Twenty-Year Survival Analysis of Adeno-Associated Virus Vector Serotype 2-Mediated Gene Therapy to the Central Nervous System for CLN2 Disease.

CLN2 disease (late infantile neuronal ceroid lipofuscinosis) is an autosomal recessive, neurodegenerative lysosomal storage disease that results from loss of function mutations in the gene, which encodes tripeptidyl peptidase 1. It affects the central nervous system (CNS) with progressive neurodegeneration and early death, typically at ages from 8 to 12 years. Twenty years ago, our phase I clinical trial treated subjects with CLN2 disease by a catheter-based CNS administration of an adeno-associated virus vector serotype 2 (AAV2) expressing the gene.

Co-delivery of dasatinib and miR-30a by liposomes targeting neuropilin-1 receptors for triple-negative breast cancer therapy.

Combinational therapy to treat triple-negative breast cancer (TNBC) by concomitantly influencing different cellular pathways has attracted attention recently. In the present study, co-delivery of dasatinib and miR30a by means of CRGDK-targeted lipopolyplexes was conducted to enhance the inhibition of cell proliferation and migration. For this purpose, we condensed the cationic copolymer poly(1-vinylimidazole--2-aminoethyl methacrylate) with miR-30a to form polyplexes.

Hybrid derivatives containing dimethyl fumarate and benzothiazole scaffolds for the potential treatment of multiple sclerosis; in silico & in vivo study.

Background: Multiple Sclerosis (MS) is a chronic autoimmune, inflammatory neurological disease of the CNS. Riluzole and dimethyl fumarate (DMF) are two FDA-approved drugs to treat amyotrophic lateral sclerosis (ALS) and MS. Riluzole (a benzothiazole derivative) inhibits glutamate release from nerve terminals by antagonizing the N-Methyl-D-Aspartate (NMDA) receptor, and DMF upregulates anti-oxidative pathways.

Co-delivery of carboplatin and doxorubicin using ZIF-8 coated chitosan-poly(N-isopropyl acrylamide) nanoparticles through a dual pH/thermo responsive strategy to breast cancer cells.

A dual pH/temperature sensitive core-shell nanoformulation has been developed based on ZIF-8 coated with chitosan-poly(N-isopropyl acrylamide) (CS-PNIPAAm) for co-delivery of doxorubicin (DOX) and carboplatin (CBP) in breast cancer cells. The resulting nanoparticles (NPs) had particle sizes around 200 nm and a zeta potential of about +30 mV. The CBP and DOX loading contents in the final NPs were 11.

Dihydropyrimidine derivatives as MDM2 inhibitors.

One of the chief pathways to regulate p53 levels is MDM2 protein, which negatively controls p53 by direct inhibition. Many cancers overproduce MDM2 protein to interrupt p53 functions. Therefore, impeding MDM2's binding to p53 can reactivate p53 in tumor cells may suggest an effective approach for tumor therapy.

Anti HER-2 aptamer functionalized gold nanoparticles of dasatinib for targeted chemo-radiotherapy in breast cancer cells.

In the present study, gold nanoparticles functionalized with anti HER-2 aptamer were designed for effective targeted delivery of dasatinib (DSB) to breast cancer cells. Anti HER-2 aptamer attached to porous or plain gold nanoparticles were compared for dasatinib delivery. Activated drug with succinic anhydride and L-cysteine linker was used for conjugation of DSB to gold nanoparticles.

Serial Sampling of the Small Airway Epithelium to Identify Persistent Smoking-dysregulated Genes.

The small airway epithelium (beyond the sixth generation), the initiation site of smoking-induced airway disorders, is highly sensitive to the stress of smoking. Because of variations over time in smoking habits, the small airway epithelium transcriptome is dynamic, fluctuating not only among smokers but also within each smoker. To perform accurate assessment of the smoking-related dysregulation of the human small airway epithelium despite the variation of smoking within the same individual and of the effects of smoking cessation on the dysregulated transcriptome.

Chitosan-Imidazolium Core-Shell Nanoparticles of Gd-Mn-Mo Polyoxometalate as Novel Potential MRI Nano-Agent for Breast Cancer Detection.

Polyoxometalates (POMs) are mineral nanoclusters with many advantages in various diagnostic fields, in particular cancer detection. This study aimed to synthesize and evaluate the performance of gadolinium-manganese-molybdenum polyoxometalate (Gd-Mn-Mo; POM) nanoparticles coated with chitosan-imidazolium (POM@CSIm NPs) for detecting 4T1 breast cancer cells by magnetic resonance imaging in vitro and in vivo. The POM@Cs-Im NPs were fabricated and characterized by FTIR, ICP-OES, CHNS, UV-visible, XRD, VSM, DLS, Zeta potential, and SEM.

Pyrimido[4,5-b]indole derivatives bearing 1,2,4-oxadiazole moiety as MDM2 inhibitor candidates in cancer treatment.

In this study, novel hybrid structures of pyrimido-indole-oxadiazole were developed as MDM2 inhibitors for restoring the regular function of the p53. A multistep chemical pathway was used to synthesize the derivatives. Nutlin-3a was used as a standard lead in molecular docking and molecular dynamics simulations.

Thermosensitive TMPO-oxidized lignocellulose/cationic agarose hydrogel loaded with deferasirox nanoparticles for photothermal therapy in melanoma.

Deferasirox (DFX) is an iron-chelating agent effective in treating various kinds of cancers, which inhibits iron metabolism in cancer cells. The recent study aimed to prepare an injectable thermosensitive hydrogel based on lignocellulose and agarose containing deferasirox-loaded polypyrrole nanoparticles for local drug delivery in a combined chemo-photothermal therapy by laser light irradiation. Polypyrrole nanoparticles containing DFX were made by the emulsification method and optimized.

Safety of Intravenous Administration of an AAV8 Vector Coding for an Oxidation-Resistant Human α1-Antitrypsin for the Treatment of α1-Antitrypsin Deficiency.

α1-antitrypsin (AAT) deficiency is a common autosomal recessive hereditary disorder, with a high risk for the development of early-onset panacinar emphysema. AAT, produced primarily in the liver, functions to protect the lung from neutrophil protease; with AAT deficiency, unimpeded neutrophil proteases destroy the lung parenchyma. AAT is susceptible to oxidative damage resulting in an inability to inhibit its target proteases, neutrophil elastase, and cathepsin G.

Design, synthesis, and cytotoxicity evaluation of novel indole-acylhydrazone derivatives of 4-pyridinone as potential histone deacetylase-2 inhibitors.

Background And Purpose: Histone deacetylation is one of the essential cellular pathways in the growth and spread of cancer, so the design of histone deacetylase (HDAC) inhibitors as anticancer agents is of great importance in pharmaceutical chemistry. Here, a series of indole acylhydrazone derivatives of 4-pyridone have been introduced as potential histone deacetylase inhibitors.

Experimental Approach: Seven indole-acylhydrazone-pyridinone derivatives were synthesized simple, straightforward chemical procedures.

Novel MR imaging nanoprobe for hepatocellular carcinoma detection based on manganese-zinc ferrite nanoparticles: in vitro and in vivo assessments.

Purpose: Achieving new contrast enhancer agents that can produce high-resolution images in magnetic resonance imaging (MRI) with a minimum dose and side effects has always been important.

Methods: Herein, the pegylated curcumin-coated manganese-zinc ferrite nanoparticles (MZF@CA-PEG-CUR NPs) have been reported as an MR imaging nanoprobe in hepatocellular carcinoma detection in the murine model for the first time. In vitro studies were done on HEPA 1-6 cancer cells and L929 as normal cells, and in vivo studies were done on hepatocellular carcinoma (HCC) using xenograft models of HCC.

Oral epithelium response of electronic cigarette users to electronic cigarette.

Background: Electronic cigarettes are increasing in popularity, but there is only little information on their biologic effects on the oral epithelium, the initial site exposed to electronic cigarette smoke.

Methods: We assessed the oral epithelium response to electronic cigarettes by comparing the histology and RNA transcriptome (mRNA and miRNA) of healthy electronic cigarette vapers to nonsmokers. mRNA was assessed based on: (1) genome-wide; (2) genes previously identified as dysregulated in the oral epithelium of electronic cigarette vapers versus nonsmokers; (3) immune and inflammatory-related genes previously identified as dysregulated in the nasal epithelium of electronic cigarette vapers compared to nonsmokers; (4) genes previously identified as dysregulated in the small airway epithelium of nonsmokers following an acute exposure to electronic cigarette; and (5) genes related to the initial steps of COVID-19 infection.

Copper-Curcumin-Bipyridine Dicarboxylate Complexes as Anticancer Candidates.

In this study, copper complexes with Curcumin (Cur) and 2,2'-bipyridine-5,5'-dicarboxylic acid (BPYD) were synthesized and their cytotoxicity on the MDA-MB-231 cell lines was evaluated. The resulting complex was characterized using FTIR, UV/VIS, CHNS, TGA, ICP-MS, and Mass spectroscopy techniques. The in-vitro cytotoxicity was studied on the MDA-MB-231 as a cancerous cell line and the HUVEC as a normal cell line.

pH-responsive glucosamine anchored polydopamine coated mesoporous silica nanoparticles for delivery of Anderson-type polyoxomolybdate in breast cancer.

Aim: This study aimed to develop novel pH-sensitive Glucosamine (Glu) targeted Polydopamine (PDA) coated mesoporous silica (SBA-15) nanoparticles (NPs) for selective delivery of anticancer Anderson-type manganese polyoxomolybdate (POMo) to breast cancer.

Methods: The POMo@SBA-PDA-Glu NPs were prepared via direct hydrothermal synthesis of SBA, POMo loading, in situ PDA post functionalization, and Glu anchoring; the chemical structures were fully studied by different characterisation methods. The anticancer activity was studied by MTT method and Annexin V-FITC apoptosis detection kit.

Redox responsive polymeric micelles of gellan gum/abietic acid for targeted delivery of ribociclib.

In most breast tumors level of glutathione reductase is much higher than in healthy tissues. In the current study, a redox-glutathione sensitive micelle based on Abietic acid-Cystamine-Gellan gum (AB-ss-GG) was designed for targeted delivery of Ribociclib (RIB) to breast cancer cells. AB is a monocarboxylic acid and a diterpenoid abietane with anti-tumor effects.

Synthesis, characterization, molecular docking, antimalarial, and antiproliferative activities of benzyloxy-4-oxopyridin benzoate derivatives.

Background And Purpose: Malaria and cancer are two major health issues affecting millions of lives annually. Maltol complexes and derivatives have been extensively investigated as chemotherapeutic and antimalarial activities. In this study, the design, synthesis, biological activities, and docking study of a novel series of pyridinones derivatives were reported.

Boron phenyl alanine targeted chitosan-PNIPAAm core-shell thermo-responsive nanoparticles: boosting drug delivery to glioblastoma in BNCT.

Boron neutron capture therapy (BNCT) is one of the best treatment modalities for glioblastoma multiform that could selectively kill the tumor cells. To be successful in BNCT, it is crucial to have enough B in the tumor. l-boron phenylalanine (l-BPA) targeted thermo-responsive core-shell nanoparticles (NPs) of chitosan-poly(N-isopropylacrylamide) (PNIPAAm) were our idea for endocytosis via sialic acid receptors, and selective delivery of B to glial cells.

The QChip1 knowledgebase and microarray for precision medicine in Qatar.

Risk genes for Mendelian (single-gene) disorders (SGDs) are consistent across populations, but pathogenic risk variants that cause SGDs are typically population-private. The goal was to develop "QChip1," an inexpensive genotyping microarray to comprehensively screen newborns, couples, and patients for SGD risk variants in Qatar, a small nation on the Arabian Peninsula with a high degree of consanguinity. Over 10 variants in 8445 Qatari were identified for inclusion in a genotyping array containing 165,695 probes for 83,542 known and potentially pathogenic variants in 3438 SGDs.

Some novel hybrid quinazoline-based heterocycles as potent cytotoxic agents.

Background And Purpose: In this study, some new cytotoxic hybrid structures were synthesized by combining pyrazolinone and imidazolinone rings with quinazoline pharmacophores.

Experimental Approach: The benzoxazinone, pyrazolo-quinazoline fused ring, and imidazolinone anchored quinazoline derivatives were synthesized by simple ring-opening, ring expansion, and ring closure strategies from oxazolones. The molecular docking studies of the final derivatives were accomplished on the epidermal growth factor receptor enzyme.

Synthesis and Antiplatelet Activity Evaluation of a Group of Novel Ethyl Acetoacetate Phenylhydrazone Derivatives.

A group of Novel phenylhydrazone derivatives of ethyl acetoacetate was synthesized and evaluated for their antiplatelet activities. Fourteen ethyl acetoacetate phenylhydrazone derivatives were synthesized using the diazonium salt of various aromatic primary amines with good yields and purity. The structure of the final compounds was confirmed and approved by spectroscopic techniques such as HNMR, FTIR, and ESI-Mass.

Boron phenyl alanine targeted ionic liquid decorated chitosan nanoparticles for mitoxantrone delivery to glioma cell line.

Nanotechnology has revolutionized drug delivery in cancer treatment. In this study, novel efficient pH-responsive boron phenylalanine (BPA) targeted nanoparticles (NPs) based on ionic liquid modified chitosan have been introduced for selective mitoxantrone (MTO) delivery to the U87MG glioma cells. Urocanic acid (UA) and imidazolium (Im) based ionic liquids were used for structural modification simultaneously.