15% NaCl. All strains exhibited protease and lipase activities on TSA but both activities decreased as the NaCl concentration increased. The function of both enzymes in high-salt soybean fermentation is therefore uncertain.

배경 및 목적: 학령기 경계선 지능 아동의 은유 이해 능력을 알아보기 위하여 은유 문장만 제시되는 비문맥 조건과 대화상황의 언어문맥이 제시되는 문맥 조건에서 일반아동과 경계선 지능 아동의 은유 이해 능력을 비교하였다. 방법: 언어 연령이 만 7-8세인 경계선 지능 아동 10명과 언어연령을 일치시킨 일반아동 10명, 총 20명이 본 연구에 참여하였다. 연구...

The rhizomes of Cyperus rotundus (cyperaceae) have been used in Korean traditional medicines for treating diverse inflammatory diseases. However, little is known about the biological activities of isocyperol, a sesquiterpene isolated from C. rotundus, and their associated molecular mechanisms. In this study, we found that isocyperol significantly inhibited lipopolysaccharide (LPS)-induced production of nitrite oxide (NO) and prostaglandin E2 (PGE2) and suppressed LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels in RAW 264.7 macrophages. In addition, isocyperol downregulated the LPS-induced expression of several proinflammatory cytokines, such as interleukin-1beta (IL-1β), IL-6, and monocyte chemotactic protein-1 (MCP-1). Isocyperol treatment suppressed the LPS-induced nuclear translocation and transcriptional activation of nuclear factor-kappaB (NF-κB) in macrophages. Moreover, the activation of STAT3, another proinflammatory signal, was suppressed by isocyperol in LPS-stimulated RAW 264.7 cells. Isocyperol pretreatment also induced heme oxygenase-1 (HO-1) expression and reduced LPS-stimulated reactive oxygen species (ROS) accumulation in macrophages. Furthermore, isocyperol significantly increased the survival rate and attenuated serum levels of NO, PGE2, and IL-6 in LPS-induced septic shock mouse model. Taken together, these data indicate that isocyperol suppress septic shock through negative regulation of pro-inflammatory factors through inhibition of the NF-κB and STAT3 pathways and ROS. To our knowledge, this is the first report on the biological activity of isocyperol and its molecular mechanism of action.

The effects of two crude bacteriocins (DF01 and K10) on lactic acid bacteria (LAB) communities and pH during kimchi fermentation were analyzed by polymerase chain reactiondenaturing gradient gel electrophoresis (PCR-DGGE). Crude LAB bacteriocins, prepared by ammonium sulfate precipitation, were added at 5 AU/mL, and kimchi was incubated at 20°C for 7 days. The pH and titratable acidity of the kimchies were determined daily, and the amplified 16S rRNA products were analyzed by PCR-DGGE. The common and main LAB were Weissella spp., Leuconostoc spp., and Lactobacillus spp. from both control and bacteriocin-treated samples. Among them, W. koreensis, W. confusa, and Lb. sakei were the predominant microorganisms throughout the fermentation period. Some obligate and facultatively heterofermentative LAB were detected from the bacteriocin-treated samples. The pH of the kimchi samples treated with each bacteriocin was higher (ca. 0.8 unit) than that of the control at day 4 and 5.

배경 및 목적: 본 연구는 학령기 다문화가정 아동의 어휘발달을 살펴보기 위하여 수용․표현 어휘력 발달에 대해 조사하였으며, 학령기 어휘발달과 관련이 높은 요인을 확인하고자 상관분석을 실시하였다. 방법: 초등 1∼4학년 다문화가정 아동 43명을 대상으로 수용․표현 어휘력 검사를 실시하였다. 연령 별 평균과 표준편차를 기준으로 어휘발달 현황을 조사하였으며 연령에 따른 차이를 살펴보기 위해 1, 2학년과 3, 4학년 두 개의 집단으로 나누어 수용․표현어휘 점수에 대해 각각 독립표본 t 검정을 실시하였다. 그리고 어휘발달과 관련이 높은 변인을 찾아보기 위하여 여러 변인들 간의 상관분석을 실시하였다. 결과: 수용․표현어휘의 학년 집단 간 차이가 유의한 것으로 나타나 연령의 증가와 더불어 수용․표현어휘력이 향상됨을 확인할 수 있었으나 연령 별 표준편차를 기준으로 살펴본 결과 수용․표현어휘발달지체에 해당하는 아동이 각각 20%였다. 상관분석 결과 수용어휘와 표현어휘는 서로 유의한 상관을 보였으며 수용․표현어휘 모두와 유의한 상관을 보인 변인은 아동 자신의 연령이었으며 그 외 수용어휘와 유의한 상관을 보인 변인으로 어머니의 거주기간이 추가되었다.

Apios americana is an important food crop producing edible tubers with high nutritional and medicinal values and is widely cultivated in many countries. Despite its usefulness, research on its secondary metabolites and biological activities has been limited. In the present study, a new coumaronochromone, (2 R,3 S)-3,7,4'-trihydroxy-5-methoxycoumaronochromone (1), and two new isoflavone glucosides, 7,2',4'-trihydroxy-5-methoxyisoflavone-4'- O-β-d-glucopyranoside (3) and 5,7,4'-trihydroxyisoflavone-7- O-β-d-gentiotrioside (5), were isolated from the tubers of A. americana via chromatographic separation. Seventeen known compounds (2, 4, and 6-20) were also obtained from this plant part. The chemical structures of 1, 3, and 5 were determined by the interpretation of spectroscopic data. The absolute structure of the new compound 1 was established from experimental and calculated electronic circular dichroism spectra. This is the first study to determine the absolute configuration of a 3-hydroxycoumaronochromone derivative. The potential anti-inflammatory activity of the 20 isolates obtained was evaluated by measuring their inhibitory effects on nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 macrophages. Among the isolates, seven compounds (1, 3, 6-8, 15, and 20) showed substantial inhibition of nitric oxide production in RAW 264.7 cells, with the most active being compound 1 (IC

We assessed the safety and biotechnological properties of 17 Enterococcus faecalis and 18 Enterococcus faecium strains isolated from Meju to select starter candidates for quality Meju production. Minimum inhibitory concentration assays showed that all strains were susceptible to ampicillin, chloramphenicol, ciprofloxacin, erythromycin, gentamicin, penicillin G, and tetracycline, as judged by the breakpoint values defined at the species level by the European Committee on Antimicrobial Susceptibility Testing, whereas two E. faecalis strains were resistant to vancomycin, which could be ascribed to acquired resistance. None of the strains exhibited α- or β-hemolytic activities or biofilm formation. Both species showed similar levels of biogenic amine production, and noticeable amounts of tyramine (3397.4 ± 172.4 ppm) were produced by all strains in the presence of precursors (histidine, lysine, ornithine, and tyrosine). All strains exhibited protease, lipase, and acid production, with decreased activity observed with increasing NaCl concentrations. This study confirmed the necessity of antibiotic resistance screening of Enterococcus species for food production, with the identification of vancomycin-resistant strains from Meju.

배경 및 목적: 마음 상태를 이해하는 것은 사회적 의사소통을 위한 기본 능력 중 하나이다. 본 연구는 사회적 기술과 화용능력에 어려움이 있는 것으로 알려진 ADHD아동의 마음 상태 이해력을 조사하고자 하였다. 방법: 3-6학년 ADHD아동 12명과 연령, 동작성 지능 및 어휘력이 일치하는 일반아동 12명에게 6가지 종류의 마음 상태가 담긴 12개의 이야기...

배경 및 목적: 동음이의어는 하나의 음운 형태이나 다른 의미를 갖는 단어들을 일컫는 것으로 학령기 아동의 어휘능력의 질적인 측면을 평가하기 위해 유용하게 사용된다. 본 연구에서는 초등학교 저학년 다문화가정 아동의 어휘능력을 살펴보기 위하여 동음이의어 이해와 정의하기 과제에 대한 수행력을 비다문화가정 아동의 수행력과 비교 분석하였다. 방법: 초등학교 저학년...

The present investigation of the chemical constituents of the stem barks of Ailanthus altissima has resulted in the isolation of six canthinone-type alkaloids, including a new compound, (R)-5-(1-hydroxyethyl)-canthine-6-one (1), and five known compounds (2-6). Moreover, four phenyl propanoids (7-10), two lignans (11 and 12), two triterpenoids (13 and 14) and a fatty acid (15) having previously known chemical structures were isolated during the same course of this study. The structure of the new compound was elucidated by physical (m.p., [α]D) and spectroscopic data (¹H-NMR, (13)C-NMR, 2D NMR, and HR-DART-MS) interpretation and its absolute configuration was determined by electronic circular dichroism (ECD) data and quantum chemical calculations. The inflammatory activities of the isolates were screened on lipopolysaccharide (LPS)-induced nitric oxide (NO), a proinflammatory mediator, in RAW 264.7 cells. Among these isolated compounds, six compounds exhibited significant inhibition of NO production, with IC50 values in the range of 5.92 ± 0.9 to 15.09 ± 1.8 μM.

Two tetrahydrofurofurano lignans (1 and 2), four phenylpropanoids (3&ndash, 6), and two alkamides (7 and 8) were isolated from the EtOAc-soluble fraction of the roots of Asarum sieboldii. The chemical structures of the isolates were identified by analysis of spectroscopic data measurements, and by a comparison of their data with published values. The isolates (1, 2, 4&ndash, 8) were evaluated for their cytotoxicity against human ovarian cancer cells (A2780 and SKOV3) and immortalized ovarian surface epithelial cells (IOSE80PC) using a MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assay. Of the isolates, (&minus, )-asarinin (1) exhibited the most potent cytotoxicity to both A2780 and SKOV3 cells. A propidium iodide/annexin V-fluorescein isothiocyanate (V-FITC) double staining assay showed that (&minus, )-asarinin (1) induces apoptotic cell death in ovarian cancer cells. In addition, (&minus, )-asarinin (1) increased the activation of caspase-3, caspase-8, and caspase-9 in ovarian cancer cells. Pretreatment with caspase inhibitors attenuated the cell death induced by (&minus, )-asarinin (1). In conclusion, our findings show that (&minus, )-asarinin (1) from the roots of A. sieboldii may induce caspase-dependent apoptotic cell death in human cancer cells.