78,378 results match your criteria preclinical clinical

Emerging biomarkers of delayed graft function in kidney transplantation.

Transplant Rev (Orlando) 2021 May 26;35(4):100629. Epub 2021 May 26.

Nephrology, Dialysis and Transplantation Unit, Advanced Research Center on Kidney Aging (A.R.K.A.), Department of Medical and Surgical Sciences, University of Foggia, Italy. Electronic address:

Delayed Graft Function (DGF) is one of the most common early complications in kidney transplantation, associated with poor graft outcomes, prolonged post-operative hospitalization and higher rejection rates. Given the severe shortage of high-quality organs for transplantation, DGF incidence is expected to raise in the next years because of the use of nonstandard kidneys from Extended Criteria Donors (ECD) and from Donors after Circulatory Death (DCD). Alongside conventional methods for the evaluation of renal allograft [e. Read More

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Anti-tumor effects of rigosertib in high-risk neuroblastoma.

Transl Oncol 2021 Jun 9;14(8):101149. Epub 2021 Jun 9.

Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden. Electronic address:

High-risk neuroblastoma has a poor prognosis despite intense treatment, demonstrating the need for new therapeutic strategies. Here we evaluated the effects of rigosertib (ON-01910.Na) in preclinical models of high-risk neuroblastoma. Read More

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The predictive value of clinical, radiographic, echocardiographic variables and cardiac biomarkers for assessing risk of the onset of heart failure or cardiac death in dogs with preclinical myxomatous mitral valve disease enrolled in the DELAY study.

J Vet Cardiol 2021 May 16;36:77-88. Epub 2021 May 16.

Clinica Veterinaria Gran Sasso, Milan, Italy.

Objectives: To identify the predictive value on time to onset of heart failure (HF) or cardiac death of clinical, radiographic, and echocardiographic variables, as well as cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I in dogs with preclinical myxomatous mitral valve disease (MMVD).

Animals: One hundred sixty-eight dogs with preclinical MMVD and left atrium to aortic root ratio ≥1.6 (LA:Ao) and normalized left ventricular end-diastolic diameter ≥1. Read More

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A review of the physiological impact of rare earth elements and their uses in biomedical Mg alloys.

Acta Biomater 2021 Jun 9. Epub 2021 Jun 9.

School of Engineering, RMIT University, Melbourne, Victoria 3001, Australia.

Magnesium (Mg) is well-tolerated by the body, displaying exceedingly low toxicity, rapid excretion, and numerous bioactive effects, including improved bone formation and protection against oxidative stresses; further, Mg alloys can be degraded in vivo to allow complete removal of an implant without surgical intervention, avoiding revision surgery and thrombosis concerns seen with permanent implants. Rare earth elements (REEs) have been of particular interest in alloying Mg alloys for nearly a century due to their unique chemical and physical properties but have attracted increasing attention in recent decades. The REEs contribute greatly to the mechanical and biological properties of metal alloys, and so are common in Mg alloys in a wide variety of applications; in particular, they represent the dominant alloying additions in current, clinically applied Mg alloys. Read More

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Exploring the alternative: fish, flies and worms as preclinical models for ALS.

Neurosci Lett 2021 Jun 9:136041. Epub 2021 Jun 9.

KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology, and Leuven Brain Institute (LBI), Leuven, Belgium; VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium. Electronic address:

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder characterized by the loss of upper and lower motor neurons. In general, patients succumb to respiratory insufficiency due to respiratory muscle weakness. Despite many promising therapeutic strategies primarily identified in rodent models, patient trials remain rather unsuccessful. Read More

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Adiponectin and cardiometabolic trait and mortality: where do we go?

Cardiovasc Res 2021 Jun 12. Epub 2021 Jun 12.

Division of Cardiovascular Disease, Gachon University Gil Hospital, Incheon, Korea, Gachon Cardiovascular Research Institute, Incheon, Korea.

Adiponectin is an adipocyte-derived cytokine known for its cardioprotective effects in preclinical studies. Early epidemiologic studies replicated these findings and drew great interest. Subsequent large-scale prospective cohorts, however, showed that adiponectin levels seemed not to relate to incident coronary artery disease (CAD). Read More

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Nanoparticle-Mediated STING Agonist Delivery for Enhanced Cancer Immunotherapy.

Macromol Biosci 2021 Jun 12:e2100133. Epub 2021 Jun 12.

CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, China.

Stimulator of interferon genes (STING) are located in the endoplasmic reticulum of cells, which have been demonstrated to show considerable potentials to achieve efficient antitumor immunity by inducing various pro-inflammatory cytokines and chemokines, such as type I interferons. A variety of STING agonists have been prepared for STING activation, and many of them have been promoted to preclinical trials or clinical applications for the immunotherapy of cancers. However, the intrinsic disadvantages of the small molecule STING agonists can limit the in vivo application and final therapeutic efficacy due to low bioavailability of targeting tissues. Read More

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Zebrafish disease models in drug discovery: from preclinical modelling to clinical trials.

Nat Rev Drug Discov 2021 Jun 11. Epub 2021 Jun 11.

Department of Pathology, Massachusetts General Research Institute, Boston, MA, USA.

Numerous drug treatments that have recently entered the clinic or clinical trials have their genesis in zebrafish. Zebrafish are well established for their contribution to developmental biology and have now emerged as a powerful preclinical model for human disease, as their disease characteristics, aetiology and progression, and molecular mechanisms are clinically relevant and highly conserved. Zebrafish respond to small molecules and drug treatments at physiologically relevant dose ranges and, when combined with cell-specific or tissue-specific reporters and gene editing technologies, drug activity can be studied at single-cell resolution within the complexity of a whole animal, across tissues and over an extended timescale. Read More

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Stem Cell Therapy in Single-Ventricle Physiology: Recent Progress and Future Directions.

Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2021 ;24:67-76

Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Feinburg School of Medicine, Chicago, Illinois. Electronic address:

Current surgical and medical treatment options for single ventricle physiology conditions remain palliative. On the long term, despite treatment, the systemic ventricle has a significant risk of developing failure. There are unmet needs to develop novel treatment modalities to help ameliorate the ventricular dysfunction. Read More

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January 2021

Identifying biophysical assays and properties that enrich for slow clearance in clinical-stage therapeutic antibodies.

MAbs 2021 Jan-Dec;13(1):1932230

Discovery & Development Technologies, Drug Disposition & Design, EMD Serono Research & Development Institute, Inc, Billerica, MA, USA.

Understanding the pharmacokinetic (PK) properties of a drug, such as clearance, is a crucial step for evaluating efficacy. The PK of therapeutic antibodies can be complex and is influenced by interactions with the target, Fc-receptors, anti-drug antibodies, and antibody intrinsic factors. A growing body of literature has linked biophysical properties of antibodies, particularly nonspecific-binding propensity, hydrophobicity and charged regions to rapid clearance in preclinical species and selected human PK studies. Read More

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Medicinal Plants for Insomnia Related to Anxiety: An Updated Review.

Planta Med 2021 Jun 11. Epub 2021 Jun 11.

Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Spain.

Sleep disorders are common among the general population and can generate health problems such as insomnia and anxiety. In addition to standard drugs and psychological interventions, there are different complementary plant-based therapies used to treat insomnia and anxiety. This review aimed to find and examine the most recent research on the use of herbal medicines for treating anxiety and insomnia as compiled from clinical trials, as well as to assess the safety and efficacy of these medicines and to elucidate their possible mechanisms of action. Read More

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Estrogen Pendulum in Schizophrenia and Alzheimer's Disease: Review of Therapeutic Benefits and Outstanding Questions.

Neurosci Lett 2021 Jun 8:136038. Epub 2021 Jun 8.

Department of Applied Neuroscience and Neuroimaging (RA) and Department of Experimental Neuroscience (SVO), National Institute of Mental Health, Topolová 748, 250 67, Klecany, Czech Republic.

Although produced largely in the periphery, gonadal steroids play a key role in regulating the development and functions of the central nervous system and have been implicated in several chronic neuropsychiatric disorders, with schizophrenia and Alzheimer's disease (AD) most prominent. Despite major differences in pathobiology and clinical manifestations, in both conditions, estrogen transpires primarily with protective effects, buffering the onset and progression of diseases at various levels. As a result, estrogen replacement therapy (ERT) emerges as one of the most widely discussed adjuvant interventions. Read More

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Modulatory Potential of Cannabidiol on the Opioid-Induced Inflammatory Response.

Cannabis Cannabinoid Res 2021 Jun;6(3):211-220

Department of Psychological & Brain Science, Indiana University, Bloomington, Indiana, USA.

Opioids are effective analgesics; however, there are many negative consequences of chronic use. One important side effect of chronic opioid use is the continuous engagement of the immune response that can exacerbate chronic pain. The opioid, morphine, initiates a Toll-like receptor 4 (TLR4) signaling cascade that drives the activation of NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome proteins, resulting in cytokine production and effectively creating a positive feedback loop for continuous TLR4 activation. Read More

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Building upon the foundational science curriculum with physiology-based grand rounds: a multi-institutional program evaluation.

Med Educ Online 2021 Dec;26(1):1937908

Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.

: Vertically integrating physiology into patient care has the potential to improve clinical reasoning. Clinical Physiology Grand Rounds (CPGR) is a case-based teaching method that brings together students from all years of medical school to focus on linking clinical presentations to core basic science concepts including anatomy, physiology, and pathophysiology. In this study, we describe the implementation of CPGR at two different institutions in the United States and assess student-reported outcomes. Read More

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December 2021

Bone healing around titanium implants in a preclinical model of bile duct ligation-induced liver injury.

Clin Oral Implants Res 2021 Jun 11. Epub 2021 Jun 11.

Department of Oral Biology, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.

Objectives: Chronic liver disease increases the risk for periodontal disease and osteoporotic fractures, but its impacts on bone regeneration remain unknown. Herein we studied the impact of liver cirrhosis on peri-implant bone formation.

Material And Methods: A total of 20 male Wistar rats were randomly divided into two groups; one with the common bile duct ligated (BDL) and the respective sham-treated control group (SHAM). Read More

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Emerging contrast agents for multispectral optoacoustic imaging and their biomedical applications.

Chem Soc Rev 2021 Jun 11. Epub 2021 Jun 11.

State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, College of Materials Science and Engineering, South China University of Technology, Wushan Road 381, Guangzhou, 510640, China.

Optoacoustic imaging is a hybrid biomedical imaging modality which collects ultrasound waves generated via photoexciting contrast agents in tissues and produces images of high resolution and penetration depth. As a functional optoacoustic imaging technique, multispectral optoacoustic imaging, which can discriminate optoacoustic signals from different contrast agents by illuminating samples with multi-wavelength lasers and then processing the collected data with specific algorithms, assists in the identification of a specific contrast agent in target tissues and enables simultaneous molecular and physiological imaging. Moreover, multispectral optoacoustic imaging can also generate three-dimensional images for biological tissues/samples with high resolution and thus holds great potential in biomedical applications. Read More

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Prodromal Dementia With Lewy Bodies: Evolution of Symptoms and Predictors of Dementia Onset.

J Geriatr Psychiatry Neurol 2021 Jun 11:8919887211023586. Epub 2021 Jun 11.

6886Virginia Commonwealth University, Richmond, VA, USA.

Background: Research criteria for prodromal dementia with Lewy bodies (DLB) were published in 2020, but little is known regarding prodromal DLB in clinical settings.

Methods: We identified non-demented participants without neurodegenerative disease from the National Alzheimer's Coordinating Center Uniform Data Set who converted to DLB at a subsequent visit. Prevalence of neuropsychiatric and motor symptoms were examined up to 5 years prior to DLB diagnosis. Read More

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Combining stem cells in myocardial infarction: The road to superior repair?

Med Res Rev 2021 Jun 11. Epub 2021 Jun 11.

Biomedical Research Institute (BIOMED), Department of Cardio and Organ Systems, UHasselt-Hasselt University, Agoralaan, Diepenbeek, Belgium.

Myocardial infarction irreversibly destroys millions of cardiomyocytes in the ventricle, making it the leading cause of heart failure worldwide. Over the past two decades, many progenitor and stem cell types were proposed as the ideal candidate to regenerate the heart after injury. The potential of stem cell therapy has been investigated thoroughly in animal and human studies, aiming at cardiac repair by true tissue replacement, by immune modulation, or by the secretion of paracrine factors that stimulate endogenous repair processes. Read More

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Temporal Lobe Epilepsy and Alzheimer's Disease: From Preclinical to Clinical Evidence of a Strong Association.

J Alzheimers Dis Rep 2021 Apr 6;5(1):243-261. Epub 2021 Apr 6.

Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, University Campus Bio-Medico, Rome, Italy.

Increasing evidence coming from both experimental and humans' studies strongly suggest the existence of a link between epilepsy, in particular temporal lobe epilepsy (TLE), and Alzheimer's disease (AD). Patients with mild cognitive impairment and AD are more prone to have seizures, and seizures seem to facilitate amyloid-β and tau deposits, thus promoting neurodegenerative processes. Consistent with this view, long-lasting drug-resistant TLE and AD have been shown to share several pathological and neuroimaging features. Read More

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-Generated CAR19-T Cells Plus Lenalidomide Cause Durable Complete Remission of Triple-Hit Refractory/Relapsed DLBCL: A Case Report.

Front Immunol 2021 25;12:599493. Epub 2021 May 25.

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

MYC/BCL2/BCL6 triple-hit lymphoma (THL) is an uncommon subset of high-grade B-cell lymphoma with aggressive clinical behavior and poor prognosis. TP53 mutation is an independently poor progonistic indicator in patients with THL, hence novel therapeutic strategies are needed for these patients. CD19-directed chimeric antigen receptor(CAR19)-T cell therapy has shown promising efficacy for relapsed/refractory diffuse large B cell lymphoma (RR DLBCL), but the majority of CAR19-T cell products to date have been manufactured using viral vectors. Read More

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COVID-19-Associated Pneumonia: Radiobiological Insights.

Front Pharmacol 2021 25;12:640040. Epub 2021 May 25.

Department of Radiation Biological Effects, French Armed Forces Biomedical Research Institute, Brétigny-sur-Orge, France.

The evolution of SARS-CoV-2 pneumonia to acute respiratory distress syndrome is linked to a virus-induced "cytokine storm", associated with systemic inflammation, coagulopathies, endothelial damage, thrombo-inflammation, immune system deregulation and disruption of angiotensin converting enzyme signaling pathways. To date, the most promising therapeutic approaches in COVID-19 pandemic are linked to the development of vaccines. However, the fight against COVID-19 pandemic in the short and mid-term cannot only rely on vaccines strategies, in particular given the growing proportion of more contagious and more lethal variants among exposed population (the English, South African and Brazilian variants). Read More

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CAR T Cell-Based Immunotherapy for the Treatment of Glioblastoma.

Front Neurosci 2021 25;15:662064. Epub 2021 May 25.

Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.

Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor in adults. Current treatment options typically consist of surgery followed by chemotherapy or more frequently radiotherapy, however, median patient survival remains at just over 1 year. Therefore, the need for novel curative therapies for GBM is vital. Read More

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Gene Therapy for Overactive Bladder: A Review of BK-Channel α-Subunit Gene Transfer.

Ther Clin Risk Manag 2021 4;17:589-599. Epub 2021 Jun 4.

Department of Urology, Albert Einstein College of Medicine, Ardsley, NY, USA.

A need exists for local (ie, bladder-specific) interventions to treat overactive bladder (OAB) with low risk of unwanted postprocedural outcomes. Gene therapy targeted to leverage endogenous physiology in bladder cells may assist in restoring normal cell and organ function. Herein, we review the potential promise of gene therapy for treating OAB, focusing on gene transfer of URO-902, a non-viral naked plasmid DNA expressing the big potassium (BK) channel. Read More

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Targeting monoamine oxidase A-regulated tumor-associated macrophage polarization for cancer immunotherapy.

Nat Commun 2021 06 10;12(1):3530. Epub 2021 Jun 10.

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA.

Targeting tumor-associated macrophages (TAMs) is a promising strategy to modify the immunosuppressive tumor microenvironment and improve cancer immunotherapy. Monoamine oxidase A (MAO-A) is an enzyme best known for its function in the brain; small molecule MAO inhibitors (MAOIs) are clinically used for treating neurological disorders. Here we observe MAO-A induction in mouse and human TAMs. Read More

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Immunotherapy using IgE or CAR T cells for cancers expressing the tumor antigen SLC3A2.

J Immunother Cancer 2021 Jun;9(6)

St John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, London, England, UK

Background: Cancer immunotherapy with monoclonal antibodies and chimeric antigen receptor (CAR) T cell therapies can benefit from selection of new targets with high levels of tumor specificity and from early assessments of efficacy and safety to derisk potential therapies.

Methods: Employing mass spectrometry, bioinformatics, immuno-mass spectrometry and CRISPR/Cas9 we identified the target of the tumor-specific SF-25 antibody. We engineered IgE and CAR T cell immunotherapies derived from the SF-25 clone and evaluated potential for cancer therapy. Read More

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Ex vivo expansion of hematopoietic stem cells: Finally transitioning from the lab to the clinic.

Blood Rev 2021 Jun 4:100853. Epub 2021 Jun 4.

Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levi Place, Box 1079, New York, NY 10029, USA. Electronic address:

Hematopoietic stem cells (HSCs) have been used for therapeutic purposes for decades in the form of autologous and allogeneic transplantation and are currently emerging as an attractive target for gene therapy. A low stem cell dose is a major barrier to the application of HSC therapy in several situations, primarily umbilical cord blood transplantation and gene modification. Strategies that promote ex vivo expansion of the numbers of functional HSCs could overcome this barrier, hence have been the subject of intense and prolonged research. Read More

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Stem cells in the treatment of renal fibrosis: a review of preclinical and clinical studies of renal fibrosis pathogenesis.

Stem Cell Res Ther 2021 Jun 10;12(1):333. Epub 2021 Jun 10.

Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, No. 69 Dongsha Road, Shantou, 515041, China.

Renal fibrosis commonly leads to glomerulosclerosis and renal interstitial fibrosis and the main pathological basis involves tubular atrophy and the abnormal increase and excessive deposition of extracellular matrix (ECM). Renal fibrosis can progress to chronic kidney disease. Stem cells have multilineage differentiation potential under appropriate conditions and are easy to obtain. Read More

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Therapies in preclinical and clinical development for Angelman syndrome.

Expert Opin Investig Drugs 2021 Jun 10. Epub 2021 Jun 10.

MDUK Oxford Neuromuscular Center, Oxford, UK.

Introduction: Angelman syndrome is a rare genetic neurodevelopmental disorder, caused by deficiency or abnormal function of the maternal ubiquitin protein-ligase E3A, known as UBE3A, in the central nervous system. Currently, there is no disease-modifying treatment available, but the therapeutic pipeline of Angelman syndrome includes at least 15 mechanistically different approaches at preclinical or clinical development. In the coming years, several clinical trials will be enrolling patients and, therefore, Angelman syndrome community needs to be aware of all options. Read More

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High-Throughput Imaging Assay for Drug Screening of 3D Prostate Cancer Organoids.

SLAS Discov 2021 Jun 11:24725552211020668. Epub 2021 Jun 11.

Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia.

New treatments are required for advanced prostate cancer; however, there are fewer preclinical models of prostate cancer than other common tumor types to test candidate therapeutics. One opportunity to increase the scope of preclinical studies is to grow tissue from patient-derived xenografts (PDXs) as organoid cultures. Here we report a scalable pipeline for automated seeding, treatment and an analysis of the drug responses of prostate cancer organoids. Read More

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