Sung-Min Kim, Youngeun Lee, Dajeong Jeong, Jiwon Yun , Sung-Soo Yoon, Sang Mee Hwang, Nuri Lee and Dong Soon Lee Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea; Department of Internal Medicine, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea; Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; Department of Laboratory Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea

Objectives: Acute cervical insufficiency accounts for 10-25 % of all mid-trimester pregnancy losses. However, the definition and description for the degree of acute cervical insufficiency were obscure and different among the many studies. The aim of this study was to suggest a new 4-digit quantification system and to evaluate the outcome according to the new system in women with acute cervical insufficiency. Study Design: A retrospective cohort study was conducted in patients with acute cervical insufficiency who underwent physical examination indicated cervical cerclage. Acute cervical insufficiency was defined as painless external os dilation with prolapsed and/or visible membranes on speculum examination. The status of fetal membranes was described using two values: 1) size of the prolapsed membrane (P, measured using ultrasound); and 2) size of visible fetal membranes (M, evaluated by speculum examination). The status of cervix was described using two values: 1) dilatation of the narrowest os (O, measured by ultrasound); and 2) functional cervical length (C, measured by ultrasound). The patients were divided into 3 groups as follows: Stage I, patients with visible fetal membranes (M > 0) but with a remaining functional cervix (C> 0) (N = 7); stage II, those with visible fetal membranes (M> 0) and a functional cervical length of 0 but without prolapsed membranes (P = 0) (N = 33); and stage III, those with prolapsed membranes (P > 0) (N = 40). Results: 1) Patients who delivered before 34 weeks of gestation had a significantly lower median gestational age at cerclage operation and a significantly higher median P, M, C values than those who delivered at or beyond 34 weeks of gestation(P <0.01 for gestational age at operation, P and M values; P < 0.05 for C value); 2) The higher the stage based on PMOC quantification system, the greater the risk of preterm delivery before <24, <32, <34, and <37 weeks of gestation (P < 0.001 for all); 3) The neonatal survival rate was 100 % (717) for stage I, 93.9 % (31/33) for stage II, and 60 % (24/40) for stage III. Conclusion: The PMOC system was a simple method to describe the individualized conditions and to predict the risk of preterm births in all spectrums of acute cervical insufficiency. (C) 2020 Elsevier B.V. All rights reserved.

Introduction: The prognostic significance of R1 resection for pancreatic ductal adenocarcinoma (PDAC) has varied in the literature due to a lack of consensus on the definition of various resection margin/surfaces. Method: We performed a prospective clinicopathological analysis of 119 PDACs, resected by pancreaticoduodenectomy specimens between March 2014 and December 2016. The entire pancreatic head were sectioned by the axial slicing method. The safety margins for all circumferential margin/surfaces (anterior, posterior, SMV/PV groove, SMA) were recorded in millimeters. Each margin status was correlated with the patient survival outcome. Result: The R1 rate was 32.8% (n=39) and 84.0% (n=100) by the 0mm and 1mm rule. By the 0mm and 1mm-rules, the anterior surface was involved in 7 (5.9%) and 42 (35.3%), posterior surface in 10 (8.4%) and 53 (44.5%), SMV/PV groove in 22 (18.5%) and 71 (59.7%), and SMA margin in 12 (10.1%) and 43 (36.1%), respectively. Involvement of the anterior and posterior surfaces by the 0mm rule was associated with significantly decreased overall survival (OS) and disease-free survival (DFS); however, when the 1mm rule was applied, only OS was decreased in anterior surface-positive cases. In contrast, involvement of the SMA margin and SMV/PV groove by both 0mm and 1mm rules was correlated with significantly decreased OS and DFS. Conclusion: A "positive margin" by the 1mm rule was significantly associated with adverse outcome for SMA margin and SMV/PV grooves. Although anterior and posterior surfaces are technically not "margins", involvement of these surfaces by the 0mm rule was significantly associated with adverse outcome and therefore should be reported.

Eicosapentanoic acid (EPA), an omega‐3 polyunsaturated fatty acids (ω‐3 PUFAs), protects against photodamage and photocarcinogenesis in mammals. Water movement across the plasma membrane can occur via two pathways: by diffusion through the lipid bilayer and by membrane inserted water channels (aquaporins; AQPs). At least 13 subtypes, denoted AQP0‐AQP12, have so far been identified in mammalian cells. AQP3 is a water/glycerol transporting protein in basal layer keratinocytes of epidermis in normal skin. We have investigated the effects of EPA on AQP3 expression and the effects of EPA on ultraviolet (UV)‐induced AQP3 down˗regulation in cultured human skin keratinocytes. EPA treatment increased AQP3 gene and protein expression in human epidermal keratinocytes (HaCaT). Using a specific inhibitor, we observed that the effect of EPA on AQP3 expression was mediated by ERK activation. UV induced AQP3 down‐regulation in HaCaT cells. EPA treatment attenuated UV‐induced AQP3 loss and cell death. Collectively, the present results show that EPA increased AQP3 expression and protected against photodamage of UV through the induction of AQP3 expression.

Commelina communis Leded.., a annual plant, has been used as an antidiabetic, antioxidant and hypoglycemic agent in korea herbal medicine. We analyzed the anti‐melanogenic effects of ethanol extracts from Commelina communis Leded. (CCL) in B16F10 cells. CCL significantly reduced tyrosinase activity of the cells about 62.76±3.5% and 52.09±7.9% at concentrations of 12.5 μg/ml and 25 μg/ml, respectively. Also, melanin synthesis of cells was decreased with 66.11% and 52.30% by CCL, respectively. Tyrosinase gene and protein expressions were inhibited by the treatment with CCL. Moreover, CCL significantly reduced α‐melanocyte stimulating hormone (α‐MSH)‐induced melanin synthesis and tyrosinase activity, also decreased α‐MSH‐induced expression of melanogenic enzyme like as tyrosinase, tyrosinase‐related protein (TRP)‐1 and TRP‐2. This results show that the anti‐melanogenic activity of CCL is correlated with the suppression of tyrosinase gene and protein expressions in B16F10 cells.

Melanin is the main component determining the color of skin and also plays an important role in protecting skin from UV light. Kaempferia galanga Linn. (Zingiberaceae) presents many chemical constituents of the volatile oil extracted from the rhizome. In this study, we examined the effects of the methanolic extract of Kaempferia galanga L. (MKG) on melanogenesis and signaling pathway in B16F10 cells. MKG significantly inhibited ¥á‐melanocyte stimulating hormone (¥á‐MSH)‐induced melanin synthesis and tyrosinase activity, and also decreased ¥á‐MSH‐induced expression of microphthalmia‐associated transcription factor (MITF) and tyrosinase‐related proteins (TRPs). Moreover, MKG reduced the level of phosphorylated cAMP‐response element binding protein (CREB), activity‐regulated transcription factor that functions in melanogenesis. These findings suggest that inhibition of phospho‐CREB and MITF expression may lead to the suppression of melanogenesis in MKG‐treated B16 cells.Grant Funding Source: None

In this study, we investigated the molecular events of melanogenesis induced by scopoletin in B16 melanoma cells. To evaluate melanin relative expression, using RT‐PCR and western blotting, B16 cells were incubated for 24 h with scopoletin. Scopoletin induced the expression of tyrosinase, TRP1 and MITF proteins. Moreover, it increased the phosphorylation ERK, CREB and p38 MAPK. Scopoletin‐induced melanogenesis was reduced by H‐89, KT5720, PKA inhibitors, or SB203580, a p38 MAPK inhibitor, but not by Ro 320432, a PKC inhibitor, which suggests the involvement of PKA and p38 MAPK in scopoletin induced melanogenesis. Scopoletin induced the activation of CRE, which suggests that scopoletin‐induced melanogenesis is mediated by PKA, which occurs downstream of scopoletin‐increased cAMP production. This result was further confirmed by the fact that scopoletin‐induced phosphorylation of CREB was inhibited by H‐89, but not by PD98059, a MEK1 inhibitor. These results demonstrate that scopoletin induces melanogenesis through CREB/PKA and p38 MAPK signaling pathway.

In the present study, we investigated the effects of gallic acid (GA) (3,4,5-trihydroxybenzoic acid), a polyhydroxyphenolic compound, isolated from Rhus chinensis, on the human monocytic lymphoma cell line U937. In vitro experiments showed that treating U937 cells with various amounts of GA inhibited cell viability and induced apoptosis in a dose-dependent manner. In order to understand the mechanism by which GA induces apoptosis, we examined the gene expression of p53, nuclear factor κB (NF-κB), and inhibitor of NF-κB (I-κB) after treating the cells with GA and found that expression levels of the genes for p53 and NF-κB increased and that for I-κB decreased. The results obtained from western blotting with U937 cells showed up-regulation of NF-κB protein and down-regulation of proliferating cell nuclear antigen and I-κB protein. These results demonstrate that GA efficiently induces apoptosis in U937 cells and that GA is a potential chemotherapeutic agent against lymphoma.

One of the CC chemokines, cutaneous T cell-attracting chemokine (CTACK/CCL27), is a skin-specific CC chemokine that is produced constitutively by keratinocytes and is highly up-regulated in inflammatory skin conditions such as atopic dermatitis and contact dermatitis. (2S)-2′-Methoxykurarinone (MOK) from Sophora flavescens has been demonstrated to have antioxidant effects. Heme oxygenase (HO)-1 has recently emerged as an important cytoprotective enzyme against oxidative stress and inflammatory responses in many cell types. This study aimed to define whether and how MOK regulates skin specific CTACK/CCL27 chemokine production in human HaCaT keratinocytes. The level of CTACK/CCL27 and HO-1 expression was measured by reverse transcription-polymerase chain reaction, and signaling was evaluated by western blot analysis. CTACK/CCL27 production was determined by enzyme-linked immunosorbent assay. Pretreatment with MOK suppressed tumor necrosis factor-α (TNF-α)- and interleukin (IL)-1ß-induced CTACK/CCL27 production in human HaCaT keratinocytes. MOK inhibited TNF-α- and IL-1ß-induced nuclear factor κB (NF-κB) activation. Interestingly, pretreatment with MOK significantly suppressed TNF-α- and IL-1ß-induced CTACK/CCL27 production through the induction of HO-1. This suppression was completely abolished by HO-1 small interfering RNA. Furthermore, carbon monoxide, but not other end products of HO-1 activity, also suppressed TNF-α- and IL-1ß-induced CTACK/CCL27 production. These results demonstrate that MOK attenuates TNF-α- and IL-1ß-induced production of CTACK/CCL27 in human HaCaT keratinocytes by inhibiting NF-κB activation and induction of HO-1.

Figs (Ficus carica L.) belong to mulberry tree (Moraceae) which is called fruit of autumn, one of the oldest fruits in the world. Figs have been used as a digestion promoter and a cure for ulcerative inflammation and eruption in Korea. The aim of this study was to develop fermented Fig Vinegar (FV) and to investigate anti‐inflammatory effects of FV. Modification of proteins by long term circulation with glucose leads to the formation of advanced glycation end products (AGEs). Recently, ligation of AGEs play an important role in the development of diabetic complications including atherosclerosis which includes activation, adhesion, and migration of monocytes. FV significantly inhibited MRM‐induced expression of pro‐inflammatory genes including tumor necrosis factor‐α, monocytes chemoattractant protein‐1, interferon‐γ‐inducible protein‐10, and cyclooxygenase‐2 in a dose dependent manner. FV also blocked in iNOS, COX‐2 protein expression level and the attendant PGE2 production. These inhibitory effects may be of benefit for diabetic vascular complications via prevention of oxidative stress in activated human monocytes.

The kind of salt used in doenjang preparation is one of the most important factors that affect the chemopreventive activities of doenjang. Bamboo salt (BS) is known to exert various therapeutic effects on several diseases. In this study, antimutagenic and anticlastogenic effects of methanol extracts of doenjang made with either one-time heat-treated BS (BS1-D), nine-times heat-treated BS (BS9-D), sun-dried salt (SDS-D), or purified salt (PS-D) using the Ames test and micronucleus test. BS1-D and BS9-D showed higher inhibitory effects than PS-D and SDS-D on mutagenicity induced by aflatoxin B(1), N-methyl-N'-nitro-N-nitrosoguanidine, and 4-nitroquinoline-1-oxide. BS1-D exerted more suppressive effects on chromosome aberration than SDS-D on mitomycin C-induced micronucleus in mice. It can be concluded that the chemopreventive effect of doenjang was significantly increased by using BS instead of the more typical commercial salts, SDS and PS (P < .05). This is probably due to the changes in the chemical and physical properties of the salt, especially increased content of K and P, during the processing of BS and to differences in fermented products formed during the doenjang fermentation in the presence of BS.

The aerial part of Artemisia iwayomogi Kitamura has traditionally been used for inflammation, infectious disease, cancer, pyretic, diuretic, liver protective effect, and choleretic purposes in Korea. We investigated that the essential oil induces apoptosis in KB cell as evidenced by Hoechst-33258 dye staining, flow cytometry (cell cycles), and DNA fragmentation for nuclear condensation and Western blotting for activation of caspases-3, -8, -9, Bax, Bcl-2, cytochrome c, and poly (ADPribose) polymerase (PARP) cleavage. In the present study, we found that the essential oil could induce apoptosis in KB cells, as characterized by DNA fragmentation, activation of caspase-3, -8, and -9, and PARP cleavage. The efficacious induction of apoptosis was observed as a dose-dependent. The essential oil-induced apoptotic cell death was accompanied by up-regulation of Bax and down-regulation of Bcl-2. The essential oil also caused the loss of mitochondrial membrane potential and cytochrome c release from mitochondria to cytosol. These findings indicate that mitochondrial pathways might be involved in the essential oil-induced apoptosis and enhance our understanding of the anticancer function of the essential oil in herbal medicine.

Sophora flavescens AITON (Leguminosae) is a typical traditional Korean medical herb considered to exhibit antibacterial, anti-inflammatory, and antipyretic effects, and is also used for the treatment of skin and mucosal ulcers, sores, diarrhea, gastrointestinal hemorrhage, arrhythmia, and eczema. In this study, the compound sophoraflavanone G was isolated from the dried roots of S. flavescens by bioassay-guided fractionation. We then investigated the effects of various concentrations of sophoraflavanone G on cell viability and the induction of apoptosis in KB cells after an incubation of 24 hr. The results were determined by the following methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-terazolium bromide (MTT) assay, Hoechst-33258 dye staining, flow cytometry (cell cycle), and Western blotting for caspase-3 and poly (ADP-ribose) polymerase (PARP). We found sophoraflavanone G induced the apoptosis of KB cells in a dose-dependent manner that was verified by DNA fragmentation, apoptotic bodies, the sub-G I ratio, caspase-3 activity, and cleavage of PARP. These results suggest that sophoraflavanone G has potent anti-proliferative effects on human oral epidermoid carcinoma cells, with the induction of apoptosis.

The antibacterial activities of methanol extract and systematic solvent fractions( -hexane, chloroform, ethyl acetate, and butanol) from Korean common type figs at different ripening stages were tested by the broth dilution method against 8 representative food-poisoning bacteria- : L. monocytogenes, S. aureus, S. enteritidis, E. coli O157:H7, E. coli, Y. enterocolitica, V. parahaemolyticus, and S. typhimurium. The methanol extracts of unripened I and II showed stronger activity than that of the ripened figs especially against L. monocytogenes, S. enteritidis, E. coli O157:H7, Y. parahaemolyticus and S. typhimurium in 10 mg/mL. The systematic solvent fractions showed stronger antibacterial activities than the methanol extract, even al the lower concentrations. The hexane fraction of ripened figs showed higher growth inhibition than those of unripened I and II against L. monocytogenes, E. coli O157:H7, Y. enterocolitica and V. parahaemolyticus. The chloroform fraction showed strong antibacterial activity in all ripening stages against E. coli O157:H7 and V. parahaemolyticus. The butanol fraction showed better inhibition activity in unripened I and II than in the ripened figs. The hexane and chloroform fractions showed inhibition activity of more than against E. coli O157:H7, V. parahaemolyticus in 0.5 mg/mL. Each fraction showed a little different antibacterial activity according to the ripening stages of the fruits and the tested strains. Especially, figs in the unripened II stage revealed superior activity relatively and the hexane and chloroform fractions revealed the strongest activity, followed by the butanol fraction, while the ethylacetate and water fractions hardly showed any activity.

Influence of amylose content on formation and characteristics of enzyme-resistant starch (RS) was investigated by scanning electron microscopy, X-ray diffractometry and differential scanning calorimetry. RS yield increased up to 36.1% as the amylose content of com starch increased. Starch granules of Amylomaize Ⅴ and Ⅶ were more rounded and smaller than those of regular corn: some were elongated and had appendages. After autoclaving-cooling cycles, the granular structure disappeared and a continuous spongy-like porous network was visible in regular com starch; the granular structure was still evident in parts in Amylomaize Ⅴ and Ⅶ starches. In all isolated RS residues, the porous structures were no longer visible and more compact formations predominated. While regular com starch showed an A-type X-ray profile, Amylomaize Ⅴ and Ⅶ starches exhibited a combination of B- and V-types. Regular corn starch lost most of its crystallinity during autoclaving, but the crystallinity was still left in Amylomaize starches as diffuse or poor B-types. All RS residues showed the presence of poor B-type regardless of amylose contents. Transition temperatures and enthalpy of native starches were a little higher in Amylomaize Ⅴ and Ⅶ starches than those of regular com starch. Regardless of amylose contents, all RS residues exhibited an endothermic transition over a similar temperature range (135~169℃), with a mean peak temperature of ~154℃, which is generally found for retrograded amylose crystallites. Higher transition temperature, enthalpy, and RS yield of Amylomaize Ⅴ and Ⅶ starches were related to granular stability shown by the microscopic and crystallographic studies.