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Biomolecules & Therapeutics

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https://www.readbyqxmd.com/read/28441795/yji-7-suppresses-ros-production-and-expression-of-inflammatory-mediators-via-modulation-of-p38mapk-and-jnk-signaling-in-raw-264-7-macrophages
#1
Hye Jin Oh, Til Bahadur Thapa Magar, Nirmala Tilija Pun, Yunji Lee, Eun Hye Kim, Eung-Seok Lee, Pil-Hoon Park
Chalcone, (2E)-1,3-Diphenylprop-2-en-1-one, and its synthetic derivatives are known to possess anti-oxidative and anti-inflammatory properties. In the present study, we prepared a novel synthetic chalcone compound, (E)-1-(4-hydroxyphenyl)-3-(2-(trifluoromethoxy)phenyl)prop-2-en-1-one name (YJI-7), and investigated its inhibitory effects on endotoxin-stimulated production of reactive oxygen species (ROS) and expression of inflammatory mediators in macrophages. We demonstrated that treatment of RAW 264.7 macrophages with YJI-7 significantly suppressed lipopolysaccharide (LPS)-stimulated ROS production...
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/28449555/capsanthin-inhibits-both-adipogenesis-in-3t3-l1-preadipocytes-and-weight-gain-in-high-fat-diet-induced-obese-mice
#11
Sung Jun Jo, Jeung Won Kim, Hye Ok Choi, Jung Hwan Kim, Hyung Joong Kim, Sun Hee Woo, Byung Hoon Han
Adipogenesis in murine preadipocyte 3T3L-1 has been used as a model system to study anti-obese bioactive molecules. During adipogenesis in 3T3-L1 preadipocytes, we found that capsanthin inhibited adipogenesis (IC₅₀; 2.5 μM) and also showed lipolytic activity in differentiated adipocytes from the preadipocytes (ED₅₀; 872 nM). We identified that the pharmacological activity of capsanthin on adipogenesis in 3T3-L1 was mainly due to its adrenoceptor-β₂-agonistic activity. In high-fat diet animal model study, capsanthin significantly enhanced spontaneous locomotive activities together with progressive weight-loss...
May 1, 2017: Biomolecules & Therapeutics
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
#12
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...
May 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28173642/a-novel-urotensin-ii-receptor-antagonist-kr-36996-inhibits-smooth-muscle-proliferation-through-erk-ros-pathway
#13
Tae-Ho Kim, Dong Gil Lee, Young-Ae Kim, Byung Ho Lee, Kyu Yang Yi, Yi-Sook Jung
Urotensin II (UII) is a mitogenic and hypertrophic agent that can induce the proliferation of vascular cells. UII inhibition has been considered as beneficial strategy for atherosclerosis and restenosis. However, currently there is no therapeutics clinically available for atherosclerosis or restenosis. In this study, we evaluated the effects of a newly synthesized UII receptor (UT) antagonist, KR- 36996, on the proliferation of SMCs in vitro and neointima formation in vivo in comparison with GSK-1440115, a known potent UT antagonist...
May 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28173639/bosentan-and-rifampin-interactions-modulate-influx-transporter-and-cytochrome-p450-expression-and-activities-in-primary-human-hepatocytes
#14
Kyoung-Moon Han, Sun-Young Ahn, Hyewon Seo, Jaesuk Yun, Hye Jin Cha, Ji-Soon Shin, Young-Hoon Kim, Hyungsoo Kim, Hye-Kyung Park, Yong-Moon Lee
The incidence of polypharmacy-which can result in drug-drug interactions-has increased in recent years. Drug-metabolizing enzymes and drug transporters are important polypharmacy modulators. In this study, the effects of bosentan and rifampin on the expression and activities of organic anion-transporting peptide (OATP) and cytochrome P450 (CYP450) 2C9 and CYP3A4 were investigated in vitro. HEK293 cells and primary human hepatocytes overexpressing the target genes were treated with bosentan and various concentrations of rifampin, which decreased the uptake activities of OATP transporters in a dose-dependent manner...
May 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/27956717/molecular-signature-that-determines-the-acute-tolerance-of-g-protein-coupled-receptors
#15
Chengchun Min, Xiaohan Zhang, Mei Zheng, Ningning Sun, Srijan Acharya, Xiaowei Zhang, Kyeong-Man Kim
Desensitization and acute tolerance are terms used to describe the attenuation of receptor responsiveness by prolonged or intermittent exposure to an agonist. Unlike desensitization of G protein-coupled receptors (GPCRs), which is commonly explained by steric hindrance caused by the β-arrestins that are translocated to the activated receptors, molecular mechanisms involved in the acute tolerance of GPCRs remain unclear. Our studies with several GPCRs and related mutants showed that the acute tolerance of GPCRs could occur independently of agonist-induced β-arrestin translocation...
May 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/27956715/intravenous-administration-of-substance-p-attenuates-mechanical-allodynia-following-nerve-injury-by-regulating-neuropathic-pain-related-factors
#16
Eunkyung Chung, Tae Gyoon Yoon, Sumin Kim, Moonkyu Kang, Hyun Jeong Kim, Youngsook Son
This study aimed to investigate the analgesic effect of substance P (SP) in an animal model of neuropathic pain. An experimental model of neuropathic pain, the chronic constriction injury (CCI) model, was established using ICR mice. An intravenous (i.v.) injection of SP (1 nmole/kg) was administered to the mice to examine the analgesic effects of systemic SP on neuropathic pain. Behavioral testing and immunostaining was performed following treatment of the CCI model with SP. SP attenuated mechanical allodynia in a time-dependent manner, beginning at 1 h following administration, peaking at 1 day post-injection, and decaying by 3 days post-injection...
May 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/27956712/induction-of-integrin-signaling-by-steroid-sulfatase-in-human-cervical-cancer-cells
#17
Dong-Jin Ye, Yeo-Jung Kwon, Sangyun Shin, Hyoung-Seok Baek, Dong-Won Shin, Young-Jin Chun
Steroid sulfatase (STS) is an enzyme responsible for the hydrolysis of aryl and alkyl sulfates. STS plays a pivotal role in the regulation of estrogens and androgens that promote the growth of hormone-dependent tumors, such as those of breast or prostate cancer. However, the molecular function of STS in tumor growth is still not clear. To elucidate the role of STS in cancer cell proliferation, we investigated whether STS is able to regulate the integrin signaling pathway. We found that overexpression of STS in HeLa cells increases the protein and mRNA levels of integrin β1 and fibronectin, a ligand of integrin α5β1...
May 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/27871158/platelet-shape-changes-and-cytoskeleton-dynamics-as-novel-therapeutic-targets-for-anti-thrombotic-drugs
#18
REVIEW
Eun-Kyung Shin, Hanseul Park, Ji-Yoon Noh, Kyung-Min Lim, Jin-Ho Chung
Platelets play an essential role in hemostasis through aggregation and adhesion to vascular injury sites but their unnecessary activation can often lead to thrombotic diseases. Upon exposure to physical or biochemical stimuli, remarkable platelet shape changes precede aggregation or adhesion. Platelets shape changes facilitate the formation and adhesion of platelet aggregates, but are readily reversible in contrast to the irrevocable characteristics of aggregation and adhesion. In this dynamic phenomenon, complex molecular signaling pathways and a host of diverse cytoskeleton proteins are involved...
May 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/27871157/synthetic-cannabinoid-induced-immunosuppression-augments-cerebellar-dysfunction-in-tetanus-toxin-treated-mice
#19
Jaesuk Yun, Sun Mi Gu, Tac-Hyung Lee, Yun Jeong Song, Seonhwa Seong, Young-Hoon Kim, Hye Jin Cha, Kyoung Moon Han, Jisoon Shin, Hokyung Oh, Kikyung Jung, Chiyoung Ahn, Hye-Kyung Park, Hyung Soo Kim
Synthetic cannabinoids are one of most abused new psychoactive substances. The recreational use of abused drug has aroused serious concerns about the consequences of these drugs on infection. However, the effects of synthetic cannabinoid on resistance to tetanus toxin are not fully understood yet. In the present study, we aimed to determine if the administration of synthetic cannabinoids increase the susceptibility to tetanus toxin-induced motor behavioral deficit and functional changes in cerebellar neurons in mice...
May 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/27871156/kahweol-from-coffee-induces-apoptosis-by-upregulating-activating-transcription-factor-3-in-human-colorectal-cancer-cells
#20
Gwang Hun Park, Hun Min Song, Jin Boo Jeong
Kahweol as a coffee-specific diterpene has been reported to induce apoptosis in human cancer cells. Although some molecular targets for kahweol-mediated apoptosis have been elucidated, the further mechanism for apoptotic effect of kahweol is not known. Activating transcription factor 3 (ATF3) has been reported to be associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which kahweol stimulates ATF3 expression and apoptosis in human colorectal cancer cells...
May 1, 2017: Biomolecules & Therapeutics
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