Displaying publications 1 - 20 of 159 in total

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  1. Ethyl cinnamate suppresses tumor growth through anti-angiogenesis by attenuating VEGFR2 signal pathway in colorectal cancer
    Wang S, Yang J, Kuang X, Li H, Du H, Wu Y, et al.
    J Ethnopharmacol, 2024 May 23;326:117913.
    PMID: 38360380 DOI: 10.1016/j.jep.2024.117913
    ETHNOPHARMACOLOGICAL RELEVANCE: Kaempferia galanga Linn. is an aromatic medicinal herb with extensively applied in India, China, Malaysia and other South Asia countries for thousands of years. It has been mentioned to treat abdominal tumors. Ethyl cinnamate (EC), one of the main chemical constituents of the rhizome of K. galanga, exhibited nematocidal, sedative and vasorelaxant activities. However, its anti-angiogenic activity, and anti-tumor effect have not been investigated.

    AIM OF THE STUDY: To investigate the anti-angiogenic mechanism of EC and its anti-tumor effect by suppressing angiogenesis.

    MATERIALS AND METHODS: The in vitro anti-angiogenic effect was evaluated using HUVECs model induced by VEGF and zebrafish model in vivo. The influence of the EC on phosphorylation of VEGFR2 and its downstream signaling pathways were evaluated by western blotting assay. Molecule docking technology was conducted to explore the interaction between EC and VEGFR2. SPR assay was used for detecting the binding affinity between EC and VEGFR2. To further investigate the molecular mechanism of EC on anti-angiogenesis, VEGFR2 knockdown in HUVECs and examined the influence of the EC. Anti-tumor activity of EC was evaluated using colony formation assay and apoptosis assay. The inhibitory effect of EC on tumor growth was explored using HT29 colon cancer xenograft model.

    RESULTS: EC obviously inhibited proliferation, migration, invasion and tube formation of VEGF-induced HUVECs. EC also induced apoptosis of HUVECs. Moreover, it inhibited the development of vessel formation in zebrafish. Further investigations demonstrated that EC could suppress the phosphorylation of VEGFR2, and its downstream signaling pathways were altered in VEGF-induced HUVECs. EC formed a hydrogen bond to bind with the ATP binding site of the VEGFR2, and EC-VEGFR2 interaction was shown in SPR assay. The suppressive effect of EC on angiogenesis was abrogated after VEGFR2 knockdown in HUVECs. EC inhibited the colon cancer cells colony formation and induced apoptosis. In addition, EC suppressed tumor growth in colon cancer xenograft model, and no detectable hepatotoxicity and nephrotoxicity. In addition, it inhibited the phosphorylation of VEGFR2, and its downstream signal pathways in tumor.

    CONCLUSIONS: EC could inhibit tumor growth in colon cancer by suppressing angiogenesis via VEGFR2 signaling pathway, and suggested EC as a promising candidate for colon cancer treatment.

    Matched MeSH terms: Zebrafish
  2. Variants in ZFX are associated with an X-linked neurodevelopmental disorder with recurrent facial gestalt
    Shepherdson JL, Hutchison K, Don DW, McGillivray G, Choi TI, Allan CA, et al.
    Am J Hum Genet, 2024 Mar 07;111(3):487-508.
    PMID: 38325380 DOI: 10.1016/j.ajhg.2024.01.007
    Pathogenic variants in multiple genes on the X chromosome have been implicated in syndromic and non-syndromic intellectual disability disorders. ZFX on Xp22.11 encodes a transcription factor that has been linked to diverse processes including oncogenesis and development, but germline variants have not been characterized in association with disease. Here, we present clinical and molecular characterization of 18 individuals with germline ZFX variants. Exome or genome sequencing revealed 11 variants in 18 subjects (14 males and 4 females) from 16 unrelated families. Four missense variants were identified in 11 subjects, with seven truncation variants in the remaining individuals. Clinical findings included developmental delay/intellectual disability, behavioral abnormalities, hypotonia, and congenital anomalies. Overlapping and recurrent facial features were identified in all subjects, including thickening and medial broadening of eyebrows, variations in the shape of the face, external eye abnormalities, smooth and/or long philtrum, and ear abnormalities. Hyperparathyroidism was found in four families with missense variants, and enrichment of different tumor types was observed. In molecular studies, DNA-binding domain variants elicited differential expression of a small set of target genes relative to wild-type ZFX in cultured cells, suggesting a gain or loss of transcriptional activity. Additionally, a zebrafish model of ZFX loss displayed an altered behavioral phenotype, providing additional evidence for the functional significance of ZFX. Our clinical and experimental data support that variants in ZFX are associated with an X-linked intellectual disability syndrome characterized by a recurrent facial gestalt, neurocognitive and behavioral abnormalities, and an increased risk for congenital anomalies and hyperparathyroidism.
    Matched MeSH terms: Zebrafish/genetics
  3. Fulltext 1H NMR metabolomics insights into comparative diabesity in male and female zebrafish and the antidiabetic activity of DL-limonene
    Benchoula K, Serpell CJ, Mediani A, Albogami A, Misnan NM, Ismail NH, et al.
    Sci Rep, 2024 Feb 15;14(1):3823.
    PMID: 38360784 DOI: 10.1038/s41598-023-45608-z
    Zebrafish have been utilized for many years as a model animal for pharmacological studies on diabetes and obesity. High-fat diet (HFD), streptozotocin and alloxan injection, and glucose immersion have all been used to induce diabetes and obesity in zebrafish. Currently, studies commonly used both male and female zebrafish, which may influence the outcomes since male and female zebrafish are biologically different. This study was designed to investigate the difference between the metabolites of male and female diabetic zebrafish, using limonene - a natural product which has shown several promising results in vitro and in vivo in treating diabetes and obesity-and provide new insights into how endogenous metabolites change following limonene treatment. Using HFD-fed male and female zebrafish, we were able to develop an animal model of T2D and identify several endogenous metabolites that might be used as diagnostic biomarkers for diabetes. The endogenous metabolites in males and females were different, even though both genders had high blood glucose levels and a high BMI. Treatment with limonene prevented high blood glucose levels and improved in diabesity zebrafish by limonene, through reversal of the metabolic changes caused by HFD in both genders. In addition, limonene was able to reverse the elevated expression of AKT during HFD.
    Matched MeSH terms: Zebrafish/metabolism
  4. Nanocomposites of iron oxide, sodium alginate, and eugenol induce apoptosis via PI3K/Akt/mTOR signaling in Hep3 cells and in vivo hepatotoxicity in the zebrafish model
    Elderdery AY, Alzerwi NAN, Alzahrani B, Alsrhani A, Alsultan A, Rayzah M, et al.
    Int J Biol Macromol, 2024 Jan;256(Pt 2):127490.
    PMID: 37979758 DOI: 10.1016/j.ijbiomac.2023.127490
    Hepatic cancer is among the most recurrently detected malignancies worldwide and one of the main contributors to cancer-associated mortality. With few available therapeutic choices, there is an instant necessity to explore suitable options. In this aspect, Nanotechnology has been employed to explore prospective chemotherapeutic approaches, especially for cancer treatment. Nanotechnology is concerned with the biological and physical properties of nanoparticles in the therapeutic use of drugs. In the current work, formulation, and characterization of α-Fe2O3-Sodium Alginate-Eugenol nanocomposites (FSE NCs) using several approaches like SEM and TEM, UV-visible, FTIR, and PL spectroscopy, XRD, EDAX, and DLS studies have been performed. With an average size of 50 nm, the rhombohedral structure of NCs was identified. Further, their anticancer activity against Hep3B liver cancer cell lines has been performed by cell viability, dual staining, DCFH-DA, Annexin-V/-FITC/PI, cell cycle analysis methods, and PI3K/Akt/mTOR signaling proteins were studied to assess the anticancer effects of the NCs in Hep3B cells. Also, anti-cancer activity on animal modeling in-vivo using zebra fishes to hematological parameters, liver enzymes, and histopathology study effectiveness was noticed. Moreover, the NCs reduced the viability, elevated the ROS accumulation, diminished the membrane integrity, reduced the antioxidants, blocked the cell cycle, and triggered the PI3K/Akt/mTOR signaling axis that eventually resulted in cell death. As a result, FSE NCs possess huge potential for use as a possible anticancer candidate.
    Matched MeSH terms: Zebrafish/metabolism
  5. Aggregation, toxicity, and biodegradability study of an ionic liquid-based formulation for effective oil spill remediation
    Nazar M, Ul Hassan Shah M, Ahmad A, Goto M, Zaireen Nisa Yahya W, Moniruzzaman M
    Chemosphere, 2023 Dec;344:140412.
    PMID: 37827466 DOI: 10.1016/j.chemosphere.2023.140412
    Chemical dispersants are extensively used for marine oil spill remediation. However, the increased toxicity and low biodegradability of these dispersants restrict their employment in the marine environment. Hence, in this work, we have developed an eco-friendly formulation composed of an ionic liquid,1-butyl-3-methylimidazolium lauroyl sarcosinate [BMIM][Lausar] and sorbitan monooleate (Span) 80. Micellar and interfacial parameters, dispersion effectiveness, as well as the toxicity and biodegradability of the developed formulation were investigated. Micellar properties confirmed a high degree of synergism among the surfactant molecules and the formation of stable micelle. The dispersion effectiveness, at dispersant-to-oil ratio (DOR) of 1:25 (v/v), against three crude oils (Arab, Ratawi, and Doba) was assessed. We achieved a dispersion effectiveness of 68.49%, 74.05%, and 83.43% for Ratawi, Doba, and Arab crude oil, respectively, using a 70:30 (w/w) ratio of Span 80 to [BMIM][Lausar]. Furthermore, the results obtained from optical microscopy and particle size analysis (PSA) indicated that the oil droplet size decreased with higher DOR. Additionally, acute toxicity experiments were conducted on zebrafish (Danio rerio) using the developed formulation, confirming its non-toxic behavior, with LC50 values of 800 mg/L after 96 h. The formulation also exhibited high biodegradability, with only 25.01% of the original quantity remaining after 28 days. Hence, these results suggest that the new formulation has the potential to be a highly effective and environmentally friendly dispersant for oil spill remediation.
    Matched MeSH terms: Zebrafish
  6. The effects of metallothionein in paraquat-induced Parkinson disease model of zebrafish
    Mohamad Najib NH, Yahaya MF, Das S, Teoh SL
    Int J Neurosci, 2023 Dec;133(8):822-833.
    PMID: 34623211 DOI: 10.1080/00207454.2021.1990916
    INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disease caused by selective degeneration of dopaminergic neurons in the substantia nigra. Metallothionein has been shown to act as a neuroprotectant in various brain injury. Thus, this study aims to identify the effects of full-length human metallothionein 2 peptide (hMT2) in paraquat-induced brain injury in the zebrafish.

    METHODOLOGY: A total of 80 adult zebrafish were divided into 4 groups namely control, paraquat-treated, pre-hMT2-treated, and post-hMT2-treated groups. Fish were treated with paraquat intraperitoneally every 3 days for 15 days. hMT2 were injected intracranially on day 0 (pre-treated group) and day 16 (post-treated group). Fish were sacrificed on day 22 and the brains were collected for qPCR, ELISA and immunohistochemistry analysis.

    RESULTS: qPCR analysis showed that paraquat treatment down-regulated the expression of genes related to dopamine activity and biosynthesis (dat and th1) and neuroprotective agent (bdnf). Paraquat treatment also up-regulated the expression of the mt2, smtb and proinflammatory genes (il-1α, il-1β, tnf-α and cox-2). hMT2 treatment was able to reverse the effects of paraquat. Lipid peroxidation decreased in the paraquat and pre-hMT2-treated groups. However, lipid peroxidation increased in the post-hMT2-treated group. Paraquat treatment also led to a reduction of dopaminergic neurons while their numbers showed an increase following hMT2 treatment.

    CONCLUSION: Paraquat has been identified as one of the pesticides that can cause the death of dopaminergic neurons and affect dopamine biosynthesis. Treatment with exogenous hMT2 could reverse the effects of paraquat in the zebrafish brain.

    Matched MeSH terms: Zebrafish/metabolism
  7. Fulltext Phytochemical analysis, antioxidant, α-glucosidase inhibitory activity, and toxicity evaluation of Orthosiphon stamineus leaf extract
    Ahda M, Jaswir I, Khatib A, Ahmed QU, Mahfudh N, Ardini YD, et al.
    Sci Rep, 2023 Oct 09;13(1):17012.
    PMID: 37813908 DOI: 10.1038/s41598-023-43251-2
    Ocimum aristatum, commonly known as O. stamineus, has been widely studied for its potential as an herbal medicine candidate. This research aims to compare the efficacy of water and 100% ethanolic extracts of O. stamineus as α-glucosidase inhibitors and antioxidants, as well as toxicity against zebrafish embryos. Based on the study findings, water extract of O. stamineus leaves exhibited superior inhibition activity against α-glucosidase, ABTS, and DPPH, with IC50 values of approximately 43.623 ± 0.039 µg/mL, 27.556 ± 0.125 µg/mL, and 95.047 ± 1.587 µg/mL, respectively. The major active compounds identified in the extract include fatty acid groups and their derivates such as linoleic acid, α-eleostearic acid, stearic acid, oleanolic acid, and corchorifatty acid F. Phenolic groups such as caffeic acid, rosmarinic acid, 3,4-Dihydroxybenzaldehyde, norfenefrine, caftaric acid, and 2-hydroxyphenylalanine and flavonoids and their derivates including 5,7-Dihydroxychromone, 5,7-Dihydroxy-2,6-dimethyl-4H-chromen-4-one, eupatorin, and others were also identified in the extract. Carboxylic acid groups and triterpenoids such as azelaic acid and asiatic acid were also present. This study found that the water extract of O. stamineus is non-toxic to zebrafish embryos and does not affect the development of zebrafish larvae at concentrations lower than 500 µg/mL. These findings highlight the potential of the water extract of O. stamineus as a valuable herbal medicine candidate, particularly for its potent α-glucosidase inhibition and antioxidant properties, and affirm its safety in zebrafish embryos at tested concentrations.
    Matched MeSH terms: Zebrafish
  8. Toxicity and teratogenicity effects of valproic acid on zebrafish (Danio rerio) embryos in relation to autism spectrum disorder
    Saleh Hodin NA, Chong SG, Bakar NA, Fahmi MSAM, Ramlan NF, Hamid NNAZZ, et al.
    Birth Defects Res, 2023 Oct 01;115(16):1475-1485.
    PMID: 37507847 DOI: 10.1002/bdr2.2227
    Valproic acid (VPA) is a widely prescribed antiepileptic drug with various medicinal efficacies. Accumulated evidence implied that prenatal exposure to VPA is highly associated with autism spectrum disorder (ASD). In this study, the zebrafish were exposed to a set of VPA concentrations (0, 5, 10, 20, 40, 80, 160, 320, 640, 1280, and 2560 μM) at 5 h post fertilization (hpf) to 120 hpf. The adverse effects of VPA were extensively studied through the evaluations on the mortality, heartbeats, spontaneous tail coiling, and hatching rate. Morphological observations were conducted at 120 hpf, following the exposure termination. Basic locomotor responses and anxiety-like behavioral alterations evaluated for behavioral impairments are the hallmark feature of ASD. The exposure to VPA at teratogenic concentrations reduced the aforementioned parameters in a dose-dependent manner (p ≤ .05). At the selected non-teratogenic concentrations of VPA, the treated larvae demonstrated profound alterations of basic locomotor responses. No significant changes of anxiety and thigmotactic behaviors were observed on the VPA-treated fish compared to the control (p ≥ .005). This study depicted that embryonic zebrafish exposure to VPA produced significant toxicity and teratogenicity effects as well as the alterations of basic behavioral responses. Overall, this study provides a fundamental insight of the toxicity effects at morphological and behavioral levels to facilitate the understanding of ASD mechanisms at different molecular levels.
    Matched MeSH terms: Zebrafish
  9. Fulltext Aquatic Peptide: The Potential Anti-Cancer and Anti-Microbial Activity of GE18 Derived from Pathogenic Fungus Aphanomyces invadans
    Velayutham M, Priya PS, Sarkar P, Murugan R, Almutairi BO, Arokiyaraj S, et al.
    Molecules, 2023 Sep 21;28(18).
    PMID: 37764521 DOI: 10.3390/molecules28186746
    Small molecules as well as peptide-based therapeutic approaches have attracted global interest due to their lower or no toxicity in nature, and their potential in addressing several health complications including immune diseases, cardiovascular diseases, metabolic disorders, osteoporosis and cancer. This study proposed a peptide, GE18 of subtilisin-like peptidase from the virulence factor of aquatic pathogenic fungus Aphanomyces invadans, which elicits anti-cancer and anti-microbial activities. To understand the potential GE18 peptide-induced biological effects, an in silico analysis, in vitro (L6 cells) and in vivo toxicity assays (using zebrafish embryo), in vitro anti-cancer assays and anti-microbial assays were performed. The outcomes of the in silico analyses demonstrated that the GE18 peptide has potent anti-cancer and anti-microbial activities. GE18 is non-toxic to in vitro non-cancerous cells and in vivo zebrafish larvae. However, the peptide showed significant anti-cancer properties against MCF-7 cells with an IC50 value of 35.34 µM, at 24 h. Besides the anti-proliferative effect on cancer cells, the peptide exposure does promote the ROS concentration, mitochondrial membrane potential and the subsequent upregulation of anti-cancer genes. On the other hand, GE18 elicits significant anti-microbial activity against P. aeruginosa, wherein GE18 significantly inhibits bacterial biofilm formation. Since the peptide has positively charged amino acid residues, it targets the cell membrane, as is evident in the FESEM analysis. Based on these outcomes, it is possible that the GE18 peptide is a significant anti-cancer and anti-microbial molecule.
    Matched MeSH terms: Zebrafish
  10. Coencapsulation of Gemcitabine and Thymoquinone in Citrem-Phosphatidylcholine Hexosome Nanocarriers Improves In Vitro Cellular Uptake in Breast Cancer Cells
    Loo YS, Zahid NI, Madheswaran T, Ikeno S, Nurdin A, Mat Azmi ID
    Mol Pharm, 2023 Sep 04;20(9):4611-4628.
    PMID: 37587099 DOI: 10.1021/acs.molpharmaceut.3c00333
    Lyotropic liquid crystalline nanoassemblies (LLCNs) are internally self-assembled (ISA)-somes formed by amphiphilic molecules in a mixture comprising a lipid, stabilizer, and/or surfactant and aqueous media/dispersant. LLCNs are unique nanoassemblies with versatile applications in a wide range of biomedical functions. However, they comprise a nanosystem that is yet to be fully explored for targeted systemic treatment of breast cancer. In this study, LLCNs proposed for gemcitabine and thymoquinone (Gem-TQ) co-delivery were prepared from soy phosphatidylcholine (SPC), phytantriol (PHYT), or glycerol monostearate (MYVR) in optimized ratios containing a component of citric and fatty acid ester-based emulsifier (Grinsted citrem) or a triblock copolymer, Pluronic F127 (F127). Hydrodynamic particle sizes determined were below 400 nm (ranged between 96 and 365 nm), and the series of nanoformulations displayed negative surface charge. Nonlamellar phases identified by small-angle X-ray scattering (SAXS) profiles comprise the hexagonal, cubic, and micellar phases. In addition, high entrapment efficiency that accounted for 98.3 ± 0.1% of Gem and 99.5 ± 0.1% of TQ encapsulated was demonstrated by the coloaded nanocarrier system, SPC/citrem/Gem-TQ hexosomes. Low cytotoxicity of SPC-citrem hexosomes was demonstrated in MCF10A cells consistent with hemo- and biocompatibility observed in zebrafish (Danio rerio) embryos for up to 96 h postfertilization (hpf). SPC/citrem/Gem-TQ hexosomes demonstrated IC50 of 24.7 ± 4.2 μM in MCF7 breast cancer cells following a 24 h treatment period with the moderately synergistic interaction between Gem and TQ retained (CI = 0.84). Taken together, biocompatible SPC/citrem/Gem-TQ hexosomes can be further developed as a multifunctional therapeutic nanodelivery approach, plausible for targeting breast cancer cells by incorporation of targeting ligands.
    Matched MeSH terms: Zebrafish
  11. Fulltext Behavioural, genomics and proteomic approach to examine Alzheimer's disease in zebrafish
    Siddiqui A, Abidin SAZ, Shah ZA, Othman I, Kumari Y
    Comp Biochem Physiol C Toxicol Pharmacol, 2023 Sep;271:109636.
    PMID: 37100105 DOI: 10.1016/j.cbpc.2023.109636
    Globally around 24 million elderly population are dealing with dementia, and this pathological characteristic is commonly seen in people suffering from Alzheimer's disease (AD). Despite having multiple treatment options that can mitigate AD symptoms, there is an imperative call to advance our understanding of the disease pathogenesis to unfold disease-modifying treatments/therapies. To explore the driving mechanisms of AD development, we stretch out further to study time-dependant changes after Okadaic acid (OKA)-induced AD-like conditions in zebrafish. We evaluated the pharmacodynamics of OKA at two-time points, i.e., after 4-days and 10-days exposure to zebrafish. T-Maze was utilized to observe the learning and cognitive behaviour, and inflammatory gene expressions such as 5-Lox, Gfap, Actin, APP, and Mapt were performed in zebrafish brains. To scoop everything out from the brain tissue, protein profiling was performed using LCMS/MS. Both time course OKA-induced AD models have shown significant memory impairment, as evident from T-Maze. Gene expression studies of both groups have reported an overexpression of 5-Lox, GFAP, Actin, APP, and OKA 10D group has shown remarkable upregulation of Mapt in zebrafish brains. In the case of protein expression, the heatmap suggested an important role of some common proteins identified in both groups, which can be explored further to investigate their mechanism in OKA-induced AD pathology. Presently, the preclinical models available to understand AD-like conditions are not completely understood. Hence, utilizing OKA in the zebrafish model can be of great importance in understanding the pathology of AD progression and as a screening tool for drug discovery.
    Matched MeSH terms: Zebrafish/metabolism
  12. Antidepressant evaluation of Andrographis paniculata Nees extract and andrographolide in chronic unpredictable stress zebrafish model
    Aldurrah Z, Mohd Kauli FS, Abdul Rahim N, Zainal Z, Afzan A, Al Zarzour RH, et al.
    Comp Biochem Physiol C Toxicol Pharmacol, 2023 Sep;271:109678.
    PMID: 37301417 DOI: 10.1016/j.cbpc.2023.109678
    Andrographis paniculata (A. paniculata) showed an anti-depressive effect in rodent models. Zebrafish has recently emerged as a worthy complementary translational model for antidepressant drug discovery study. This study investigates the anti-depressive effect of A. paniculata extract and andrographolide in the chronic unpredictable stress (CUS)- zebrafish model. Four groups of zebrafish (n = 10/group), i.e. control, CUS (stressed, untreated), CUS + A. paniculata (100 mg/L) and CUS + fluoxetine (0.01 mg/L) were assessed in open-field and social interaction tests, 24 h after treatment. After extract screening, behavioural and cortisol analysis of andrographolide (5, 25 and 50 mg/kg, i.p.) and fluoxetine (10 mg/kg, i.p.) were evaluated. Before the behavioural study, acute toxicity and characterization of A. paniculata extract using UHPLC-ESI-MS/MS were performed. A significant reduction in freezing duration was found in A. paniculata- (t-test, p = 0.0234) and fluoxetine-treated groups (t-test, p 
    Matched MeSH terms: Zebrafish
  13. Fulltext Biocompatible and Biodegradable Surfactants from Orange Peel for Oil Spill Remediation
    Wang PS, Ahmad A, Nazar M, Rahmah AU, Moniruzzaman M
    Molecules, 2023 Aug 01;28(15).
    PMID: 37570764 DOI: 10.3390/molecules28155794
    Oil spill remediation plays a vital role in mitigating the environmental impacts caused by oil spills. The chemical method is one of the widely recognized approaches in chemical surfactants. However, the most commonly used chemical surfactants are toxic and non-biodegradable. Herein, two biocompatible and biodegradable surfactants were synthesized from orange peel using the ionic liquid 1-butyl-3-methylimidazolium chloride (BMIMCl) and organic solvent dimethylacetamide (CH3CN(CH3)2) as reaction media. The acronyms SOPIL and SOPOS refer to the surfactants prepared with BMIMCl and dimethylacetamide, respectively. The surface tension, dispersant effectiveness, optical microscopy, and emulsion stability test were conducted to examine the comparative performance of the synthesized surfactants. The Baffled flask test (BFT) was carried out to determine the dispersion effectiveness. The toxicity test was performed against zebrafish (Danio rerio), whereas the closed bottle test (CBT) evaluated biodegradability. The results revealed that the critical micelle concentration (CMC) value of SOPIL was lower (8.57 mg/L) than that of SOPOS (9.42 mg/L). The dispersion effectiveness values for SOPIL and SOPOS were 69.78% and 40.30%, respectively. The acute toxicity test demonstrated that SOPIL was 'practically non-toxic' with a median lethal concentration of more than 1000 mg/L after 96 h. The biodegradation rate was recorded as higher than 60% for both surfactants within 28 days, demonstrating their readily biodegradable nature. Considering these attributes, biocompatible and biodegradable surfactants derived from orange peel emerge as a promising and sustainable alternative for oil spill remediation.
    Matched MeSH terms: Zebrafish/metabolism
  14. Fulltext In Silico and In Vitro Methods in the Characterization of Beta-Carotene as Pharmaceutical Material via Acetylcholine Esterase Inhibitory Actions
    Muthuraman A, Ramesh M, Mustaffa F, Nadeem A, Nishat S, Paramakrishnan N, et al.
    Molecules, 2023 May 26;28(11).
    PMID: 37298835 DOI: 10.3390/molecules28114358
    Molecular docking is widely used in the assessment of the therapeutic potential of pharmaceutical agents. The binding properties of beta-carotene (BC) to acetylcholine esterase (AChE) proteins were characterized using the molecular docking method. The mechanism of AChE inhibition was assessed by an experimental in vitro kinetic study. In addition, the role of BC action was tested by the zebrafish embryo toxicity test (ZFET). The results of the docking ability of BC to AChE showed significant ligand binding mode. The kinetic parameter, i.e., the low AICc value shown as the compound was the competitive type of inhibition of AChE. Further, BC also showed mild toxicity at a higher dose (2200 mg/L) in ZFET assessment with changes in biomarkers. The LC50 value of BC is 1811.94 mg/L. Acetylcholine esterase (AChE) plays a pivotal role in the hydrolysis of acetylcholine, which leads to the development of cognitive dysfunction. BC possesses the regulation of acetylcholine esterase (AChE) and acid phosphatase (AP) activity to prevent neurovascular dysfunction. Therefore, the characterization of BC could be used as a pharmaceutical agent for the treatment of cholinergic neurotoxicity-associated neurovascular disorders such as developmental toxicity, vascular dementia, and Alzheimer's disease due to its AChE and AP inhibitory actions.
    Matched MeSH terms: Zebrafish/metabolism
  15. Fulltext Discovery of Ruthenium(II) Metallocompound and Olaparib Synergy for Cancer Combination Therapy
    Yusoh NA, Tiley PR, James SD, Harun SN, Thomas JA, Saad N, et al.
    J Med Chem, 2023 May 25;66(10):6922-6937.
    PMID: 37185020 DOI: 10.1021/acs.jmedchem.3c00322
    Synergistic drug combinations can extend the use of poly(ADP-ribose) polymerase inhibitors (PARPi) such as Olaparib to BRCA-proficient tumors and overcome acquired or de novo drug resistance. To identify new synergistic combinations for PARPi, we screened a "micro-library" comprising a mix of commercially available drugs and DNA-binding ruthenium(II) polypyridyl complexes (RPCs) for Olaparib synergy in BRCA-proficient triple-negative breast cancer cells. This identified three hits: the natural product Curcumin and two ruthenium(II)-rhenium(I) polypyridyl metallomacrocycles. All combinations identified were effective in BRCA-proficient breast cancer cells, including an Olaparib-resistant cell line, and spheroid models. Mechanistic studies indicated that synergy was achieved via DNA-damage enhancement and resultant apoptosis. Combinations showed low cytotoxicity toward non-malignant breast epithelial cells and low acute and developmental toxicity in zebrafish embryos. This work identifies RPC metallomacrocycles as a novel class of agents for cancer combination therapy and provides a proof of concept for the inclusion of metallocompounds within drug synergy screens.
    Matched MeSH terms: Zebrafish
  16. Hazard and health risk assessment of exposure to pharmaceutical active compounds via toxicological evaluation by zebrafish
    Ben Chabchoubi I, Lam SS, Pane SE, Ksibi M, Guerriero G, Hentati O
    Environ Pollut, 2023 May 01;324:120698.
    PMID: 36435277 DOI: 10.1016/j.envpol.2022.120698
    The uncontrolled or continuous release of effluents from wastewater treatment plants leads to the omnipresence of pharmaceutical active compounds (PhACs) in the aquatic media. Today, this is a confirmed problem becoming a main subject of twin public and scientific concerns. However, still little information is available about the long-term impacts of these PhACs on aquatic organisms. In this review, efforts were made to reveal correlation between the occurrence in the environment, ecotoxicological and health risks of different PhACs via toxicological evaluation by zebrafish (Danio rerio). This animal model served as a bioindicator for any health impacts after the exposure to these contaminants and to better understand the responses in relation to human diseases. This review paper focused on the calculation of Risk Quotients (RQs) of 34 PhACs based on environmental and ecotoxicological data available in the literature and prediction from the ECOSAR V2.2 software. To the best of the authors' knowledge, this is the first report on the risk assessment of PhACs by the two different methods as mentioned above. RQs showed greater difference in potential environmental risks of the PhACs. These differences in risk values underline the importance of environmental and experimental factors in exposure conditions and the interpretation of RQ values. While the results showed high risk to Danio rerio of the majority of PhACs, risk qualification of the others varied between moderate to insignifiant. Further research is needed to assess pharmaceutical hazards when present in wastewater before discharge and monitor the effectiveness of treatment processes. The recent new advances in the morphological assessment of toxicant-exposed zebrafish larvae for the determination of test compounds effects on the developmental endpoints were also discussed. This review emphasizes the need for strict regulations on the release of PhACs into environmental media in order to minimize their toxicity to aquatic organisms.
    Matched MeSH terms: Zebrafish*
  17. Metabolites characterisation of endophytic Phyllosticta fallopiae L67 isolated from Aloe vera with antimicrobial activity on diabetic wound microorganisms
    Taher MA, Tan WN, Chear NJ, Leong CR, Rashid SA, Tong WY
    Nat Prod Res, 2023 May;37(10):1674-1679.
    PMID: 35879820 DOI: 10.1080/14786419.2022.2103127
    This study aimed to assess the antimicrobial activity of endophytic Phyllosticta fallopiae L67 isolated from Aloe vera against diabetic wound microorganisms and characterise their active fraction for biologically important metabolites. The dichloromethane (DCM) extract exhibited the most significant activity with inhibition zones ranging from 11.33 to 38.33 mm. The minimal inhibitory and lethality concentrations of DCM extract ranged from 78.13 to 2500.00 µg/ml and 625.00 to 5000.00 µg/ml, respectively. The extract showed teratogenicity and lethality in the zebrafish model, where peritoneal and hepatic oedema occurred at 62.50 µg/ml, and no abnormality appeared at 31.25 µg/ml. The extract also inhibited more than 82% biofilm formation. Bioassay-guided fractionation on DCM extract yielded 18 fractions and the most active fraction was subjected to UPLC-QTOF-MS/MS analysis. Flavones, stilbenes, flavanonols, isoflavonoids, phenolic glycosides and phenol derivatives were detected. In conclusion, endophytic P. fallopiae possessed bioactive metabolites with significant antimicrobial activity against diabetic wound microorganisms.
    Matched MeSH terms: Zebrafish
  18. Enolase in Meyerozyma guilliermondii strain SO: Sequential and structural insights of MgEno4581 as a putative virulence factor and host-fungal interactions through comprehensive in silico approaches
    Amran AI, Lim SJ, Muhd Noor ND, Salleh AB, Oslan SN
    Microb Pathog, 2023 Mar;176:106025.
    PMID: 36754101 DOI: 10.1016/j.micpath.2023.106025
    Meyerozyma guilliermondii is a rare opportunistic fungal pathogen that causes deadly invasive candidiasis in human. M. guilliermondii strain SO is a local yeast isolate that possesses huge industrial interests but also pathogenic towards zebrafish embryos. Enolases that bind to human extracellular matrix (ECM) proteins are among the fungal virulence factors. To understand its pathogenicity mechanism down to molecular level, especially in the rare M. guilliermondii, this study aimed to identify and characterize the potentially virulence-associated enolase in M. guilliermondii strain SO using bioinformatics approaches. Profile Hidden-Markov model was implemented to identify enolase-related sequences in the fungal proteome. Sequence analysis deciphered only one (MgEno4581) out of nine sequences exhibited potent virulence traits observed similarly in the pathogenic Candida albicans. MgEno4581 structure that was predicted via SWISS-MODEL using C. albicans enolase (CaEno1; PDB ID: 7vrd) as the homology modeling template portrayed a highly identical motif with CaEno1 that facilitates ECM proteins binding. Amino acid substitutions (D234K, K235A, Y238H, K239D, G243K, V248C and Y254F) in ECM-binding motif of Saccharomyces cerevisiae enolase (ScEno) compared to MgEno4581 and CaEno1 caused changes in motif's surface charges. Protein-protein docking indicated F253 in ScEno only interacted hydrophobically with human plasminogen (HPG). Hydrogen linkages were observed for both MgEno4581 and CaEno1, suggesting a stronger interaction with HPG in the hydrophilic host microenvironments. Thus, our in silico characterizations on MgEno4581 provided new perspectives on its potential roles in candidiasis (fungal-host interactions) caused by M. guilliermondii, especially M. guilliermondii strain SO on zebrafish embryos that mimic the immunocompromised individuals as previously evident.
    Matched MeSH terms: Zebrafish*
  19. Fulltext Integrative Roles of Dopamine Pathway and Calcium Channels Reveal a Link between Schizophrenia and Opioid Use Disorder
    Thiagarajan SK, Mok SY, Ogawa S, Parhar IS, Tang PY
    Int J Mol Sci, 2023 Feb 17;24(4).
    PMID: 36835497 DOI: 10.3390/ijms24044088
    Several theories have been proposed to explain the mechanisms of substance use in schizophrenia. Brain neurons pose a potential to provide novel insights into the association between opioid addiction, withdrawal, and schizophrenia. Thus, we exposed zebrafish larvae at 2 days post-fertilization (dpf) to domperidone (DPM) and morphine, followed by morphine withdrawal. Drug-induced locomotion and social preference were assessed, while the level of dopamine and the number of dopaminergic neurons were quantified. In the brain tissue, the expression levels of genes associated with schizophrenia were measured. The effects of DMP and morphine were compared to vehicle control and MK-801, a positive control to mimic schizophrenia. Gene expression analysis revealed that α1C, α1Sa, α1Aa, drd2a, and th1 were up-regulated after 10 days of exposure to DMP and morphine, while th2 was down-regulated. These two drugs also increased the number of positive dopaminergic neurons and the total dopamine level but reduced the locomotion and social preference. The termination of morphine exposure led to the up-regulation of th2, drd2a, and c-fos during the withdrawal phase. Our integrated data implicate that the dopamine system plays a key role in the deficits in social behavior and locomotion that are common in the schizophrenia-like symptoms and opioid dependence.
    Matched MeSH terms: Zebrafish
  20. Centella asiatica (L.) Urb. Extract ameliorates branched-chain amino acid (BCAA) metabolism in acute reserpine-induced stress zebrafish model via 1H Nuclear Magnetic Resonance (NMR)-based metabolomics approach
    Zakaria F, Akhtar MT, Wan Norhamidah WI, Noraini AB, Muhamad A, Shohaimi S, et al.
    Comp Biochem Physiol C Toxicol Pharmacol, 2023 Feb;264:109501.
    PMID: 36336330 DOI: 10.1016/j.cbpc.2022.109501
    Depression is a common mental disorder that can adversely affect psychosocial function and quality of life. However, the exact aetiology and pathogenesis of depression are still unclear. Stress plays a major role in the pathogenesis of depression. The use of currently prescribed antidepressants has many side effects. Centella asiatica (C. asiatica) has shown promising antidepressant activity in rodent models. Here, we developed a reserpine-induced zebrafish stress-like model and performed behavioural analysis, cortisol measurement and 1H-Nuclear Magnetic Resonance (1H NMR) spectroscopy-based metabolomics analysis to test the anti-stress activity of ethanolic extract of C. asiatica (RECA). A significant increase in total distance travelled (F(8,8) = 8.905, p = 0.0054) and a reduction in freezing duration (F(9, 9) = 10.38, p = 0.0018) were found in the open field test (OFT). Asiaticoside, one of tested C.asiatica's triterpenoid gives a significant increase in contact duration (F(5,5) = 142.3, (p = 0.0330) at 2.5 mg/kg). Eight biomarkers were found, i.e. ß-hydroxyisovaleric acid, leucine, threonine, scylloinositol, lactate, betaine, valine, choline and l-fucose, to be responsible for the class separation between stress and RECA-treated groups. Metabolic pathway alteration in zebrafish brain upon treatment with RECA was identified as valine, leucine and isoleucine biosynthesis, while alanine, aspartate, glutamate and glycerophospholipid metabolism was involved after fluoxetine treatment.
    Matched MeSH terms: Zebrafish
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