Loss of the DNA-binding domain of the farnesoid X receptor gene causes severe liver and kidney injuries.

Farnesoid X receptor (FXR) regulates bile acid synthesis, lipid metabolism, and glucose homeostasis in metabolic organs. FXR-knockout (FXR-KO) mice lacking the last exon of the FXR gene develop normally and display no prenatal and early postnatal lethality, whereas human patients with mutations in the DNA-binding domain of the FXR gene develop severe hepatic dysfunction. In this study, we generated novel FXR-KO mice lacking the DNA-binding domain of the FXR gene using CRISPR-Cas9 technology and evaluated their phenotypes.

Optimization of piggyBac transposon-mediated gene transfer method in common marmoset embryos.

Generating non-human primate models of human diseases is important for the development of therapeutic strategies especially for neurodegenerative diseases. The common marmoset has attracted attention as a new experimental animal model, and many transgenic marmosets have been produced using lentiviral vector-mediated transgenesis. However, lentiviral vectors have a size limitation of up to 8 kb in length for transgene applications.

Deciphering two rounds of cell lineage segregations during bovine preimplantation development.

Blastocyst formation gives rise to the inner cell mass (ICM) and trophectoderm (TE) and is followed by the differentiation of the epiblast (Epi) and primitive endoderm (PrE) within the ICM. Although these two-round cell lineage differentiations underpin proper embryogenesis in every mammal, their spatiotemporal dynamics are quite diverse among species. Here, molecular details of the blastocyst stage in cattle were dissected using an optimized in vitro culture method.

Requirement for expression of WW domain containing transcription regulator 1 in bovine trophectoderm development.

WW domain-containing transcription regulator 1 (WWTR1) is one of the primary effectors in the Hippo pathway, which plays essential roles in cell differentiation into trophectoderm (TE) and inner cell mass cell lineages at the blastocyst stage. However, little is known about the roles of WWTR1 in preimplantation development. The present study aimed to explore the significance of WWTR1 expression in preimplantation development using an mRNA knockdown (KD) system in bovine embryos.

The role of RHOA signaling in trophectoderm cell-fate decision in cattle.

Mammalian blastocysts are composed of two distinct cell lineages, namely the inner cell mass (ICM) and trophectoderm (TE). TE cells that give rise to the embryonic placenta are marked by an exclusive expression of the key determinant transcription factor, CDX2. Although Hippo signaling pathway is known to be responsible for this TE-specific expression of CDX2, the upstream regulator of this pathway in mammalian embryos is still controversial.

Trophectoderm regeneration to support full-term development in the inner cell mass isolated from bovine blastocyst.

Which comes first: tissue structure or cell differentiation? Although different cell types establish distinct structures delineating the inside and outside of an embryo, they progressively become specified by the blastocyst stage, when two types of cell lineages are formed: the inner cell mass (ICM) and the trophectoderm (TE). This inside-outside aspect can be experimentally converted by the isolation of the ICM from a blastocyst, leading to externalization of the blastomeres composing the outermost layer of the ICM. Here, we investigated the totipotency of isolated mouse and bovine ICMs to determine whether they are competent for TE regeneration.

Conserved roles of fibroblast growth factor receptor 2 signaling in the regulation of inner cell mass development in bovine blastocysts.

A common process during preimplantation mammalian development is blastocyst formation, which utilizes signaling through fibroblast growth factor receptor 2 (FGFR2), yet the mechanisms through which FGFR2 signaling affect preimplantation development in bovine embryos remain incompletely understood. Here, we used RNA-interference to investigate the in vitro development, the frequency of blastomere apoptosis, and the mRNA expression of developmental marker genes in FGF receptor 2-knockdown (FGFR2-KD) bovine embryos. A reduction in FGFR2 mRNA did not affect preimplantation development or the frequency of apoptotic blastomeres, but did enhanced proliferation of the inner cell mass in blastocysts (P < 0.

Requirement for nuclear autoantigenic sperm protein mRNA expression in bovine preimplantation development.

Nuclear autoantigenic sperm protein (NASP) is associated with DNA replication, cell proliferation, and cell cycle progression through its specific binding to histones. The aim of this study was to examine the roles of NASP in bovine preimplantation embryonic development. Using NASP gene knockdown (KD), we confirmed the reduction of NASP messenger RNA (mRNA) expression during preimplantation development.

Preimplantation death of xenomitochondrial mouse embryo harbouring bovine mitochondria.

Mitochondria, cellular organelles playing essential roles in eukaryotic cell metabolism, are thought to have evolved from bacteria. The organization of mtDNA is remarkably uniform across species, reflecting its vital and conserved role in oxidative phosphorylation (OXPHOS). Our objectives were to evaluate the compatibility of xenogeneic mitochondria in the development of preimplantation embryos in mammals.

Efficacy and Safety of a Lidocaine and Ropivacaine Mixture for Scalp Nerve Block and Local Infiltration Anesthesia in Patients Undergoing Awake Craniotomy.

Background: Mixtures of various local anesthetics, such as lidocaine and ropivacaine, have been widely used. However, their efficacy and safety for scalp nerve blocks and local infiltration during awake craniotomy have not been fully elucidated.

Methods: We prospectively investigated 53 patients who underwent awake craniotomy.

[Preparation of water in oil type cream with high content of water containing Kochia scoparia fruit and Cnidium monnieri fruit].

Kikisui is a herbal lotion containing Kochia scoparia Fruit and Cnidium monnieri Fruit that is clinically used as an antipruritic for itchy dry skin. However, this formulation is unsuitable for inducing a prolonged effect. Here, we attempted to change the formulation from a lotion to a cream.

The use of an in vitro dissolution and absorption system to evaluate oral absorption of two weak bases in pH-independent controlled-release formulations.

The aim of this study was to compare the oral absorption of two weak bases including their pH-independent controlled-release preparations using an in vitro evaluation system. This system is able to simulate dissolution of drugs, pH change and permeation of drugs through the epithelial cell membrane in the gastrointestinal tract. Albendazole-polymers solid dispersion and pH-independent sustained-release granules of dipyridamole were prepared by using a solvent method.

[Preparing oral dosage form of ketamine in the hospital for simplicity and patient compliance--preparations using agar].

Ketamine has been widely used in the operation as intravenous and intramuscular injections, since ketamine has dissociative anesthetic properties. When it is given in sub-anesthetic dose, ketamine is known to have an analgesic effect. The analgesic effect is observed for patients with neuropathic pain when administrated not only by injection but also orally.

[Content determination of baicalin and baicalein in shuanghuanglian powdery injection by the method of HPLC-ECD].

The contents of baicalin and baicalein in Shuanghuanglian Powdery Injection have been determined by the method of HPLC-ECD under following conditions: column-ERC-ODS-1161, 6 mm x 100 mm; temperature-55 degrees C; mobile phase-0.1 mol/L KH2PO4, acetic acid and tetrahydrofuran (1000:100:190); flow rate-0.8 ml/min; detector voltage-+650 mV.

Improving the oral bioavailability of albendazole in rabbits by the solid dispersion technique.

We have investigated the oral bioavailability of granules of albendazole, a drug used for treating echinococcosis in man, prepared by the solid dispersion technique. Rapid dissolution and supersaturation were observed when hydroxypropylmethylcellulose and hydroxypropylmethylcellulose phthalate were used as carriers in the solid dispersion. They inhibited the crystallization of albendazole from the supersaturated solution and maintained an amorphous state for 8 h.

Purification by ceftibuten-affinity chromatography and the functional reconstitution of oligopeptide transporter(s) in rat intestinal brush-border membrane.

The transport activity of ceftibuten, a dianionic peptide-like compound, was extracted from rat intestinal brush-border membrane by n-octylglucoside and reconstituted into asolectin liposomes by dialysis. The proteoliposomes prepared from the membrane extract showed an inward H+-gradient-dependent uptake of ceftibuten and glycylsarcosine. Ceftibuten-immobilized affinity chromatography of the membrane extract permitted the isolation of two polypeptides (apparent molecular mass of 117 and 127 kDa) that can recognize the dianionic peptide structure of ceftibuten.

Purification and liposomal reconstitution of the oligopeptide transport activity in rat renal cortex using ceftibuten-affinity chromatography.

The carrier protein(s) responsible for the transport of ceftibuten, a peptide-like dianionic cefem, in rat renal brush-border membrane were solubilized and purified by a ceftibuten-ligand specific affinity chromatography technique. The proteoliposomes reconstituted from the solubilized brush-border membrane proteins by dialysis had H+-sensitive uptake of ceftibuten and trans-stimulative effect by cephalexin. A specific uptake activity for ceftibuten was found in the 3.

Improving the oral bioavailability of sulpiride by a gastric-retained form in rabbits.

To improve the limited oral bioavailability of sulpiride, a gastric-retained form was developed and evaluated using gastric-emptying-controlled rabbits. The AUC value after oral administration of sulpiride as an aqueous solution was less than that after oral administration of sulpiride original powder. The dissolution was not important as a rate limiting factor for sulpiride oral absorption.