56,088 results match your criteria vivo oral

Characterization of PFOS toxicity on in-vivo and ex-vivo mouse pancreatic islets.

Environ Pollut 2021 Jul 26;289:117857. Epub 2021 Jul 26.

Croucher Institute for Environmental Sciences, Department of Biology, Hong Kong Baptist University, Hong Kong SAR, China. Electronic address:

Considerable human data have shown that the exposure to perfluorooctane sulfonate (PFOS) correlates to the risk of metabolic diseases, however the underlying effects are not clearly elucidated. In this study, we investigated the impacts of PFOS treatment, using in-vivo, ex-vivo and in-vitro approaches, on pancreatic β-cell functions. Mice were oral-gavage with 1 and 5 μg PFOS/g body weight/day for 21 days. Read More

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3-Methyl-imidazo[2,1-b]thiazole derivatives as a new class of antifolates: Synthesis, in vitro/in vivo bio-evaluation and molecular modeling simulations.

Bioorg Chem 2021 Jul 24;115:105205. Epub 2021 Jul 24.

Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.. Electronic address:

Inhibiting the Dihydrofolate reductase (DHFR) enzyme has been validated in multiple clinical manifestations related to bacterial infection, malaria, and multiple types of cancer. Herein, novel series of 3-methyl-imidazo[2,1-b] thiazole-based analogs were synthesized and biologically evaluated for their in vitro inhibitory profile towards DHFR. Compounds 22 and 23 exhibited potent inhibitory profile targeting DHFR (IC 0. Read More

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N-(3-cyano-1H-indol-5-yl)isonicotinamide and N-(3-cyano-1H-indol-5-yl)-1H-benzo[d]imidazole-5-carboxamide derivatives: Novel amide-based xanthine oxidase inhibitors.

Bioorg Chem 2021 Jul 15;115:105181. Epub 2021 Jul 15.

School of Pharmacy, China Medical University, 77 Puhe Road, North New Area, Shenyang 110122, China. Electronic address:

Our previous work demonstrated that amide is an efficient linker to explore chemical space of xanthine oxidase (XO) inhibitors that are entirely different from febuxostat and topiroxostat. In this effort, with 3-cyano-1H-indol-5-yl as a key moiety, two series of amide-based XO inhibitors, N-(3-cyano-1H-indol-5-yl)isonicotinamides (2a-w) and N-(3-cyano-1H-indol-5-yl)-1H-benzo[d]imidazole-5-carboxamides (3a-i), were designed and synthesized. The structure-activity relationship investigation identified N-(3-cyano-1-cyclopentyl-1H-indol-5-yl)-1H-benzo[d]imidazole-5-carboxamide (3i, IC = 0. Read More

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Cyclodextrin based bone regenerative inclusion complex for Resveratrol in Postmenopausal Osteoporosis.

Eur J Pharm Biopharm 2021 Jul 27. Epub 2021 Jul 27.

Pharmaceutics and Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow 226 031, India. Electronic address:

Recent preclinical studies have shown that resveratrol (RSV), is a promising remedy for osteoporosis owing to its estrogenic, anti-inflammatory, and antioxidant properties. However, RSV has met limited success due to its poor oral bioavailability and inefficient systemic delivery. In this study, we prepared the inclusion complex of RSV with sulfo-butyl ether β-cyclodextrin (SBE-β-CD) to enhance the aqueous solubility of RSV. Read More

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Bioequivalence assessment of pharmaceutical aerosol products through IVIVC.

Dennis Sandell

Adv Drug Deliv Rev 2021 Jul 27:113895. Epub 2021 Jul 27.

S5 Consulting, Ekvägen 8, 27562 Blentarp, Sweden. Electronic address:

Many pharmaceutical developers of generic orally inhaled products (OIPs) are facing significant issues in passing the regulatory requirement to show pharmacokinetic (PK) bioequivalence (BE) to the originator product. The core of the issue is that no reliable in vitro-in vivo correlation (IVIVC) is available to guide their development. In this paper, several issues are identified and means to improve the data used for developing an IVIVC are discussed. Read More

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In Situ Membrane Biotinylation Enables the Direct Labeling and Accurate Kinetic Analysis of Small Extracellular Vesicles in Circulation.

Anal Chem 2021 Jul 30. Epub 2021 Jul 30.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China.

Circulating small extracellular vesicles (sEVs) are naturally occurring nanosized membrane vesicles that convey bioactive molecules between cells. Conventionally, to evaluate their behaviors in vivo, circulating sEVs have to be isolated from the bloodstream, then labeled with imaging materials in vitro, and finally injected back into the circulation of animals for subsequent detection. The tedious isolation-labeling-reinfusion procedures might have an undesirable influence on the natural properties of circulating sEVs, thereby changing their behaviors and the detected kinetics in vivo. Read More

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Fate and transformation of silver nanoparticles in different biological conditions.

Beilstein J Nanotechnol 2021 7;12:665-679. Epub 2021 Jul 7.

Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10 000 Zagreb, Croatia.

The exploitation of silver nanoparticles (AgNPs) in biomedicine represents more than one third of their overall application. Despite their wide use and significant amount of scientific data on their effects on biological systems, detailed insight into their in vivo fate is still lacking. This study aimed to elucidate the biotransformation patterns of AgNPs following oral administration. Read More

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Osteocytes but not osteoblasts directly build mineralized bone structures.

Int J Biol Sci 2021 11;17(10):2430-2448. Epub 2021 Jun 11.

Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, TX 75246, USA.

Bone-forming osteoblasts have been a cornerstone of bone biology for more than a century. Most research toward bone biology and bone diseases center on osteoblasts. Overlooked are the 90% of bone cells, called osteocytes. Read More

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Antiviral Drug Delivery System for Enhanced Bioactivity, Better Metabolism and Pharmacokinetic Characteristics.

Int J Nanomedicine 2021 22;16:4959-4984. Epub 2021 Jul 22.

Chongqing Research Center for Pharmaceutical Engineering, School of Pharmacy, Chongqing Medical University, Chongqing, 400016, People's Republic of China.

Antiviral drugs (AvDs) are the primary resource in the global battle against viruses, including the recent fight against corona virus disease 2019 (COVID-19). Most AvDs require multiple medications, and their use frequently leads to drug resistance, since they have poor oral bioavailability and low efficacy due to their low solubility/low permeability. Characterizing the in vivo metabolism and pharmacokinetic characteristics of AvDs may help to solve the problems associated with AvDs and enhance their efficacy. Read More

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In vitro monitoring of HTR2A-positive neurons derived from human-induced pluripotent stem cells.

Sci Rep 2021 Jul 29;11(1):15437. Epub 2021 Jul 29.

Department of Prosthodontics, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ohta-ku, Tokyo, 145-8515, Japan.

The serotonin 5-HT receptor (5-HTR) has been receiving increasing attention because its genetic variants have been associated with a variety of neurological diseases. To elucidate the pathogenesis of the neurological diseases associated with 5-HTR gene (HTR2A) variants, we have previously established a protocol to induce HTR2A-expressing neurons from human-induced pluripotent stem cells (hiPSCs). Here, we investigated the maturation stages and electrophysiological properties of HTR2A-positive neurons induced from hiPSCs and constructed an HTR2A promoter-specific reporter lentivirus to label the neurons. Read More

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Osseodensification enables bone healing chambers with improved low-density bone site primary stability: an in vivo study.

Sci Rep 2021 Jul 29;11(1):15436. Epub 2021 Jul 29.

Clinical Research Laboratory, Dentistry School, Universidade Federal Fluminense, Rua Mario Santos Braga, 28/4 Floor, Niterói, RJ, Brazil.

Primary implant stability is a prerequisite for successful implant osseointegration. The osseodensification technique (OD) is a non-subtractive drilling technique that preserves the bone tissue, increases osteotomy wall density, and improves the primary stability. This study aimed to investigate the hypothesis that OD, through a wider osteotomy, produces healing chambers (HCs) at the implant-bone interface without impacting low-density bone primary stability. Read More

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Pseudoboehmite as a drug delivery system for acyclovir.

Sci Rep 2021 Jul 29;11(1):15448. Epub 2021 Jul 29.

School of Engineering, Mackenzie Presbyterian University, Rua da Consolação, 930, Building 33, Consolação, São Paulo, SP, 01302-907, Brazil.

Herpes simplex virus is among the most prevalent sexually transmitted infections. Acyclovir is a potent, selective inhibitor of herpes viruses and it is indicated for the treatment and management of recurrent cold sores on the lips and face, genital herpes, among other diseases. The problem of the oral bioavailability of acyclovir is limited because of the low permeability across the gastrointestinal membrane. Read More

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Preclinical Mechanisms of Topical PRN473, a Bruton Tyrosine Kinase Inhibitor, in Immune-Mediated Skin Disease Models.

Immunohorizons 2021 Jul 29;5(7):581-589. Epub 2021 Jul 29.

Principia Biopharma Inc., a Sanofi Company, South San Francisco, CA.

The expression of Bruton tyrosine kinase (BTK) in B cells and innate immune cells provides essential downstream signaling for BCR, Fc receptors, and other innate immune cell pathways. The topical covalent BTK inhibitor PRN473 has shown durable, reversible BTK occupancy with rapid on-rate and slow off-rate binding kinetics and long residence time, resulting in prolonged, localized efficacy with low systemic exposure in vivo. Mechanisms of PRN473 include inhibition of IgE (FcεR)-mediated activation of mast cells and basophils, IgG (FcγR)-mediated activation of monocytes, and neutrophil migration. Read More

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Effects of shikonin on the development of ovarian follicles and female germline stem cells.

J Int Med Res 2021 Jul;49(7):3000605211029461

Key Laboratory of Reproductive Physiology and Pathology of Jiangxi Province, Nanchang University, Nanchang, Jiangxi Province, China.

Objective: To investigate the effects and potential mechanism of action of shikonin (SHK) on the development of ovarian follicles and female germline stem cells (FGSCs).

Methods: Female Kunming adult mice were administered SHK (0, 20 and 50 mg/kg) by oral gavage. Cultures of FGSCs were treated with SHK 32 μmol/l for 24 h. Read More

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Calcium signaling induces a partial EMT.

EMBO Rep 2021 Jul 29:e51872. Epub 2021 Jul 29.

Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Epithelial plasticity, or epithelial-to-mesenchymal transition (EMT), is a well-recognized form of cellular plasticity, which endows tumor cells with invasive properties and alters their sensitivity to various agents, thus representing a major challenge to cancer therapy. It is increasingly accepted that carcinoma cells exist along a continuum of hybrid epithelial-mesenchymal (E-M) states and that cells exhibiting such partial EMT (P-EMT) states have greater metastatic competence than those characterized by either extreme (E or M). We described recently a P-EMT program operating in vivo by which carcinoma cells lose their epithelial state through post-translational programs. Read More

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Irradiation of the Normal Murine Tongue Causes Upregulation and Activation of Transient Receptor Potential (TRP) Ion Channels.

Radiat Res 2021 07 29. Epub 2021 Jul 29.

Department of Clinical Sciences, North Carolina State University, Raleigh, North Carolina.

Signal transduction at sensory neurons occurs via transmembrane flux of cations, which is largely governed by the transient receptor potential (TRP) family of ion channels. It is unknown whether TRP channel activation contributes to the pain that accompanies radiation-induced oral mucositis. This study sought to characterize changes in TRP channel expression and function that occur in the locally irradiated tissues and afferent neurons of mice. Read More

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Gingipain-Responsive Thermosensitive Hydrogel Loaded with SDF-1 Facilitates Periodontal Tissue Regeneration.

ACS Appl Mater Interfaces 2021 Jul 29. Epub 2021 Jul 29.

Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong 250012, China.

Existing local drug delivery systems for periodontitis suffer from poor antibacterial effect and unsatisfied periodontal regeneration. In this study, a smart gingipain-responsive hydrogel ([email protected]) was synthesized as an environmentally sensitive carrier for on-demand drug delivery. The [email protected] hydrogel was synthesized from polyethylene glycol diacrylate (PEG-DA) based scaffolds, dithiothreitol (DTT), and a novel designed functional peptide module (FPM) via Michael-type addition reaction, and the hydrogel was further loaded with stromal cell derived factor-1 (SDF-1). Read More

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Tongue muscle contractile, fatigue and fiber type properties in rats.

J Appl Physiol (1985) 2021 07 29. Epub 2021 Jul 29.

Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, United States.

The intrinsic and extrinsic tongue muscles manipulate the position and shape of the tongue and are activated during many oral and respiratory behaviors. In the present study in 6-month-old Fischer 344 rats, we examined mechanical and fatigue properties, of tongue muscles in relation to their fiber type composition. In an ex vivo preparation, isometric force and fatigue was assessed by direct muscle stimulation. Read More

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Anatomy assessment of permanent mandibular premolar teeth in a selected Iranian population using cone-beam computed tomography.

Dent Res J (Isfahan) 2021 24;18:40. Epub 2021 May 24.

Department of Endodontics, Dental Research Center, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Appropriate cleaning and shaping and three-dimensional obturation of the root canal system lead to a successful endodontic treatment. To achieve this, complete knowledge of the internal anatomy of root canals is necessary. Therefore, this study evaluated the number and shape of mandibular premolar roots and canals and classified their Vertucci classification using cone-beam computed tomography (CBCT) images of an Iranian sample population. Read More

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A Novel Mechanism of Carvedilol Efficacy for Rosacea Treatment: Toll-Like Receptor 2 Inhibition in Macrophages.

Front Immunol 2021 12;12:609615. Epub 2021 Jul 12.

Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, China.

Background: Rosacea, a chronic inflammatory skin disorder etiologically associated with immune cells and the antibacterial peptide cathelicidin LL-37, can be effectively treated by oral carvedilol administration.

Objective: To investigate the molecular mechanisms underlying carvedilol efficacy in rosacea treatment.

Methods: Skin samples of patients with rosacea were subjected to histopathological (hematoxylin and eosin) and immunohistochemical (CD68, Toll-like receptor 2 (TLR2), kallikrein 5, cathelicidin, TNF-α, and IL-1β) evaluation. Read More

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Anemoside B4 inhibits enterovirus 71 propagation in mice through upregulating 14-3-3 expression and type I interferon responses.

Acta Pharmacol Sin 2021 Jul 28. Epub 2021 Jul 28.

Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

Enterovirus 71 (EV71) is the major pathogens of human hand, foot, and mouth disease (HFMD). EV71 efficiently escapes innate immunity responses of the host to cause infection. At present, no effective antiviral drugs for EV71 are available. Read More

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Epstein-Barr virus-encoded circular RNA circBART2.2 promotes immune escape of nasopharyngeal carcinoma by regulating PD-L1.

Cancer Res 2021 Jul 28. Epub 2021 Jul 28.

Cancer Research Institute, Central South University

Epstein-Barr virus (EBV) infection is an established cause of nasopharyngeal carcinoma (NPC) and is involved in a variety of malignant phenotypes, including tumor immune escape. EBV can encode a variety of circular RNAs; however, little is known regarding the biological functions of these circRNAs in NPC. In this study, EBV-encoded circBART2. Read More

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Biomaterials with structural hierarchy and controlled 3D nanotopography guide endogenous bone regeneration.

Sci Adv 2021 Jul 28;7(31). Epub 2021 Jul 28.

Department of Surgery-Transplant and Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Biomaterials without exogenous cells or therapeutic agents often fail to achieve rapid endogenous bone regeneration with high quality. Here, we reported a class of three-dimensional (3D) nanofiber scaffolds with hierarchical structure and controlled alignment for effective endogenous cranial bone regeneration. 3D scaffolds consisting of radially aligned nanofibers guided and promoted the migration of bone marrow stem cells from the surrounding region to the center in vitro. Read More

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Rabbit haemorrhagic disease virus Lagovirus europaeus/GI.1d strain: genome sequencing, in vivo virus replication kinetics, and viral dose effect.

BMC Vet Res 2021 Jul 28;17(1):257. Epub 2021 Jul 28.

Ploufragan-Plouzané-Niort Laboratory, Avian and Rabbit Virology Immunology and Parasitology Unit, French Agency for Food, Environmental and Occupational Health and Safety (ANSES), BP 53, F-22440, Ploufragan, France.

Background: Rabbit haemorrhagic disease virus Lagovirus europaeus/GI.1d variant (GI.1d/RHDV) was identified in 1990 in France, and until the emergence of the new genotype GI. Read More

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Trop-2 induces ADAM10-mediated cleavage of E-cadherin and drives EMT-less metastasis in colon cancer.

Neoplasia 2021 Jul 25;23(9):898-911. Epub 2021 Jul 25.

Laboratory of Cancer Pathology, Center for Advanced Studies and Technology (CAST), "G. d' Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy; Oncoxx Biotech, 66034 Lanciano (Chieti), Italy; Unit of Medical Genetics, Department of Biomedical Sciences - BIOMORF, University of Messina, 98125 Messina, Italy. Electronic address:

We recently reported that activation of Trop-2 through its cleavage at R87-T88 by ADAM10 underlies Trop-2-driven progression of colon cancer. However, the mechanism of action and pathological impact of Trop-2 in metastatic diffusion remain unexplored. Through searches for molecular determinants of cancer metastasis, we identified TROP2 as unique in its up-regulation across independent colon cancer metastasis models. Read More

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Targeting Mycobacterium tuberculosis response to environmental cues for the development of effective antitubercular drugs.

PLoS Biol 2021 Jul 28;19(7):e3001355. Epub 2021 Jul 28.

Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.

Sensing and response to environmental cues, such as pH and chloride (Cl-), is critical in enabling Mycobacterium tuberculosis (Mtb) colonization of its host. Utilizing a fluorescent reporter Mtb strain in a chemical screen, we have identified compounds that dysregulate Mtb response to high Cl- levels, with a subset of the hits also inhibiting Mtb growth in host macrophages. Structure-activity relationship studies on the hit compound "C6," or 2-(4-((2-(ethylthio)pyrimidin-5-yl)methyl)piperazin-1-yl)benzo[d]oxazole, demonstrated a correlation between compound perturbation of Mtb Cl- response and inhibition of bacterial growth in macrophages. Read More

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Metabolic map of the antiviral drug podophyllotoxin provides insights into hepatotoxicity.

Xenobiotica 2021 Jul 28:1-36. Epub 2021 Jul 28.

Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

Podophyllotoxin (POD) is a natural compound with antiviral and anticancer activities. The purpose of the present study was to determine the metabolic map of POD in vitro and in vivo.Mouse and human liver microsomes were employed to identify POD metabolites in vitro and recombinant drug-metabolizing enzymes were used to identify the mono-oxygenase enzymes involved in POD metabolism. Read More

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Clinical wear and quality assessment of monolithic and lithium disilicate layered zirconia restorations.

Aust Dent J 2021 Jul 28. Epub 2021 Jul 28.

Faculty of Dentistry, Department of Prosthodontics, Uşak University, Uşak, Turkey.

Background: Wear and quality assessment of translucent monolithic zirconia and CAD-on restorations were performed.

Methods: Forty 3-unit posterior FDP in 18 patients (age:18-50yrs) were made from translucent monolithic zirconia (tm) (Zenostar T) and zirconia-frameworked, lithium disilicate layered (c) (CAD-on), materials in a split-mouth design. Restorations were digitally fabricated and their internal and marginal adaptations were measured before cementation followed by luting (Multilink Speed). Read More

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Molecular Characteristics of IS Carrying Multidrug Resistance Gene Cluster in Serotype III/Sequence Type 19 Group B Streptococcus.

mSphere 2021 Jul 28:e0054321. Epub 2021 Jul 28.

Research Division for Biotechnology, Korea Atomic Energy Research Institutegrid.418964.6, Jeongeup, Republic of Korea.

Streptococcus agalactiae is the leading cause of meningitis in newborns and a significant cause of invasive diseases in pregnant women and adults with underlying diseases. Antibiotic resistance against erythromycin and clindamycin in group B streptococcus (GBS) isolates has been increasing worldwide. GBS expresses the Srr1 and Srr2 proteins, which have important roles in bacterial infection. Read More

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Free Gingival-Bone Graft in the Anterior Maxilla: A Clinical Case Report.

J Contemp Dent Pract 2021 May 1;22(5):568-571. Epub 2021 May 1.

Department of Surgical Science and Integrated Diagnostics (DISC), University of Genova, Genova, Italy.

Aim: To present the healing, development, and long-term clinical results after a combined gingival-bone graft as an alternative treatment for the management of critical extraction sites in the esthetic zone.

Background: To enhance the knowledge of soft and hard tissue remodeling, in this case report, we observed the healing, development, and long-term clinical results after a case of a combined gingival-bone graft as an alternative treatment for the management of critical extraction sites.

Case Description: Autogenous grafts of gingival and bone tissue were placed in a 56-year-old female patient, where a hopeless upper left central incisor with an evident loss of both the buccal and the palatal bony plates and with endodontic problems was due for extraction. Read More

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