29,007 results match your criteria preclinical trials

Identification of plant-based multitargeted leads for Alzheimer's disease: In-vitro and in-vivo validation of Woodfordia fruticosa (L.) Kurz.

Phytomedicine 2021 Jul 21;91:153659. Epub 2021 Jul 21.

Natural Products & Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-180001, India; Academy of Scientific & Innovative Research (AcSIR), Ghaziabad-201002, India. Electronic address:

Background: Alzheimer's disease (AD) is a complex neurodegenerative disease with no availability of disease-modifying therapeutics. The complex etiology and recent failures in clinical trials indicate the need for multitargeted agents.

Purpose: The present study aims to discover new plant-based multitargeted anti-AD leads. Read More

View Article and Full-Text PDF

Positron emission tomographic imaging in drug discovery.

Drug Discov Today 2021 Jul 28. Epub 2021 Jul 28.

Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Drive, Singapore 636921; Cognitive Neuroimaging Centre, 59 Nanyang Drive, Nanyang Technological University, Singapore 636921, Singapore; Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institute and Stockholm County Council, SE-171 76 Stockholm, Sweden.

Positron emission tomography (PET) is an extensively used nuclear functional imaging technique, especially for central nervous system (CNS) and oncological disorders. Currently, drug development is a lengthy and costly pursuit. Imaging with PET radiotracers could be an effective way to hasten drug discovery and advancement, because it facilitates the monitoring of key facets, such as receptor occupancy quantification, drug biodistribution, pharmacokinetic (PK) analyses, validation of target engagement, treatment monitoring, and measurement of neurotransmitter concentrations. Read More

View Article and Full-Text PDF

Turmeric and Curcumin: From Traditional to Modern Medicine.

Adv Exp Med Biol 2021 ;1291:15-39

Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

The rhizome of turmeric (Curcuma longa L.) has been used as an herbal medicine, coloring agent, spice, and food additive for thousands of years in different parts of the world particularly in Asian countries. It has been used for a range of diseases in many traditional medical schools, including Islamic traditional medicine, Chinese traditional medicine, and Ayurveda. Read More

View Article and Full-Text PDF
January 2021

Intratumoral talimogene laherparepvec injection with concurrent preoperative radiation in patients with locally advanced soft-tissue sarcoma of the trunk and extremities: phase IB/II trial.

J Immunother Cancer 2021 Jul;9(7)

Internal Medicine, The University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.

Background: Soft-tissue sarcomas (STS) in the extremities and trunk treated with standard-of-care preoperative external beam radiation therapy (EBRT) followed by surgical resection are associated with local and distant relapses. In preclinical studies, oncolytic virotherapy in sarcoma has demonstrated antitumor effects via direct intratumoral oncolysis and cytotoxic T-cell-mediated immune responses. Talimogene laherparepvec (TVEC) is a replication-competent, immune-enhanced, oncolytic herpes simplex virus type 1 engineered for intratumoral injection; it has been approved by the FDA for the treatment of locally advanced and metastatic melanoma. Read More

View Article and Full-Text PDF

Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer.

Cancer Treat Res Commun 2021 May 25;28:100405. Epub 2021 May 25.

Cancer Care Center, Blacktown Hospital, Sydney, NSW, Australia. Electronic address:

Background: Agents targeting programmed cell death protein 1 (PD-1) have been approved as monotherapy for patients with small cell lung cancer (SCLC). In preclinical models, the combined targeting of PD-1 and delta-like protein 3 resulted in enhanced antitumor activity. Herein, we report results from the expansion arm of study NCT03000257 evaluating the combination of the anti-PD-1 antibody budigalimab and the targeted antibody-drug conjugate rovalpituzumab tesirine (Rova-T) in patients with previously treated SCLC. Read More

View Article and Full-Text PDF

Autosomic dominant polycystic kidney disease and metformin: Old knowledge and new insights on retarding progression of chronic kidney disease.

Med Res Rev 2021 Jul 30. Epub 2021 Jul 30.

Department of Health Sciences, Renal Unit, "Magna Graecia" University, Catanzaro, Italy.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common congenital kidney disorder, generally caused by mutations in the PKD1 and PKD2 genes, coding for polycystins 1 and 2. Its pathogenesis is accompanied by alterations of the cAMP, mTOR, MAPK/ERK, and JAK/STAT pathways. ADPKD is clinically characterized by the formation of many growing cysts with kidney enlargement and a progressive damage to the parenchyma, up to its complete loss of function, and the onset of end-stage renal disease (ESRD). Read More

View Article and Full-Text PDF

Drug-induced phospholipidosis confounds drug repurposing for SARS-CoV-2.

Science 2021 07 22;373(6554):541-547. Epub 2021 Jun 22.

Department of Pharmaceutical Chemistry, University of California San Francisco (UCSF), San Francisco, CA, USA.

Repurposing drugs as treatments for COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has drawn much attention. Beginning with sigma receptor ligands and expanding to other drugs from screening in the field, we became concerned that phospholipidosis was a shared mechanism underlying the antiviral activity of many repurposed drugs. For all of the 23 cationic amphiphilic drugs we tested, including hydroxychloroquine, azithromycin, amiodarone, and four others already in clinical trials, phospholipidosis was monotonically correlated with antiviral efficacy. Read More

View Article and Full-Text PDF

Preventing type 1 diabetes in childhood.

Science 2021 07;373(6554):506-510

Wellcome Centre for Human Genetics, Nuffield Department of Medicine, National Institute for Health Research (NIHR) Biomedical Research Centre, University of Oxford, Oxford, UK.

Type 1 diabetes (T1D) is an autoimmune disease in which the insulin-producing β cells of the pancreas are destroyed by T lymphocytes. Recent studies have demonstrated that monitoring for pancreatic islet autoantibodies, combined with genetic risk assessment, can identify most children who will develop T1D when they still have sufficient β cell function to control glucose concentrations without the need for insulin. In addition, there has been recent success in secondary prevention using immunotherapy to delay the progression of preclinical disease, and primary prevention approaches to inhibiting the initiating autoimmune process have entered large-scale clinical trials. Read More

View Article and Full-Text PDF

Rilpivirine inhibits SARS-CoV-2 protein targets: A potential multi-target drug.

J Infect Public Health 2021 Jul 21. Epub 2021 Jul 21.

Texas Tech University Health Sciences Center, El Paso, TX, USA.

Background: COVID-19 disease caused by SARS-CoV-2 is lacking efficient medication although certain medications are used to relief its symptoms.

Objectives: We tested an FDA-approved antiviral medication namely rilpivirine to find a drug against SARS-CoV-2.

Methods: The inhibition of rilpivirine against multiple SARS-CoV-2 therapeutic targets was studied using in silico method. Read More

View Article and Full-Text PDF

Type 2 diabetic women are not small type 2 diabetic men: Sex-and-gender differences in antidiabetic drugs.

Curr Opin Pharmacol 2021 Jul 26;60:40-45. Epub 2021 Jul 26.

Laboratorio Nazionale di Farmacologia e Medicina di Genere, Istituto Nazionale Biostrutture Biosistemi, 07100, Sassari, Italy.

Many pieces of evidence have accumulated over time suggesting sex-and-gender differences in type 2 diabetes, the most relevant being the greater excess risk of cardiovascular diseases in women with diabetes than in men. Drugs available for the treatment of diabetes have, meanwhile, increased in number and effectiveness over the last 20 years. Nonetheless, overall metabolic control of diabetes continues to be suboptimal, with a clear further disadvantage for women. Read More

View Article and Full-Text PDF

Mechanistic insights into the efficacy of memantine in treating certain drug addictions.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Jul 27;111:110409. Epub 2021 Jul 27.

Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA; Department of Psychiatry and Psychology, Mayo Clinic, 5777 E Mayo Blvd, Phoenix, AZ, USA. Electronic address:

The deleterious effects of the drug addiction epidemic are compounded by treatment strategies that are only marginally efficacious. Memantine is a unique glutamatergic medication with proven ability to attenuate drug addiction in preclinical models. However, clinical translational studies are inconsistent. Read More

View Article and Full-Text PDF

Cavitation modulated inflammatory response following focused ultrasound blood-brain barrier opening.

J Control Release 2021 Jul 26. Epub 2021 Jul 26.

Department of Biomedical Engineering, Columbia University, New York, NY, USA; Department of Radiology, Columbia University, New York, NY, USA. Electronic address:

Focused ultrasound (FUS) in combination with systemically injected microbubbles can be used to non-invasively open the blood-brain barrier (BBB) in targeted regions for a variety of therapeutic applications. Over the past two decades, preclinical research into the safety and efficacy of FUS-induced BBB opening has proven this technique to be transient and efficacious, propelling FUS-induced BBB opening into several clinical trials in recent years. However, as clinical trials further progress, the neuroinflammatory response to FUS-induced BBB opening needs to be better understood. Read More

View Article and Full-Text PDF

Rebalancing TGF-β/Smad7 signaling via Compound kushen injection in hepatic stellate cells protects against liver fibrosis and hepatocarcinogenesis.

Clin Transl Med 2021 Jul;11(7):e410

State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Liver fibrosis and fibrosis-related hepatocarcinogenesis are a rising cause for morbidity and death worldwide. Although transforming growth factor-β (TGF-β) is a critical mediator of chronic liver fibrosis, targeting TGF-β isoforms and receptors lead to unacceptable side effect. This study was designed to explore the antifibrotic effect of Compound kushen injection (CKI), an approved traditional Chinese medicine formula, via a therapeutic strategy of rebalancing TGF-β/Smad7 signaling. Read More

View Article and Full-Text PDF

Breast cancer resistance mechanisms: challenges to immunotherapy.

Breast Cancer Res Treat 2021 Jul 28. Epub 2021 Jul 28.

Department of Medicine, Breast Cancer Research Program, Vanderbilt University Medical Center, Nashville, TN, USA.

Purpose: The clinical implementation of immunotherapy has profoundly transformed cancer treatment. Targeting the immune system to mount anti-tumor responses can elicit a systemically durable response. Employing immune checkpoint blockade (ICB) has suppressed tumor growth and vastly improved patient overall and progression-free survival in several cancer types, most notably melanoma and non-small cell lung carcinoma. Read More

View Article and Full-Text PDF

APE1/Ref-1 as a Novel Target for Retinal Diseases.

J Cell Signal 2021 ;2(2):133-138

Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202, USA.

APE1/Ref-1 (also called Ref-1) has been extensively studied for its role in DNA repair and reduction-oxidation (redox) signaling. The review titled: " by Caston et. al. Read More

View Article and Full-Text PDF
January 2021

Can Broadly Neutralizing HIV-1 Antibodies Help Achieve an ART-Free Remission?

Front Immunol 2021 12;12:710044. Epub 2021 Jul 12.

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States.

Many broadly neutralizing antibodies (bnAbs) targeting the HIV-1 envelope glycoprotein are being assessed in clinical trials as strategies for HIV-1 prevention, treatment, and antiretroviral-free remission. BnAbs can neutralize HIV-1 and target infected cells for elimination. Concerns about HIV-1 resistance to single bnAbs have led to studies of bnAb combinations with non-overlapping resistance profiles. Read More

View Article and Full-Text PDF

Lipid metabolism in cancer: A systematic review.

J Carcinog 2021 6;20. Epub 2021 May 6.

Department of Oral and Maxillofacial Surgery, Faculty of Dental Sciences, M.S. Ramaiah University of Applied Sciences, Bengaluru, Karnataka, India.

Preclinical studies and clinical trials have emphasized the decisive role of lipid metabolism in tumor proliferation and metastasis. This systematic review aimed to explore the existing literature to evaluate the role and significance of the genes and pathways most commonly involved in the regulation of lipid metabolism in cancer. The literature search was performed as per Preferred Reporting Items for Systematic Reviews and Meta-analyses. Read More

View Article and Full-Text PDF

Pleotropic Effects of Polyphenols in Cardiovascular System.

Biomed Pharmacother 2020 Oct 28;130:110714. Epub 2020 Sep 28.

"Nicolae Balcescu" Land Force Academy, Sibiu, Romania.

Numerous epidemiological and clinical studies demonstrate the beneficial effects of naturally occurring, polyphenol supplementations, on cardiovascular system. The present review emphasizes on the risk factors associated with cardiovascular disorders (involving heart and blood vessels), and overview of preclinical and clinical trials on polyphenols for the treatment of cardiovascular diseases. The review collaborates PUBMED, Google Scholar and Research gate databases, which were explored using keywords and their combinations such as polyphenols, cardiovascular disease, flavonoids, atherosclerosis, cardiovascular risk factors and several others, to create an eclectic manuscript. Read More

View Article and Full-Text PDF
October 2020

Progress toward the Clinical Application of Mesenchymal Stromal Cells and Other Disease-Modulating Regenerative Therapies: Examples from the Field of Nephrology.

Kidney360 2021 Mar;2(3):542-557

Regenerative Medicine Institute (REMEDI) at CÚRAM Centre for Research in Medical Devices, School of Medicine, National University of Ireland Galway, Ireland.

Drawing from basic knowledge of stem-cell biology, embryonic development, wound healing, and aging, regenerative medicine seeks to develop therapeutic strategies that complement or replace conventional treatments by actively repairing diseased tissue or generating new organs and tissues. Among the various clinical-translational strategies within the field of regenerative medicine, several can be broadly described as promoting disease resolution indirectly through local or systemic interactions with a patient's cells, without permanently integrating or directly forming new primary tissue. In this review, we focus on such therapies, which we term disease-modulating regenerative therapies (DMRT), and on the extent to which they have been translated into the clinical arena in four distinct areas of nephrology: renovascular disease (RVD), sepsis-associated AKI (SA-AKI), diabetic kidney disease (DKD), and kidney transplantation (KTx). Read More

View Article and Full-Text PDF

Cognitively unimpaired individuals with a low burden of Aβ pathology have a distinct CSF biomarker profile.

Alzheimers Res Ther 2021 Jul 27;13(1):134. Epub 2021 Jul 27.

Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Wellington 30, 08005, Barcelona, Spain.

Background: Understanding the changes that occur in the transitional stage between absent and overt amyloid-β (Aβ) pathology within the Alzheimer's continuum is crucial to develop therapeutic and preventive strategies. The objective of this study is to test whether cognitively unimpaired individuals with a low burden of Aβ pathology have a distinct CSF, structural, and functional neuroimaging biomarker profile.

Methods: Cross-sectional study of 318 middle-aged, cognitively unimpaired individuals from the ALFA+ cohort. Read More

View Article and Full-Text PDF

Recent Achievements about Targeted Alpha Therapy-Based Targeting Vectors and Chelating Agents.

Anticancer Agents Med Chem 2021 Jul 27. Epub 2021 Jul 27.

Department of Nuclear Medicine and Molecular Imaging, Clinical Development Research Unit of Farshchian Heart Center, Hamadan University of Medical Sciences, Hamadan, Iran.

One of the most rapidly growing options in the management of cancer therapy is Targeted Alpha Therapy (TAT) through which lethal α-emitting radionuclides conjugated to tumor-targeting vectors selectively deliver high amount of radiation to cancer cells.Ac, Bi, At, Bi, and Ra have been investigated by plenty of clinical trials and preclinical researches for the treatment of smaller tumor burdens, micro-metastatic disease, and post-surgery residual disease. In order to send maximum radiation to tumor cells while minimizing toxicity in normal cells, a high affinity of targeting vectors to cancer tissue is essential. Read More

View Article and Full-Text PDF

Transplantation of an obesity-associated human gut microbiota to mice induces vascular dysfunction and glucose intolerance.

Gut Microbes 2021 Jan-Dec;13(1):1940791

Department of Food Science & Human Nutrition, Colorado State University, Fort Collins, CO, USA.

Recent preclinical data suggest that alterations in the gut microbiota may be an important factor linking obesity to vascular dysfunction, an early sign of cardiovascular disease. The purpose of this study was to begin translation of these preclinical data by examining whether vascular phenotypes in humans are transmissible through the gut microbiota. We hypothesized that germ-free mice colonized with gut microbiota from obese individuals would display diminished vascular function compared to germ-free mice receiving microbiota from lean individuals. Read More

View Article and Full-Text PDF

Current Treatments and Therapeutic Options for COVID-19 Patients: A Systematic Review.

Infect Disord Drug Targets 2021 Jul 26. Epub 2021 Jul 26.

Université Aix-Marseille, Institut deNeuro-physiopathologie (INP),UMR 7051, Faculté de Pharmacie,27 Bd Jean Moulin, 13385Marseille Cedex, France.

Introduction: COVID-19 is the third rising epidemic in the 21st century that quickly turned into a worldwide pandemic. Many clinical studies have been achieved to investigate treatments to confrontation of COVID-19. Therefore, we conducted a systematic reviewto describe the recent treatment strategies to treat COVID-19 patients. Read More

View Article and Full-Text PDF

Mesenchymal stem/stromal cells as next-generation drug delivery vehicles for cancer therapeutics.

Expert Opin Drug Deliv 2021 Jul 27. Epub 2021 Jul 27.

Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.

Introduction: : Drug delivery to solid tumors remains a significant therapeutic challenge. Mesenchymal stem/stromal cells (MSCs) home to tumor tissues and can be employed as tumor targeted drug/gene delivery vehiclesReportedly, therapeutic gene- or anti-cancer drug-loaded MSCs have shown remarkable anti-tumor effects in preclinical studies, and some clinical trials for assessing therapeutic MSCs in patients with cancer have been registered.

Areas Covered: : In the present review, we first discuss the source and interdonor heterogeneity of MSCs, their tumor-homing mechanism, and the route of MSC administration in MSC-based cancer therapy. Read More

View Article and Full-Text PDF

Volatile phenolics: A comprehensive review of the anti-infective properties of an important class of essential oil constituents.

Phytochemistry 2021 Jul 23;190:112864. Epub 2021 Jul 23.

Department of Pharmaceutical Sciences, Tshwane University of Technology, Private Bag X680, Pretoria, 0001, South Africa; SAMRC Herbal Drugs Research Unit, Department of Pharmaceutical Sciences, Tshwane University of Technology, Private Bag X680, Pretoria, 0001, South Africa. Electronic address:

Historically, essential oils and their lead molecules have been extensively recognised for their anti-infective properties. In this context, certain volatile phenolics (VPs) have emerged as important antimicrobial compounds with excellent inhibitory activity against pathogenic bacteria and fungi, which further extends to drug-resistant and biofilm-forming micro-organisms. In this review, we aim to collate and discuss a number of published papers on the anti-infective activities of naturally occurring VPs with special emphasis on eugenol, isoeugenol, thymol and carvacrol, using Scopus Web of Science and PubMed databases. Read More

View Article and Full-Text PDF

Chemical update on the potential for serotonin 5-HT and 5-HT receptor agents in the treatment of Alzheimer's disease.

Bioorg Med Chem Lett 2021 Jul 23:128275. Epub 2021 Jul 23.

Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University, Medical College, Medyczna 9, PL 30-688, Kraków, Poland. Electronic address:

Despite the better understanding of the mechanisms underlying Alzheimer's Disease (AD) and launched clinical trials, no AD-modifying treatment based on a synthetic drug has been introduced for almost twenty years. The serotonin 5-HT and 5-HT receptors turned out to be promising biological targets for modulation of central nervous system dysfunctions including cognitive impairment. Within this paper, we evaluate the pharmacological potency of both, 5-HTR and 5-HTR, agents in search for novel AD treatment. Read More

View Article and Full-Text PDF

Advancing precision medicine for acute respiratory distress syndrome.

Lancet Respir Med 2021 Jul 23. Epub 2021 Jul 23.

Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, and Department of Anesthesia, University of California San Francisco, San Francisco, CA, USA.

Acute respiratory distress syndrome (ARDS) is a heterogeneous clinical syndrome. Understanding of the complex pathways involved in lung injury pathogenesis, resolution, and repair has grown considerably in recent decades. Nevertheless, to date, only therapies targeting ventilation-induced lung injury have consistently proven beneficial, and despite these gains, ARDS morbidity and mortality remain high. Read More

View Article and Full-Text PDF

New horizons in early drugs development in solid cancers.

Curr Opin Oncol 2021 Jul 23. Epub 2021 Jul 23.

Oncology Medicine Department Laboratoire d'oncologie clinique et expérimentale (LOCE), Jules Bordet Institute, Brussels, Belgium.

Purpose Of Review: Drug development is the process of bringing new anticancer agents into clinical practice. From the basic research to clinical research each step is essential and intimately linked. The aim of this review is to describe emerging preclinical models and to provide an overview of selected drugs recently developed in oncology. Read More

View Article and Full-Text PDF

3D Bioprinted Multicellular Vascular Models.

Adv Healthc Mater 2021 Jul 26:e2101141. Epub 2021 Jul 26.

Biomedical Engineering, College of Engineering, Texas A&M University, College Station, TX, 77843, USA.

3D bioprinting is an emerging additive manufacturing technique to fabricate constructs for human disease modeling. However, current cell-laden bioinks lack sufficient biocompatibility, printability, and structural stability needed to translate this technology to preclinical and clinical trials. Here, a new class of nanoengineered hydrogel-based cell-laden bioinks is introduced, that can be printed into 3D, anatomically accurate, multicellular blood vessels to recapitulate both the physical and chemical microenvironments of native human vasculature. Read More

View Article and Full-Text PDF

A systematic review of (pre)clinical studies on the therapeutic potential and safety profile of kratom in humans.

Hum Psychopharmacol 2021 Jul 26:e2805. Epub 2021 Jul 26.

Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands.

Introduction: Kratom (Mitragyna speciosa) is a tropical plant traditionally used as an ethnomedicinal remedy for several conditions in South East Asia. Despite the increased interest in its therapeutical benefits in Western countries, little scientific evidence is available to support such claims, and existing data remain limited to kratom's chronic consumption.

Objective: Our study aims to investigate (pre)clinical evidence on the efficacy of kratom as a therapeutic aid and its safety profile in humans. Read More

View Article and Full-Text PDF