9,355 results match your criteria mice single-dose

Persistent mTORC1 activation via Depdc5 deletion results in spontaneous hepatocellular carcinoma but does not exacerbate carcinogen- and high-fat diet-induced hepatic carcinogenesis in mice.

Biochem Biophys Res Commun 2021 Sep 20;578:142-149. Epub 2021 Sep 20.

School of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan, China; Xinxiang Key Laboratory of Metabolism and Integrative Physiology, Xinxiang Medical University, Xinxiang, Henan, China. Electronic address:

The mechanistic target of rapamycin complex 1 (mTORC1) acts as a central regulator of metabolic pathways that drive cellular growth. Abnormal activation of mTORC1 occurs at high frequency in human and mouse hepatocellular carcinoma (HCC). DEP domain-containing protein 5 (DEPDC5), a component of GATOR1 complex, is a repressor of amino acid-sensing branch of the mTORC1 pathway. Read More

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September 2021

Exposure to Systemic Immunosuppressive Ultraviolet Radiation Alters T Cell Recirculation through Sphingosine-1-Phosphate.

J Immunol 2021 Sep 24. Epub 2021 Sep 24.

School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia;

Systemic suppression of adaptive immune responses is a major way in which UV radiation contributes to skin cancer development. Immune suppression is also likely to explain how UV protects from some autoimmune diseases, such as multiple sclerosis. However, the mechanisms underlying UV-mediated systemic immune suppression are not well understood. Read More

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September 2021

Histone deacetylase inhibitor AR-42 and achiral analogues kill malaria parasites in vitro and in mice.

Int J Parasitol Drugs Drug Resist 2021 Aug 23;17:118-127. Epub 2021 Aug 23.

Griffith Institute for Drug Discovery, Griffith University, Queensland, 4111, Australia. Electronic address:

Malaria is caused by infection with Plasmodium parasites and results in significant health and economic impacts. Malaria eradication is hampered by parasite resistance to current drugs and the lack of a widely effective vaccine. Compounds that target epigenetic regulatory proteins, such as histone deacetylases (HDACs), may lead to new therapeutic agents with a different mechanism of action, thereby avoiding resistance mechanisms to current antimalarial drugs. Read More

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Cytochrome P450 isoforms 1A1, 1B1 AND 2W1 as targets for therapeutic intervention in head and neck cancer.

Sci Rep 2021 Sep 23;11(1):18930. Epub 2021 Sep 23.

Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford, BD7 1DP, West Yorkshire, UK.

Epidemiological studies have shown that head and neck cancer (HNC) is a complex multistage process that in part involves exposure to a combination of carcinogens and the capacity of certain drug-metabolising enzymes including cytochrome P450 (CYP) to detoxify or activate such carcinogens. In this study, CYP1A1, CYP1B1 and CYP2W1 expression in HNC was correlated with potential as target for duocarmycin prodrug activation and selective therapy. In the HNC cell lines, elevated expression was shown at the gene level for CYP1A1 and CYP1B1 whereas CYP2W1 was hardly detected. Read More

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September 2021

Berberine is an insulin secretagogue targeting the KCNH6 potassium channel.

Nat Commun 2021 Sep 23;12(1):5616. Epub 2021 Sep 23.

Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, 100730, Beijing, China.

Coptis chinensis is an ancient Chinese herb treating diabetes in China for thousands of years. However, its underlying mechanism remains poorly understood. Here, we report the effects of its main active component, berberine (BBR), on stimulating insulin secretion. Read More

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September 2021

Combined exposure to polychlorinated biphenyls and high-fat diet modifies the global epitranscriptomic landscape in mouse liver.

Environ Epigenet 2021 17;7(1):dvab008. Epub 2021 Sep 17.

Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY 40292, USA.

Exposure to a single dose of polychlorinated biphenyls (PCBs) and a 12-week high-fat diet (HFD) results in nonalcoholic steatohepatitis (NASH) in mice by altering intracellular signaling and inhibiting epidermal growth factor receptor signaling. Post-transcriptional chemical modification (PTM) of RNA regulates biological processes, but the contribution of epitranscriptomics to PCB-induced steatosis remains unknown. This study tested the hypothesis that PCB and HFD exposure alters the global RNA epitranscriptome in male mouse liver. Read More

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September 2021

Securinine Promotes Neuronal Development and Exhibits Antidepressant-like Effects via mTOR Activation.

ACS Chem Neurosci 2021 Sep 20. Epub 2021 Sep 20.

JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong, China.

Impaired differentiation of newborn neurons or abnormalities at the synapses resulted from stress maladaptation could be the key etiology of depression. Recent studies have shown that mTOR, a crucial factor for neuronal differentiation and synapse development, acts as a common factor that mediates the rapid antidepression effects of several new-class antidepressants. In this study, the antidepressant-like activity of securinine, an alkaloid that has central nervous system stimulation ability, was investigated. Read More

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September 2021

Febuxostat, an inhibitor of xanthine oxidase, ameliorates ionizing radiation-induced lung injury by suppressing caspase-3, oxidative stress and NF-κB.

Drug Chem Toxicol 2021 Sep 19:1-8. Epub 2021 Sep 19.

Department of Radiopharmacy, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

Febuxostat (FBX), a selective inhibitor of xanthine oxidase, has several biological properties such as antioxidant, anti-inflammatory and anti-apoptosis activities. The purpose of this study was to evaluate the protective effect of FBX against ionizing radiation (IR)-induced lung injury through mitigation of oxidative stress, inflammation and apoptosis. Sixty-four mice were randomized into eight groups as control, FBX (5, 10, and 15 mg/kg), IR (6 Gy), and IR + FBX (IR + FBX in three doses). Read More

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September 2021

Selective acetyl-CoA carboxylase 1 inhibitor improves hepatic steatosis and hepatic fibrosis in a pre-clinical NASH model.

J Pharmacol Exp Ther 2021 Sep 17. Epub 2021 Sep 17.

Takeda Pharmaceutical Company Limited, United States

Acetyl-CoA carboxylase (ACC) 1 and ACC2 are essential rate-limiting enzymes that synthesize malonyl-CoA (M-CoA) from acetyl-CoA. ACC1 is predominantly expressed in lipogenic tissues and regulates the lipogenesis (DNL) flux. It is upregulated in the liver of patients with nonalcoholic fatty liver disease (NAFLD), ultimately leading to the formation of fatty liver. Read More

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September 2021

Long-term functional correction of cystathionine β-synthase deficiency in mice by adeno-associated viral gene therapy.

J Inherit Metab Dis 2021 Sep 16. Epub 2021 Sep 16.

Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA, USA.

Cystathionine β-synthase (CBS) deficiency is a recessive inborn error of sulfur metabolism characterized by elevated blood levels of total homocysteine (tHcy). Patients diagnosed with CBS deficiency are currently treated by a combination of vitamin supplementation and restriction of foods containing the homocysteine precursor methionine, but the effectiveness of this therapy is limited due to poor compliance. A mouse model for CBS deficiency (Tg-I278T Cbs ) was used to evaluate a potential gene therapy approach to treat CBS deficiency utilizing an AAVrh. Read More

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September 2021

Evaluation of acute and subacute toxicity of ethanolic extract and fraction of alkaloids from bark of Aspidosperma nitidum in mice.

Sci Rep 2021 Sep 14;11(1):18283. Epub 2021 Sep 14.

Post-graduate Program in Biodiversity and Biotechnology (BIONORTE), Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil.

This study investigated the acute and subacute toxicity of the ethanolic extract (EE) and alkaloid fraction (FA) from A. nitidum. The EE was obtained from trunk bark with ethanol, FA was obtained from the fractionation of EE. Read More

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September 2021

MicroRNA-497 induced by Clonorchis sinensis enhances the TGF-β/Smad signaling pathway to promote hepatic fibrosis by targeting Smad7.

Parasit Vectors 2021 Sep 14;14(1):472. Epub 2021 Sep 14.

Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Key Laboratory of Infection and Immunity, Xuzhou Medical University, Jiangsu, 221004, Xuzhou, People's Republic of China.

Background: Various stimuli, including Clonorchis sinensis infection, can cause liver fibrosis. Liver fibrosis is characterized by the activation of hepatic stellate cells (HSCs) with massive production of extracellular matrix (ECM). Our previous study showed that the TGF-β-induced Smad signaling pathway played a critical role in the activation of HSCs during liver fibrosis induced by worm infection; however, the mechanisms that modulate the TGF-β/Smad signaling pathway are still poorly understood. Read More

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September 2021

Bispecific binder redirected lentiviral vector enables in vivo engineering of CAR-T cells.

J Immunother Cancer 2021 Sep;9(9)

UNC/NCSU Joint Department of Biomedical Engineering, UNC-Chapel Hill, Chapel Hill, North Carolina, USA

Background: Chimeric antigen receptor (CAR) T cells have shown considerable promise as a personalized cellular immunotherapy against B cell malignancies. However, the complex and lengthy manufacturing processes involved in generating CAR T cell products ex vivo result in substantial production time delays and high costs. Furthermore, ex vivo expansion of T cells promotes cell differentiation that reduces their in vivo replicative capacity and longevity. Read More

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September 2021

Recombinant Expressing SARS-CoV-2 Receptor-Binding Domain as a Vaccine Candidate Against SARS-CoV-2 Infections.

Front Immunol 2021 27;12:712274. Epub 2021 Aug 27.

Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, South Korea.

At present, concerns that the recent global emergence of SARS-CoV-2 variants could compromise the current vaccines have been raised, highlighting the urgent demand for new vaccines capable of eliciting T cell-mediated immune responses, as well as B cell-mediated neutralizing antibody production. In this study, we developed a novel recombinant expressing the SARS-CoV-2 receptor-binding domain (RBD) (rMpg-RBD-7) that is capable of eliciting RBD-specific immune responses in vaccinated mice. The potential use of rMpg-RBD-7 as a vaccine for SARS-CoV-2 infections was evaluated in using mouse models of two different modules, one for single-dose vaccination and the other for two-dose vaccination. Read More

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September 2021

Visualizing Muscle Sialic Acid Expression in the GNED207VTgGne-/- Cmah-/- Model of GNE Myopathy: A Comparison of Dietary and Gene Therapy Approaches.

J Neuromuscul Dis 2021 Sep 10. Epub 2021 Sep 10.

Center for Gene Therapy, Abigail Wexner Research Institute Children's Drive Columbus, OH, USA.

Background: GNE myopathy (GNEM) is a rare, adult-onset, inclusion body myopathy that results from partial loss of function mutations in the GNE gene. GNE encodes UDP-GlcNAc epimerase/Mannose-6 kinase, a protein with two enzymatic activities that comprise the committed step in biosynthesis of sialic acid (SA), an essential glycan that appears on the terminal positions of many extracellular oligosaccharide chains. These GNE mutations can cause a reduction of SA in many tissues, although pathology is restricted to skeletal muscles through a poorly understood mechanism. Read More

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September 2021

Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice.

Proc Natl Acad Sci U S A 2021 09;118(38)

Bioqual, Inc., Rockville, MD 20850.

Global containment of COVID-19 still requires accessible and affordable vaccines for low- and middle-income countries (LMICs). Recently approved vaccines provide needed interventions, albeit at prices that may limit their global access. Subunit vaccines based on recombinant proteins are suited for large-volume microbial manufacturing to yield billions of doses annually, minimizing their manufacturing cost. Read More

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September 2021

Trivalent Subunit Vaccine Candidates for COVID-19 and Their Delivery Devices.

J Am Chem Soc 2021 09 7;143(36):14748-14765. Epub 2021 Sep 7.

Institute for Antiviral Research, Utah State University, Logan, Utah 84322, United States.

The COVID-19 pandemic highlights the need for platform technologies enabling rapid development of vaccines for emerging viral diseases. The current vaccines target the SARS-CoV-2 spike (S) protein and thus far have shown tremendous efficacy. However, the need for cold-chain distribution, a prime-boost administration schedule, and the emergence of variants of concern (VOCs) call for diligence in novel SARS-CoV-2 vaccine approaches. Read More

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September 2021

Evaluation of the antiulcerogenic activity of hydromethanol extracts of L. (Solanaceae) leaves and roots in mice; single and repeated dose study.

Metabol Open 2021 Sep 24;11:100119. Epub 2021 Aug 24.

Department of Pharmacology, School of Pharmacy, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.

Objective: The aim of this study was to evaluate the antiulcer activity of hydromethanol extracts of L. (Solanaceae) leaves and roots in mice.

Methods: The antiulcerogenic activity of the plant extracts were evaluated using Pylorus ligation and ethanol induced gastric ulcers in fasted mice. Read More

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September 2021

Modulation of Peripheral CD4CD25Foxp3 Regulatory T Cells Ameliorates Surgical Stress-Induced Atherosclerotic Plaque Progression in ApoE-Deficient Mice.

Front Cardiovasc Med 2021 12;8:682458. Epub 2021 Aug 12.

Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany.

Systemic inflammation associated with major surgery rapidly accelerates atherosclerotic plaque progression in mice. Regulatory T cells (Tregs) have emerged as important modulators of atherogenesis. In coronary artery disease patients, low frequency of Tregs constitutes an independent risk factor for cardiovascular complications after non-cardiac surgery. Read More

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Graphene-Induced Hyperthermia (GIHT) Combined With Radiotherapy Fosters Immunogenic Cell Death.

Front Oncol 2021 16;11:664615. Epub 2021 Aug 16.

Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University of Erlangen-Nürnberg (FAU), Universitätsklinikum Erlangen, Erlangen, Germany.

Radiotherapy and chemotherapy are the standard interventions for cancer patients, although cancer cells often develop radio- and/or chemoresistance. Hyperthermia reduces tumor resistance and induces immune responses resulting in a better prognosis. We have previously described a method to induce tumor cell death by local hyperthermia employing pegylated reduced graphene oxide nanosheets and near infrared light (graphene-induced hyperthermia, GIHT). Read More

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Tail-vein injection of MSC-derived small extracellular vesicles facilitates the restoration of hippocampal neuronal morphology and function in APP / PS1 mice.

Cell Death Discov 2021 Sep 4;7(1):230. Epub 2021 Sep 4.

Mini-invasive Neurosurgery and Translational Medical Center, Xi'an Central Hospital, Xi'an Jiaotong University, No. 161, West 5th Road, Xincheng District, 710003, Xi'an, P.R. China.

Mesenchymal stem-cell-derived small extracellular vesicles (MSC-EVs), as a therapeutic agent, have shown great promise in the treatment of neurological diseases. To date, the neurorestorative effects and underlying mechanism of MSC-EVs in Alzheimer's disease (AD) are not well known. Herein, we aimed to investigate the action of MSC-EVs on the neuronal deficits in β-amyloid protein (Aβ)-stimulated hippocampal neurons, or AD cell (SHSY5Y cell lines) and animal (APPswe / PS1dE9 mice) models. Read More

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September 2021

Targeting SARS-CoV-2 receptor-binding domain to cells expressing CD40 improves protection to infection in convalescent macaques.

Nat Commun 2021 09 1;12(1):5215. Epub 2021 Sep 1.

Vaccine Research Institute, Creteil, France.

Achieving sufficient worldwide vaccination coverage against SARS-CoV-2 will require additional approaches to currently approved viral vector and mRNA vaccines. Subunit vaccines may have distinct advantages when immunizing vulnerable individuals, children and pregnant women. Here, we present a new generation of subunit vaccines targeting viral antigens to CD40-expressing antigen-presenting cells. Read More

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September 2021

Quercitrin Rapidly Alleviated Depression-like Behaviors in Lipopolysaccharide-Treated Mice: The Involvement of PI3K/AKT/NF-κB Signaling Suppression and CREB/BDNF Signaling Restoration in the Hippocampus.

ACS Chem Neurosci 2021 09 1;12(18):3387-3396. Epub 2021 Sep 1.

Interdisciplinary Institute for Personalized Medicine in Brain Disorders, Jinan University, Guangzhou 510632, China.

Quercitrin (Qc) is a well-known flavonoid compound that exerts anti-inflammation effects on various diseases. The present study aimed to investigate the antidepressant-like response of Qc and its underlying mechanisms concerning neuroinflammation and neuroplasticity in mice with lipopolysaccharide (LPS)-induced depression-like behaviors. The results showed a single dose of Qc (10 mg/kg) produced an antidepressant-like effect at 2 h postadministration and lasted for at least 3 days. Read More

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September 2021

Eribulin improves tumor oxygenation demonstrated by F-DiFA hypoxia imaging, leading to radio-sensitization in human cancer xenograft models.

Eur J Nucl Med Mol Imaging 2021 Sep 1. Epub 2021 Sep 1.

Central Institute of Isotope Science, Hokkaido University, Sapporo, Japan.

Purpose: Eribulin, an inhibitor of microtubule dynamics, is known to show antitumor effects through its remodeling activity in the tumor vasculature. However, the extent to which the improvement of tumor hypoxia by eribulin affects radio-sensitivity remains unclear. We utilized 1-(2,2-dihydroxymethyl-3-F-fluoropropyl)-2-nitroimidazole (F-DiFA), a new PET probe for hypoxia, to investigate the effects of eribulin on tumor hypoxia and evaluate the radio-sensitivity during eribulin treatment. Read More

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September 2021

Antihyperglycemic and hypoglycemic activities of the aqueous leaf extract of (Rosacea) in mice.

Metabol Open 2021 Sep 13;11:100118. Epub 2021 Aug 13.

Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.

Background: The prevalence of diabetes mellitus is on the inexorable rise despite the promises of a wide range of conventional medications. Thus, there is a need to scientifically investigate plants for antidiabetic effect.

Methods: After the Engl (Rosaceae) leaf has been decocted, the plant extract's antidiabetic activity was first investigated and then . Read More

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September 2021

Different properties of mammary carcinogenesis induced by two chemical carcinogens, DMBA and PhIP, in heterozygous BALB/c knockout mice.

Oncol Lett 2021 Oct 16;22(4):738. Epub 2021 Aug 16.

Central Animal Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan.

Chemical carcinogens, such as 7,12-dimethylbenz[a]anthracene (DMBA) and 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), are known to induce mammary carcinomas in mice and rats. In the present study, the phenotypic and genotypic characteristics of carcinogen-induced mammary carcinogenesis in heterozygous BALB/c tumor protein p53 () knockout mice were examined with reference to published data surrounding human breast cancer. A significantly accelerated induction of mammary carcinomas was observed following a single dose of DMBA (50 mg/kg of body weight at 7 weeks of age), and a modest acceleration was induced by PhIP (50 mg/kg of body weight) administered by gavage 6 times/2 weeks from 7 weeks of age. Read More

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October 2021

Single-dose intranasal vaccination elicits systemic and mucosal immunity against SARS-CoV-2.

iScience 2021 Sep 26;24(9):103037. Epub 2021 Aug 26.

Department of Chemical and Biomolecular Engineering, University of Houston, Houston, TX 77204, USA.

Despite remarkable progress in the development and authorization of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a need to validate vaccine platforms for broader application. The current intramuscular vaccines are designed to elicit systemic immunity without conferring mucosal immunity in the nasal compartment, which is the first barrier that SARS-CoV-2 virus breaches before dissemination to the lung. We report the development of an intranasal subunit vaccine that uses lyophilized spike protein and liposomal STING agonist as an adjuvant. Read More

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September 2021

Sequential administration of PEG-Span 80 niosome enhances anti-tumor effect of doxorubicin-containing PEG liposome.

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

Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan. Electronic address:

To improve the anti-tumor effect of polyethylene glycol-modified liposome containing doxorubicin (DOX-PEG liposome), the effect of sequential administration of PEG-Span 80 niosome was investigated for Colon-26 cancer cells (C26)-bearing mice. The concept of the current study is as follows: Since both particulates would be accumulated in the tumor tissue due to the enhanced permeability and retention (EPR) effect, PEG-Span 80 niosome, mainly composed of synthetic surfactant (Span 80), would interact with DOX-PEG liposome and be a trigger to induce the release of DOX from the liposome within the tumor tissue, leading to the improvement of anti-tumor effect of DOX-PEG liposome. To find out an adequate liposome for this strategy, several PEG liposomes with different compositions were examined in terms of drug release enhancement and it was found that PEG-Span80 niosome could significantly enhance the release of calcein and DOX from a PEG liposome composed of 90% hydrogenated soybean phosphatidylcholine (HSPC) and 10% cholesterol. Read More

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Impact of dose, duration and immune status on efficacy of ultrashort telacebec regimens in mouse models of Buruli ulcer.

Antimicrob Agents Chemother 2021 Aug 30:AAC0141821. Epub 2021 Aug 30.

Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

Telacebec (Q203) is a new anti-tuberculosis drug in clinical development with extremely potent activity against , the causative agent of Buruli ulcer (BU). The potency of Q203 has prompted investigation of its potential role in ultra-short, even single-dose, treatment regimens for BU in mouse models. However, the relationships of Q203 dose, dose schedule, duration and host immune status to treatment outcomes remain unclear, as does the risk of emergence of drug resistance with Q203 monotherapy. Read More

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Preclinical Characterization of a Novel Anti-Cancer PD-L1 Inhibitor RPH-120.

Front Pharmacol 2021 11;12:723038. Epub 2021 Aug 11.

R-Pharm Overseas Inc, San Diego, CA, United States.

RPH-120 is a novel fully human anti-PD-L1 IgG1 monoclonal antibody with specifically designed Asn300Ala mutation in Fc fragment. Surface plasmon resonance assay showed that affinity of the RPH-120 to the dimeric form of human PD-L1-Fc fusion protein was much higher than affinity to the monomeric His-tagged PD-L1. Further binding studies demonstrated that RPH-120 is able to bind to human and monkey but not mouse PD-L1. Read More

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