60,211 results match your criteria gene delivery

Induction of cellular senescence as a late effect and BDNF-TrkB signaling-mediated ameliorating effect on disruption of hippocampal neurogenesis after developmental exposure to lead acetate in rats.

Toxicology 2021 Apr 13:152782. Epub 2021 Apr 13.

Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan; Cooperative Division of Veterinary Sciences, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan; Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan. Electronic address:

Lead (Pb) exposure causes cognitive deficits in children. The present study investigated the effect of developmental exposure to Pb acetate (PbAc) on postnatal hippocampal neurogenesis. Pregnant rats were administered drinking water containing 0, 2000, or 4000 ppm PbAc from gestational day 6 until day 21 post-delivery (weaning), and offspring were maintained without PbAc exposure until adulthood on postnatal day (PND) 77. Read More

View Article and Full-Text PDF

miR-30c inhibits angiogenesis by targeting delta-like ligand 4 in liver sinusoidal endothelial cell to attenuate liver fibrosis.

FASEB J 2021 May;35(5):e21571

Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Liver fibrosis is a common feature of liver dysfunction during chronic liver diseases and is frequently associated with angiogenesis, a dynamic process that forms new blood vessels from preexisting vasculature. MicroRNAs (miRNAs), which act as posttranscriptional regulators of gene expression, have been shown to regulate liver fibrosis; however, how miRNAs regulate angiogenesis and its mechanism in fibrosis are not well understood. We aimed to elucidate the role and mechanism of miR-30c in attenuating liver fibrosis. Read More

View Article and Full-Text PDF

Zinc(II)-Dipicolylamine Analogs Mediated PEI1.8k/pDNA Vector: Effect of Ligand Structure on the Gene Transport Process.

Macromol Biosci 2021 Apr 16:e2100048. Epub 2021 Apr 16.

Key Laboratory, of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin, 300071, China.

Zinc ion complexes of dipicolylamine analogs, due to the strong synergistic effect between the Zn complex of containing polypyridine derivatives and polycations in each key step of pDNA transport, have been used as the third component to mediate polyethyleneimine with molecular weight 1.8 kDa (PEI1.8k)/DNA gene delivery system. Read More

View Article and Full-Text PDF

Interaction of a triantennary quinoline glycoconjugate with Asialoglycoprotein receptor.

ChemMedChem 2021 Apr 16. Epub 2021 Apr 16.

Indian Institute of Chemical Biology CSIR, Organic and Medicinal Chemistry, 4, Raja S.C Mullick Road, Jadavpur, 700032, Kolkata, INDIA.

Targeted intracellular delivery is an efficient strategy for developing therapeutics against cancer and other intracellular infections. Non-specific drug delivery show limited clinical applications owing to their high dosage, cytotoxicity, non-specific action, high cost, etc. So, targeted delivery of less cytotoxic drug candidates to hepatocytes through ASGPR mediated endocytosis could be an efficient strategy to surmount the prevailing shortcomings. Read More

View Article and Full-Text PDF

Nanomedicines for combating multidrug resistance of cancer.

Wiley Interdiscip Rev Nanomed Nanobiotechnol 2021 Apr 15:e1715. Epub 2021 Apr 15.

State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.

Chemotherapy typically involves the use of specific chemodrugs to inhibit the proliferation of cancer cells, but the frequent emergence of a variety of multidrug-resistant cancer cells poses a tremendous threat to our combat against cancer. The fundamental causes of multidrug resistance (MDR) have been studied for decades, and can be generally classified into two types: one is associated with the activation of diverse drug efflux pumps, which are responsible for translocating intracellular drug molecules out of the cells; the other is linked with some non-efflux pump-related mechanisms, such as antiapoptotic defense, enhanced DNA repair ability, and powerful antioxidant systems. To overcome MDR, intense efforts have been made to develop synergistic therapeutic strategies by introducing MDR inhibitors or combining chemotherapy with other therapeutic modalities, such as phototherapy, gene therapy, and gas therapy, in the hope that the drug-resistant cells can be sensitized toward chemotherapeutics. Read More

View Article and Full-Text PDF

Enhancement of oral bioavailability and anti-hyperuricemic activity of aloe emodin via novel Soluplus®-glycyrrhizic acid mixed micelle system.

Drug Deliv Transl Res 2021 Apr 15. Epub 2021 Apr 15.

Department of Pharmaceutics, School of Pharmacy, Centre for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang, 212013, People's Republic of China.

The objective of this study was to fabricate a novel drug delivery system using Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) and glycyrrhizic acid to improve solubility, bioavailability, and anti-hyperuricemic activity of aloe emodin (AE). The AE-loaded mixed micelles (AE-M) were prepared by thin-film hydration method. The optimal AE-M contained small-sized (30. Read More

View Article and Full-Text PDF

Ultrasound-Responsive Nanocarriers in Cancer Treatment: A Review.

ACS Pharmacol Transl Sci 2021 Apr 3;4(2):589-612. Epub 2021 Mar 3.

Department of Chemical Engineering, American University of Sharjah, Sharjah, United Arab Emirates.

The safe and effective delivery of anticancer agents to diseased tissues is one of the significant challenges in cancer therapy. Conventional anticancer agents are generally cytotoxins with poor pharmacokinetics and bioavailability. Nanocarriers are nanosized particles designed for the selectivity of anticancer drugs and gene transport to tumors. Read More

View Article and Full-Text PDF

A Local and Low-Dose Chemotherapy/Autophagy-Enhancing Regimen Treatment Markedly Inhibited the Growth of Established Solid Tumors Through a Systemic Antitumor Immune Response.

Front Oncol 2021 30;11:658254. Epub 2021 Mar 30.

Institute of Clinical Oncology, Research Center of Cancer Diagnosis and Therapy, and Department of Clinical Oncology, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Chemotherapy is one of the main options for the treatment of a variety of malignant tumors. However, the severe side effects resulting from the killing of normal proliferating cells limit the application of cancer-targeting chemotherapeutic drugs. To improve the efficacy of classic systemic chemotherapy, the local delivery of high-dose chemotherapeutic drugs was developed as a method to enhance local drug concentrations and minimize systemic toxicity. Read More

View Article and Full-Text PDF

The Anesthetic Management of a Parturient With Osteogenesis Imperfecta Type I Undergoing Cesarean Delivery.

Cureus 2021 Mar 12;13(3):e13849. Epub 2021 Mar 12.

Anesthesiology and Perioperative Medicine, Loma Linda University Medical Center, Loma Linda, USA.

Osteogenesis imperfecta (OI) is a rare disorder of bone fragility caused by mutations in the COL1A1/2 genes, which encode type I procollagen. It commonly manifests with bone fractures, joint dislocations, and easy bruising. OI patients presenting for surgery may pose multiple challenges to the anesthesiologist such as management of a potentially difficult airway and heightened positional fracture risks. Read More

View Article and Full-Text PDF

Role of Cigarette Smoke on Angiotensin-Converting Enzyme-2 Protein Membrane Expression in Bronchial Epithelial Cells Using an Air-Liquid Interface Model.

Front Pharmacol 2021 30;12:652102. Epub 2021 Mar 30.

Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.

Prevalence studies of current smoking, among hospitalized COVID-19 patients, demonstrated an unexpectedly low prevalence among patients with COVID-19. The aim of the present study was to evaluate the effect of smoke from cigarettes on ACE-2 in bronchial epithelial cells. Normal bronchial epithelial cells (H292) were exposed to smoke by an air-liquid-interface (ALI) system and ACE-2 membrane protein expression was evaluated after 24 h from exposure. Read More

View Article and Full-Text PDF

GM1 Gangliosidosis: Mechanisms and Management.

Appl Clin Genet 2021 9;14:209-233. Epub 2021 Apr 9.

Scott-Ritchey Research Center, Auburn University, Auburn, AL, 36849, USA.

The lysosomal storage disorder, GM1 gangliosidosis (GM1), is a neurodegenerative condition resulting from deficiency of the enzyme β-galactosidase (β-gal). Mutation of the gene, which codes for β-gal, prevents cleavage of the terminal β-1,4-linked galactose residue from GM1 ganglioside. Subsequent accumulation of GM1 ganglioside and other substrates in the lysosome impairs cell physiology and precipitates dysfunction of the nervous system. Read More

View Article and Full-Text PDF

Intravital imaging of real-time endogenous actin dysregulation in proximal and distal tubules at the onset of severe ischemia-reperfusion injury.

Sci Rep 2021 Apr 15;11(1):8280. Epub 2021 Apr 15.

Department of Immunology and Physiology, College of Medicine and Health Sciences, Pre-medicine Bridge Program, College of Arts and Sciences, Khalifa University of Science and Technology, PO Box 127788, Abu Dhabi, UAE.

Severe renal ischemia-reperfusion injury (IRI) can lead to acute and chronic kidney dysfunction. Cytoskeletal modifications are among the main effects of this condition. The majority of studies that have contributed to the current understanding of IRI have relied on histological analyses using exogenous probes after the fact. Read More

View Article and Full-Text PDF

Ultrasonic actuation of a fine-needle improves biopsy yield.

Sci Rep 2021 Apr 15;11(1):8234. Epub 2021 Apr 15.

Medical Ultrasonics Laboratory (MEDUSA), Department of Neuroscience and Biomedical Engineering, Aalto University, 02150, Espoo, Finland.

Despite the ubiquitous use over the past 150 years, the functions of the current medical needle are facilitated only by mechanical shear and cutting by the needle tip, i.e. the lancet. Read More

View Article and Full-Text PDF

Autism-associated synaptic vesicle transcripts are differentially expressed in maternal plasma exosomes of physiopathologic pregnancies.

J Transl Med 2021 Apr 15;19(1):154. Epub 2021 Apr 15.

Sino-US Center of Translational Medicine for Development Disabilities, Southern Medical University, Guangzhou, 510515, China.

Background: During intrauterine development, the formation and function of synaptic vesicles (SVs) are thought to be fundamental conditions essential for normal development of the brain. Lacking advanced technology during the intrauterine period, such as longitudinal real-time monitoring of the SV-associated transcripts (SVATs), which include six pairs of lncRNA-mRNA, has limited acquisition of the dynamic gene expression profile (GEP) of SVATs. We previously reported the differential expression of SVATs in the peripheral blood of autistic children. Read More

View Article and Full-Text PDF

Preclinical safety evaluation of a recombinant plasmid vector encoding mature human neutrophil peptide-1 by repeated local administrations in nonhuman primates.

Hum Gene Ther 2021 Apr 15. Epub 2021 Apr 15.

Sichuan University West China Hospital, 34753, State Key Laboratory of Biotherapy and Cancer Center, Institute of Drug Clinical Trial, Chengdu, Sichuan, China;

In our previous studies, a novel gene therapy approach was developed based on a plasmid vector pSecTag2B in which recombinant HNP1 gene was regulated under a cytomegalovirus promoter to encode a mature HNP1 form. We showed for the first time in various tumor models including human cancer xenografts that overexpression of HNP1 in the tumor milieu by intratumoral pSecTag-HNP1 (pHNP1) administration efficiently attenuated in vivo tumor progression, mediated host immune responses to tumors, and produced a synergistic effect when combined with chemotherapeutics. In current study, a preclinical safety investigation of HNP1 gene therapy was conducted in non-human primates. Read More

View Article and Full-Text PDF

Anti-Proliferative and Apoptotic Effect of Gemini Curcumin in p53-Wild Type and p53-Mutant Colorectal Cancer Cell Lines.

Int J Pharm 2021 Apr 12:120592. Epub 2021 Apr 12.

Department of Animal Biology, School of Natural Sciences, University of Tabriz, Tabriz, Iran.

Background: Despite recent advances in therapy, colorectal cancer remains a leading cause of death in affected people. Curcumin is the main bioactive compound of turmeric that has been demonstrated as an effective agent against cancer. However, its poor stability and bioavailability limit therapeutic application. Read More

View Article and Full-Text PDF

Challenges and strategies for the delivery of biologics to the cornea.

J Control Release 2021 Apr 12. Epub 2021 Apr 12.

Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, Belgium. Electronic address:

Biologics, like peptides, proteins and nucleic acids, have proven to be promising drugs for the treatment of numerous diseases. However, besides the off label use of the monoclonal antibody bevacizumab for the treatment of corneal neovascularization, to date no other biologics for corneal diseases have reached the market. Indeed, delivering biologics in the eye remains a challenge, especially at the level of the cornea. Read More

View Article and Full-Text PDF

fvVaginal drug delivery approaches for localized management of cervical cancer.

Adv Drug Deliv Rev 2021 Apr 12. Epub 2021 Apr 12.

State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, P. R. China. Electronic address:

Cervical cancer or cervical intraepithelial neoplasia (CIN) remain a major public health problem among women globally. Traditional methods such as surgery are often associated with possible complications which may impact future pregnancies and childbirth especially for young female patients. Vagina with a high contact surface is a suitable route for the local and systemic delivery of drugs but its abundant mucus in continuous exchange presents a barrier for the popularization of conventional vaginal formulations including suppositories, gel, patch, creams and so on. Read More

View Article and Full-Text PDF

Bacterial Extracellular Vesicles and the Gut-Microbiota Brain Axis: Emerging Roles in Communication and Potential as Therapeutics.

Adv Biol (Weinh) 2021 Apr 15:e2000540. Epub 2021 Apr 15.

Fischell Department of Bioengineering and Program in Molecular and Cell Biology, University of Maryland, 3116 A. James Clark Hall, College Park, MD, 20742, USA.

Bacterial extracellular vesicles (BEVs) have emerged as candidate signaling vectors for long-distance interkingdom communication within the gut-microbiota brain axis. Most bacteria release these nanosized vesicles, capable of signaling to the brain via their abundant protein and small RNA cargo, possibly directly via crossing the blood-brain barrier. BEVs have been shown to regulate brain gene expression and induce pathology at most stages of neuroinflammation and neurodegeneration, and thus they may play a causal role in diseases such as Alzheimer's, Parkinson's, and depression/anxiety. Read More

View Article and Full-Text PDF

The known burden of Huntington disease in the North of Scotland: prevalence of manifest and identified pre-symptomatic gene expansion carriers in the molecular era.

J Neurol 2021 Apr 15. Epub 2021 Apr 15.

Medical Genetics Group, School of Medicine, Medical Sciences, Nutrition and Dentistry, University of Aberdeen, Aberdeen, AB25 2ZD, UK.

Background: Huntington disease prevalence was first estimated in Grampian, northern Scotland in 1984. Molecular testing has since increased ascertainment.

Objective: To estimate the prevalence of manifest Huntington disease and identified pre-symptomatic gene expansion carriers (IPGEC) in northern Scotland, and estimate the magnitude of biases in prevalence studies that rely upon routine coding in primary care records. Read More

View Article and Full-Text PDF

Two-pronged pulmonary gene delivery strategy: a surface-modified fullerene nanoparticle and a hypotonic vehicle.

Angew Chem Int Ed Engl 2021 Apr 14. Epub 2021 Apr 14.

Johns Hopkins University, 400 N. Broadway, Smith Building 6029, 21231, Baltimore, UNITED STATES.

Inhaled gene therapy poses a unique potential of curing chronic lung diseases which are currently managed primarily by symptomatic treatments. However, it has been challenging to achieve therapeutically-relevant gene transfer efficacy in the lung thus far due to the presence of numerous biological delivery barriers. Here, we introduce a simple combinatorial approach that overcomes both extracellular and cellular barriers to enhance gene transfer efficacy in the lung in vivo . Read More

View Article and Full-Text PDF

RNA ImmunoGenic Assay: A Method to Detect Immunogenicity of Transcribed mRNA in Human Whole Blood.

Bio Protoc 2020 Dec 20;10(24):e3850. Epub 2020 Dec 20.

Department of Pediatrics I, Pediatric Infectiology and Immunology, Translational Genomics and Gene Therapy in Pediatrics, University of Tuebingen, Germany.

The mRNA therapeutics is a new class of medicine to treat many various diseases. However, transcribed (IVT) mRNA triggers immune responses due to recognition by human endosomal and cytoplasmic RNA sensors, but incorporation of modified nucleosides have been shown to reduce such responses. Therefore, an assay signifying important aspects of the human immune system is still required. Read More

View Article and Full-Text PDF
December 2020

Methods and Techniques to Facilitate the Development of NT as an Effective, Therapeutic Oncolytic Bacteria.

Front Microbiol 2021 29;12:624618. Epub 2021 Mar 29.

Cell and Molecular Biology Program, North Dakota State University, Fargo, ND, United States.

The tumor microenvironment is characterized by anomalous vascularization, hypoxia, and acidity at the core of solid tumors that culminates in concentrated necrosis and immune system dysregulation among other effects. While this environment presents several challenges for the development of oncotherapeutics that deliver their activity via the enhanced permeability and retention (EPR) effect of the leaky blood vessels around a tumor, oncolytic bacteria, or a class of bacteria with a noted capacity to lyse solid tumors, are attracted to the very environment found at the center of solid tumors that confounds other therapeutics. It is this capacity that allows for a potent, active penetration from the tumor margins into the core, and subsequent colonization to facilitate lysis and immune reactivation. Read More

View Article and Full-Text PDF

Advances and challenges in adeno-associated viral inner-ear gene therapy for sensorineural hearing loss.

Mol Ther Methods Clin Dev 2021 Jun 10;21:209-236. Epub 2021 Mar 10.

Department of Otorhinolaryngology, Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

There is growing attention and effort focused on treating the root cause of sensorineural hearing loss rather than managing associated secondary characteristic features. With recent substantial advances in understanding sensorineural hearing-loss mechanisms, gene delivery has emerged as a promising strategy for the biological treatment of hearing loss associated with genetic dysfunction. There are several successful and promising proof-of-principle examples of transgene deliveries in animal models; however, there remains substantial further progress to be made in these avenues before realizing their clinical application in humans. Read More

View Article and Full-Text PDF

Acerola exosome-like nanovesicles to systemically deliver nucleic acid medicine via oral administration.

Mol Ther Methods Clin Dev 2021 Jun 10;21:199-208. Epub 2021 Mar 10.

Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan.

Extracellular vesicles derived from mammalian cells could be useful carriers for drug delivery systems (DDSs); however, with regard to clinical application, there are several issues to be overcome. Acerola ( DC.) is a popular health food. Read More

View Article and Full-Text PDF

Novel reporter mouse models useful for evaluating gene editing and for optimization of methods of delivering genome editing tools.

Mol Ther Nucleic Acids 2021 Jun 5;24:325-336. Epub 2021 Mar 5.

Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Kanagawa, Japan.

The clustered regularly interspersed palindromic repeats (CRISPR) system is a powerful genome-editing tool to modify genomes, virtually in any species. The CRISPR tool has now been utilized in many areas of medical research, including gene therapy. Although several proof-of-concept studies show the feasibility of gene therapy applications for correcting disease-causing mutations, and new and improved tools are constantly being developed, there are not many choices of suitable reporter models to evaluate genome editor tools and their delivery methods. Read More

View Article and Full-Text PDF

Radiation enhances the delivery of antisense oligonucleotides and improves chemo-radiation efficacy in brain tumor xenografts.

Cancer Gene Ther 2021 Apr 14. Epub 2021 Apr 14.

Department of Neurology, Oregon Health and Sciences University, Portland, OR, USA.

Overexpression of O-methylguanine DNA methyltransferase (MGMT) contributes to resistance to chemo-radiation therapy (CRT) in brain tumors. We previously demonstrated that non-ablative radiation improved delivery of anti-MGMT morpholino oligonucleotides (AMONs) to reduce MGMT levels in subcutaneous tumor xenografts. We evaluate this approach to enhance CRT efficacy in rat brain tumor xenograft models. Read More

View Article and Full-Text PDF

Genetic Factors associated with Pain Severity, Daily Opioid Dose Requirement, and Pain Response among Advanced Cancer Patients receiving Supportive Care.

J Pain Symptom Manage 2021 Apr 10. Epub 2021 Apr 10.

Department of Palliative care, Rehabilitation Medicine, and Integrative Medicine UT MD Anderson Cancer Center, Houston, United States.

Background: Current understanding of genetic factors associated with pain severity, and improvement of pain with opioids in advanced cancer patients (AC) is inadequate for delivery of personalized pain therapy(PPT). Therefore, the aim of this study was to determine the genetic factors associated with pain severity, daily opioid dose, and pain response in AC patients receiving supportive care.

Methods: In this prospective study, AC patients were eligible if they had cancer pain ≥4/10 on Edmonton Symptom Assessment Scale (ESAS) - Pain Item and needed opioid rotation for pain control by specialist at the outpatient supportive care center. Read More

View Article and Full-Text PDF

Implementing CRISPR-Cas12a for Efficient Genome Editing in Yarrowia lipolytica.

Methods Mol Biol 2021 ;2307:111-121

Department of Chemical, Biochemical and Environmental Engineering, University of Maryland Baltimore County, Baltimore, MD, USA.

The oleaginous yeast Yarrowia lipolytica has emerged as an industrially relevant chassis to produce various valuable chemicals. Metabolic engineering of Y. lipolytica relies on the availability of genetic engineering tools. Read More

View Article and Full-Text PDF
January 2021