188,136 results match your criteria models vivo

Synthesis, in silico, in vitro and in vivo evaluations of isatin aroylhydrazones as highly potent anticonvulsant agents.

Bioorg Chem 2021 Apr 24;112:104943. Epub 2021 Apr 24.

Department of Pharmacology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran. Electronic address:

In this study, a series of new isatin aroylhydrazones (5a-e and 6a-e) was synthesized and evaluated for their anticonvulsant activities. The (Z)-configuration of compounds was confirmed by H NMR. In vivo studies using maximal electroshock (MES) and pentylenetetrazole (PTZ) models of epilepsy in mice revealed that while most of compounds had no effect on chemically-induced seizures at the higher dose of 100 mg/kg but showed significant protection against electrically-induced seizures at the lower dose of 5 mg/kg. Read More

View Article and Full-Text PDF

Decoding the microstructural properties of white matter using realistic models.

Neuroimage 2021 May 5:118138. Epub 2021 May 5.

Radboud University, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands.

Multi-echo gradient echo (ME-GRE) magnetic resonance signal evolution in white matter has a strong dependence on the orientation of myelinated axons with respect to the main static field. Although analytical solutions have been able to predict some of the white matter (WM) signal behaviour of the hollow cylinder model, it has been shown that realistic models of WM offer a better description of the signal behaviour observed. In this work, we present a pipeline to (i) generate realistic 2D WM models with their microstructure based on real axon morphology with adjustable fiber volume fraction (FVF) and g-ratio. Read More

View Article and Full-Text PDF

Cocktail strategy for 'cold' tumors therapy via active recruitment of CD8+ T cells and enhancing their function.

J Control Release 2021 May 5. Epub 2021 May 5.

College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China. Electronic address:

In immunotherapy, 'cold' tumors, with low T cells infiltration, hardly benefit from the treatment of immune checkpoint inhibitors (ICIs). To address this issue, we screened two 'cold' tumor models for mice with high expression of galectin-3 (Gal-3) and designed a cocktail strategy to actively recruit CD8+ T cells into the tumor microenvironment (TME), which reversed 'cold' tumors into 'hot' and remarkably elevated their ICIs-responsiveness. Gal-3, an important driving force of tumorigenesis, inhibits T cell infiltration into tumor tissue that shapes 'cold' tumor phenotype, and promotes tumor metastasis. Read More

View Article and Full-Text PDF

Enhanced neuroprotective and antidepressant activity of curcumin-loaded nanostructured lipid carriers in lipopolysaccharide-induced depression and anxiety rat model.

Int J Pharm 2021 May 5:120670. Epub 2021 May 5.

Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan. Electronic address:

The present study aims to develop curcumin-loaded nanostructured lipid carriers (CUR-NLCs) and investigate their neuroprotective effects in lipopolysaccharide (LPS)-induced depression and anxiety model. Nanotemplate engineering technique was used to prepare CUR-NLCs with Compritol 888 ATO and oleic acid as solid and liquid lipid, respectively. Poloxamer 188, Tween 80 and Span 80 were used as stabilizing agents for solid-liquid lipid core. Read More

View Article and Full-Text PDF

HDAC9 exacerbates myocardial infarction via inactivating Nrf2 pathways.

J Pharm Pharmacol 2021 May 8. Epub 2021 May 8.

First Department of Cardiology, Tangshan Gongren Hospital, Hebei, China.

Objectives: Myocardial infarction (MI) is the leading cause of death worldwide. Histone deacetylases (HDACs) collectively participate in the initiation and progression of heart diseases, including MI. This study aimed to investigate the roles of histone deacetylase 9 (HDAC9) in the development of MI. Read More

View Article and Full-Text PDF

Cardiac metabolic imaging using hyperpolarized [1- C]lactate as a substrate.

NMR Biomed 2021 May 8:e4532. Epub 2021 May 8.

Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.

Hyperpolarized (HP) [1- C]lactate is an attractive alternative to [1- C]pyruvate as a substrate to investigate cardiac metabolism in vivo: it can be administered safely at a higher dose and can be polarized to a degree similar to pyruvate via dynamic nuclear polarization. While C cardiac experiments using HP lactate have been performed in small animal models, they have not been demonstrated in large animal models or humans. Utilizing the same hardware and data acquisition methods as the first human HP C cardiac study, C metabolic images were acquired following injections of HP [1- C]lactate in porcine hearts. Read More

View Article and Full-Text PDF

3D Printing of Strontium Silicate Microcylinder-Containing Multicellular Biomaterial Inks for Vascularized Skin Regeneration.

Adv Healthc Mater 2021 May 8:e2100523. Epub 2021 May 8.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, P. R. China.

The reconstruction of dermal blood vessels is essential for skin regeneration process. However, the lack of vascular structure, insufficient angiogenesis induction, and ineffective graft-host anastomosis of the existing skin substitutes are major bottle-necks for permanent skin replacement in tissue engineering. In this study, the uniform strontium silicate (SS) microcylinders are successfully synthesized and integrated into the biomaterial ink to serve as stable cell-induced factors for angiogenesis, and then a functional skin substitute based on a vascularization-induced biomimetic multicellular system is prepared via a "cell-writing" bioprinting technology. Read More

View Article and Full-Text PDF

Therapeutic Antibodies Targeting Potassium Ion Channels.

Handb Exp Pharmacol 2021 May 8. Epub 2021 May 8.

TetraGenetics Inc, Arlington, MA, USA.

Monoclonal antibodies combine specificity and high affinity binding with excellent pharmacokinetic properties and are rapidly being developed for a wide range of drug targets including clinically important potassium ion channels. Nonetheless, while therapeutic antibodies come with great promise, K channels represent particularly difficult targets for biologics development for a variety of reasons that include their dynamic structures and relatively small extracellular loops, their high degree of sequence conservation (leading to immune tolerance), and their generally low-level expression in vivo. The process is made all the more difficult when large numbers of antibody candidates must be screened for a given target, or when lead candidates fail to cross-react with orthologous channels in animal disease models due to their highly selective binding properties. Read More

View Article and Full-Text PDF

Mitochondria-targeted antioxidant MitoQ ameliorates ischaemia-reperfusion injury in kidney transplantation models.

Br J Surg 2021 May 8. Epub 2021 May 8.

Department of Surgery, University of Cambridge, Cambridge, UK.

Background: Ischaemia-reperfusion (IR) injury makes a major contribution to graft damage during kidney transplantation. Oxidative damage to mitochondria is an early event in IR injury. Therefore, the uptake, safety, and efficacy of the mitochondria-targeted antioxidant MitoQ were investigated in models of transplant IR injury. Read More

View Article and Full-Text PDF

Introduction to the mini special issue on next generation drug discovery and development: rethinking translational pharmacology for accelerated drug development.

Drug Metab Rev 2021 May 7:1-2. Epub 2021 May 7.

Gilead Alberta ULC, Edmonton, Canada.

AbstratThe coronavirus disease (COVID-19) pandemic further revealed the barriers to accelerated discovery and development of transformative medicines for life threatening diseases. To effectively and efficiently respond to unmet medical needs, efforts should be directed towards revolutionizing the predictive capability of non-clinical surrogates that inform drug discovery and development programs. I developed this mini special issue amidst the COVID-19 pandemic to evaluate recent advancements and opportunities for four main subthemes that support drug discovery and development including prediction of metabolic pathways, translational pharmacokinetic and pharmacodynamic studies, pharmacogenomics, and trends in bioanalysis. Read More

View Article and Full-Text PDF

Redd1 knockdown prevents doxorubicin-induced cardiac senescence.

Aging (Albany NY) 2021 May 6;13. Epub 2021 May 6.

Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.

Regulated in development and DNA damage response-1 (Redd1) is a stress-response gene that is transcriptionally induced by diverse stressful stimuli to influence cellular growth and survival. Although evidence suggests that aging may drive Redd1 expression in skeletal muscles, the expression patterns and functions of Redd1 in senescent cardiomyocytes remain unspecified. To address this issue, and models of cardiomyocyte senescence were established by administration of doxorubicin (Dox). Read More

View Article and Full-Text PDF

TAK1 is a novel target in Hepatocellular Carcinoma and contributes to sorafenib resistance.

Cell Mol Gastroenterol Hepatol 2021 May 4. Epub 2021 May 4.

Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China; Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment 310016, Hangzhou, China; Zhejiang University Cancer Center, 310058, Hangzhou, China; Liangzhu Laboratory, Zhejiang University Medical Center, 311121, Hangzhou, China. Electronic address:

Background & Aims: Identifying novel and actional targets in hepatocellular carcinoma (HCC) remains an unmet medical need. TAK1 was originally identified as a TGF-β-activated kinase and was further proved to phosphorylate and activate numerous downstream targets and promote cancer progression. However, the role of TAK1 in developed HCC progression and targeted therapy resistance is poorly understood. Read More

View Article and Full-Text PDF

Multidimensional analysis of the epigenetic alterations in toxicities induced by mycotoxins.

Food Chem Toxicol 2021 May 4:112251. Epub 2021 May 4.

Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100083, China. Electronic address:

Mycotoxins contaminate all types of food and feed, threatening human and animal health through food chain accumulation, producing various toxic effects. Increasing attention is being focused on the molecular mechanism of mycotoxin-induced toxicity in all kinds of in vivo and in vitro models. Epigenetic alterations, including DNA methylation, non-coding RNAs (ncRNAs), and protein post-translational modifications (PTMs), were identified as being involved in various types of mycotoxin-induced toxicity. Read More

View Article and Full-Text PDF

Bone marrow-derived macrophages converted into cancer-associated fibroblast-like cells promote pancreatic cancer progression.

Cancer Lett 2021 May 4. Epub 2021 May 4.

Department of Surgery and Oncology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. Electronic address:

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a desmoplastic reaction caused by cancer-associated fibroblasts (CAFs), which provokes treatment resistance. CAFs are newly proposed to be heterogeneous populations with different functions within the PDAC microenvironment. The most direct sources of CAFs are resident tissue fibroblasts and mesenchymal stem cells, however, the origins and functions of CAF subtypes remain unclear. Read More

View Article and Full-Text PDF

Lacto-N-fucopentaose-III (LNFPIII) ameliorates acute aberrations in hippocampal synaptic transmission in a Gulf War Illness animal model.

Brain Res 2021 May 4:147513. Epub 2021 May 4.

Department of Physiology and Pharmacology; Interdisciplinary Toxicology Program. Electronic address:

Approximately one-third of Persian Gulf War veterans are afflicted by Gulf War Illness (GWI), a chronic multisymptom condition that fundamentally presents with cognitive deficits (i.e., learning and memory impairments) and neuroimmune dysfunction (i. Read More

View Article and Full-Text PDF

Development and Testing of an Anatomic in vitro Kidney Model for Measuring Intrapelvic Pressure During Ureteroscopy.

Urology 2021 May 4. Epub 2021 May 4.

Department of Urology, University of Michigan, Ann Arbor, MI, USA. Electronic address:

Objectives: To create an in vitro anatomic bench model that can mimic in vivo intrapelvic pressure (IPP) during ureteroscopy (URS) and compare it against existing in vivo and ex vivo data.

Methods: A silicone kidney model (Simagine Health) that permits intrarenal endoscopic navigation was engineered to have a fluid-tight seal for the ureteral opening and a Tuohy-Borst valve in the renal pelvis incorporating a 0.2 mm pressure sensor (Opsens). Read More

View Article and Full-Text PDF

ERK1/2 kinases and dopamine D2 receptors participate in the anticonvulsant effects of a new derivative of benzoylpyridine oxime and valproic acid.

Eur J Pharmacol 2021 May 4:174150. Epub 2021 May 4.

Laboratory of Molecular Mechanisms of Biological Adaptation, Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 119991, Moscow, Russia. Electronic address:

Inhibition of the activity of extracellular signal-regulated kinases (ERK1/2) induced by the activation of the dopamine D2 receptor signalling cascade may be a promising pharmacological target. The aim of this work was to study the involvement of ERK1/2 and dopamine D2 receptor in the mechanism of the anticonvulsant action of valproic acid (VA) and a new benzoylpyridine oxime derivative (GIZH-298), which showed antiepileptic activity in different models of epilepsy. We showed that subchronic exposure to maximal electroshock seizures (MES) for 5 days reduced the density of dopamine D2 receptors in the striatum of mice. Read More

View Article and Full-Text PDF

Ferulic acid positively modulates the inflammatory response to septic liver injury through the GSK-3β/NF-κB/CREB pathway.

Life Sci 2021 May 4:119584. Epub 2021 May 4.

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China. Electronic address:

Aims: Ferulic acid (FA) is a component found in plants that has free radical scavenging and liver-protective properties. Acute liver injury (ALI) is a serious complication of sepsis and is closely associated with changes in the levels of inflammatory factors. This study was taken to examine the role of FA in cecal ligation and perforation (CLP)-induced murine ALI and lipopolysaccharide (LPS)-induced cellular ALI models. Read More

View Article and Full-Text PDF

Spontaneous Extension Wave for In Vivo Assessment of Arterial Wall Anisotropy.

Am J Physiol Heart Circ Physiol 2021 May 7. Epub 2021 May 7.

Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Konggrid.194645.b.

Another type of natural wave, traced from longitudinal wall motion and propagation along the artery, is unprecedentedly observed in our in vivo human carotid artery experiments. We coin it as extension wave (EW) and hypothesize that EW velocity (EWV) is associated with arterial longitudinal stiffness. The EW is thus assumed to complement the PW, whose velocity (PWV) is tracked from the radial wall displacement and linked to arterial circumferential stiffness through the Moens-Korteweg equation, as indicators for arterial mechanical anisotropy quantification by noninvasive high-frame-rate ultrasound. Read More

View Article and Full-Text PDF

Using Rotenone to Model Parkinson's Disease in Mice: A Review of the Role of Pharmacokinetics.

Chem Res Toxicol 2021 May 7. Epub 2021 May 7.

Institute of Biomedicine and Translational Medicine, Ravila 19, University of Tartu, 50411 Tartu, Estonia.

Rotenone is a naturally occurring toxin that inhibits complex I of the mitochondrial electron transport chain. Several epidemiological studies have shown an increased risk of Parkinson's disease (PD) in individuals exposed chronically to rotenone, and it has received great attention for its ability to reproduce many critical features of PD in animal models. Laboratory studies of rotenone have repeatedly shown that it induces in vivo substantia nigra dopaminergic cell loss, a hallmark of PD neuropathology. Read More

View Article and Full-Text PDF

3-O-trans-caffeoyloleanolic acid improves acute lung injury via antiinflammation and antioxidative stress involved PI3K/AKT pathway.

Chem Biol Drug Des 2021 May 7. Epub 2021 May 7.

Department of Respiratory and Critical Care Medicine, Jiangxi Chest (Third people) Hospital, Nanchang, Jiangxi, 330006, PR China.

3-O-trans-caffeoyloleanolic acid (COA) is a pentacyclic triterpenoid compound, with significant anti-inflammatory effects. In this study, we report the protective effects of COA on LPS-induced acute lung injury (ALI) and explored its mechanism of action. LPS was used to construct in vivo mouse ALI models to observe the effects of COA pretreatment on lung pathology, inflammation and oxidative stress. Read More

View Article and Full-Text PDF

Reply to Yurekli et al.

Eur J Cardiothorac Surg 2021 May 7. Epub 2021 May 7.

Northern Clinical School of Medicine, University of Sydney, Kolling Institute, St Leonards, Sydney, NSW, Australia.

View Article and Full-Text PDF

Persistent effects of pair bonding in lung cancer cell growth in monogamous .

Elife 2021 May 7;10. Epub 2021 May 7.

Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, United States.

Epidemiological evidence suggests that social interactions and especially bonding between couples influence tumorigenesis, yet whether this is due to lifestyle changes, homogamy (likelihood of individuals to marry people of similar health), or directly associated with host-induced effects in tumors remains debatable. In the present study, we explored if tumorigenesis is associated with the bonding experience in monogamous rodents at which disruption of pair bonds is linked to anxiety and stress. Comparison of lung cancer cell spheroids that formed in the presence of sera from bonded and bond-disrupted deer mice showed that in monogamous and , but not in polygamous , the disruption of pair bonds altered the size and morphology of spheroids in a manner that is consistent with the acquisition of increased oncogenic potential. Read More

View Article and Full-Text PDF

3D Spheroids Versus 3D Tumor-Like Microcapsules: Confinement and Mechanical Stress May Lead to the Expression of Malignant Responses in Cancer Cells.

Adv Biol (Weinh) 2021 May 7:e2000349. Epub 2021 May 7.

Institute of Biomaterials, Friedrich-Alexander Universität Erlangen-Nürnberg, Cauerstraße 6, 91058, Erlangen, Germany.

As 2D surfaces fail to resemble the tumoral milieu, current discussions are focused on which 3D cell culture strategy may better lead the cells to express in vitro most of the malignant hints described in vivo. In this study, this question is assessed by analyzing the full genetic profile of MCF7 cells cultured either as 3D spheroids-considered as "gold standard" for in vitro cancer research- or immobilized in 3D tumor-like microcapsules, by RNA-Seq and transcriptomic methods, allowing to discriminate at big-data scale, which in vitro strategy can better resemble most of the malignant features described in neoplastic diseases. The results clearly show that mechanical stress, rather than 3D morphology only, stimulates most of the biological processes involved in cancer pathogenicity, such as cytoskeletal organization, migration, and stemness. Read More

View Article and Full-Text PDF

Establishment and characterization of a novel treatment-related neuroendocrine prostate cancer cell line KUCaP13.

Cancer Sci 2021 May 7. Epub 2021 May 7.

Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

The prevalence of neuroendocrine prostate cancer (NEPC) arising from adenocarcinoma (AC) upon potent androgen receptor pathway inhibition is increasing. Deeper understanding of NEPC biology and development of novel therapeutic agents are needed. However, research is hindered by the paucity of research models, especially cell lines developed from NEPC patients. Read More

View Article and Full-Text PDF

Computational study on subfamilies of piperidine derivatives: QSAR modelling, model external verification, the inter-subset similarity determination, and structure-based drug designing.

SAR QSAR Environ Res 2021 May 7:1-30. Epub 2021 May 7.

Chemometrics Laboratory, Chemistry Department, Faculty of Science, University of Kurdistan, Sanandaj, Iran.

A new subset of furan-pyrazole piperidine derivatives was used for QSAR model development. These compounds exhibit good Akt1 inhibitory activity; moreover, antiproliferative activities in vitro against OVCAR-8 (Human ovarian carcinoma cells) and HCT116 (human colon cancer cells), were confirmed for them. Based on the relevant three-dimensional (3D) and 2D autocorrelation descriptors, selected by genetic algorithm (GA), multiple linear regression (MLR) was established on half maximal-inhibitory concentration (IC), in Akt1 and cancer cell lines independently. Read More

View Article and Full-Text PDF

Lansoprazole Alone or in Combination With Gefitinib Shows Antitumor Activity Against Non-small Cell Lung Cancer A549 Cells and .

Front Cell Dev Biol 2021 20;9:655559. Epub 2021 Apr 20.

Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, China.

Lansoprazole (Lpz) is an FDA-approved proton pump inhibitor (PPI) drug for the therapy of acid-related diseases. Aiming to explore the new application of old drugs, we recently investigated the antitumor effect of Lpz. We demonstrated that the PPI Lpz played a tumor suppressive role in non-small cell lung cancer (NSCLC) A549 cells. Read More

View Article and Full-Text PDF

Intravital Metabolic Autofluorescence Imaging Captures Macrophage Heterogeneity Across Normal and Cancerous Tissue.

Front Bioeng Biotechnol 2021 20;9:644648. Epub 2021 Apr 20.

Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, United States.

Macrophages are dynamic immune cells that govern both normal tissue function and disease progression. However, standard methods to measure heterogeneity in macrophage function within tissues require tissue excision and fixation, which limits our understanding of diverse macrophage function . Two-photon microscopy of the endogenous metabolic co-enzymes NAD(P)H and flavin adenine dinucleotide (FAD) (metabolic autofluorescence imaging) enables dynamic imaging of mouse models . Read More

View Article and Full-Text PDF

An Investigation Into the Role of Strain and Structure on Vascular Smooth Muscle Cell Growth.

Front Bioeng Biotechnol 2021 20;9:641794. Epub 2021 Apr 20.

Trinity Centre for Biomedical Engineering, Trinity College Dublin, Trinity Biomedical Sciences Institute, Dublin, Ireland.

The orientation of vascular cells can greatly influence the mechanical properties and functionality of soft vascular tissues. How cell orientation mediates the growth response of cells is of critical importance in understanding the response of soft tissues to mechanical stimuli or injury. To date, considerable evidence has shown that cells align with structural cues such as collagen fibers. Read More

View Article and Full-Text PDF

Effects of a Traditional Caraway Formulation on Experimental Models of Vitiligo and Mechanisms of Melanogenesis.

Evid Based Complement Alternat Med 2021 19;2021:6675657. Epub 2021 Apr 19.

State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, and Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China.

Background: Kursi Karwiya or caraway tablet (CWT), a traditional medicine formula, is widely used in Xinjiang, China, for treating vitiligo, a common autoimmune disease for which there is currently no satisfactory cure. Clinical interventions include pharmacological treatment with psoralens, often in conjunction with UVA radiation, but toxic side effects limit this application. Studies on the activities and mechanisms of CWT are scarce. Read More

View Article and Full-Text PDF