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Biomolecules & Therapeutics

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https://www.readbyqxmd.com/read/28365978/establishment-of-immortalized-primary-human-foreskin-keratinocytes-and-their-application-to-toxicity-assessment-and-three-dimensional-skin-culture-construction
#1
Moonju Choi, Minkyung Park, Suhyon Lee, Jeong Woo Lee, Min Chul Cho, Minsoo Noh, Choongho Lee
In spite of frequent usage of primary human foreskin keratinocytes (HFKs) in the study of skin biology, senescence-induced blockage of in vitro proliferation has been a big hurdle for their effective utilization. In order to overcome this passage limitation, we first isolated ten HFK lines from circumcision patients and successfully immortalized four of them via a retroviral transduction of high-risk human papillomavirus (HPV) E6 and E7 oncogenes. We confirmed expression of a keratinocyte marker protein, keratin 14 and two viral oncoproteins in these immortalized HFKs...
April 6, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28365977/spermidine-protects-against-oxidative-stress-in-inflammation-models-using-macrophages-and-zebrafish
#2
Jin-Woo Jeong, Hee-Jae Cha, Min Ho Han, Su Jung Hwang, Dae-Sung Lee, Jong Su Yoo, Il-Whan Choi, Suhkmann Kim, Heui-Soo Kim, Gi-Young Kim, Su Hyun Hong, Cheol Park, Hyo-Jong Lee, Yung Hyun Choi
Spermidine is a naturally occurring polyamine compound that has recently emerged with anti-aging properties and suppresses inflammation and oxidation. However, its mechanisms of action on anti-inflammatory and antioxidant effects have not been fully elucidated. In this study, the potential of spermidine for reducing pro-inflammatory and oxidative effects in lipopolysaccharide (LPS)-stimulated macrophages and zebrafish was explored. Our data indicate that spermidine significantly inhibited the production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2), and cytokines including tumor necrosis factor-α and interleukin-1β in RAW 264...
April 6, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28365976/new-anticoagulants-for-the-prevention-and-treatment-of-venous-thromboembolism
#3
REVIEW
Joo Hee Kim, Kyung-Min Lim, Hye Sun Gwak
Anticoagulant drugs, like vitamin K antagonists and heparin, have been the mainstay for the treatment and prevention of venous thromboembolic disease for many years. Although effective if appropriately used, traditional anticoagulants have several limitations such as unpredictable pharmacologic and pharmacokinetic responses and various adverse effects including serious bleeding complications. New oral anticoagulants have recently emerged as an alternative because of their rapid onset/offset of action, predictable linear dose-response relationships and fewer drug interactions...
April 6, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28365975/neuroprotective-effect-of-duloxetine-on-chronic-cerebral-hypoperfusion-induced-hippocampal-neuronal-damage
#4
Jin-A Park, Choong-Hyun Lee
Chronic cerebral hypoperfusion (CCH), which is associated with onset of vascular dementia, causes cognitive impairment and neuropathological alterations in the brain. In the present study, we examined the neuroprotective effect of duloxetine (DXT), a potent and balanced serotonin/norepinephrine reuptake inhibitor, on CCH-induced neuronal damage in the hippocampal CA1 region using a rat model of permanent bilateral common carotid arteries occlusion. We found that treatment with 20 mg/kg DXT could attenuate the neuronal damage, the reduction of phosphorylations of mTOR and p70S6K as well as the elevations of TNF-α and IL- 1β levels in the hippocampal CA1 region at 28 days following CCH...
April 6, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28365974/diosmetin-alleviates-lipopolysaccharide-induced-acute-lung-injury-through-activating-the-nrf2-pathway-and-inhibiting-the-nlrp3-inflammasome
#5
Qinmei Liu, Xinxin Ci, Zhongmei Wen, Liping Peng
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common clinical syndrome of diffuse lung inflammation with high mortality rates and limited therapeutic methods. Diosmetin, an active component from Chinese herbs, has long been noticed because of its antioxidant and anti-inflammatory activities. The aim of this study was to evaluate the effects of diosmetin on LPS-induced ALI model and unveil the possible mechanisms. Our results revealed that pretreatment with diosmetin effectively alleviated lung histopathological changes, which were further evaluated by lung injury scores...
April 6, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28274097/induction-of-cell-death-by-betulinic-acid-through-induction-of-apoptosis-and-inhibition-of-autophagic-flux-in-microglia-bv-2-cells
#6
Jeongbin Seo, Juneyoung Jung, Dae Sik Jang, Joungmok Kim, Jeong Hee Kim
Betulinic acid (BA), a natural pentacyclic triterpene found in many medicinal plants is known to have various biological activity including tumor suppression and anti-inflammatory effects. In this study, the cell-death induction effect of BA was investigated in BV-2 microglia cells. BA was cytotoxic to BV-2 cells with IC₅₀ of approximately 2.0 μM. Treatment of BA resulted in a dosedependent chromosomal DNA degradation, suggesting that these cells underwent apoptosis. Flow cytometric analysis further confirmed that BA-treated BV-2 cells showed hypodiploid DNA content...
March 10, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28274096/effect-of-enhancers-on-in-vitro-and-in-vivo-skin-permeation-and-deposition-of-s-methyl-l-methionine
#7
Ki Taek Kim, Ji Su Kim, Min-Hwan Kim, Ju-Hwan Park, Jae-Young Lee, WooIn Lee, Kyung Kuk Min, Min Gyu Song, Choon-Young Choi, Won-Serk Kim, Hee Kyung Oh, Dae-Duk Kim
S-methyl-L-methionine (SMM), also known as vitamin U, is commercially available as skin care cosmetic products for its wound healing and photoprotective effects. However, the low skin permeation expected of SMM due to its hydrophilic nature with a log P value of -3.3, has not been thoroughly addressed. The purpose of this study thus was to evaluate the effect of skin permeation enhancers on the skin permeation/deposition of SMM. Among the enhancers tested for the in vitro skin permeation and deposition of SMM, oleic acid showed the most significant enhancing effect...
March 10, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28274095/sphingosylphosphorylcholine-induces-thrombospondin-1-secretion-in-mcf10a-cells-via-erk2
#8
June Hee Kang, Hyun Ji Kim, Mi Kyung Park, Chang Hoon Lee
Sphingosylphosphorylcholine (SPC) is one of the bioactive phospholipids that has many cellular functions such as cell migration, adhesion, proliferation, angiogenesis, and Ca²⁺ signaling. Recent studies have reported that SPC induces invasion of breast cancer cells via matrix metalloproteinase-3 (MMP-3) secretion leading to WNT activation. Thrombospondin-1 (TSP-1) is a matricellular and calcium-binding protein that binds to a wide variety of integrin and non-integrin cell surface receptors. It regulates cell proliferation, migration, and apoptosis in inflammation, angiogenesis and neoplasia...
March 10, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28274094/calculation-of-a-first-in-man-dose-of-7-o-succinyl-macrolactin-a-based-on-allometric-scaling-of-data-from-mice-rats-and-dogs
#9
Keumhan Noh, Wonku Kang
7-O-succinyl macrolactin A (SMA) exerts several pharmacological effects including anti-bacterial, anti-inflammation, and anticancer activities. Recently, SMA has been extensively evaluated as an anti-cancer drug. Thus, the objectives of the present study were to characterise the pharmacokinetics of SMA via both non-compartmental and compartmental analysis in mice, rats, and dogs, and to derive an appropriate first-in-man dose based on allometric scaling of the animal data. The time courses of plasma SMA concentrations after intravenous administration to rats and dogs were analysed retrospectively, as were data collected after intraperitoneal SMA injection in mice...
March 10, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28274093/canonical-transient-receptor-potential-channels-and-their-link-with-cardio-cerebro-vascular-diseases
#10
REVIEW
Xiong Xiao, Hui-Xia Liu, Kuo Shen, Wei Cao, Xiao-Qiang Li
The canonical transient receptor potential channels (TRPCs) constitute a series of nonselective cation channels with variable degrees of Ca²⁺ selectivity. TRPCs consist of seven mammalian members, TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, TRPC6, and TRPC7, which are further divided into four subtypes, TRPC1, TRPC2, TRPC4/5, and TRPC3/6/7. These channels take charge of various essential cell functions such as contraction, relaxation, proliferation, and dysfunction. This review, organized into seven main sections, will provide an overview of current knowledge about the underlying pathogenesis of TRPCs in cardio/cerebrovascular diseases, including hypertension, pulmonary arterial hypertension, cardiac hypertrophy, atherosclerosis, arrhythmia, and cerebrovascular ischemia reperfusion injury...
March 10, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28208014/improved-antitumor-efficacy-of-hyaluronic-acid-complexed-paclitaxel-nanoemulsions-in-treating-non-small-cell-lung-cancer
#11
Joo-Eun Kim, Young-Joon Park
Paclitaxel (PTX) is a effectively chemotherapeutic agent which is extensively able to treat the non-small cell lung, pancreatic, breast and other cancers. But it is a practically insoluble drug with water solubility less than 1 µg/mL, which restricts its therapeutic application. To overcome the problem, hyaluronic acid-complexed paclitaxel nanoemulsions (HPNs) were prepared by ionic complexation of paclitaxel (PTX) nanoemulsions and hyaluronic acid (HA) to specifically target non-small cell lung cancer. HPNs were composed of DL-α-tocopheryl acetate, soybean oil, polysorbate 80, ferric chloride, and HA and fabricated by high-pressure homogenization...
February 17, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28208013/sex-differences-in-autism-like-behavioral-phenotypes-and-postsynaptic-receptors-expression-in-the-prefrontal-cortex-of-tert-transgenic-mice
#12
Ki Chan Kim, Kyu Suk Cho, Sung Min Yang, Edson Luck Gonzales, Schley Valencia, Pyeong Hwa Eun, Chang Soon Choi, Darine Froy Mabunga, Ji-Woon Kim, Judy Kyoungju Noh, Hee Jin Kim, Se Jin Jeon, Seol-Heui Han, Geon Ho Bahn, Chan Young Shin
Autism spectrum disorder (ASD) remains unexplained and untreated despite the high attention of research in recent years. Aside from its various characteristics is the baffling male preponderance over the female population. Using a validated animal model of ASD which is the telomerase reverse transcriptase overexpressing mice (TERT-tg), we conducted ASD-related behavioral assessments and protein expression experiments to mark the difference between male and females of this animal model. After statistically analyzing the results, we found significant effects of TERT overexpression in sociability, social novelty preference, anxiety, nest building, and electroseizure threshold in the males but not their female littermates...
February 17, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28208012/hypothermia-inhibits-endothelium-independent-vascular-contractility-via-rho-kinase-inhibition
#13
Yoon Hee Chung, Keon Woong Oh, Sung Tae Kim, Eon Sub Park, Hyun Dong Je, Hyuk-Jun Yoon, Uy Dong Sohn, Ji Hoon Jeong, Hyen-Oh La
The present study was undertaken to investigate the influence of hypothermia on endothelium-independent vascular smooth muscle contractility and to determine the mechanism underlying the relaxation. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Hypothermia significantly inhibited fluoride-, thromboxane A₂-, phenylephrine-, and phorbol ester-induced vascular contractions regardless of endothelial nitric oxide synthesis, suggesting that another pathway had a direct effect on vascular smooth muscle...
February 17, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28208011/glucosylsphingosine-activates-serotonin-receptor-2a-and-2b-implication-of-a-novel-itch-signaling-pathway
#14
Ramsha Afzal, Won-Sik Shim
Recent reports claimed that glucosylsphingosine (GS) is highly accumulated and specifically evoking itch-scratch responses in the skins of atopic dermatitis (AD) patients. However, it was unclear how GS can trigger itch-scratch responses, since there were no known molecular singling pathways revealed yet. In the present study, it was verified for the first time that GS can activate mouse serotonin receptor 2a (mHtr2a) and 2b (mHtr2b), but not 2c (mHtr2c) that are expressed in HEK293T cells. Specifically, effects of GS on all mouse serotonin receptor 2 subfamily were evaluated by calcium imaging techniques...
February 17, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28208010/circulating-plasma-and-exosomal-micrornas-as-indicators-of-drug-induced-organ-injury-in-rodent-models
#15
Young-Eun Cho, Sang-Hyun Kim, Byung-Heon Lee, Moon-Chang Baek
This study was performed to evaluate whether microRNAs (miRNAs) in circulating exosomes may serve as biomarkers of drug-induced liver, kidney, or muscle-injury. Quantitative PCR analyses were performed to measure the amounts of liver-specific miRNAs (miR-122, miR-192, and miR-155), kidney-specific miR-146a, or muscle-specific miR-206 in plasma and exosomes from mice treated with liver, kidney or muscle toxicants. The levels of liver-specific miRNAs in circulating plasma and exosomes were elevated in acetaminophen-induced liver injury and returned to basal levels by treatment with antioxidant N-acetyl-cysteine...
February 17, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28190320/nuclear-receptor-ppar%C3%AE-agonist-wy-14-643-ameliorates-hepatic-cell-death-in-hepatic-ikk%C3%AE-deficient-mice
#16
Taehyeong Kim, Lilik Duwi Wahyudi, Frank J Gonzalez, Jung-Hwan Kim
Inhibitor of nuclear factor kappa-B kinase beta (IKKβ) plays a critical role in cell proliferation and inflammation in various cells by activating NF-κB signaling. However, the interrelationship between Peroxisome proliferator-activated receptor α (PPARα) and IKKβ in cell proliferation is not clear. In this study, we investigated the possible role of PPARα in the hepatic cell death in the absence of IKKβ gene using liver-specific Ikkb-null (Ikkb(F/F-AlbCre)) mice. To examine the function of PPARα activation in hepatic cell death, wild-type (Ikkb(F/F)) and Ikkb(F/F-AlbCre) mice were treated with PPARα agonist Wy-14,643 (0...
February 13, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28190319/lncrna-meg3-regulates-imatinib-resistance-in-chronic-myeloid-leukemia-via-suppressing-microrna-21
#17
Xiangyu Zhou, Ping Yuan, Qi Liu, Zhiqiang Liu
Imatinib resistance has become a major clinical problem for chronic myeloid leukemia. The aim of the present study was to investigate the involvement of MEG3, a lncRNA, in imatinib resistance and demonstrate its underlying mechanisms. RNAs were extracted from CML patients' peripheral blood cells and human leukemic K562 cells, and the expression of MEG3 was measured by RT-qPCR. Cell proliferation and cell apoptosis were evaluated. Western blotting was used to measure the protein expression of several multidrug resistant transporters...
February 13, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28190318/sedative-effect-of-sophora-flavescens-and-matrine
#18
Hyun-Ju Lee, Sun-Young Lee, Daehyuk Jang, Sun-Yong Chung, Insop Shim
The present study investigated the sedative effects of Sophora flavescens (SF) and its bioactive compound, matrine through performing locomotor activity test and the electroencephalography (EEG) analysis in the rat. The underlying neural mechanism of their beneficial effects was determined by assessing c-Fos immunoreactivity and serotonin (5-HT) in the brain utilizing immunohistochemical method and enzyme linked immunosorbent assay. The results showed that SF and matrine administration had an effect on normalization of caffeine-induced hyperactivity and promoting a shift toward non-rapid eye movement (NREM) sleep...
February 13, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28190317/potential-for-dependence-on-lisdexamfetamine-in-vivo-and-in-vitro-aspects
#19
Jaesuk Yun, Kwang-Wook Lee, Jang-Hyeon Eom, Young-Hoon Kim, Jisoon Shin, Kyoungmoon Han, Hye-Kyung Park, Hyung Soo Kim, Hye Jin Cha
Although lisdexamfetamine is used as a recreational drug, little research exists regarding its potential for dependence or its precise mechanisms of action. This study aims to evaluate the psychoactivity and dependence profile of lisdexamfetamine using conditioned place preference and self-administration paradigms in rodents. Additionally, biochemical techniques are used to assess alterations in the dopamine levels in striatal synaptosomes following administration of lisdexamfetamine. Lisdexamfetamine increased both conditioned place preference and self-administration...
February 13, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28190316/4-o-methylhonokiol-protects-hacat-cells-from-tgf-%C3%AE-1-induced-cell-cycle-arrest-by-regulating-of-canonical-and-non-canonical-pathways-of-tgf-%C3%AE-signaling
#20
Sang-Cheol Kim, Jung-Il Kang, Jin-Won Hyun, Ji-Hoon Kang, Young-Sang Koh, Young-Heui Kim, Ki-Ho Kim, Ji-Hee Ko, Eun-Sook Yoo, Hee-Kyoung Kang
4-O-methylhonokiol, a neolignan compound from Magnolia Officinalis, has been reported to have various biological activities including hair growth promoting effect. However, although transforming growth factor-β (TGF-β) signal pathway has an essential role in the regression induction of hair growth, the effect of 4-O-methylhonokiol on the TGF-β signal pathwayhas not yet been elucidated. We thus examined the effect of 4-O-methylhonokiol on TGF-β-induced canonical and noncanonical pathways in HaCaT human keratinocytes...
February 13, 2017: Biomolecules & Therapeutics
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