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Fulltext Effects of Pegagan (Centella asiatica L.) Ethanolic Extract SNEDDS (Self-nanoemulsifying Drug Delivery Systems) on the Development of Zebrafish (Danio rerio) Embryos

Hayati F, Chabib L, Fauzi IS, Awaluddin R, Sumayya, Faizah WS, et al.

J Pharm Bioallied Sci, 2020 10 08;12(4):457-461.
PMID: 33679093 DOI: 10.4103/jpbs.JPBS_297_19

Introduction: Pegagan is a traditional medicinal plant with three major bioactive properties, triterpenoid, steroids, and saponin. It has the properties of antioxidant, antistress, and wound healing. Pegagan extract is prepared in self-nanoemulsifying drug delivery systems (SNEDDS) to overcome the problem of low water-solubility level.
Objectives: This study aimed to observe the effect of pegagan ethanolic extract SNEDDS on the development of zebrafish embryos.
Materials and Methods: This study used 12 sets of zebrafish embryos presented in five sets of extract SNEDDS with different concentrations, that is, 20, 10, 5, 2.5, and 1.25 μg, five sets of SNEDDS without extract with different concentrations, that is, 20, 10, 5, 2.5, and 1.25 μg, a set of positive control (3.4-DCA 4 mg/L) with one control set (diluted with water), and a negative control (SNEDDS without extract). The procedure was conducted for 96 h with observations every 24 h. The parameters observed were embryonic coagulation, formation of somites, detachment of tail bud from the yolk, and abnormality of embryo.
Results: The results showed that in 96 h the 20ppm concentration caused 100% mortality. Embryo abnormality appeared as coagulation of embryo, somite malformation, and abnormal tail.
Discussion: There is a correlation between the concentration of SNEDDS and the incidence of embryo coagulation. The malformation in the group of pegagan extract SNEDDS is characterized by cardiac edema, somite malformation, and abnormal tail.
Conclusion: Pegagan ethanolic extract SNEDDS of 20ppm can inhibit the development of zebrafish embryos.
Fulltext Electrosprayed Alginate Nanoparticles as CRISPR Plasmid DNA Delivery Carrier: Preparation, Optimization, and Characterization

Alallam B, Altahhan S, Taher M, Mohd Nasir MH, Doolaanea AA

Pharmaceuticals (Basel), 2020 Jul 22;13(8).
PMID: 32707857 DOI: 10.3390/ph13080158

Therapeutic gene editing is becoming more feasible with the emergence of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) system. However, the successful implementation of CRISPR/Cas9-based therapeutics requires a safe and efficient in vivo delivery of the CRISPR components, which remains challenging. This study presents successful preparation, optimization, and characterization of alginate nanoparticles (ALG NPs), loaded with two CRISPR plasmids, using electrospray technique. The aim of this delivery system is to edit a target gene in another plasmid (green fluorescent protein (GFP)). The effect of formulation and process variables were evaluated. CRISPR ALG NPs showed mean size and zeta potential of 228 nm and -4.42 mV, respectively. Over 99.0% encapsulation efficiency was achieved while preserving payload integrity. The presence of CRISPR plasmids in the ALG NPs was confirmed by Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy. The tests revealed that the nanoparticles were cytocompatible and successfully introduced the Cas9 transgene in HepG2 cells. Nanoparticles-transfected HepG2 was able to edit its target plasmid by introducing double-strand break (DSB) in GFP gene, indicating the bioactivity of CRISPR plasmids encapsulated in alginate nanoparticles. This suggests that this method is suitable for biomedical application in vitro or ex vivo. Future investigation of theses nanoparticles might result in nanocarrier suitable for in vivo delivery of CRISPR/Cas9 system.
Fulltext The Promise of the Zebrafish Model for Parkinson's Disease: Today's Science and Tomorrow's Treatment

Razali K, Othman N, Mohd Nasir MH, Doolaanea AA, Kumar J, Ibrahim WN, et al.

Front Genet, 2021;12:655550.
PMID: 33936174 DOI: 10.3389/fgene.2021.655550

The second most prevalent neurodegenerative disorder in the elderly is Parkinson's disease (PD). Its etiology is unclear and there are no available disease-modifying medicines. Therefore, more evidence is required concerning its pathogenesis. The use of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the basis of most animal models of PD. MPTP is metabolized by monoamine oxidase B (MAO B) to MPP + and induces the loss of dopaminergic neurons in the substantia nigra in mammals. Zebrafish have been commonly used in developmental biology as a model organism, but owing to its perfect mix of properties, it is now emerging as a model for human diseases. Zebrafish (Danio rerio) are cheap and easy to sustain, evolve rapidly, breed transparent embryos in large amounts, and are readily manipulated by different methods, particularly genetic ones. Furthermore, zebrafish are vertebrate species and mammalian findings obtained from zebrafish may be more applicable than those derived from genetic models of invertebrates such as Drosophila melanogaster and Caenorhabditis elegans. The resemblance cannot be taken for granted, however. The goal of the present review article is to highlight the promise of zebrafish as a PD animal model. As its aminergic structures, MPTP mode of action, and PINK1 roles mimic those of mammalians, zebrafish seems to be a viable model for studying PD. The roles of zebrafish MAO, however, vary from those of the two types of MAO present in mammals. The benefits unique to zebrafish, such as the ability to perform large-scale genetic or drug screens, should be exploited in future experiments utilizing zebrafish PD models.
Fulltext Global research Activity on olfactory marker protein (OMP): A bibliometric and visualized analysis

Ab Aziz S, Mohd Nasir MH, Jusoh AR, Azman KF, Ismail CAN, Ahmad AH, et al.

Heliyon, 2024 Feb 29;10(4):e26106.
PMID: 38390049 DOI: 10.1016/j.heliyon.2024.e26106

Olfactory marker protein (OMP) is extensively studied in mature olfactory receptor neurons (ORNs) for understanding olfaction physiology. However, no bibliometric analysis on this topic exists. We conducted a bibliometric analysis of OMP research articles, wherein the publication count was assessed by year, country, journal, and author, collaboration by country, and productivity of the authors. Additionally, key terms and research themes were identified. Using the search phrase "olfactory marker protein" in Scopus, we retrieved 691 original research articles by 2487 authors since 1974. Publications showed an increasing trend, with the United States leading in quantity and collaboration. Our thematic map highlights "Olfactory bulb, regeneration, olfactory" as the primary research domain, while "olfaction, olfactory sensory neuron, glomerulus" and "olfactory receptor neurons, apoptosis, olfactory dysfunction" emerge as essential future research topics. These bibliometric findings offer insights into the global OMP research landscape, guiding researchers in potential collaborations and intriguing future research fields.
Fulltext Fabrication and characterization of Agarwood extract-loaded nanocapsules and evaluation of their toxicity and anti-inflammatory activity on RAW 264.7 cells and in zebrafish embryos

Eissa MA, Hashim YZH, Mohd Nasir MH, Nor YA, Salleh HM, Isa MLM, et al.

Drug Deliv, 2021 Dec;28(1):2618-2633.
PMID: 34894947 DOI: 10.1080/10717544.2021.2012307

Aquilaria malaccensis has been traditionally used to treat several medical disorders including inflammation. However, the traditional claims of this plant as an anti-inflammatory agent has not been substantially evaluated using modern scientific techniques. The main objective of this study was to evaluate the anti-inflammatory effect of Aquilaria malacensis leaf extract (ALEX-M) and potentiate its activity through nano-encapsulation. The extract-loaded nanocapsules were fabricated using water-in-oil-in-water (w/o/w) emulsion method and characterized via multiple techniques including DLS, TEM, FTIR, and TGA. The toxicity and the anti-inflammatory activity of ALEX-M and the extract-loaded nanocapsules (ALEX-M-PNCs) were evaluated in-vitro on RAW 264.7 macrophages and in-vivo on zebrafish embryos. The nanocapsules demonstrated spherical shape with mean particle diameter of 167.13 ± 1.24 nm, narrow size distribution (PDI = 0.29 ± 0.01), and high encapsulation efficiency (87.36 ± 1.81%). ALEX-M demonstrated high viability at high concentrations in RAW 264.7 cells and zebrafish embryos, however, ALEX-M-PNCs showed relatively higher cytotoxicity. Both free and nanoencapsulated extract expressed anti-inflammatory effects through significant reduction of the pro-inflammatory mediator nitric oxide (NO) production in LPS/IFNγ-stimulated RAW 264.7 macrophages and zebrafish embryos in a concentration-dependent manner. The findings highlight that ALEX-M can be recognized as a potential anti-inflammatory agent, and its anti-inflammatory activity can be potentiated by nano-encapsulation. Further studies are warranted toward investigation of the mechanistic and immunomodulatory roles of ALEX-M.