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1.
CNS Neurol Disord Drug Targets ; 22(1): 51-65, 2023.
Article in English | MEDLINE | ID: mdl-35249508

ABSTRACT

Neuropsychiatric disorders that affect the central nervous system cause considerable pressures on the health care system and have a substantial economic burden on modern societies. The present treatments based on available drugs are mostly ineffective and often costly. The molecular process of neuropsychiatric disorders is closely connected to modifying the genetic structures inherited or caused by damage, toxic chemicals, and some current diseases. Gene therapy is presently an experimental concept for neurological disorders. Clinical applications endeavor to alleviate the symptoms, reduce disease progression, and repair defective genes. Implementing gene therapy in inherited and acquired neurological illnesses entails the integration of several scientific disciplines, including virology, neurology, neurosurgery, molecular genetics, and immunology. Genetic manipulation has the power to minimize or cure illness by inducing genetic alterations at endogenous loci. Gene therapy that involves treating the disease by deleting, silencing, or editing defective genes and delivering genetic material to produce therapeutic molecules has excellent potential as a novel approach for treating neuropsychiatric disorders. With the recent advances in gene selection and vector design quality in targeted treatments, gene therapy could be an effective approach. This review article will investigate and report the newest and the most critical molecules and factors in neuropsychiatric disorder gene therapy. Different genome editing techniques available will be evaluated, and the review will highlight preclinical research of genome editing for neuropsychiatric disorders while also evaluating current limitations and potential strategies to overcome genome editing advancements.


Subject(s)
Genetic Therapy , Mental Disorders , Humans , Mental Disorders/genetics , Mental Disorders/therapy
2.
Future Sci OA ; 7(9): FSO744, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34737885

ABSTRACT

The purpose of this review is to highlight recent scientific developments and provide an overview of virus self-assembly and viral particle dynamics. Viruses are organized supramolecular structures with distinct yet related features and functions. Plant viruses are extensively used in biotechnology, and virus-like particulate matter is generated by genetic modification. Both provide a material-based means for selective distribution and delivery of drug molecules. Through surface engineering of their capsids, virus-derived nanomaterials facilitate various potential applications for selective drug delivery. Viruses have significant implications in chemotherapy, gene transfer, vaccine production, immunotherapy and molecular imaging.

3.
Ther Deliv ; 12(3): 235-244, 2021 03.
Article in English | MEDLINE | ID: mdl-33624533

ABSTRACT

The COVID-19 pandemic continues to endanger world health and the economy. The causative SARS-CoV-2 coronavirus has a unique replication system. The end point of the COVID-19 pandemic is either herd immunity or widespread availability of an effective vaccine. Multiple candidate vaccines - peptide, virus-like particle, viral vectors (replicating and nonreplicating), nucleic acids (DNA or RNA), live attenuated virus, recombinant designed proteins and inactivated virus - are presently under various stages of expansion, and a small number of vaccine candidates have progressed into clinical phases. At the time of writing, three major pharmaceutical companies, namely Pfizer and Moderna, have their vaccines under mass production and administered to the public. This review aims to investigate the most critical vaccines developed for COVID-19 to date.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Humans , Pandemics
4.
Curr Mol Pharmacol ; 14(1): 79-87, 2021.
Article in English | MEDLINE | ID: mdl-32394847

ABSTRACT

BACKGROUND: Glioblastoma is one of the most aggressive tumors of the central nervous system. Galbanic acid, a natural sesquiterpene coumarin, has shown favorable effects on cancerous cells in previous studies. OBJECTIVE: The aim of the present work was to evaluate the effects of galbanic acid on proliferation, migration, and apoptosis of the human malignant glioblastoma (U87) cells. METHODS: The anti-proliferative activity of the compound was determined by the MTT assay. Cell cycle alterations and apoptosis were analyzed via flow cytometry. Action on cell migration was evaluated by scratch assay and gelatin zymography. Quantitative Real-Time PCR was used to determine the expression of genes involved in cell migration (matrix metalloproteinases, MMPs) and survival (the pathways of PI3K/Akt/mTOR and WNT/ß-catenin). Alteration in the level of protein Akt was determined by Western blotting. RESULTS: Galbanic acid significantly decreased cell proliferation, inhibited cell cycle, and stimulated apoptosis of the glioblastoma cells. Moreover, it could decrease the migration capability of glioblastoma cells, which was accompanied by inhibition in the activity and expression of MMP2 and MMP9. While galbanic acid reduced the gene expression of Akt, mTOR, and PI3K and increased the PTEN expression, it had no significant effect on WNT, ß-catenin, and APC genes. In addition, the protein level of p-Akt decreased after treatment with galbanic acid. The effects of galbanic acid were observed at concentrations lower than those of temozolomide. CONCLUSION: Galbanic acid decreased proliferation, cell cycle progression, and survival of glioblastoma cells through inhibiting the PI3K/Akt/mTOR pathway. This compound also reduced the migration capability of the cells by suppressing the activity and expression of MMPs.


Subject(s)
Antineoplastic Agents/chemistry , Coumarins/chemistry , Glioblastoma/drug therapy , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Coumarins/pharmacology , Gene Expression Regulation/drug effects , Humans , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Wnt Proteins/metabolism , beta Catenin/metabolism
5.
Curr Pharm Des ; 26(15): 1729-1741, 2020.
Article in English | MEDLINE | ID: mdl-32003685

ABSTRACT

Glioblastoma (GBM) is the most common and malignant astrocytic glioma, accounting for about 90% of all brain tumors with poor prognosis. Despite recent advances in understanding molecular mechanisms of oncogenesis and the improved neuroimaging technologies, surgery, and adjuvant treatments, the clinical prognosis of patients with GBM remains persistently unfavorable. The signaling pathways and the regulation of growth factors of glioblastoma cells are very abnormal. The various signaling pathways have been suggested to be involved in cellular proliferation, invasion, and glioma metastasis. The Wnt signaling pathway with its pleiotropic functions in neurogenesis and stem cell proliferation is implicated in various human cancers, including glioma. In addition, the PI3K/Akt/mTOR pathway is closely related to growth, metabolism, survival, angiogenesis, autophagy, and chemotherapy resistance of GBM. Understanding the mechanisms of GBM's invasion, represented by invasion and migration, is an important tool in designing effective therapeutic interventions. This review will investigate two main signaling pathways in GBM: PI3K/Akt/mTOR and Wnt/beta-catenin signaling pathways.


Subject(s)
Brain Neoplasms , Glioblastoma , Brain Neoplasms/drug therapy , Cell Line, Tumor , Cell Proliferation , Drug Design , Glioblastoma/drug therapy , Humans , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/metabolism , beta Catenin
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