Exploring Novel Cocrystalline Forms of Oxyresveratrol to Enhance Aqueous Solubility and Permeability across a Cell Monolayer.
Abstract Oxyresveratrol (ORV) is a naturally extracted compound with many pharmacological activities. However, information about the crystalline form is not known when considering the development of a form for oral dosage. Cocrystal engineering offers drug molecular understanding and drug solubility improvements. Thus, we attempted cocrystallization of ORV using 10 carboxylic acids as a coformer at a 1:1 M ratio. Each combination was processed with liquid-assisted grinding, solvent evaporation and a slurry method, then characterized by powder X-ray powder diffraction (PXRD), conventional and low-frequency R...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Suzuki Y, Muangnoi C, Thaweesest W, Teerawonganan P, Ratnatilaka Na Bhuket P, Titapiwatanakun V, Yoshimura-Fujii M, Sritularak B, Likhitwitayawuid K, Rojsitthisak P, Fukami T Tags: Biol Pharm Bull Source Type: research

Design, Synthesis and Biological Evaluation of 4-Aryl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one Derivatives as a PI3K α Inhibitor.
Design, Synthesis and Biological Evaluation of 4-Aryl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one Derivatives as a PI3Kα Inhibitor. Biol Pharm Bull. 2019;42(6):1013-1018 Authors: Hu S, Zhao Z, Ni Y, Xin H, Yan H, Song X Abstract A novel series of 4-aryl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one derivatives were designed as a phosphoinositide 3-kinase α (PI3Kα) inhibitor by scaffold hopping. The target compounds, characterized by 1H-NMR, 13C-NMR and high resolution (HR)-MS, were synthesized from diethyl malonate and ethyl chloroacetate by nucleophilic substitution, ring-closure, c...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Hu S, Zhao Z, Ni Y, Xin H, Yan H, Song X Tags: Biol Pharm Bull Source Type: research

A Photo-Activatable Peptide Mimicking Functions of Apolipoprotein A-I.
In this study, we developed a photo-activatable peptide, 2F*, which is an 18 amino acid peptide mimicking apoA-I bearing an internal photocleavable caging group that is designed to assume an α-helical structure in response to a light stimulus and trigger efflux of cholesterol from cells. Without light irradiation, 2F* peptide showed a low tendency for the formation of α-helices, and therefore did not associate with lipids and failed to induce efflux of cholesterol. In addition, 2F* did not cause hemolysis under our experimental condition. Mass spectrometry indicated that, after light exposure, the caging group ...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Kawahara H, Miyashita N, Tachibana K, Tsuda Y, Morimoto K, Tsuji K, Shigenaga A, Otaka A, Ishida T, Okuhira K Tags: Biol Pharm Bull Source Type: research

Co-administration of Magnesium Oxide Reduces the Serum Concentration of Hydrophobic Basic Drugs in Patients Treated with Antipsychotic Drugs.
Abstract Magnesium oxide (MgO) is a widely used laxative. Because many antipsychotic drugs are lipophilic-basic-compounds, their solubility decreases with increasing pH and changes markedly as the pH of the solution approaches their pKa. It is highly important to clarify the effect of co-administration of MgO on the serum drug concentration for effective, safe, and appropriate medication therapy. However, the relationship between MgO administration and the serum concentration of antipsychotic drugs in patients with schizophrenia has not been reported. Therefore, in the present study, we investigated the effect of ...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Yoshida H, Takahashi M, Honda M, Amayasu H, Ando M Tags: Biol Pharm Bull Source Type: research

The Effective Allergenic Reactivity of House Dust Mite Sublingual Immunotherapy Tablets Is Determined by Tablet Formulation.
Abstract House dust mite (HDM) sublingual immunotherapy (SLIT) in the form of SLIT-tablets is now an established treatment option for HDM allergy and HDM-induced allergic asthma. In SLIT-tablet immunotherapy allergen extracts are formulated as dry tablets and administered under the tongue where it must be solubilized in saliva in order to be able to interact with the immune system of the sublingual mucosa. Solubilization of the extract must occur within a short time span of about one minute after administration, determined by the sublingual holding time recommended by the manufacturer. Currently, two types of HDM ...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Kito H, Du W, Nakazawa H, Lund K, Ohashi-Doi K Tags: Biol Pharm Bull Source Type: research

A Redox-Inactive Derivative of Tocotrienol Suppresses Tumor Growth of Mesothelioma Cells in a Xenograft Model.
In this study, we compared the plasma concentrations of T3E to that of T3 using mice to clarify differences in pharmacokinetics. Blood was sequentially collected after oral administration of T3 or T3E, and plasma concentrations were analyzed by HPLC. The area under the plasma T3 and T3E concentration-time curve from 0 to 24 h (AUC0-24 h) of T3E was two times higher than that of T3. In addition, we evaluated the effect of T3E oral administration on tumor growth using a xenograft model of mice that were transplanted with human MM cells (H2052 cell line). Tumor volume was significantly reduced without body weigh...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Sato A, Arai T, Fusegi M, Ando A, Yano T Tags: Biol Pharm Bull Source Type: research

Functional CLOCK Is Not Essentially Associated with Metabolic Disruption Caused by Sleep Phase Feeding in Mice.
Abstract Consuming food at uncommon times during the day might be associated with obesity in experimental animals and humans. We previously reported that mice become obese and their metabolism becomes disrupted when they consume food during the daytime (sleep phase feeding; SPF), but not during the nighttime (active phase feeding; APF). The goal of the present study was to clarify whether the molecular circadian clock is associated with the mechanisms that underly the metabolic disorders in mice brought about by SPF. We compared the effects of dominant negative Clock gene mutation on metabolic disruption and obesi...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Oishi K, Okauchi H Tags: Biol Pharm Bull Source Type: research

Attenuation of Macrophage Migration Inhibitory Factor-Stimulated Signaling via S-Nitrosylation.
Abstract Nitric oxide (NO) is a key signaling molecule that has various effects via S-nitrosylation, a reversible post-translational modification that affects the enzymatic activity, localization, and metabolism of target proteins. As chronic nitrosative stress correlates with neurodegeneration, the targets have received focused attention. Macrophage migration inhibitory factor (MIF) plays a pivotal role in the induction of gene expression to control inflammatory responses. MIF acts as a ligand for CD74 receptor and activates the Src-p38 mitogen-activated protein kinase (MAPK) cascade. MIF also elevates the expres...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Nakahara K, Fujikawa K, Hiraoka H, Miyazaki I, Asanuma M, Ito A, Takasugi N, Uehara T Tags: Biol Pharm Bull Source Type: research

Effect of Equol on Vasocontractions in Rat Carotid Arteries Treated with High Insulin.
This study investigated whether equol was beneficial for vascular function under high insulin conditions. Using organ culture techniques, rat carotid arteries were treated for 23 ± 1 h with a vehicle, high insulin (100 nM), or equol (100 µM) plus high insulin (100 nM). Vascular isometric forces were measured by the organ bath technique. In each endothelium-intact ring, the contractions induced by high-K+, noradrenaline, or by serotonin (5-HT) were similar for the vehicle, insulin, and equol + insulin treatments. Contractions induced by a selective 5-HT2A ...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Matsumoto T, Takayanagi K, Kobayashi S, Kojima M, Taguchi K, Kobayashi T Tags: Biol Pharm Bull Source Type: research

Abnormal Amino Acid Profiles of Blood and Cerebrospinal Fluid from Cystathionine β-Synthase-Deficient Mice, an Animal Model of Homocystinuria.
Abnormal Amino Acid Profiles of Blood and Cerebrospinal Fluid from Cystathionine β-Synthase-Deficient Mice, an Animal Model of Homocystinuria. Biol Pharm Bull. 2019;42(6):1054-1057 Authors: Akahoshi N, Yokoyama A, Nagata T, Miura A, Kamata S, Ishii I Abstract Mental retardation is the most common feature among inborn errors of amino acid metabolism. Patients with homocystinuria/homocysteinemia caused by cystathionine β-synthase (CBS) deficiency suffer from thromboembolism and mental retardation from early ages; therefore, detection by newborn screening is performed. Furthermore, elevated lev...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Akahoshi N, Yokoyama A, Nagata T, Miura A, Kamata S, Ishii I Tags: Biol Pharm Bull Source Type: research

Role of Connexins in Chronic Pain and Their Potential as Therapeutic Targets for Next-Generation Analgesics.
Abstract Chronic pain, including inflammatory, neuropathic pain, is a serious clinical issue. There are increasing numbers of patients with chronic pain due to the growing number of elderly and it is estimated that about 25% of the global population will develop chronic pain. Chronic pain patients are refractory to medications used to treat acute pain such as opioids and non-steroidal anti-inflammatory drugs. Furthermore, the complexity and diversity of chronic pain mechanisms hinder the development of new analgesics. Thus, a better understanding of the mechanism of chronic pain is needed, which would facilitate t...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Morioka N, Nakamura Y, Zhang FF, Hisaoka-Nakashima K, Nakata Y Tags: Biol Pharm Bull Source Type: research

NMR Characterization of Conformational Dynamics and Molecular Assemblies of Proteins.
Abstract Dynamic conformational transitions and molecular assemblies are essential properties of proteins, and relevant to their biological and pathological functions. Neurodegenerative diseases are known to be caused by abnormal, toxic assemblies of related proteins, e.g., amyloid β (Aβ) in Alzheimer's disease. Growing evidence indicates that the aggregation of various amyloidogenic proteins, including Aβ, can be highly enhanced at glycolipid membranes, suggesting that dynamic glycolipid-dependent conformational changes of proteins constitute crucial steps for their subsequent pathogenic amyloid fi...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Yagi-Utsumi M Tags: Biol Pharm Bull Source Type: research

The Design, Synthesis and Preliminary Pharmacokinetic Evaluation of d3-Poziotinib Hydrochloride.
Abstract To establish a synthetic route to d3-poziotinib hydrochloride. Treatment of 4-chloro-7-hydroxyquinazolin-6-yl pivalate (1) with d3-methyliodide afforded the etherization product, which reacted with 3,4-dichloro-2-fluoroaniline to generate the key intermediate d3-4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yl pivalate (3). Followed the de-protection reaction, the nucleophilic substitution (SN2) reaction with tert-butyl 4-(tosyloxy)piperidine-1-carboxylate (TSP), and the de-protection reaction of t-butoxycarbonyl (Boc) group, and the amide formation reaction with acrylyl chloride, d3-poziotin...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Ma S, Wang L, Ouyang B, Bai X, Ji Q, Yao L Tags: Biol Pharm Bull Source Type: research

Protein Tyrosine Phosphatase Inhibitor, Orthovanadate, Induces Contraction via Rho Kinase Activation in Mouse Thoracic Aortas.
Abstract Orthovanadate (OVA), a protein tyrosine phosphatase inhibitor, induces contraction in endothelium-denuded mouse thoracic aortas. OVA-induced contraction was significantly (vs. control rings) suppressed by Rho kinase (Y-27632, 10 µM), extracellular signal-regulated kinase 1 and 2 (Erk1/2, FR180204, 10 µM), Erk1/2 kinase (MEK, PD98059, 10 µM), epidermal growth factor receptor (EGFR, AG1478, 10 µM), and Src inhibitors, and was partially suppressed by c-Jun N-terminal kinase (JNK, AS601245, 10 µM) and p38 (SB203580, 10 µM) inhibitor...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Terada Y, Higashi N, Hidaka Y, Isomoto Y, Yayama K Tags: Biol Pharm Bull Source Type: research

Sac1 Phosphoinositide Phosphatase Regulates Foam Cell Formation by Modulating SR-A Expression in Macrophages.
Abstract Macrophages endocytose modified low-density lipoproteins (LDL) vigorously via scavenger receptor A (SR-A) to become foam cells. In the present study, we found that Sac1, a member of the Sac family of phosphoinositide phosphatases, increases the protein level of SR-A and upregulates foam cell formation. Mouse macrophages (RAW264.7) were transfected with short hairpin RNAs (shRNAs) against Sac1. Sac1 knockdown decreased cell surface SR-A levels and impaired acetylated LDL-induced foam cell formation. Transfection of Sac1-knockdown cells with shRNA-resistant flag-Sac1 effectively rescued the expression of SR...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Nigorikawa K, Matsumura T, Sakamoto H, Morioka S, Kofuji S, Takasuga S, Hazeki K Tags: Biol Pharm Bull Source Type: research

Effects of Zoledronate on Local and Systemic Production of IL-1 β, IL-18, and TNF-α in Mice and Augmentation by Lipopolysaccharide.
Effects of Zoledronate on Local and Systemic Production of IL-1β, IL-18, and TNF-α in Mice and Augmentation by Lipopolysaccharide. Biol Pharm Bull. 2019;42(6):929-936 Authors: Funayama H, Tashima I, Okada S, Ogawa T, Yagi H, Tada H, Wakita R, Asada Y, Endo Y Abstract Bisphosphonates (BPs) containing nitrogen (N-BPs) exhibit far stronger anti-bone-resorptive effects than non-N-BPs. However, repeated administration of N-BPs causes osteonecrosis selectively in jawbones. As BPs accumulate in large amounts within inflamed bones, any N-BP released from the pool accumulated within jawbones might d...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Funayama H, Tashima I, Okada S, Ogawa T, Yagi H, Tada H, Wakita R, Asada Y, Endo Y Tags: Biol Pharm Bull Source Type: research

Stereoisomer-Specific Induction of G2/M Phase Arrest and Apoptosis by 9-(E,Z)-Hydroxyoctadecadienoic Acid in Mouse Lymphoma Cells.
In conclusion, 9-(E,Z)-HODE specifically induced G2/M phase arrest and apoptosis, and the decrease of NEDD8 expression might be involved in this effect. PMID: 31155590 [PubMed - in process] (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Kodaka A, Hayakawa Y, AlSayegh RJ, Yasuhara T, Tomoda H, Oku T, Dan S, Tsuiji M, Tsuji T Tags: Biol Pharm Bull Source Type: research

Selective Protein Expression Changes of Leukocyte-Migration-Associated Cluster of Differentiation Antigens at the Blood-Brain Barrier in a Lipopolysaccharide-Induced Systemic Inflammation Mouse Model without Alteration of Transporters, Receptors or Tight Junction-Related Protein.
Abstract Leukocyte migration across the blood-brain barrier (BBB) is an important step in the progression of brain dysfunction in systemic inflammation. The purpose of this study was to identify the key regulatory molecule(s) at the BBB among the cluster of differentiation (CD) antigens involved in leucocyte migration in lipopolysaccharide (LPS)-induced systemic inflammation based on their absolute protein expressions. Here, we identified the absolute expression levels of 17 CD antigens in isolated brain capillaries (Bcap) of LPS-administered mice. Among them, the expression levels of CD54 and CD106 were dramatica...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Sato K, Tachikawa M, Watanabe M, Uchida Y, Terasaki T Tags: Biol Pharm Bull Source Type: research

Ameliorative Effect of High-Dose Vitamin C Administration on Dextran Sulfate Sodium-Induced Colitis Mouse Model.
In this study, we examined the effects of intraperitoneal administration of high-dose vitamin C (4 g/kg) on dextran sodium sulfate (DSS)-induced ulcerative colitis. We prepared a mouse ulcerative colitis model by administering DSS for 7 d along with high-dose vitamin C each day during DSS treatment. Ulcerative colitis induced by DSS was ameliorated by high-dose vitamin C administration. Blood levels of interleukin-6, tumor necrosis factor-α, hydrogen peroxide (H2O2), and iron were elevated in DSS-treated mice but lowered by high-dose vitamin C administration. Contrarily, the levels of H2O2 and iron and ...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Kondo K, Hiramoto K, Yamate Y, Goto K, Sekijima H, Ooi K Tags: Biol Pharm Bull Source Type: research

Adenosine N1-Oxide Exerts Anti-inflammatory Effects through the PI3K/Akt/GSK-3 β Signaling Pathway and Promotes Osteogenic and Adipocyte Differentiation.
Adenosine N1-Oxide Exerts Anti-inflammatory Effects through the PI3K/Akt/GSK-3β Signaling Pathway and Promotes Osteogenic and Adipocyte Differentiation. Biol Pharm Bull. 2019;42(6):968-976 Authors: Ohashi E, Kohno K, Arai N, Harashima A, Ariyasu T, Ushio S Abstract Previously, we reported that adenosine N1-oxide (ANO), which is found in royal jelly, inhibited the secretion of inflammatory mediators by activated macrophages and reduced lethality in lipopolysaccharide (LPS)-induced endotoxin shock. Here, we examined the regulatory mechanisms of ANO on the release of pro-inflammatory cytokines, with...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Ohashi E, Kohno K, Arai N, Harashima A, Ariyasu T, Ushio S Tags: Biol Pharm Bull Source Type: research

Development of a Method That Delivers Drugs to Enveloped Viruses.
In this study, we developed a novel viral-specific drug delivery method. Enveloped viruses, including HCV, expose an anionic phospholipid, phosphatidylserine (PS), on their surface to mediate their binding and entry into cells for infection. To target such exposed PS on HCV, we developed a chimeric recombinant protein containing human IFN and mouse lactadherin (also known as milk fat globule epidermal growth factor 8), which binds with high affinity to PS. The IFN-lactadherin fusion protein showed a high binding affinity toward PS and HCV and consequently blocked viral replication in the infected cells more efficiently tha...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Bahrini I, Hanayama R Tags: Biol Pharm Bull Source Type: research

Selective Cytotoxicity of Staphylococcal α-Hemolysin (α-Toxin) against Human Leukocyte Populations.
Selective Cytotoxicity of Staphylococcal α-Hemolysin (α-Toxin) against Human Leukocyte Populations. Biol Pharm Bull. 2019;42(6):982-988 Authors: Tsuiji M, Shiohara K, Takei Y, Shinohara Y, Nemoto S, Yamaguchi S, Kanto M, Itoh S, Oku T, Miyashita M, Seyama Y, Kurihara M, Tsuji T Abstract Staphylococcus aureus produces a variety of exoproteins that interfere with host immune systems. We attempted to purify cytotoxins against human leukocytic cells from the culture supernatant of S. aureus by a combination of ammonium sulfate precipitation, ion-exchange chromatography on a CM-cellulose column...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Tsuiji M, Shiohara K, Takei Y, Shinohara Y, Nemoto S, Yamaguchi S, Kanto M, Itoh S, Oku T, Miyashita M, Seyama Y, Kurihara M, Tsuji T Tags: Biol Pharm Bull Source Type: research

Cellular Uptake and Release of Intact Lactoferrin and Its Derivatives in an Intestinal Enterocyte Model of Caco-2 Cells.
Abstract An Intact form of lactoferrin (LF) is known to be absorbed from the small intestine and transported into the blood circulation. We reevaluated the cellular uptake and release of LF using an enterocyte model of human small intestinal cells derived from the Caco-2 cell line. In contrast to a previous report, we observed that intact bovine LF was taken up into seven and 21 d-cultured Caco-2 cells and successfully released back into the culture medium, even though the human intestinal LF receptor, intelectin-1, was not immunochemically detectable. Similar observations were made for human LF and its der...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Matsuzaki T, Nakamura M, Nogita T, Sato A Tags: Biol Pharm Bull Source Type: research

Design of a Novel PEGylated Liposomal Vector for Systemic Delivery of siRNA to Solid Tumors.
Abstract A small interfering RNA (siRNA) delivery system using dioleylphosphate-diethylenetriamine conjugate (DOP-DETA)-based liposomes (DL) was assessed for systemic delivery of siRNA to tumors. DL carrying siRNA capable of inducing efficient gene silencing with low doses of siRNA were modified with polyethylene glycol (PEG-DL/siRNA) for systemic injection of siRNA. The biodistribution of DL and siRNA in the PEG-DL/siRNA was studied by using radiolabeled DL and fluorescence-labeled siRNA, respectively. DL in the PEG-DL/siRNA showed a high retention in the plasma, accumulation in the tumor, and low accumulation in...
Source: Biological and Pharmaceutical Bulletin - June 4, 2019 Category: Drugs & Pharmacology Authors: Song F, Sakurai N, Okamoto A, Koide H, Oku N, Dewa T, Asai T Tags: Biol Pharm Bull Source Type: research

Hypoglycemic Effect of Acidic Polysaccharide from Schisandra Chinensis on T2D Rats Induced by High-Fat Diet Combined with STZ.
Abstract Polysaccharide is a key bioactive component of Schisandra chinensis and has significant pharmacological activities. The aim of this study was to evaluate the anti-diabetic effect of acidic polysaccharide from Schisandra chinensis (SCAP). Type 2 diabetic (T2D) rats were developed by giving a high-fat diet (HFD) combined with low-dose streptozotocin (STZ), and administered orally with SCAP (25, 50 mg/kg) for 8 weeks. Fasting blood glucose (FBG), fasting insulin (FINS), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), malon...
Source: Biological and Pharmaceutical Bulletin - June 1, 2019 Category: Drugs & Pharmacology Authors: Du XX, Tao X, Liang S, Che JY, Yang S, Li H, Chen JG, Wang CM Tags: Biol Pharm Bull Source Type: research

Qiliqiangxin attenuates oxidative stress-induced mitochondrion-dependent apoptosis in cardiomyocytes via PI3K/AKT/GSK3 β signaling pathway.
Qiliqiangxin attenuates oxidative stress-induced mitochondrion-dependent apoptosis in cardiomyocytes via PI3K/AKT/GSK3β signaling pathway. Biol Pharm Bull. 2019 May 28;: Authors: Zhao Q, Li H, Chang L, Wei C, Yin Y, Bei H, Wang Z, Liang J, Wu Y Abstract Qiliqiangxin capsule (QLQX) is a well-known traditional Chinese medicine that exhibits cardioprotective effects in heart failure patients. However, it remains unclear whether and by which mechanism QLQX attenuates oxidative stress-induced mitochondria-dependent myocardial apoptosis. In vivo, SD rats received left anterior descending coronary arter...
Source: Biological and Pharmaceutical Bulletin - May 28, 2019 Category: Drugs & Pharmacology Authors: Zhao Q, Li H, Chang L, Wei C, Yin Y, Bei H, Wang Z, Liang J, Wu Y Tags: Biol Pharm Bull Source Type: research

The cell death phenotype of MGC-803 cells inducing with"dextran-magnetic layered double hydroxide-fluorouracil" drug delivery system and fluorouracil.
The cell death phenotype of MGC-803 cells inducing with"dextran-magnetic layered double hydroxide-fluorouracil" drug delivery system and fluorouracil. Biol Pharm Bull. 2019 May 18;: Authors: Pei Q, Wang R, Shu C, Pei X, Li X, Gou G Abstract The purpose of the paper is to study the differences in cell death mechanism of MGC-803 induced by "dextran-magnetic layered double hydroxide-fluorouracil" (DMF) drug delivery system and 5-Fluorouracil (5-Fu), respectively. The inhibitory effect on the proliferation was detected via CCK-8. The morphology of cell death was detected by transmissio...
Source: Biological and Pharmaceutical Bulletin - May 18, 2019 Category: Drugs & Pharmacology Authors: Pei Q, Wang R, Shu C, Pei X, Li X, Gou G Tags: Biol Pharm Bull Source Type: research

Biogenesis and Function of Peroxisomes in Human Disease with a Focus on the ABC Transporter.
Abstract Peroxisomes are indispensable organelles in mammals including humans. They are involved in the β-oxidation of very long chain fatty acids, and the synthesis of ether phospholipids and bile acids. Pre-peroxisomes bud from endoplasmic reticulum and peroxisomal membrane and matrix proteins are imported to the pre-peroxisomes. Then, matured peroxisomes grow by division. Impairment of the biogenesis and function of peroxisomes results in severe diseases. Since I first undertook peroxisome research in Prof. de Duve's laboratory at Rockefeller University in 1985, I have continuously studied peroxisomes for ...
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Imanaka T Tags: Biol Pharm Bull Source Type: research

Maternal Immune Activation in Pregnant Mice Produces Offspring with Altered Hippocampal Ripples.
Abstract Psychiatric disorders, such as schizophrenia and autism spectrum disorder, are associated with sleep disturbances and deficits in memory consolidation; however, the relationship between these symptoms remains unclear. Here, we focused on hippocampal sharp-wave ripples (SWRs), a form of transient high-frequency oscillations that occur during sleep and behavioral immobility and contribute to memory consolidation. We activated the maternal immune system with polyinosinic-polycytidylic acid (poly(I : C)), one of the major pharmacological models of psychiatric disorders, to investigate whether SW...
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Gao M, Orita K, Ikegaya Y Tags: Biol Pharm Bull Source Type: research

Adverse Effects in Skeletal Muscle Following the Medicinal Use of Nicotiana glauca.
Abstract Nicotiana glauca is a cosmopolitan shrub, used in medicine to treat swellings, wounds, sores and cancer. However, its users lack of knowledge of the adverse effects. We seek to evaluate the effects of lipid extracts from N. glauca on myoblasts, identifying the compounds which cause undesirable effects. Myoblasts are important in muscle homeostasis, thus a high death rate of them cause myopathies. We performed an ethanolic extraction from leaves of N. glauca and the extract was successively partitioned with hexane, chloroform and ethyl acetate. The effects of extracts in C2C12 cells were analysed by termin...
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Musso F, Lincor D, Vasconsuelo A, Pronsato L, Faraoni B, Milanesi L Tags: Biol Pharm Bull Source Type: research

Evaluation and Comparison of Daiokanzoto and Lubiprostone for Constipation: A Retrospective Cohort Study.
This study examined the effectiveness, adverse events, and medical economic efficiency of DKT and LPS for constipation. Patients who received DKT (DKT group) and those who received LPS (LPS group) during admission to Ogaki Municipal Hospital between November 2012 and May 2016 were enrolled. Drug efficacy was evaluated based on the median value of bowel movement frequency over 1 week before and after drug administration, and their safety was evaluated by the presence or absence of diarrhea, abdominal pain, nausea, and vomiting. To assess medical economic efficiency, drug costs for constipation per week were calculated. The ...
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Yoshida A, Hirose T, Kuroda A, Mitsuoka M, Shinoda Y, Mori K, Kawachi Y, Tanaka K, Takeda A, Sugiyama T, Yoshimura T Tags: Biol Pharm Bull Source Type: research

Ursolic Acid Inhibits Tumor Growth via Epithelial-to-Mesenchymal Transition in Colorectal Cancer Cells.
Abstract Ursolic acid (UA), a natural pentacyclic triterpenoid, is a promising compound for cancer prevention and therapy. However, its mechanisms of action have not been well elucidated in colorectal cancer cells. Here, using cultured human colon cancer cell lines SW620 and HCT116, this assay demonstrates that UA reduces cell viability, inhibits cell clone formation, and induces caspase-3 mediated apoptosis. Additional experiments show that UA inhibits cell migration and epithelial-mesenchymal transition (EMT), including E-cadherin, Vimentin, Integrin, Twist, and Zeb1 biomakers. These results suggest that UA inhi...
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Wang X, Wang T, Yi F, Duan C, Wanwg Q, He N, Zhu L, Li Q, Deng W Tags: Biol Pharm Bull Source Type: research

Cigarette Smoke Particles-Induced Airway Hyperreactivity in Vivo and in Vitro.
In conclusion, the present study demonstrates that DSP could induce AHR in vivo and in vitro. In addition to this, the upregulation of bradykinin receptors in airway is most likely one of the underlying molecular mechanisms involved. PMID: 31061312 [PubMed - in process] (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Jia M, Zhang Y, Zhang H, Qin Q, Xu CB Tags: Biol Pharm Bull Source Type: research

Analysis of Adverse Reactions Caused by Potentially Inappropriate Prescriptions and Related Medical Costs That Are Avoidable Using the Beers Criteria: The Japanese Version and Guidelines for Medical Treatment and Its Safety in the Elderly 2015.
Abstract We conducted a retrospective study to investigate adverse drug reactions and associated medical costs among elderly individuals that could be avoided if pharmacotherapy was performed in accordance with the Beers Criteria: the Japanese Version (BCJV) and Guidelines for Medical Treatment and Its Safety in the Elderly 2015 (GL2015). Patients aged at least 65 years who were either hospitalized at Gifu Municipal Hospital between October 1 and November 30, 2014 (n = 1236) or had outpatient examinations at Gifu Municipal Hospital on October 1-2, 2014 (n = 980) were included in the stu...
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Tachi T, Kanematsu Y, Aoyama S, Katsuno H, Otsubo M, Ueno A, Sugita I, Yoshida A, Noguchi Y, Yasuda M, Mizui T, Goto C, Teramachi H Tags: Biol Pharm Bull Source Type: research

The Reparative Effect of Dendrobium officinale Protocorms against Photodamage Caused by UV-Irradiation in Hairless Mice.
Abstract Dendrobium officinale protocorms (DOPs) are a specific developmental stage of Dendrobium officinale KIMURA et MIGO, which is used in folk medicine to ease skin issues, such as wrinkles and erythema. The purpose of the current study was to evaluate the effect of DOPs on UV irradiation-induced skin damage in bc_nu hairless mice, using matrixyl as a positive control. Hairless mice were randomly separated into 6 groups (8 mice per group). The normal control group received solvent and was not exposed to UV irradiation, while the model control group received solvent and was exposed to UV irradiation. The positi...
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Mai Y, Niu Z, He W, Lai X, Huang S, Zheng X Tags: Biol Pharm Bull Source Type: research

Noradrenaline-Induced Relaxation of Urinary Bladder Smooth Muscle Is Primarily Triggered through the β3-Adrenoceptor in Rats.
In this study, to determine whether noradrenaline is a ligand of UBSM β3-adrenoceptors, noradrenaline-induced relaxation was analyzed pharmacologically using rat UBSM. We also assessed whether noradrenaline metabolites were ligands in UBSM. In isolated rat urinary bladder tissues, mRNAs for β1-, β2-, and β3-adrenoceptors were detected using RT-PCR. In UBSM preparations contracted with methacholine (3 × 10-5 M), noradrenaline-induced relaxation was not inhibited by the following antagonists: atenolol (10-6 M; selective β1-adrenoceptor antagonist), ICI-118,551 (3&thi...
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Obara K, Suzuki S, Shibata H, Yoneyama N, Hamamatsu S, Yamaki F, Higai K, Tanaka Y Tags: Biol Pharm Bull Source Type: research

MicroRNA-146a-5p Downregulates the Expression of P-Glycoprotein in Rats with Lithium-Pilocarpine-Induced Status Epilepticus.
Abstract Increasing evidence supports that the efflux transporters, especially P-glycoprotein (P-gp), have vital roles on drug resistance in epilepsy. Overexpression of P-gp in the brain could reduce the anti-epileptic drugs (AEDs) concentration in the epileptogenic zone, resulting in drug resistance. Studies have demonstrated that recurrent seizures induce the expression of P-gp and status epilepticus (SE) could upregulate the expression of P-gp, resulting in drug resistance. MicroRNAs (miRNAs), as endogenous regulators, represent small regulatory RNA molecules that have been shown to act as negative regulators o...
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Deng X, Shao Y, Xie Y, Feng Y, Wu M, Wang M, Chen Y Tags: Biol Pharm Bull Source Type: research

Feasibility of Trypsin Digestion as a Sample Preparation for Daptomycin Quantification in Murine Skeletal Muscles.
Abstract It is important to evaluate the amount of daptomycin (DAP) distributed to skeletal muscles to elucidate the mechanisms related to penetration and side effects, such as myopathies. However, no attempt has been made to measure DAP concentrations in skeletal muscles. The study's aim to investigate the feasibility of trypsin digestion, as a muscle sample preparation technique for the determination of DAP in murine skeletal muscle, was evaluated in conjunction with a conventional HPLC-UV analysis. Compared with trypsin digestion, DAP was less recovered from spiked skeletal muscle by the conventional extraction...
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Sakai Y, Murakami E, Kato H, Ohyama K, Esaka Y, Yamamoto T, Hagihara M, Mikamo H, Uno B Tags: Biol Pharm Bull Source Type: research

WRNIP1 Controls the Amount of PrimPol.
Abstract Werner helicase-interacting protein 1 (WRNIP1) was originally identified as a protein that interacts with WRN, the product of the gene responsible for Werner syndrome. Our previous studies suggested that WRNIP1 is implicated in translesion synthesis (TLS), a process in which specialized TLS polymerases replace replicative DNA polymerase and take over DNA synthesis on damaged templates. We proposed that a novel error-free pathway involving DNA polymerase δ and primase-polymerase (PrimPol) functions to synthesize DNA on UV-damaged DNA templates in the absence of WRNIP1 and the TLS polymerase Polη....
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Yoshimura A, Oikawa M, Jinbo H, Hasegawa Y, Enomoto T, Seki M Tags: Biol Pharm Bull Source Type: research

Inhibition Mechanisms of Hepatitis C Virus Infection by Caffeic Acid and Tannic Acid.
Abstract Previously, we reported that coffee extract and its constituents, caffeic acid (CA) and p-coumaric acid, inhibit infection by the hepatitis C virus (HCV). In the present report, we identified another coffee-related compound, tannic acid (TA), which also inhibits HCV infection. We systematically evaluated which steps of the viral lifecycle were affected by CA and TA. TA substantially inhibits HCV RNA replication and egression, while CA does not. The infectivity of the HCV pretreated with CA or TA was almost lost. Cellular attachment of HCV particles and their interaction with apolipoprotein E, which is ess...
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Shirasago Y, Inamori Y, Suzuki T, Tanida I, Suzuki T, Sugiyama K, Wakita T, Hanada K, Fukasawa M Tags: Biol Pharm Bull Source Type: research

Fragility Fractures in Older People in Japan Based on the National Health Insurance Claims Database.
This study provides quantitative data for older patients throughout Japan who, although otherwise relatively healthy, sustained fragility fractures and were hospitalized for them. The National Database of Health Insurance Claims and Specific Health Checkups of Japan was accessed to target patients aged 65 years or older who sustained fractures between May 2013 and September 2014 and were not hospitalized for at least 13 months prior to fracture. We investigated whether the first fracture sustained was fragility related at any of four locations (proximal humerus, distal radius, vertebra, or femoral neck) and whether it nece...
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Iihara N, Ohara E, Bando Y, Yoshida T, Ohara M, Kirino Y Tags: Biol Pharm Bull Source Type: research

Effect of Serum Parathyroid Hormone on Tacrolimus Therapy in Kidney Transplant Patients: A Possible Biomarker for a Tacrolimus Dosage Schedule.
Abstract The mechanism responsible for the decreased extra-renal CYP3A activity in chronic kidney disease (CKD) patients remains unknown. Using an animal model, we previously found that elevated levels of serum intact parathyroid hormone (iPTH) caused a reduced CYP3A activity. This retrospective observational study assessed the relationship between serum iPTH levels and the blood concentration or dosage of tacrolimus, a CYP3A substrate, after oral administration in kidney transplant patients. Thirty-four patients were enrolled who had kidney transplants between April 2014 and March 2016 and who had been administra...
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Hirata K, Watanabe H, Toyoda M, Sugimoto R, Ikegami K, Imafuku T, Matsuzaka K, Ichimizu S, Maeda H, Uekihara S, Jingami S, Maruyama T Tags: Biol Pharm Bull Source Type: research

Discovery of a New STAT3 Inhibitor Acting on the Linker Domain.
Abstract Signal transducer and activator of transcription 3 (STAT3) is a latent transcription factor that contributes to tumor cell growth and survival and is often constitutively active in several types of cancers, which makes it an attractive target for cancer therapy. We identified 5,5'-(pentane-1,5'-diyl)bis(2-methyl-1,4-benzoquinone) (BPMB) as a new STAT3 inhibitor. BPMB inhibited the transcriptional activities of STAT3, despite its inability to reduce the phosphorylation and nuclear translocation of STAT3. BPMB selectively inhibited the proliferation of human breast cancer cell lines with constitutively acti...
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Koseki T, Suehiro N, Masuda Y, Miyoshi N, Muraoka D, Ogo N, Asai A Tags: Biol Pharm Bull Source Type: research

Current Status of Adverse Events Related with Opioid Analgesics in Japan: Assessment Based on Japanese Adverse Drug Event Report Database.
Abstract Opioid analgesics have greatly contributed to the advancement of pain management. However, although opioids have been appropriately used in Japan, they rarely induce serious adverse events, such as respiratory depression. The present study aimed to investigate the temporal changes in the occurrence of opioid-related adverse events and deaths between 2004 and 2017 in Japan using the Japanese Adverse Drug Event Report (JADER) database. We analyzed the following points using data extracted from JADER website: 1) temporal changes in the number and proportion of opioid-related adverse event reports; 2) tempora...
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Suga Y, Uchida M, Suzuki S, Sugawara H, Torigoe K, Futamura A, Uesawa Y, Nakagawa T, Takase H Tags: Biol Pharm Bull Source Type: research

Elevated Expression of Vascular Adhesion Molecule-1, Plasminogen Activator Inhibitor-1, Cyclooxygenase-2, and Thrombomodulin in Human Umbilical Vein Endothelial Cells from Hospitalized Gestational Diabetes Mellitus Patients.
Abstract Protein expression in human umbilical vein endothelial cells (HUVECs) is a useful indicator of maternal condition and the intrauterine environment during pregnancy. Therefore, we investigated protein expression in HUVECs obtained from patients with gestational diabetes mellitus (GDM). HUVECs were prepared from the umbilical cords of GDM patients and controls who underwent planned cesarean section between 2013 and 2014 at Teikyo University Hospital (Tokyo, Japan). There were no differences in blood glucose levels between the GDM patients and controls at admission. However, pre-pregnancy body mass index (BM...
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Takata Y, Nomura K, Ishibashi K, Kido K, Sasamori Y, Hiraike H, Ayabe T, Atsumi GI Tags: Biol Pharm Bull Source Type: research

Preparation of 99mTc-Labeled Mannan-S-Cysteine and Effect of Molecular Size of Mannan on Its Biodistribution.
In this study, we prepared new MMR-targeting probes from yeast mannan (85 kDa), and its bioditribution was investigated. In-vivo evaluation showed that 11.9% of injected dose of 99mTc-labeled mannan-S-cysteines (99mTc-MSCs) was accumulated in popliteal lymph node (the SLN in this model), however, significant level of radioactivity (approximately 80%) was remained in injection site. Interestingly, 99mTc-labeled low molecular weight mannan-S-cysteine mannan (99mTc-LSC) prepared from 50 and 25 kDa mannan showed a decreased specific accumulation of 99mTc-LSC in the popliteal lymph node, while the radioactivity at...
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Hagiwara Y, Higashi K, Hagita H, Uehara T, Ito D, Hanaoka H, Suzuki H, Arano Y, Toida T Tags: Biol Pharm Bull Source Type: research

A I131V Substitution in the Fusion Glycoprotein of Human Parainfluenza Virus Type 1 Enhances Syncytium Formation and Virus Growth.
Abstract Human parainfluenza virus type 1 (hPIV1) has two spike glycoproteins, the hemagglutinin-neuraminidase (HN) glycoprotein as a receptor-binding protein and the fusion (F) glycoprotein as a membrane-fusion protein. The F glycoprotein mediates both membrane fusion between the virus and cell and membrane fusion between cells, called syncytium formation. Wild-type C35 strain (WT) of hPIV1 shows little syncytium formation of infected cells during virus growth. In the present study, we isolated a variant virus (Vr) from the WT that showed enhanced syncytium formation of infected cells by using our previously esta...
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Fukushima K, Takahashi T, Takaguchi M, Ito S, Suzuki C, Agarikuchi T, Kurebayashi Y, Minami A, Suzuki T Tags: Biol Pharm Bull Source Type: research

Anti-proliferative Activities towards Human Brain Glioma U251 Cells and Human Carcinoma Cells (KB3-1) of Some Twin-Drug Type Bivalent C2-Symmetrical Phenylboronic Acid Derivatives.
Abstract Derivatives of C2-symmetrical bivalent phenylboronic acid exhibit several remarkable biological activities such as anti-herpes simplex virus (HSV)-1 and cytotoxic activities against Vero cells and they can reverse the effect of anticancer drugs. Novel symmetrical bivalent molecules were synthesized and their biological activities were evaluated in vitro using a human brain glioma cell line (U251) and a human carcinoma cell line (KB3-1). Among the tested compounds (1a-i), bivalent C2-symmetrical phenylboronic acid derivative 1g showed the highest anti-proliferative activity towards both U251 and KB3-1 cell...
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Furutachi M, Gondo T, Ikeda R, Yoshikawa N, Yokota T, Takeda Y, Yokomizo K, Zhou JR, Kashige N, Miake F, Sumoto K Tags: Biol Pharm Bull Source Type: research

Lactic Acid Promotes Cell Survival by Blocking Autophagy of B16F10 Mouse Melanoma Cells under Glucose Deprivation and Hypoxic Conditions.
In this study, effects of lactic acid on cell death of B16F10 cells under hypoxic and glucose-depleted double stress conditions were investigated. The double stress promoted autophagic cell death earlier than glucose-depleted stress alone. Lactic acid repressed the double stress-induced cell death by inhibiting autophagy. These results suggest that lactic acid serves for cell survival under microenvironmental stress conditions in B16F10 melanoma cells. PMID: 31061328 [PubMed - in process] (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Matsuo T, Daishaku S, Sadzuka Y Tags: Biol Pharm Bull Source Type: research

An Openable Artificial Intestinal Tract System Enables the Evaluation of Drug Absorption in Caco-2 Cells through the Reduction in Thickness of the Unstirred Water Layer.
Abstract In drug absorption and permeability experiments, an unstirred water layer (UWL) is known to cause differences in the estimated permeability of drugs between in vitro and in vivo experiments. Therefore, it is necessary to develop a new method to allow for accurate measurements of in vitro drug absorption through the reduction of the UWL effect. Previously, we have developed an artificial intestinal tract that mimics the tubular structure of the human intestine and enables study of drug absorption under flow conditions. In order to determine whether our artificial intestinal tract has the potential to reduc...
Source: Biological and Pharmaceutical Bulletin - May 8, 2019 Category: Drugs & Pharmacology Authors: Kono Y, Konishi S, Fujita T Tags: Biol Pharm Bull Source Type: research