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Biomolecules & Therapeutics

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https://www.readbyqxmd.com/read/29129047/hepaprotective-effect-of-standardized-ecklonia-stolonifera-formulation-on-ccl%C3%A2-induced-liver-injury-in-sprague-dawley-rats
#1
Jae-Hyuk Byun, Jun Kim, Se-Young Choung
The liver is an essential organ for the detoxification of exogenous xenobiotics, drugs and toxic substances. The incidence rate of non-alcoholic liver injury increases due to dietary habit change and drug use increase. Our previous study demonstrated that Ecklonia stolonifera (ES) formulation has hepatoprotective effect against alcohol-induced liver injury in rat and tacrine-induced hepatotoxicity in HepG2 cells. This present study was designated to elucidate hepatoprotective effects of ES formulation against carbon tetrachloride (CCl₄)-induced liver injury in Sprague Dawley rat...
November 13, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29129046/acebutolol-a-cardioselective-beta-blocker-promotes-glucose-uptake-in-diabetic-model-cells-by-inhibiting-jnk-jip1-interaction
#2
Yi Li, Nan-Young Jung, Jae Cheal Yoo, Yul Kim, Gwan-Su Yi
The phosphorylation of JNK is known to induce insulin resistance in insulin target tissues. The inhibition of JNK-JIP1 interaction, which interferes JNK phosphorylation, becomes a potential target for drug development of type 2 diabetes. To discover the inhibitors of JNK-JIP1 interaction, we screened out 30 candidates from 4320 compound library with In Cell Interaction Trap method. The candidates were further confirmed and narrowed down to five compounds using the FRET method in a model cell. Among those five compounds, Acebutolol showed notable inhibition of JNK phosphorylation and elevation of glucose uptake in diabetic models of adipocyte and liver cell...
November 13, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29129045/development-of-s-methylmethionine-sulfonium-derivatives-and-their-skin-protective-effect-against-ultraviolet-exposure
#3
Won-Serk Kim, Wang-Kyun Kim, Nahyun Choi, Wonhee Suh, Jinu Lee, Dae-Duk Kim, Ikyon Kim, Jong-Hyuk Sung
In a previous study, we have demonstrated that S-methylmethionine sulfonium (SMMS) confers wound-healing and photoprotective effects on the skin, suggesting that SMMS can be used as a cosmetic raw material. However, it has an unpleasant odor. Therefore, in the present study, we synthesized odor-free SMMS derivatives by eliminating dimethyl sulfide, which is the cause of the unpleasant odor and identified two derivatives that exhibited skin-protective effects: one derivative comprised (2S,4S)- and (2R,4S)-2-phenylthiazolidine-4-carboxylic acid and the other comprised (2S,4R)-, (2S,4S)-, (2R,4R)-, and (2R,4S)-2-phenyl-1,3-thiazinane-4-carboxylic acid...
November 13, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28934823/comprehensive-analysis-of-non-synonymous-natural-variants-of-g-protein-coupled-receptors
#4
Hee Ryung Kim, Nguyen Minh Duc, Ka Young Chung
G protein-coupled receptors (GPCRs) are the largest superfamily of transmembrane receptors and have vital signaling functions in various organs. Because of their critical roles in physiology and pathology, GPCRs are the most commonly used therapeutic target. It has been suggested that GPCRs undergo massive genetic variations such as genetic polymorphisms and DNA insertions or deletions. Among these genetic variations, non-synonymous natural variations change the amino acid sequence and could thus alter GPCR functions such as expression, localization, signaling, and ligand binding, which may be involved in disease development and altered responses to GPCR-targeting drugs...
September 19, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28835002/cripto-enhances-proliferation-and-survival-of-mesenchymal-stem-cells-by-up-regulating-jak2-stat3-pathway-in-a-grp78-dependent-manner
#5
SeungPil Yun, Chul Won Yun, Jun Hee Lee, SangMin Kim, Sang Hun Lee
Cripto is a small glycosylphosphatidylinositol-anchored signaling protein that can detach from the anchored membrane and stimulate proliferation, migration, differentiation, vascularization, and angiogenesis. In the present study, we demonstrated that Cripto positively affected proliferation and survival of mesenchymal stem cells (MSCs) without affecting multipotency. Cripto also increased expression of phosphorylated janus kinase 2 (p-JAK2), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), 78 kDa glucose-regulated protein (GRP78), c-Myc, and cyclin D1...
August 25, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29081092/galangin-suppresses-pro-inflammatory-gene-expression-in-polyinosinic-polycytidylic-acid-stimulated-microglial-cells
#6
Min-Ji Choi, Jin-Sun Park, Jung-Eun Park, Han Su Kim, Hee-Sun Kim
Galangin (3,5,7-trihydroxyflavone) is a polyphenolic compound abundant in honey and medicinal herbs, such as Alpinia officinarum. In this study, we investigated the anti-inflammatory effects of galangin under in vitro and in vivo neuroinflammatory conditions caused by polyinosinic-polycytidylic acid (poly(I:C)), a viral mimic dsRNA analog. Galangin suppressed the production of nitric oxide, reactive oxygen species, and pro-inflammatory cytokines in poly(I:C)-stimulated BV2 microglia. On the other hand, galangin enhanced anti-inflammatory interleukin (IL)-10 production...
November 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29081091/rifampicin-alleviates-atopic-dermatitis-like-response-in-vivo-and-in-vitro
#7
Seung Hyun Kim, Ki Man Lee, Geum Seon Lee, Ju-Won Seong, Tae Jin Kang
Atopic dermatitis (AD) is a common inflammatory skin disorder mediated by inflammatory cells, such as macrophages and mast cells. Rifampicin is mainly used for the treatment of tuberculosis. Recently, it was reported that rifampicin has anti-inflammatory and immune-suppressive activities. In this study, we investigated the effect of rifampicin on atopic dermatitis in vivo and in vitro. AD was induced by treatment with 2, 4-dinitrochlorobenzene (DNCB) in NC/Nga mice. A subset of mice was then treated with rifampicin by oral administration...
November 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29081090/sinomenine-an-alkaloid-derived-from-sinomenium-acutum-potentiates-pentobarbital-induced-sleep-behaviors-and-non-rapid-eye-movement-nrem-sleep-in-rodents
#8
Jae Hyeon Yoo, Tae-Woo Ha, Jin Tae Hong, Ki-Wan Oh
Sinomenium acutum has been long used in the preparations of traditional medicine in Japan, China and Korea for the treatment of various disorders including rheumatism, fever, pulmonary diseases and mood disorders. Recently, it was reported that Sinomenium acutum, has sedative and anxiolytic effects mediated by GABA-ergic systems. These experiments were performed to investigate whether sinomenine (SIN), an alkaloid derived from Sinomenium acutum enhances pentobarbital-induced sleep via γ-aminobutyric acid (GABA)-ergic systems, and modulates sleep architecture in mice...
November 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29081089/evaluation-of-the-abuse-potential-of-novel-amphetamine-derivatives-with-modifications-on-the-amine-nbna-and-phenyl-eda-pmea-2-apn-sites
#9
Raly James Perez Custodio, Chrislean Jun Botanas, Seong Shoon Yoon, June Bryan de la Peña, Irene Joy Dela Peña, Mikyung Kim, Taeseon Woo, Joung-Wook Seo, Choon-Gon Jang, Yong Ho Kwon, Nam Yong Kim, Yong Sup Lee, Hee Jin Kim, Jae Hoon Cheong
Recently, there has been a rise in the number of amphetamine derivatives that serve as substitutes for controlled substances (e.g. amphetamine and methamphetamine) on the global illegal drug market. These substances are capable of producing rewarding effects similar to their parent drug. In anticipation of the future rise of new and similar psychoactive substances, we designed and synthesized four novel amphetamine derivatives with N-benzyl, N-benzylamphetamine HCl (NBNA) substituent on the amine region, 1,4-dioxane ring, ethylenedioxy-amphetamine HCl (EDA), methyl, para-methylamphetamine HCl (PMEA), and naphthalene, 2-(aminopropyl) naphthalene HCl (2-APN) substituents on the phenyl site...
November 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29081088/potential-immunotherapeutics-for-immunosuppression-in-sepsis
#10
REVIEW
Jinwook Shin, Mirim Jin
Sepsis is a syndrome characterized by systemic inflammatory responses to a severe infection. Acute hyper-inflammatory reactions in the acute phase of sepsis have been considered as a primary reason for organ dysfunction and mortality, and advances in emergency intervention and improved intensive care management have reduced mortalities in the early phase. However it has been recognized that increased deaths in the late phase still maintain sepsis mortality high worldwide. Patients recovered from early severe illness are unable to control immune system with sepsis-induced immunosuppression such as immunological tolerance, exhaustion and apoptosis, which make them vulnerable to nosocomial and opportunistic infections ultimately leading to threat to life...
November 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28822990/%C3%AE-%C3%AE-mangostins-induce-autophagy-and-show-synergistic-effect-with-gemcitabine-in-pancreatic-cancer-cell-lines
#11
Myoungjae Kim, Young-Won Chin, Eun Joo Lee
Pancreatic cancer is one of the most lethal and aggressive cancers in the world. However, no effective treatment is currently available for pancreatic cancer. The objective of this study was to determine the anti-pancreatic cancer effect of α-mangostin (αM) and γ-mangostin (γM) extracted from the pericarp of Garcinia mangostana L.. Both αM and γM reduced the viability of pancreatic cancer cells MIA PaCa-2 and PANC-1 in a dose-dependent manner. These compounds induced apoptosis by increasing c-PARP and c-Caspase 3 levels...
November 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28605830/sustained-intracellular-acidosis-triggers-the-na%C3%A2-%C2%BA-h%C3%A2-%C2%BA-exchager-1-activation-in-glutamate-excitotoxicity
#12
Bo Kyung Lee, Yi-Sook Jung
The Na⁺/H⁺ exchanger-1 (NHE-1) is a ubiquitously expressed pH-regulatory membrane protein that functions in the brain, heart, and other organs. It is increased by intracellular acidosis through the interaction of intracellular H⁺ with an allosteric modifier site in the transport domain. In the previous study, we reported that glutamate-induced NHE-1 phosphorylation mediated by activation of protein kinase C-β (PKC-β) in cultured neuron cells via extracellular signal-regulated kinases (ERK)/p90 ribosomal s6 kinases (p90RSK) pathway results in NHE-1 activation...
November 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28605829/application-of-metabolomics-to-quality-control-of-natural-product-derived-medicines
#13
REVIEW
Kyung-Min Lee, Jun-Yeong Jeon, Byeong-Ju Lee, Hwanhui Lee, Hyung-Kyoon Choi
Metabolomics has been used as a powerful tool for the analysis and quality assessment of the natural product (NP)-derived medicines. It is increasingly being used in the quality control and standardization of NP-derived medicines because they are composed of hundreds of natural compounds. The most common techniques that are used in metabolomics consist of NMR, GC-MS, and LC-MS in combination with multivariate statistical analyses including principal components analysis (PCA) and partial least squares-discriminant analysis (PLS-DA)...
November 1, 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
#14
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 dose-dependent chromosomal DNA degradation, suggesting that these cells underwent apoptosis. Flow cytometric analysis further confirmed that BA-treated BV-2 cells showed hypodiploid DNA content...
November 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28274095/sphingosylphosphorylcholine-induces-thrombospondin-1-secretion-in-mcf10a-cells-via-erk2
#15
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...
November 1, 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
#16
Keumhan Noh, Ψ Wonku Kang
7-O-Succinyl macrolactin A (SMA) exerts several pharmacological effects including anti-bacterial, anti-inflammation, and anti-cancer 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...
November 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28190317/potential-for-dependence-on-lisdexamfetamine-in-vivo-and-in-vitro-aspects
#17
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...
November 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28173640/tanshinone-iia-protects-endothelial-cells-from-h%C3%A2-o%C3%A2-induced-injuries-via-pxr-activation
#18
Haiyan Zhu, Zhiwu Chen, Zengchun Ma, Hongling Tan, Chengrong Xiao, Xianglin Tang, Boli Zhang, Yuguang Wang, Yue Gao
Tanshinone IIA (Tan IIA) is a pharmacologically active substance extracted from the rhizome of Salvia miltiorrhiza Bunge (also known as the Chinese herb Danshen), and is widely used to treat atherosclerosis. The pregnane X receptor (PXR) is a nuclear receptor that is a key regulator of xenobiotic and endobiotic detoxification. Tan IIA is an efficacious PXR agonist that has a potential protective effect on endothelial injuries induced by xenobiotics and endobiotics via PXR activation. Previously numerous studies have demonstrated the possible effects of Tan IIA on human umbilical vein endothelial cells, but the further mechanism for its exerts the protective effect is not well established...
November 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28835003/regulation-of-pharmacogene-expression-by-microrna-in-the-cancer-genome-atlas-tcga-research-network
#19
Nayoung Han, Yun-Kyoung Song, Gilbert J Burckart, Eunhee Ji, In-Wha Kim, Jung Mi Oh
Individual differences in drug responses are associated with genetic and epigenetic variability of pharmacogene expression. We aimed to identify the relevant miRNAs which regulate pharmacogenes associated with drug responses. The miRNA and mRNA expression profiles derived from data for normal and solid tumor tissues in The Cancer Genome Atlas (TCGA) Research Network. Predicted miRNAs targeted to pharmacogenes were identified using publicly available databases. A total of 95 pharmacogenes were selected from cholangiocarcinoma and colon adenocarcinoma, as well as kidney renal clear cell, liver hepatocellular, and lung squamous cell carcinomas...
September 1, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28822992/low-dose-bisphenol-a-increases-bile-duct-proliferation-in-juvenile-rats-a-possible-evidence-for-risk-of-liver-cancer-in-the-exposed-population
#20
Ji Seong Jeong, Ki Taek Nam, Buhyun Lee, Aryo Dimas Pamungkas, Daeun Song, Minjeong Kim, Wook-Joon Yu, Jinsoo Lee, Sunha Jee, Youngja H Park, Kyung-Min Lim
Increasing concern is being given to the association between risk of cancer and exposure to low-dose bisphenol A (BPA), especially in young-aged population. In this study, we investigated the effects of repeated oral treatment of low to high dose BPA in juvenile Sprague-Dawley rats. Exposing juvenile rats to BPA (0, 0.5, 5, 50, and 250 mg/kg oral gavage) from post-natal day 9 for 90 days resulted in higher food intakes and increased body weights in biphasic dose-effect relationship. Male mammary glands were atrophied at high dose, which coincided with sexual pre-maturation of females...
September 1, 2017: Biomolecules & Therapeutics
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