Displaying publications 1 - 20 of 159 in total

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  1. Behavioral and cortisol analysis of the anti-stress effect of Polygonum minus (Huds) extracts in chronic unpredictable stress (CUS) zebrafish model
    Abdul Rahim N, Nordin N, Ahmad Rasedi NIS, Mohd Kauli FS, Wan Ibrahim WN, Zakaria F
    Comp Biochem Physiol C Toxicol Pharmacol, 2022 Jun;256:109303.
    PMID: 35202824 DOI: 10.1016/j.cbpc.2022.109303
    The World Health Organization (WHO) recorded approximately 350 million people worldwide have suffered from mental health disorders, such as depression, anxiety, schizophrenia, and addictive behaviors. The search for new drugs from nature has drawn on many biological resources and human practices. In this study, leaves of Polygonum minus standardized extract (Biokesum®), 1 and 100 mg/L were used to evaluate the anti-stress effect in the chronic unpredictable stress (CUS) zebrafish model. Five groups of zebrafish were manipulated in this study, comprising control, chronic unpredictable stress (CUS), CUS + Biokesum® 1 mg/L (4 days, 20 min/day, immersion) CUS + Biokesum® 100 mg/L (4 days, 20 min/day, immersion) and CUS + fluoxetine 0.6 mg/L (4 days, 20 min/day, immersion). Four different behavioral tests were used, i.e. open-field test, social interaction test, light and dark test, and exploratory test. After four consecutive days of treatment, the zebrafish were sacrificed for whole-body cortisol analysis. The exploratory test showed a significant change upon P. minus treatment (one-way ANOVA; p = 0.0011). Cortisol analysis showed a decrease of cortisol level after treatment with the extract and fluoxetine, without significant difference. These results showed that zebrafish is a reliable model to study the anti-stress effect of compounds or herbal extract.
    Matched MeSH terms: Zebrafish*
  2. 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
  3. Fulltext The effects of Piper sarmentosum aqueous extracts on zebrafish (Danio rerio) embryos and caudal fin tissue regeneration
    Zainol Abidin IZ, Fazry S, Jamar NH, Ediwar Dyari HR, Zainal Ariffin Z, Johari AN, et al.
    Sci Rep, 2020 08 25;10(1):14165.
    PMID: 32843675 DOI: 10.1038/s41598-020-70962-7
    In Malaysia, Piper sarmentosum or 'kaduk' is commonly used in traditional medicines. However, its biological effects including in vivo embryonic toxicity and tissue regenerative properties are relatively unknown. The purpose of this study was to determine zebrafish (Danio rerio) embryo toxicities and caudal fin tissue regeneration in the presence of P. sarmentosum aqueous extracts. The phytochemical components and antioxidant activity of the extract were studied using GC-MS analysis and DPPH assay, respectively. Embryo toxicity tests involving survival, heartbeat, and morphological analyses were conducted to determine P. sarmentosum extract toxicity (0-60 µg/mL); concentrations of 0-400 µg/mL of the extract were used to study tissue regeneration in the zebrafish caudal fin. The extract contained several phytochemicals with antioxidant activity and exhibited DPPH scavenging activity (IC50 = 50.56 mg/mL). Embryo toxicity assays showed that a concentration of 60 μg/mL showed the highest rates of lethality regardless of exposure time. Slower embryogenesis was observed at 40 µg/mL, with non-viable embryos first detected at 50 µg/mL. Extracts showed significant differences (p 
    Matched MeSH terms: Zebrafish/embryology*
  4. Fulltext Klebsiella virus UPM2146 lyses multiple drug-resistant Klebsiella pneumoniae in vitro and in vivo
    Assafiri O, Song AA, Tan GH, Hanish I, Hashim AM, Yusoff K
    PLoS One, 2021;16(1):e0245354.
    PMID: 33418559 DOI: 10.1371/journal.pone.0245354
    Klebsiella pneumoniae are opportunistic bacteria found in the gut. In recent years they have been associated with nosocomial infections. The increased incidence of multiple drug-resistant K. pneumoniae makes it necessary to find new alternatives to treat the disease. In this study, phage UPM2146 was isolated from a polluted lake which can lyse its host K. pneumoniae ATCC BAA-2146. Observation from TEM shows that UPM2146 belongs to Caudoviriales (Order) based on morphological appearance. Whole genome analysis of UPM2146 showed that its genome comprises 160,795 bp encoding for 214 putative open reading frames (ORFs). Phylogenetic analysis revealed that the phage belongs to Ackermannviridae (Family) under the Caudoviriales. UPM2146 produces clear plaques with high titers of 1010 PFU/ml. The phage has an adsorption period of 4 min, latent period of 20 min, rise period of 5 min, and releases approximately 20 PFU/ bacteria at Multiplicity of Infection (MOI) of 0.001. UPM2146 has a narrow host-range and can lyse 5 out of 22 K. pneumoniae isolates (22.72%) based on spot test and efficiency of plating (EOP). The zebrafish larvae model was used to test the efficacy of UPM2146 in lysing its host. Based on colony forming unit counts, UPM2146 was able to completely lyse its host at 10 hours onwards. Moreover, we show that the phage is safe to be used in the treatment against K. pneumoniae infections in the zebrafish model.
    Matched MeSH terms: Zebrafish
  5. The immune response of a warm water fish orange-spotted grouper (Epinephelus coioides) infected with a typical cold water bacterial pathogen Aeromonas salmonicida is AhR dependent
    Huang L, Qi W, Zuo Y, Alias SA, Xu W
    Dev Comp Immunol, 2020 12;113:103779.
    PMID: 32735958 DOI: 10.1016/j.dci.2020.103779
    The present study reported the first pathogenic Aeromonas salmonicida (SRW-OG1) isolated from the warm water fish orange-spotted grouper (Epinephelus coioides), and investigated the function of Aryl hydrocarbon receptor (AhR), a ligand-dependent transcriptional factor which has been recently found to be closely associated with immune response in mammals and E. coioides. Our results showed that AhR was activated by an unknown ligand in the spleen, intestine and macrophages. Meanwhile, ahr1a and ahr1b were significantly increased in the spleen, intestine and macrophages, whereas ahr2 was only increased in the intestine, which indicated that the contribution of AhR2 to the immune response may be less than that of AhR1a and AhR1b. Some key genes involved in the macrophage inflammatory response, bacterial recognition, and intestinal immunity were significantly up-regulated in the SRW-OG1 infected E. coioides. Nevertheless, declining macrophage ROS production and down-regulation of related genes were also observed, suggesting that SRW-OG1 utilized its virulence mechanisms to prevent macrophage ROS production. Furthermore, AhR inhibitor 3', 4'-DMF and the silence of ahr1a or ahr1b significantly rescued the increased IL-1β and IL-8 induced by SRW-OG1 infection, which proved that the induction of IL-1β and IL-8 in E. coioides macrophages was mediated by AhR. However, BPI/LBP, ROS production and related genes were not affected by AhR. The survival rate and immune escape rate of SRW-OG1 in the ahr1a/ahr1b knocked-down and 3', 4'-DMF treated macrophages were significantly increased compared with those in wild type macrophages. Taken together, it was preliminarily confirmed that ahr1a and ahr1b played an important role in the immune response against A. salmonicida SRW-OG1.
    Matched MeSH terms: Zebrafish Proteins/genetics; Zebrafish Proteins/metabolism*
  6. Expression of zTOR-associated microRNAs in zebrafish embryo treated with rapamycin
    Khor ES, Noor SM, Wong PF
    Life Sci, 2016 Apr 1;150:67-75.
    PMID: 26916825 DOI: 10.1016/j.lfs.2016.02.076
    MicroRNAs (miRNAs) are vital in modulating lifespan and various biological processes including vascular function. The pivotal roles of mammalian target of rapamycin (mTOR) in regulating senescence and angiogenesis have been extensively described. However, the roles of its orthologue, zebrafish target of rapamycin (zTOR) in senescence and angiogenesis remain to be unravelled. In the present study, we aimed to investigate the role of zTOR and identify miRNAs associated with senescence and angiogenesis.
    Matched MeSH terms: Zebrafish
  7. Fulltext Understanding the Role of ztor in Aging-related Diseases Using the Zebrafish Model
    Khor ES, Noor SM, Wong PF
    In Vivo, 2019 10 31;33(6):1713-1720.
    PMID: 31662495 DOI: 10.21873/invivo.11661
    The mammalian target of rapamycin (mTOR), a 289 kDa serine/threonine protein kinase of the phosphoinositide 3-kinase (PI3K)-related family is known for its role in regulating lifespan and the aging process in humans and rodents. Aging in zebrafish very much resembles aging in humans. Aged zebrafish often manifest with spinal curvature, cataracts and cognitive frailty, akin to human age-related phenotypical effects such as osteoarthritis, dwindling vision and cognitive dysfunction. However, the role of the zebrafish orthologue of mTOR, ztor, is less defined in these areas. This review paper discusses the tale of growing old in the zebrafish, the physiological roles of ztor in normal developmental processes and its involvement in the pathogenesis of aging-related diseases such as metabolic disorders and cancers.
    Matched MeSH terms: Zebrafish/metabolism*
  8. 5'-flanking sequences of zebrafish fast myosin heavy chain genes regulate unique expression in the anterior, medial subsection and posterior tail somites of the skeletal muscle
    Asaduzzaman M, Shakur Ahammad AK, Asakawa S, Kinoshita S, Watabe S
    Comp Biochem Physiol B Biochem Mol Biol, 2016 Jan;191:1-12.
    PMID: 26335505 DOI: 10.1016/j.cbpb.2015.08.009
    In zebrafish, fast muscle-specific myosin heavy chain genes have their unique expression patterns in a well-defined and restricted region of the skeletal muscle. However, the transcriptional regulatory mechanisms involved have remained unclear. Here, we examined the regulation of spatio-temporal expression patterns of myhz1 (myhz1.1, myhz1.2 and myhz1.3) and myhz2 during their development by using transient gene and stable transgenic techniques. Embryos microinjected with different length 5'-flanking sequences of myhz1 conjugated with the enhanced green fluorescent protein (EGFP) gene showed EGFP expression in the anterior and medial subsections of somites, but not in the tail somite region. In contrast, embryos microinjected with different length 5'-flanking sequences of myhz2 showed EGFP expression exclusively at the posterior tail somite domain. Promoter deletion analyses demonstrated that reduced EGFP fluorescence typically is correlated with smaller 5'-flanking sequences. The immunohistochemical observation revealed that zebrafish larvae provided with the transient gene and those from stable transgenic lines consistently expressed EGFP in the fast muscle fibers. r-VISTA plot identified one common conserved region of about 140°bp among myhz1.1, myhz1.2 and myhz1.3. Deletion of this conserved region from the 5'-flanking sequence of each myhz1 markedly reduced EGFP expression in its unique spatial somite region. Deletion mutation analysis demonstrated that myhz2 expression in the tail somite region might be mediated by Tbx (family of transcription factors having a common DNA-binding sequence known as T-box) binding elements. In summary, 5'-flanking sequences of myhz1 and myhz2 regulate their unique expression patterns in a well-defined and restricted somite region of the skeletal muscle in zebrafish.
    Matched MeSH terms: Zebrafish
  9. Fulltext Regulation of embryonic hematopoiesis by a cytokine-inducible SH2 domain homolog in zebrafish
    Lewis RS, Noor SM, Fraser FW, Sertori R, Liongue C, Ward AC
    J Immunol, 2014 Jun 15;192(12):5739-48.
    PMID: 24835394 DOI: 10.4049/jimmunol.1301376
    Cytokine-inducible SH2 domain-containing protein (CISH), a member of the suppressor of cytokine signaling family of negative feedback regulators, is induced by cytokines that activate STAT5 and can inhibit STAT5 signaling in vitro. However, demonstration of a definitive in vivo role for CISH during development has remained elusive. This study employed expression analysis and morpholino-mediated knockdown in zebrafish in concert with bioinformatics and biochemical approaches to investigate CISH function. Two zebrafish CISH paralogs were identified, cish.a and cish.b, with high overall conservation (43-46% identity) with their mammalian counterparts. The cish.a gene was maternally derived, with transcripts present throughout embryogenesis, and increasing at 4-5 d after fertilization, whereas cish.b expression commenced at 8 h after fertilization. Expression of cish.a was regulated by the JAK2/STAT5 pathway via conserved tetrameric STAT5 binding sites (TTCN3GAA) in its promoter. Injection of morpholinos targeting cish.a, but not cish.b or control morpholinos, resulted in enhanced embryonic erythropoiesis, myelopoiesis, and lymphopoiesis, including a 2- 3-fold increase in erythrocytic markers. This occurred concomitantly with increased activation of STAT5. This study indicates that CISH functions as a conserved in vivo target and regulator of STAT5 in the control of embryonic hematopoiesis.
    Matched MeSH terms: Zebrafish/genetics; Zebrafish/immunology*; Zebrafish Proteins/genetics; Zebrafish Proteins/immunology*
  10. Fulltext Comparison of neurotoxic effects of ethanol and endosulfan on biochemical changes of brain tissues in Javanese medaka (Oryzias Javanicus) and zebrafish (Danio Reri
    Nurul Farhana Ramlan, Noraini Abu Bakar, Albert, Emmellie Laura, Syaizwan Zahmir Zulkifli, Syahida Ahmad, Mohammad Noor Amal Azmai, et al.
    Pertanika Journal of Science & Technology, 2020;28(2):689-701.
    MyJurnal
    An ideal model organism for neurotoxicology research should meet several characteristics, such as low cost and amenable for high throughput testing. Javanese medaka (JM) has been widely used in the ecotoxicological studies related to the marine and freshwater environment, but rarely utilized for biomedical research. Therefore, in this study, the applicability of using JM in the neurotoxicology research was assessed using biochemical comparison with an established model organism, the zebrafish. Identification of biochemical changes due to the neurotoxic effects of ethanol and endosulfan was assessed using Fourier Transform Infrared (FTIR) analysis. Treatment with ethanol affected the level of lipids, proteins, glycogens and nucleic acids in the brain of JM. Meanwhile, treatment with endosulfan showed alteration in the level of lipids and nucleic acids. For the zebrafish, exposure to ethanol affected the level of protein, fatty acid and amino acid, and exposure to endosulfan induced alteration in the fatty acids, amino acids, nucleic acids and protein in the brain of zebrafish. The sensitive response of the JM toward chemicals exposure proved that it was a valuable model for neurotoxicology research. More studies need to be conducted to further develop JM as an ideal model organism for neurotoxicology research.
    Matched MeSH terms: Zebrafish
  11. Determination toxic effects of Hystrix Brachyura Bezoar extracts using cancer cell lines and embryo zebrafish (Danio rerio) models and identification of active principles through GC-MS analysis
    Firus Khan AY, Ahmed QU, Nippun TS, Hilles A, Jalal TK, Teh LK, et al.
    J Ethnopharmacol, 2020 Nov 15;262:113138.
    PMID: 32726681 DOI: 10.1016/j.jep.2020.113138
    ETHNOPHARMACOLOGICAL RELEVANCE: Porcupine bezoar (PB) is used as folk medicine for various medical conditions including cancer treatment in Malaysia. However, its toxicity profile has never been thoroughly ascertained to confirm its safe nature as an efficacious traditional medicine in the treatment of cancer as well as other ailments.

    AIM OF THE STUDY: This study was aimed to reveal three different PBs' aqueous extracts(viz. PB-A, PB-B, PB-C) chemical constituent's profile using GC-MS analysis, anticancer property on A375, HeLa and MCF7 cancer cells, toxicity profile on zebrafish embryo morphology, EC50, LC50 and teratogenicity index.

    MATERIALS AND METHODS: PBs' extracts characterization was performed through GC-MS analysis, in vitro anticancer effect was carried out on A375, HeLa and MCF7 cancer cell lines and finally and toxicity properties on three different PBs aqueous extracts (viz. PB-A, PB-B, PB-C) were determined using zebrafish embryo model.

    RESULTS: The GC-MS analysis revealed 10 similar compounds in all PBs' extracts. Dilauryl thiodipropionate was found to be a major compound in all PBs' extracts followed by tetradecanoic acid. An in vitro anticancer study revealed PB extracts exerted median inhibition concentration (IC50) <50 μg/mL, on cancer cells viz. A375, HeLa and MCF7 with no significant toxicity on normal cells viz. NHDF cells. In vivo toxicity of PBs extracts found affecting tail detachment, hatching, craniofacial, brain morphology, soft tissues, edema, spinal, somites, notochord and cardiovascular system (brachycardia, disruption of blood circulation) deformities. The LC50 and EC50 demonstrated PB extracts effect as dose and time dependent with median concentration <150.0 μg/mL. Additionally, teratogenicity index (TI) viz. >1.0 revealed teratogenic property for PB extracts.

    CONCLUSIONS: The findings revealed that all three PBs aqueous extracts possessed anticancer activity and exhibited significant toxicological effects on zebrafish embryos with high teratogenicity index. Hence, its use as an anticancer agent requires further investigation and medical attentions to determine its safe dose.

    Matched MeSH terms: Zebrafish
  12. Fulltext Anticancer activity of grassy Hystrix brachyura bezoar and its mechanisms of action: An in vitro and in vivo based study
    Khan AYF, Ahmed QU, Narayanamurthy V, Razali S, Asuhaimi FA, Saleh MSM, et al.
    Biomed Pharmacother, 2019 Jun;114:108841.
    PMID: 30981106 DOI: 10.1016/j.biopha.2019.108841
    Porcupine bezoar (PB) is a calcified undigested material generally found in porcupine's (Hystrix brachyura) gastrointestinal tract. The bezoar is traditionally used in South East Asia and Europe for the treatment of cancer, poisoning, dengue, typhoid, etc. However, limited scientific studies have been performed to verify its anticancer potential to substantiate its traditional claims in the treatment of cancers. Hence, this study was aimed at investigating the in vitro and in vivo anticancer properties of two grassy PB aqueous extract (PB-A and PB-B) using A375 cancer cell line and zebrafish model, respectively. This paper presents the first report on in vitro A375 cell viability assay, apoptosis assay, cell cycle arrest assay, migration assay, invasion assay, qPCR experimental assay and in vivo anti-angiogenesis assay using the grassy PBs. Experimental findings revealed IC50 value are 26.59 ± 1.37 μg/mL and 30.12 ± 3.25 μg/mL for PB-A and PB-B respectively. PBs showed anti-proliferative activity with no significant cytotoxic effect on normal human dermal fibroblast (NHDF). PBs were also found to induce apoptosis via intrinsic pathway and arrest cell cycle at G2/M phase. Additionally, the findings indicated its ability to debilitate migration and invasion of A375 cells. Further evaluation using embryo zebrafish model revealed LC50 = 450.0 ± 2.50 μg/mL and 58.7 ± 5.0 μg/mL for PB-A and PB-B which also exerted anti-angiogenesis effect in zebrafish. Moreover, stearic acid, ursodeoxycholic acid and pregnenolone were identified as possible metabolites that might contribute to the anticancer effect of the both PBs. Overall, this study demonstrated that PB-A and PB-B possess potential in vitro and in vivo anticancer effects which are elicited through selective cytotoxic effect, induction of apoptosis, inhibition of migration and invasion and anti-angiogenesis. This study provides scientific evidence that the porcupine bezoar do possess anti-cancer efficacy and further justifies its traditional utility. However, more experiments with higher vertebrae models are still warranted to validate its traditional claims as an anticancer agent.
    Matched MeSH terms: Zebrafish
  13. Fulltext Reproductive Neuroendocrine Pathways of Social Behavior
    Parhar IS, Ogawa S, Ubuka T
    Front Endocrinol (Lausanne), 2016;7:28.
    PMID: 27065948 DOI: 10.3389/fendo.2016.00028
    Social behaviors are key components of reproduction, because they are essential for successful fertilization. Social behaviors, such as courtship, mating, and aggression, are strongly associated with sex steroids, such as testosterone, estradiol, and progesterone. Secretion of sex steroids from the gonads is regulated by the hypothalamus-pituitary-gonadal (HPG) axis in vertebrates. Gonadotropin-releasing hormone (GnRH) is a pivotal hypothalamic neuropeptide that stimulates gonadotropin release from the pituitary. In recent years, the role of neuropeptides containing the C-terminal Arg-Phe-NH2 (RFamide peptides) has been emphasized in vertebrate reproduction. In particular, two key RFamide peptides, kisspeptin and gonadotropin-inhibitory hormone (GnIH), emerged as critical accelerator and suppressor of gonadotropin secretion. Kisspeptin stimulates GnRH release by directly acting on GnRH neurons, whereas GnIH inhibits gonadotropin release by inhibiting kisspeptin, GnRH neurons, or pituitary gonadotropes. These neuropeptides can regulate social behavior by regulating the HPG axis. However, distribution of neuronal fibers of GnRH, kisspeptin, and GnIH neurons is not limited within the hypothalamus, and the existence of extrahypothalamic neuronal fibers suggests direct control of social behavior within the brain. It has traditionally been shown that central administration of GnRH can stimulate female sexual behavior in rats. Recently, it was shown that Kiss1, one of the paralogs of kisspeptin peptide family, regulates fear responses in zebrafish and GnIH inhibits sociosexual behavior in birds. Here, we highlight recent findings regarding the role of GnRH, kisspeptin, and GnIH in the regulation of social behaviors in fish, birds, and mammals and discuss their importance in future biological and biomedical research.
    Matched MeSH terms: Zebrafish
  14. 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
  15. G2/M cell cycle arrest on HT-29 cancer cells and toxicity assessment of triphenylphosphanegold(I) carbonimidothioates, Ph3PAu[SC(OR)=NPh], R=Me, Et, and iPr, during zebrafish development
    Ooi KK, Yeo CI, Mahandaran T, Ang KP, Akim AM, Cheah YK, et al.
    J Inorg Biochem, 2017 01;166:173-181.
    PMID: 27865929 DOI: 10.1016/j.jinorgbio.2016.11.008
    Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NPh], R=Me (1), Et (2) and iPr (3), were previously shown to be significantly cytotoxic toward HT-29 cancer cells and to induce cell death by both intrinsic and extrinsic apoptotic pathways whereby 1 activated the p73 gene, and each of 2 and 3 activated p53; 2 also caused apoptotic cell death via the c-Jun N-terminal kinase/mitogen-activated protein kinase pathway. Apoptosis pathways have been further evaluated by mitochondrial cytochrome c measurements and annexin V screening, confirming apoptotic pathways of cell death. Cell cycle analysis showed the majority of treated HT-29 cells were arrested at the G2/M checkpoint after 24h; results of both assays were confirmed by changes in populations of relevant genes (PCR array analysis). Cell invasion studies showed inhibition of metastasis through Matrigel™ matrix to 17-22% cf. untreated cells. LC50values were determined in zebrafish (8.36, 8.17, and 7.64μM for 1-3). Finally, the zebrafish tolerated doses of 1 and 2 up to 0.625μM, and 3 was tolerated at even higher doses of up to 1.25μM.
    Matched MeSH terms: Zebrafish/embryology*
  16. Modeling Parkinson's Disease in Zebrafish
    Najib NHM, Nies YH, Abd Halim SAS, Yahaya MF, Das S, Lim WL, et al.
    CNS Neurol Disord Drug Targets, 2020;19(5):386-399.
    PMID: 32640968 DOI: 10.2174/1871527319666200708124117
    Parkinson's Disease (PD) is one of the most common neurodegenerative disorders that affects the motor system, and includes cardinal motor symptoms such as resting tremor, cogwheel rigidity, bradykinesia and postural instability. Its prevalence is increasing worldwide due to the increase in life span. Although, two centuries since the first description of the disease, no proper cure with regard to treatment strategies and control of symptoms could be reached. One of the major challenges faced by the researchers is to have a suitable research model. Rodents are the most common PD models used, but no single model can replicate the true nature of PD. In this review, we aim to discuss another animal model, the zebrafish (Danio rerio), which is gaining popularity. Zebrafish brain has all the major structures found in the mammalian brain, with neurotransmitter systems, and it also possesses a functional blood-brain barrier similar to humans. From the perspective of PD research, the zebrafish possesses the ventral diencephalon, which is thought to be homologous to the mammalian substantia nigra. We summarize the various zebrafish models available to study PD, namely chemical-induced and genetic models. The zebrafish can complement the use of other animal models for the mechanistic study of PD and help in the screening of new potential therapeutic compounds.
    Matched MeSH terms: Zebrafish*
  17. Fulltext Zebrafish: A Pharmacological Model for Learning and Memory Research
    Tan JK, Nazar FH, Makpol S, Teoh SL
    Molecules, 2022 Oct 30;27(21).
    PMID: 36364200 DOI: 10.3390/molecules27217374
    Learning and memory are essential to organism survival and are conserved across various species, especially vertebrates. Cognitive studies involving learning and memory require using appropriate model organisms to translate relevant findings to humans. Zebrafish are becoming increasingly popular as one of the animal models for neurodegenerative diseases due to their low maintenance cost, prolific nature and amenability to genetic manipulation. More importantly, zebrafish exhibit a repertoire of neurobehaviors comparable to humans. In this review, we discuss the forms of learning and memory abilities in zebrafish and the tests used to evaluate the neurobehaviors in this species. In addition, the pharmacological studies that used zebrafish as models to screen for the effects of neuroprotective and neurotoxic compounds on cognitive performance will be summarized here. Lastly, we discuss the challenges and perspectives in establishing zebrafish as a robust model for cognitive research involving learning and memory. Zebrafish are becoming an indispensable model in learning and memory research for screening neuroprotective agents against cognitive impairment.
    Matched MeSH terms: Zebrafish*
  18. 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
  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. Fulltext CNPase, a 2',3'-Cyclic-nucleotide 3'-phosphodiesterase, as a Therapeutic Target to Attenuate Cardiac Hypertrophy by Enhancing Mitochondrial Energy Production
    Tan KS, Wang D, Lu Z, Zhang Y, Li S, Lin Y, et al.
    Int J Mol Sci, 2021 Oct 06;22(19).
    PMID: 34639145 DOI: 10.3390/ijms221910806
    Heart failure is the end-stage of all cardiovascular diseases with a ~25% 5-year survival rate, and insufficient mitochondrial energy production to meet myocardial demand is the hallmark of heart failure. Mitochondrial components involved in the regulation of ATP production remain to be fully elucidated. Recently, roles of 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) in the pathophysiological processes of heart diseases have emerged, implicated by evidence that mitochondrial CNPase proteins are associated with mitochondrial integrity under metabolic stress. In this study, a zebrafish heart failure model was established, by employing antisense morpholino oligonucleotides and the CRISPR-Cas9 gene-editing system, which recapitulates heart failure phenotypes including heart dysfunction, pericardial edema, ventricular enlargement, bradycardia, and premature death. The translational implications of CNPase in the pathophysiological process of heart failure were tested in a pressure overload-induced heart hypertrophy model, which was carried out in rats through transverse abdominal aorta constriction (TAAC). AAV9-mediated myocardial delivery of CNPase mitigated the hypertrophic response through the specific hydrolysis of 2'-3'-cyclic nucleotides, supported by the decrease of cardiac hypertrophy and fibrosis, the integrity of mitochondrial ultrastructure, and indicators of heart contractility in the AAV9-TAAC group. Finally, the biometrics of a mitochondrial respiration assay carried out on a Seahorse cellular energy analyzer demonstrated that CNPase protects mitochondrial respiration and ATP production from AngII-induced metabolic stress. In summary, this study provides mechanistic insights into CNPase-2',3'-cyclic nucleotide metabolism that protects the heart from energy starvation and suggests novel therapeutic approaches to treat heart failure by targeting CNPase activity.
    Matched MeSH terms: Zebrafish
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