Factors determining the efficacy of recombinant human thrombomodulin in the treatment of sepsis-induced disseminated intravascular coagulation
Biol Pharm Bull. 2021 Feb 20. doi: 10.1248/bpb.b20-00371. Online ahead of print.ABSTRACTRecombinant human thrombomodulin (rhTM) is an anti-coagulant used to treat disseminated intravascular coagulation (DIC). The efficacy of rhTM in patients with sepsis-induced DIC has been proved in some clinical trials, but the determining factors are not known. The aim of this study was to identify patients for whom rhTM will be effective and the factors that determine rhTM efficacy in alleviating DIC. A single-center, retrospective, observational study was conducted in patients with sepsis-induced DIC who were treated with rhTM in Okay...
Source: Biological and Pharmaceutical Bulletin - February 22, 2021 Category: Drugs & Pharmacology Authors: Kazumasa Kotake Takashi Hongo Akihiro Tahira Nana Niimi Ikue Haisa Yasuhiro Kawakami Source Type: research

Rivaroxaban Attenuates Right Ventricular Remodeling in Rats with Pulmonary Arterial Hypertension
The objectives of this study are to investigate effects of rivaroxaban on RV remodeling in a rat model of PAH, created with Sugen5416 and chronic hypoxia, and the in vitro effects of rivaroxaban on human cardiac microvascular endothelial cells (HCMECs). To create the PAH model, male Sprague-Dawley rats were subcutaneously injected with Sugen5416 (20 mg/kg) and exposed to 2 weeks of hypoxia (10% O2), followed by 2 weeks of exposure to normoxia. The animals were then divided into 2 groups with or without administration of rivaroxaban (1.2 mg/kg/day) for a further 4 weeks. HCMECs were cultured under hypoxic conditions (37°...
Source: Biological and Pharmaceutical Bulletin - February 22, 2021 Category: Drugs & Pharmacology Authors: Hideki Imano Ryuji Kato Atsuo Nomura Maki Tamura Yudai Yamaguchi Yoshio Ijiri Hong Wu Takashi Nakano Yoshikatsu Okada Takehiro Yamaguchi Yasukatsu Izumi Minoru Yoshiyama Michio Asahi Tetsuya Hayashi Source Type: research

Increase in blood pressure by local injection of ketamine into the amygdala in rats
Biol Pharm Bull. 2021 Feb 11. doi: 10.1248/bpb.b20-00881. Online ahead of print.ABSTRACTTo confirm that an increase in blood pressure induced by ketamine is mediated through the central nervous system, we examined the effect of ketamine, applied directly to the amygdala, on blood pressure. Six male Sprague-Dawley rats were used in the study. Under head-restrained and unanesthetized condition, 0.2 μl (5 mg/ml) of ketamine was injected in and around the amygdala at a flow rate of 0.2 μl/min through a glass pipette, and the blood pressure was recorded while monitoring the state of the animals by electroencephalogram and...
Source: Biological and Pharmaceutical Bulletin - February 15, 2021 Category: Drugs & Pharmacology Authors: Issei Morimoto Yoshimasa Koyama Masahiro Murakawa Source Type: research

Increase in blood pressure by local injection of ketamine into the amygdala in rats.
Abstract To confirm that an increase in blood pressure induced by ketamine is mediated through the central nervous system, we examined the effect of ketamine, applied directly to the amygdala, on blood pressure. Six male Sprague-Dawley rats were used in the study. Under head-restrained and unanesthetized condition, 0.2 μl (5 mg/ml) of ketamine was injected in and around the amygdala at a flow rate of 0.2 μl/min through a glass pipette, and the blood pressure was recorded while monitoring the state of the animals by electroencephalogram and electromyogram. After ketamine injection, the injection site was mark...
Source: Biological and Pharmaceutical Bulletin - February 11, 2021 Category: Drugs & Pharmacology Authors: Morimoto I, Koyama Y, Murakawa M Tags: Biol Pharm Bull Source Type: research

Anti-inflammatory Effects of Sanhuang-Siwu-Tang in Lipopolysaccharide-stimulated RAW264.7 Macrophages and BV2 Microglial Cells.
Abstract Sanhuang-Siwu-Tang (SST), composed of seven medicinal herbs, is a well-known herbal formula used for the treatment of gynecologic diseases. To expand the clinical use of SST, we explored the anti-inflammatory or anti-neuroinflammatory effects of SST water extract in lipopolysaccharide-stimulated RAW264.7 macrophages and BV2 microglial cells. According to HPLC analysis, the main components of SST were from Scutellariae Radix, Coptidis Rhizoma, and Paeoniae Radix. SST significantly inhibited pro-inflammatory mediators including lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and prostagland...
Source: Biological and Pharmaceutical Bulletin - February 9, 2021 Category: Drugs & Pharmacology Authors: Li J, Kim KW, Oh H, Kim YC Tags: Biol Pharm Bull Source Type: research

Evaluation of Agonistic Activity of Fluorinated and Nonfluorinated Fentanyl Analogs on μ-Opioid Receptor Using a Cell-Based Assay System.
Evaluation of Agonistic Activity of Fluorinated and Nonfluorinated Fentanyl Analogs on μ-Opioid Receptor Using a Cell-Based Assay System. Biol Pharm Bull. 2021;44(2):159-161 Authors: Kanamori T, Okada Y, Segawa H, Yamamuro T, Kuwayama K, Tsujikawa K, Iwata YT Abstract The agonistic activity of fluorinated and nonfluorinated fentanyl analogs on µ-opioid receptor was investigated using a cell-based assay system. Based on the activity, fentanyl analogs were ranked as follows: fentanyl > isobutyrylfentanyl ≈ butyrylfentanyl ≈ methoxyacetylf...
Source: Biological and Pharmaceutical Bulletin - February 2, 2021 Category: Drugs & Pharmacology Authors: Kanamori T, Okada Y, Segawa H, Yamamuro T, Kuwayama K, Tsujikawa K, Iwata YT Tags: Biol Pharm Bull Source Type: research

Effects of Simulated Weightlessness on Metabolizing Enzymes and Pharmacokinetics of Folic Acid in SD Rats.
Abstract Folic acid (FA) affect human physiology and drug metabolism. Up to now, the effect of microgravity on the pharmacokinetics of FA remains unclear. The pharmacokinetics of FA in Sprague-Dawley (SD) rats are laying a foundation for safe medicine administration of astronauts. Proteins expression of such FA metabolic enzymes as Methyltetrahydrofolate reductase (MTHFR), Cystathionine beta synthase (CBS) and Methionine synthase (MS) in a variety of organs was analyzed with Western-Blot, and mRNA expression was detected by RT-PCR. The plasma concentration-time profile of FA in normal or tail-suspended SD rats was...
Source: Biological and Pharmaceutical Bulletin - February 2, 2021 Category: Drugs & Pharmacology Authors: Zhang Y, Zhao J, Jing J, Zhang R, Zhou X, Gao J, Wang J, Li Y, Liu X, Wang Q Tags: Biol Pharm Bull Source Type: research

Transient Receptor Potential Melastatin 3 Is Functionally Expressed in Oligodendrocyte Precursor Cells and Is Upregulated in Ischemic Demyelinated Lesions.
In conclusion, TRPM3 is functionally expressed in OPCs in vivo and in vitro and is upregulated in inflammatory conditions such as ischemic insults and TNFα treatment, implying that TRPM3 is involved in the regulation of specific behaviors of OPCs in pathological conditions. PMID: 33518671 [PubMed - in process] (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - February 2, 2021 Category: Drugs & Pharmacology Authors: Ohashi K, Shibasaki K, Nakazawa H, Kunimasa R, Nagayasu K, Shirakawa H, Kaneko S Tags: Biol Pharm Bull Source Type: research

Preventive and Therapeutic Efficacy of ONO-4641, a Selective Agonist for Sphingosine 1-Phosphate Receptor 1 and 5, in Preclinical Models of Type 1 Diabetes Mellitus.
The objective of the present study was to explore other potential indications for ONO-4641 based on its immunomodulatory effects. ONO-4641 was tested in non-obese diabetic (NOD) mice, an animal model of spontaneous type 1 diabetes mellitus, an autoimmune disease with unmet medical needs. ONO-4641 at a dose of 0.1 mg/kg prevented the onset of diabetes mellitus in NOD mice. Furthermore, ONO-4641 at doses of 0.03 and 0.1 mg/kg decreased diabetic prevalence in NOD mice after the onset of diabetes mellitus in a dose-dependent manner. Histopathological analysis demonstrated that insulin-positive areas in the islets...
Source: Biological and Pharmaceutical Bulletin - February 2, 2021 Category: Drugs & Pharmacology Authors: Shioya H, Inagaki Y, Hiraizumi K, Hoshino T, Kurata H, Habashita H, Sato K, Nakade S Tags: Biol Pharm Bull Source Type: research

Evaluation of Combinatory Effects of Plasmodium Circumsporozoite Protein and Complement Regulatory Protein Expression of Recombinant Baculovirus Vectors.
In this study, we investigated the combination of CSP and CRPs in a BV system to evaluate transduction efficacy along with complement resistance. To accomplish the combination of CSP and CRPs, we generated insect Sf9 cells stably expressing CRPs, to which CSP type BV was infected. The BVs collected from these infected cells were confirmed to possess both CSP and CRPs in virions. We demonstrated that CSP-CD46-DAF-CD59 type BV, containing both CSP and CD46-DAF-CD59, showed a significant increase in transduction efficacy in human hepatoma HepG2 cells under intact serum exposure compared with control type BV or CSP type BV, re...
Source: Biological and Pharmaceutical Bulletin - February 2, 2021 Category: Drugs & Pharmacology Authors: Kawabata C, Kawai Y, Tamura T Tags: Biol Pharm Bull Source Type: research

Tranexamic Acid Improves the Disrupted Formation of Collagen and Fibrillin-1 Fibers Produced by Fibroblasts Repetitively Irradiated with UVA.
In this study, we examined the potential of TXA as an anti-skin aging agent using repetitively UVA-irradiated fibroblasts as a model for fibroblasts located in chronically sun-exposed dermis. Repetitively UVA-irradiated fibroblasts had higher secretion levels of PGE2. In addition, fibroblasts repetitively irradiated with UVA or treated with PGE2 produced disrupted collagen and fibrillin-1 fibers. Treatment with TXA improved the formation of both types of fibers by repetitively UVA-irradiated fibroblasts by restoring the expression of fiber-related proteins at the mRNA and protein levels. Thus, these results demonstrate tha...
Source: Biological and Pharmaceutical Bulletin - February 2, 2021 Category: Drugs & Pharmacology Authors: Endo K, Niki Y, Ohashi Y, Masaki H Tags: Biol Pharm Bull Source Type: research

Antiplatelet Effect of Mirtazapine via Co-blocking of the 5-HT2A and α2-Adrenergic Receptors on Platelets.
In this study, we investigated the antiplatelet effect of MTZ in mice via light transmission aggregometry to elucidate the mechanism of MTZ-induced bleeding. The results of the ex vivo study showed that the oral administration of MTZ (20 or 100 mg/kg) significantly suppressed platelet aggregation mediated by the synergic interaction of 5-hydroxytryptamine (5-HT) and adrenaline. Additionally, MTZ significantly suppressed platelet aggregation, mediated by the synergic interaction of ADP and 5-HT or adrenaline. Similar results were obtained in vitro, under the condition of 5-HT- and adrenaline-induced platelet aggregat...
Source: Biological and Pharmaceutical Bulletin - February 2, 2021 Category: Drugs & Pharmacology Authors: Kawano Y, Katsuyama M, Nagata M, Obana M, Nakamatsu S, Mori A, Sakamoto N, Mano Y, Negishi K, Shimada S, Aoyama T Tags: Biol Pharm Bull Source Type: research

Anti-allergic Inflammatory Components from the Leaves of Piper crocatum Ruiz & Pav.
Anti-allergic Inflammatory Components from the Leaves of Piper crocatum Ruiz & Pav. Biol Pharm Bull. 2021;44(2):245-250 Authors: Gong Y, Li HX, Guo RH, Widowati W, Kim YH, Yang SY, Kim YR Abstract Piper crocatum Ruiz & Pav. (P. crocatum), a traditional medicinal plant, has been shown to possess various pharmacological activities, including anticancer activity, antioxidant activity, antibacterial activity, anti-hyperglycemic activity, anti-allergic inflammatory activity and others. To identify the potential anti-allergic inflammatory effective constituents of P. crocatum, 13 single compounds we...
Source: Biological and Pharmaceutical Bulletin - February 2, 2021 Category: Drugs & Pharmacology Authors: Gong Y, Li HX, Guo RH, Widowati W, Kim YH, Yang SY, Kim YR Tags: Biol Pharm Bull Source Type: research

In Vitro and in Vivo Comparative Study of Oral Nanoparticles and Gut Iontophoresis as Oral Delivery Systems for Insulin.
Abstract Multiple daily injections of insulin for diabetes cause many hazards for diabetic patients. Oral noninvasive insulin delivery could be more convenient and less painful than parenteral route. In past decades transdermal iontophoresis had been studied for insulin delivery across the skin with or without chemical permeation enhancers. However, the results of these studies were not efficacious and serum insulin levels were not therapeutically effective. In the present study an advanced technology "gut iontophoresis" for insulin delivery across the gut wall was compared with traditional oral insulin ...
Source: Biological and Pharmaceutical Bulletin - February 2, 2021 Category: Drugs & Pharmacology Authors: Elkhatib MM, Ali AI, Al-Badrawy AS Tags: Biol Pharm Bull Source Type: research

Possible Role of Electrolytes on the Formation of Precipitates during the Infusion of Nafamostat Mesilate in Hemodialysis.
We report herein on an examination of possible factors that could cause this. The effects of electrolytes such as phosphates, citrates or succinates on the formation of precipitates were examined by mixing NFM with aqueous solutions or plasma that contained these electrolytes. The formation of precipitates was observed in all electrolyte solutions when higher concentrations of NFM were mixed at around physiological pH. In the case of plasma, precipitates were observed when solutions containing higher concentrations of NFM were mixed with plasma that contained phosphate and citrate. In addition, the formation of precipitate...
Source: Biological and Pharmaceutical Bulletin - February 2, 2021 Category: Drugs & Pharmacology Authors: Yamasaki K, Nishi K, Tsukigawa K, Taguchi K, Otagiri M, Seo H Tags: Biol Pharm Bull Source Type: research

Neutralization of Acidic Tumor Microenvironment (TME) with Daily Oral Dosing of Sodium Potassium Citrate (K/Na Citrate) Increases Therapeutic Effect of Anti-cancer Agent in Pancreatic Cancer Xenograft Mice Model.
In this study, we showed that daily oral dosing of sodium potassium citrate (K/Na citrate) increased blood HCO3- concentrations, corresponding to increase of HCO3- concentrations and pHs in urine, and neutralized the tumor pHe. Neutralization of acidic TME by alkaline substance like HCO3-, an active metabolite of K/Na citrate, well potentiated the therapeutic effect of anticancer agent TS-1®, an orally active 5-fuluoro-uracil derivative, in Panc-1 pancreatic cancer-xenograft murine model. Neutralization of acidic TME by using an alkaline K/Na citrate is a smart approach for enhancement of the therapeutic effects of ant...
Source: Biological and Pharmaceutical Bulletin - February 2, 2021 Category: Drugs & Pharmacology Authors: Ando H, Eshima K, Ishida T Tags: Biol Pharm Bull Source Type: research

Analgesic Effects of Sokeikakketsuto on Chemotherapy-Induced Mechanical Allodynia and Cold Hyperalgesia in Rats.
In this study, the analgesic effects of SOKT on oxaliplatin-, paclitaxel-, and bortezomib-induced peripheral neuropathy were investigated in rat models. Rats were treated with oxaliplatin (4 mg/kg, intraperitoneally (i.p.), twice a week for four weeks), paclitaxel (4 mg/kg, i.p., twice a week for two weeks), or bortezomib (0.2 mg/kg, i.p., twice a week for two weeks). SOKT (0.3 or 1.0 g/kg) or duloxetine hydrochloride (30 mg/kg, as a positive control) was administered orally after neuropathy developed. Mechanical allodynia and cold hyperalgesia were assessed using the von Frey test and th...
Source: Biological and Pharmaceutical Bulletin - February 2, 2021 Category: Drugs & Pharmacology Authors: Nakamura H, Kawashiri T, Kobayashi D, Uchida M, Egashira N, Shimazoe T Tags: Biol Pharm Bull Source Type: research

Analysis of α-Defensin 5 Secretion in Differentiated Caco-2 Cells: Comparison of Cell Bank Origin.
In conclusion, Caco-2 cells may be a simple model for screening health food components and drugs that affect α-defensin 5 secretion. PMID: 33518681 [PubMed - in process] (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - February 2, 2021 Category: Drugs & Pharmacology Authors: Yasuda G, Kobayashi M, Kubota A, Narumi K, Furugen A, Saito Y, Satoh T, Suzuki N, Iseki K Tags: Biol Pharm Bull Source Type: research

A Pilot Study to Develop a New Method of Assisting Children in Taking Their Medication by Using Immersive Virtual Reality.
Abstract Taking bitter-tasting drugs can be stressful for children who have underdeveloped swallowing skills and do not understand the meaning of medication. Furthermore, the senses of vision and smell are known to majorly influence taste. This pilot study was aimed at determining the effect of visual stimulation by immersive virtual reality (iVR) on taste and the safety of this approach for developing a new method to assist children with taking medication. Ten subjects participated in this study, and their mean (standard deviation (S.D.)) age was 21.8 (0.8) years. The subjects tasted the bitter aqueous solution (...
Source: Biological and Pharmaceutical Bulletin - February 2, 2021 Category: Drugs & Pharmacology Authors: Niki K, Yasui M, Iguchi M, Isono T, Kageyama H, Ueda M Tags: Biol Pharm Bull Source Type: research

Complete Deletion of Slc52a2 Causes Embryonic Lethality in Mice.
Abstract Riboflavin (vitamin B2) plays an important role in cellular growth and function. Riboflavin transporter 2 (RFVT2) is widely expressed in several tissues, especially in the brain and salivary glands, and plays an important role in the tissue disruption of riboflavin. During the last 10 years, mutations in SLC52A2 have been documented in patients with a rare neurological disorder known as Brown-Vialetto-Van Laere syndrome. However, no suitable animal model of this disease has been reported. Here, we aimed to clarify the physiological role of RFVT2 using Slc52a2-mutant mice. The appearance, body weight, and ...
Source: Biological and Pharmaceutical Bulletin - February 2, 2021 Category: Drugs & Pharmacology Authors: Jin C, Matsui Y, Yonezawa A, Imai S, Ogihara T, Itohara K, Nakagawa S, Nakagawa T, Matsubara K Tags: Biol Pharm Bull Source Type: research

Validity of Selection Breeding for High Ephedrine-Alkaloid Content in E. sinica under Different Environments in Japan.
This study aimed to assess the validity of selection breeding on TA content of E. sinica in several locations in Japan. In this experiment, we grew approximately 350 seedlings and divided them randomly into seven groups. Nearly fifty plants were cultivated at each of seven locations. In Ibaraki, Yamanashi, and Shizuoka, average TA content of whole samples satisfied the criteria for Ephedra herb defined in Japanese Pharmacopoeia (7.0 mg/g of dry weight (DW)). Plants with high and intermediate TA content at four locations were selected and transplanted to Ibaraki. There were significant differences in TA content betwe...
Source: Biological and Pharmaceutical Bulletin - February 2, 2021 Category: Drugs & Pharmacology Authors: Hiyama H, Ozawa A, Makino B, Yoshioka Y, Ohsawa R Tags: Biol Pharm Bull Source Type: research

Candidone inhibits migration and invasion, and induces apoptosis in HepG2 cells.
Abstract The aim of the study was to investigate the inhibitory activity of candidone, the active constituent of Derris (D.) indica, on the proliferation, migration, and invasiveness of human hepatoblastoma (HepG2) cells. Cancer cell death was assessed using an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, and apoptosis-associated morphological changes were observed by phase contrast microscopy. Additionally, western blotting was used to study protein expression following treatment with candidone, and transwell migration and invasion assays were used for observing cancer cell migration ...
Source: Biological and Pharmaceutical Bulletin - January 28, 2021 Category: Drugs & Pharmacology Authors: Boonyarat C, Sangchavee K, Plekratoke K, Yenjai C, Reubroycharoen P, Kaewamatawong R, Waiwut P Tags: Biol Pharm Bull Source Type: research

Phosphorylation of Specificity protein 3 is critical for activation of β4-galactosyltransferase 3 gene promoter in SH-SY5Y human neuroblastoma cell line.
This study demonstrates that the phosphorylation of Sp3 plays important roles in the transcriptional activation of the β4GalT3 gene in human neuroblastoma. PMID: 33504757 [PubMed - as supplied by publisher] (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - January 27, 2021 Category: Drugs & Pharmacology Authors: Tange R, Tachibana R, Sato T Tags: Biol Pharm Bull Source Type: research

Characterization of an expanded IL-10-producing-suppressive T cell population associated with immune tolerance.
In conclusion, expanded TIGIT+CD39+GITR+Foxp3-CD4+ T cells shifted from an effector Th1 to IL-10-producing-suppressor T cell phenotype, which may promote an immune-tolerant state. PMID: 33504740 [PubMed - as supplied by publisher] (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - January 26, 2021 Category: Drugs & Pharmacology Authors: Yoshida Y, Mikami N, Nakanishi Y, Saimoto M, Nagaike A, Shimono H, Nakano S, Tsuji T, Kohno T Tags: Biol Pharm Bull Source Type: research

Topical Application of BMS-509744, a Selective Inhibitor of Interleukin-2-inducible T cell Kinase, Ameliorates Imiquimod-induced Skin Inflammation in Mice.
In this study, we investigated the effect of the topically administered selective ITK inhibitor BMS-509744 on imiquimod (IMQ)-induced psoriasis-like skin inflammation in mice. Topically administered BMS-509744 ameliorated IMQ-induced psoriasis-like skin inflammation as shown by decreased skin lesions, epidermal thickening, and cell infiltration into the dermis. These suppressive effects occurred with lower numbers of cluster of differentiation antigen-3+ (CD3+) T cells and T helper subset 17 (Th17)-related cytokine expression in IMQ-treated skin. IMQ-induced upregulation of proinflammatory cytokine expression was also inhi...
Source: Biological and Pharmaceutical Bulletin - January 20, 2021 Category: Drugs & Pharmacology Authors: Otake S, Otsubaki T, Uesato N, Ueda Y, Murayama T, Hayashi M Tags: Biol Pharm Bull Source Type: research

Study on the inhibitory activity and possible mechanism of myriocin on clinically relevant drug-resistant Candida albicans and its biofilms.
CONCLUSION: Myriocin had significant antifungal activity against C. albicans, and the antifungal mechanisms might be cell wall and membrane damage. Myriocin effectively inhibited and eliminated biofilms, and its mechanism may be related to the inhibition of EPS and CSH. PMID: 33441497 [PubMed - as supplied by publisher] (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - January 13, 2021 Category: Drugs & Pharmacology Authors: Yang X, Pei Z, Hu R, Zhang Z, Lou Z, Sun X Tags: Biol Pharm Bull Source Type: research

Physcion induces hemolysis and premature phosphatidylserine externalization in human erythrocytes.
In conclusion, this report shows, for the first time, that PSN is cytotoxic to RBCs by inducing hemolysis and programmed cell death which may limit its success as a chemotherapeutic agent. PMID: 33431739 [PubMed - as supplied by publisher] (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - January 9, 2021 Category: Drugs & Pharmacology Authors: Akiel M, Alsughayyir J, Basudan AM, Alamri HS, Dera A, Barhoumi T, Subayyil AMA, Basmaeil YS, Aldakheel FM, Alakeel R, Ghneim HK, Al-Sheikh YA, Alraey Y, Asiri S, Alfhili MA Tags: Biol Pharm Bull Source Type: research

Design of Functional Nanoparticles for Intractable Disease Therapy.
Abstract Protein affinity reagents are widely used for basic research, diagnostics, and disease therapy. Antibodies and their fragments are known as the most common protein affinity reagents. They specifically and strongly bind to target molecules and inhibit their functions. Thus, antibody drugs have increased in the recent two decades for disease therapy, such as cancer. These strong protein-protein interactions are composed of a nexus of multiple weak interactions. Synthetic polymers that bind to target molecules have been developed by the imitation of protein-protein interactions. These polymers show nanomolar...
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Koide H Tags: Biol Pharm Bull Source Type: research

Functional Alterations of Multidrug Resistance-Associated Proteins 2 and 5, and Breast Cancer Resistance Protein upon Snail-Induced Epithelial-Mesenchymal Transition in HCC827 Cells.
Abstract Our previous report indicated that Snail-induced epithelial-mesenchymal transition (EMT) enhanced P-glycoprotein (P-gp) function and drug resistance to P-gp substrate anticancer drug in a human non-small cell lung cancer (NSCLC) cell line, HCC827. Our objective is to evaluate the changes in the mRNA and protein expression levels and the functions of multidrug resistance-associated protein (MRP) 2, MRP5 and breast cancer resistance protein (BCRP). Snail-expressing HCC827 cells showed increased mRNA levels of Snail and a mesenchymal marker vimentin, and decreased mRNA levels of an epithelial marker E-cadher...
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Yano K, Todokoro I, Kamioka H, Tomono T, Ogihara T Tags: Biol Pharm Bull Source Type: research

Suppression of Hepatic Stellate Cell Death by Toxic Advanced Glycation End-Products.
In this study, we examined the effect of TAGE on the activation of hepatic stellate cells that are involved in liver fibrosis. LX-2 cells treated with transforming growth factor-β1 (TGF-β1) significantly reduced cell viability by apoptosis. However, the decrease in cell viability with TGF-β1 treatment was significantly suppressed by TAGE co-treatment. The levels of α-smooth muscle actin (α-SMA) and platelet-derived growth factor (PDGF)-Rβ and its ligand PDGF-B were increased in LX-2 cells following TGF-β1 treatment, suggesting that these cells were activated; however, these increases we...
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Takino JI, Sato T, Nagamine K, Sakasai-Sakai A, Takeuchi M, Hori T Tags: Biol Pharm Bull Source Type: research

Acute Kidney Injury Impacts on Hypokalemia Associated with Yokukansan Preparation: A Retrospective Observational Study.
Abstract The time course of acute kidney injury and hypokalemia remains unelucidated. We investigated whether altered renal function impacts hypokalemia and clinical predictors for acute kidney injury in patients who used Yokukansan preparation. We performed a secondary analysis of retrospective observational cohort data from adult patients who started Yokukansan preparation. The study was conducted from June 2015 to May 2019 at Tokyo Women's Medical University, Medical Center East. The effect of acute kidney injury (>1.5-fold increase from baseline serum creatinine level) or renal function recovery on hypokale...
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Hirai T, Yamaga R, Kei M, Hosohata K, Itoh T Tags: Biol Pharm Bull Source Type: research

Expression, Purification and Characterization of CAR/NCOA-1 Tethered Protein in E. coli Using Maltose-Binding Protein Fusion Tag and Gelatinized Corn Starch.
Abstract The constitutive active/androstane receptor (CAR) is a nuclear receptor that functions as a xenobiotic sensor, which regulates the expression of enzymes involved in drug metabolism and of efflux transporters. Evaluation of the binding properties between CAR and a drug was assumed to facilitate the prediction of drug-drug interaction, thereby contributing to drug discovery. The purpose of this study is to construct a system for the rapid evaluation of interactions between CAR and drugs. We prepared recombinant CAR protein using the Escherichia coli expression system. Since isolated CAR protein is known to ...
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Kobashigawa Y, Namikawa M, Sekiguchi M, Inada Y, Yamauchi S, Kimoto Y, Okazaki K, Toyota Y, Sato T, Morioka H Tags: Biol Pharm Bull Source Type: research

Lysophosphatidic Acid Augments the Gene Expression and Production of Matrix Metalloproteinases-1 and -3 in Human Synovial Fibroblasts in Vitro.
Abstract Rheumatoid arthritis (RA) is an inflammatory disease with joint dysfunction following cartilage degradation. The level of lysophosphatidic acid (LPA) has been reported to be augmented in human synovial fluid from patients with RA. However, it remains to be elucidated whether LPA participates in cartilage destruction. In the present study, we have demonstrated that the production of promatrix metalloproteinases (proMMPs)-1 and -3 was augmented along with an increase of extracellular signal-regulated kinase (ERK)1/2 phosphorylation through LPA receptor 1 (LPAR1) in human synovial fibroblasts. These results ...
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Mizuno K, Komiya M, Okuyama K, Imada K, Sato T Tags: Biol Pharm Bull Source Type: research

Production of Optically Active Hexahydrocurcumin by Human Intestinal Bacterium in Vitro.
Abstract A hexahydrocurcumin-producing bacterium named 2a1-2b was isolated from human feces. It was observed that the bacterium had more than 99% similarity with Enterococcus avium ATCC14025T according to 16S ribosomal DNA (rDNA) sequence. The strain 2a1-2b produced optically active 5R-hexahydrocurcumin (enantiomeric excess (e.e.) > 95%) from tetrahydrocurcumin but not from curcumin. Our results showed that intestine is an important place for producing hexahydrocurcumin. PMID: 33390541 [PubMed - in process] (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Niwa T, Yokoyama SI, Mochizuki M, Osawa T Tags: Biol Pharm Bull Source Type: research

Human Induced Pluripotent Stem Cell-Based Skin for Assessing Transdermal Drug Permeability and Irritancy.
Abstract To establish a system for assessing drug permeation and irritation of the skin, the permeation of benzoic acid and isosorbide dinitrate, which are listed in the Pharmacopoeia, and the chemical irritation were evaluated using skin generated from human induced pluripotent stem cells (iPSCs). Multilayer structures and cellular markers (keratin 14 and 10, which are in basal and suprabasal epidermal layers) were clearly detected in our iPSC-based skin. Transepidermal water loss (TEWL) decreased after iPSC-derived keratinocytes were cultured on collagen gels from human primary fibroblasts. These results indicat...
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Naito C, Yamaguchi T, Katsumi H, Kimura S, Kamei S, Morishita M, Kawabata K, Yamamoto A Tags: Biol Pharm Bull Source Type: research

Protective Effect of Edaravone against Cationic Lipid-Mediated Oxidative Stress and Apoptosis.
In this study, suppression of the cationic toxicity was evaluated using an ROS scavenger, edaravone, which is a low-molecular-weight antioxidant drug clinically approved for acute-phase cerebral infarction and amyotrophic lateral sclerosis. Cell viability assay in the mouse macrophage-like cell line RAW264 indicated that the concomitant use of edaravone were not able to suppress the cytotoxicity induced by cationic liposomes comprised of monovalent cationic lipid N-(1-[2,3-dioleyloxy]propyl)-N,N,N-trimethylammonium chloride (DOTMA) over a short period of time. Cationic lipids-induced necrosis was assumed to be involved in ...
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Terada T, Kulkarni JA, Huynh A, Tam YYC, Cullis P Tags: Biol Pharm Bull Source Type: research

Different Renal Chronotoxicity of Bromobenzene and Its Intermediate Metabolites in Mice.
Abstract Bromobenzene (BB) is known to pose a serious threat to human health. We previously demonstrated that BB showed chronotoxicity, that is, daily fluctuations in the severity of hepatotoxicity induced in mice. Although BB showed mild nephrotoxicity, a daily fluctuation was not observed in this toxicity. This might be attributed to the fact that BB-induced chronotoxicity is observed only in the liver and not in the kidneys and that the damage caused by BB is prominent in the liver, masking the daily fluctuation in nephrotoxicity. To confirm these two possibilities, we examined the daily fluctuations in nephrot...
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Yoshioka H, Tominaga S, Nishikawa M, Shinohara Y, Nakao M, Yoshikawa M, Maeda T, Miura N Tags: Biol Pharm Bull Source Type: research

Epigallocatechin-3-Gallate Suppresses the Expression of TNF- α-Induced MMP-1 via MAPK/ERK Signaling Pathways in Human Dermal Fibroblasts.
In this study, we evaluated the inhibitory effect of EGCG on MMP-1 gene expression and secretion in tumor necrosis factor-α (TNF-α)-treated human dermal fibroblast cells (Hs68 cells). Pre-treatment with EGCG (10 and 20 µM) suppressed TNF-α-induced MMP-1 expression and secretion. EGCG also reduced the phosphorylation of extracellular signal regulated kinase (ERK) significantly but not that of p38 activation and c-Jun N-terminal kinase (JNK). Besides, EGCG (10 and 20 µM) showed the inhibitory effect on mitogen-activated protein extracellular kinase (MEK) and Src phosphorylation whi...
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Won HR, Lee P, Oh SR, Kim YM Tags: Biol Pharm Bull Source Type: research

Linarin Protects the Kidney against Ischemia/Reperfusion Injury via the Inhibition of Bioactive ETS2/IL-12.
Abstract Ischemia/reperfusion injury (IRI), a participant in acute kidney injury (AKI), can occur as a series of pathological processes such as inflammation. Linarin (LIN) has been widely used for different diseases. To confirm the anti-inflammatory value and relevant mechanism of LIN during IRI, in vivo and vitro models were established. LIN or dissolvent was given, and histologic analysis, quantitative (q)RT-PCR, serum creatinine and blood urea nitrogen testing were used to evaluate kidney injury. Microarray analysis, protein-protein interaction (PPI) analysis and molecular docking were used to identify the targ...
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Chengyu Y, Long Z, Bin Z, Hong L, Xuefei S, Congjuan L, Caixia C, Yan X Tags: Biol Pharm Bull Source Type: research

Juzentaihoto Suppresses Muscle Atrophy and Decreased Motor Function in SAMP8 Mice.
In this study, we evaluated the effect that juzentaihoto hot water extract (JTT) has on skeletal muscle atrophy and motor function by administering it to senescence-accelerated mouse prone-8 (SAMP8). The group treated with JTT displayed larger gastrocnemius muscle (GA) and extensor digitorum longus (EDL) weights, larger GA muscle fiber cross-sectional areas, and motor function decline during rota-rod tests. JTT also increased IGF-1 serum levels, as well as mRNA Sirt1 levels in GA. Serum levels of tumor necrosis factor-α, interleukin-6, and mRNA levels of Atrogin1 and MuRF1 in GA were reduced by JTT. The muscle fiber ...
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Morita Y, Ishida T, Morisawa S, Jobu K, Ou Y, Fujita H, Hanazaki K, Miyamura M Tags: Biol Pharm Bull Source Type: research

The Japanese Herbal (Kampo) Medicine Hochuekkito Attenuates Lung Inflammation in Lung Emphysema.
In conclusion, our study sheds light on the anti-inflammatory effects of TJ-41 in lung emphysema. This establishes its potential as a new anti-inflammatory therapy and a preventive medicine for exacerbations during the long-time maintenance of COPD patients. PMID: 33390548 [PubMed - in process] (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Isago H, Mitani A, Kohno S, Nagoshi S, Ishimori T, Saito M, Tamiya H, Miyashita N, Ishii T, Matsuzaki H, Yatomi Y, Nagase T, Jo T Tags: Biol Pharm Bull Source Type: research

Suppression of Lipid Accumulation in 3T3-L1 Adipocytes by α-Tocopheryl Succinate.
In this study, we found for the first time that TS significantly suppressed lipid accumulation in mouse 3T3-L1 adipocytes. TS treatment reduced the amount of triglycerides in the culture medium, and inhibited activity of glycerol-3-phosphate dehydrogenase, a marker of lipid synthesis. Furthermore, TS accelerated lipolysis. Treatment of adipocytes with TS for 24 h induced no significant cytotoxicity. In TS-treated cells, phosphorylation of Akt, which is involved in fatty acid synthesis via sterol regulatory element-binding proteins (SREBP), was prevented, while levels of phosphorylated protein kinase A (PKA) did not ...
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Majima D, Mitsuhashi R, Yamasaki M, Kajimoto K, Fukuta T, Kogure K Tags: Biol Pharm Bull Source Type: research

Cytotoxic Effects of Water-Soluble Extracts of Coarse and Fine Atmospheric Particulate Matter on Mast Cell Lines.
This study showed that cytotoxicity and particulate concentrations are not always correlated. Thus, we should focus not only on the quantity of atmospheric particulate matter, but also on its quality. PMID: 33390550 [PubMed - in process] (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Kataoka H, Tanaka K, Tazuya-Murayama K, Yamashita T, Nishikawa JI Tags: Biol Pharm Bull Source Type: research

Potential Estrogenic Properties of 17 β-Hydroxy-ethylimine Estradiol Derivative Targeted to Menopause Stage.
CONCLUSION: IE2 produced an uterotrophic effect, lordotic behavior, and anxiolytic effect in a dose-dependent manner, similar to E2. IE2 depicted estrogenicity, indicating potential clinical use as hormone replacement therapy during menopause. PMID: 33390551 [PubMed - in process] (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Jimenez-Sánchez GL, Segovia-Mendoza M, Figueroa A, Lemini C Tags: Biol Pharm Bull Source Type: research

Vitamin K2 Suppresses Proliferation and Inflammatory Cytokine Production in Mitogen-Activated Lymphocytes of Atopic Dermatitis Patients through the Inhibition of Mitogen-Activated Protein Kinases.
We examined the molecular targets of vitamin K2 to suppress proliferation and cytokine production in T-cell mitogen-activated PBMCs of atopic dermatitis patients from the viewpoint of mitogen-activated protein kinase signaling molecules. The study population included 16 pediatric vitamin K2 patients and 21 healthy subjects. The effect of vitamin K2 on concanavalin A-activated PBMC proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell counting assays. T-helper (Th)1/Th2/Th17 cytokine profiles in plasma and PBMC-culture supernatants were analyzed by a cytometric beads arra...
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Zhang M, Miura T, Suzuki S, Chiyotanda M, Tanaka S, Sugiyama K, Kawashima H, Hirano T Tags: Biol Pharm Bull Source Type: research

High-Dose Vitamin C Administration Inhibits the Invasion and Proliferation of Melanoma Cells in Mice Ovary.
Abstract Several studies have been conducted to explore the anticancer effects of vitamin C (VC). However, the effect of high-dose VC administration on melanoma is still unknown. Therefore, in this study, we investigated the effects of high-dose VC (4 g/kg) on the invasion and proliferation of melanoma cells in various organs of mice. B16 melanoma cells (1 × 106 cells/100 µL) were intravenously injected into the tails of female mice, and VC solution (4 g/kg) was orally administered once a day for 14 d. On the 15th day, samples from the liver, lungs, jejunum, an...
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Nakanishi K, Hiramoto K, Sato EF, Ooi K Tags: Biol Pharm Bull Source Type: research

Role of Epoxyeicosatrienoic Acids in Acetylcholine-Induced Dilation of Rat Retinal Arterioles in Vivo.
Abstract CYP epoxygenase-derived epoxyeicosatrienoic acids (EETs) contribute to endothelium-dependent hyperpolarization (EDH)-related dilation in multiple vascular beds. The present study aimed to determine the role of EETs in the acetylcholine (ACh)-induced dilation of retinal arterioles in rats in vivo. The vasodilator responses were assessed by determining the change in diameter of the retinal arterioles on images of the ocular fundus. The intravitreal injection of 17-octadecynoic acid (1.4 nmol/eye), an inhibitor of CYP epoxygenase, and 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EE-5(Z)-E; 2 nmol/e...
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Mori A, Yano E, Sakamoto K, Ishii K, Nakahara T Tags: Biol Pharm Bull Source Type: research

Acute Peripheral Inflammation Increases Plasma Concentration of Hypoglycemic Agent Nateglinide with Decreased Hepatic Drug-Metabolizing Activity in Rats.
Abstract The effects of inflammation on hypoglycemic agents were evaluated in male rats with acute peripheral inflammation (API). Nateglinide (NTG) was utilized as a model compound, since it is a hepatically-metabolized compound and its metabolism is mainly mediated by CYP 2C11 enzyme. In the experiments, rats were subjected to carrageenan injection into their hind paws for API induction, and the plasma concentration profiles of NTG were then examined. In addition, pooled liver microsomes were prepared from control and API rats, and the hepatic drug-metabolizing activity toward NTG and the hepatic expression of CY...
Source: Biological and Pharmaceutical Bulletin - January 6, 2021 Category: Drugs & Pharmacology Authors: Kojina M, Suzuki K, Nishiwaki A, Aiba T Tags: Biol Pharm Bull Source Type: research

Lycium barbarum polysaccharide antagonizes LPS-induced inflammation by altering the glycolysis and differentiation of macrophages by triggering the degradation of PKM2.
In conclusion, LBP suppressed the LPS-induced inflammation by altering glycolysis and the M1 differentiation of macrophages. The effects of LBP were mediated by the downregulation of PKM2 via enhanced ubiquitination. PMID: 33390389 [PubMed - as supplied by publisher] (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - December 26, 2020 Category: Drugs & Pharmacology Authors: Ding H, Wang JJ, Zhang XY, Yin L, Feng T Tags: Biol Pharm Bull Source Type: research

Streptococcus thermophilus MN-ZLW-002 can inhibit pre-adipocyte differentiation through macrophage activation.
This study was conducted to investigate the possibility of probiotics to activate macrophages in the hosts, thus alter the differentiation of pre-adipocytes. In this study, Streptococcus thermophilus MN-ZLW-002 (MN-ZLW-002) was co-cultured with RAW264.7 macrophages, with Lactobacillus rhamnosus GG (LGG) as a control. The conditioned medium (CM) of the co-culture was collected and then added to 3T3-L1 pre-adipocytes. Viable and heat-killed (80 °C, 30 min) MN-ZLW-002 stimulated RAW264.7 cells to produce significant amounts of interleukin (IL)-6 and tumor necrosis factor (TNF)-α and induced intense phosphorylation o...
Source: Biological and Pharmaceutical Bulletin - December 25, 2020 Category: Drugs & Pharmacology Authors: Kang X, Liang H, Luo Y, Li Z, He F, Han X, Zhang L Tags: Biol Pharm Bull Source Type: research