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Fulltext Synthesis, Characterization, and Toxicity Assessment of Pluronic F127-Functionalized Graphene Oxide on the Embryonic Development of Zebrafish (Danio rerio)

Shamsi S, Alagan AA, Sarchio SNE, Md Yasin F

Int J Nanomedicine, 2020;15:8311-8329.
PMID: 33149578 DOI: 10.2147/IJN.S271159

Background: In the current literature, there are ongoing debates on the toxicity of graphene oxide (GO) that demonstrate contradictory findings regarding its toxicity profile. As a potential drug carrier, these findings are very concerning due to the safety concerns in humans, as well as the dramatic rise of GO being excreted into the environment. Therefore, there is an imperative need to mitigate the potential toxicity of GO to allow for a safer application in the future.
Purpose: The present study aims to address this issue by functionalizing GO with Pluronic F127 (PF) as a means to mitigate toxicity and resolve the biocompatibility of GO. Although results from previous studies generally indicated that Pluronic functionalized GO exhibits relatively low toxicity to living organisms, reports that emphasize on its toxicity, particularly during embryonic developmental stage, are still scarce.
Methods: In the present study, two different sizes of native GO samples, GO and NanoGO, as well as PF-functionalized GO, GO-PF and NanoGO-PF, were prepared and characterized using DLS, UV-Vis, Raman spectroscopy, FTIR, and FESEM analyses. Toxicological assessment of all GO samples (0-100 µg/mL) on zebrafish embryonic developmental stages (survival, hatching and heart rates, and morphological changes) was recorded daily for up to 96 hours post-fertilization (hpf).
Results: The toxicity effects of each GO sample were observed to be higher at increasing concentrations and upon prolonged exposure. NanoGO demonstrated lower toxicity effects compared to GO. GO-PF and NanoGO-PF were also found to have lower toxicity effects compared to native GO samples. GO-PF showed the lowest toxicity response on zebrafish embryo.
Conclusion: These findings highlight that toxicity is dependent on the concentration, size, and exposure period of GO. Functionalization of GO with PF through surface coating could potentially mitigate the toxicity effects of GO in embryonic developmental stages, but further investigation is warranted for broader future applications.
Detection of Infiltrating Mast Cells Using a Modified Toluidine Blue Staining

Puebla-Osorio N, Sarchio SNE, Ullrich SE, Byrne SN

Methods Mol Biol, 2017;1627:213-222.
PMID: 28836204 DOI: 10.1007/978-1-4939-7113-8_14

Mast cells are part of the immune system and characteristically contain histamine- and heparin-rich basophilic granules. While these cells are usually associated with allergy and anaphylaxis, they also promote wound healing and angiogenesis and confer protection against pathogens. The presence of these cells is sometimes indicative of a poor prognosis, especially in skin cancer, pancreatic cancer, and lymphoma. Toluidine blue staining of acid-fast granules is an established method for the identification and quantification of mast cells. Generating detailed information on the location of mast cells within tissues is problematic using this technique and often requires serial sections from adjacent tissue to be separately stained with hematoxylin and eosin (H&E). Staining serial sections is not always possible, particularly if the sample is very small or rare. In such cases, a method of simultaneously identifying and localizing mast cells in a tissue would be advantageous. Toluidine blue and H&E are not commonly combined because H&E includes repetitive washes in water, which may affect the efficacy of the aqueous-soluble toluidine blue. We have developed and tested a novel staining technique that integrates toluidine blue between hematoxylin and eosin in one simple procedure. This protocol works on both frozen and formalin-fixed, paraffin-embedded tissue and readily allows for the identification of purple-stained mast cells against a clean H&E background. This facilitates a more accurate localization and proper counting of mast cells in normal and affected tissue.
Fulltext Pharmacologically antagonizing the CXCR4-CXCL12 chemokine pathway with AMD3100 inhibits sunlight-induced skin cancer

Sarchio SNE, Scolyer RA, Beaugie C, McDonald D, Marsh-Wakefield F, Halliday GM, et al.

J Invest Dermatol, 2014 Apr;134(4):1091-1100.
PMID: 24226205 DOI: 10.1038/jid.2013.424

One way sunlight causes skin cancer is by suppressing anti-tumor immunity. A major mechanism involves altering mast cell migration via the C-X-C motif chemokine receptor 4-C-X-C motif chemokine ligand 12 (CXCR4-CXCL12) chemokine pathway. We have discovered that pharmacologically blocking this pathway with the CXCR4 antagonist AMD3100 prevents both UV radiation-induced immune suppression and skin cancer. The majority of control mice receiving UV-only developed histopathologically confirmed squamous cell carcinomas. In contrast, skin tumor incidence and burden was significantly lower in AMD3100-treated mice. Perhaps most striking was that AMD3100 completely prevented the outgrowth of latent tumors that occurred once UV irradiation ceased. AMD3100 protection from UV immunosuppression and skin cancer was associated with reduced mast cell infiltration into the skin, draining lymph nodes, and the tumor itself. Thus a major target of CXCR4 antagonism was the mast cell. Our results indicate that interfering with UV-induced CXCL12 by antagonizing CXCR4 significantly inhibits skin tumor development by blocking UV-induced effects on mast cells. Hence, the CXCR4-CXCL12 chemokine pathway is a novel therapeutic target in the prevention of UV-induced skin cancer.
Fulltext Insomnia and depression levels among Malaysian undergraduate students in the Faculty of Medicine and Health Sciences (FMHS), Universiti Putra Malaysia (UPM) during Movement Control Order (MCO)

Iqbal RM, Binti Riza Effendi NI, Syed Alwi SS, Saidi HI, Sarchio SNE

PLoS One, 2023;18(10):e0283098.
PMID: 37816038 DOI: 10.1371/journal.pone.0283098

Rapid outbreak of coronavirus disease 2019 has caused the implementation of the movement control order (MCO) which aimed to reduce the spread in Covid-19 infections. While some may find it easy to adjust to the new norm, others found it difficult to switch from their normal routines and habits as according to the MCO SOP. This resulted in a more frequent insomnia and depression that subsequently impacted their mental health. Insomnia and depression levels are examined in this study as they relate to the Covid-19 Pandemic and the MCO among Malaysian undergraduate health sciences students at the Faculty of Medicine and Health Sciences, UPM. Random sampling methods were utilised with consideration of inclusion and exclusion criteria. The Patient Health Questionnaire-9 (PHQ-9) and the Insomnia Severity Index (ISI) were the instrument packages used in this investigation. An internet platform was used to distribute the questionnaire. Based on the results, it is concluded that depression and insomnia are significantly correlated, with a p-value of 0.05. This study also revealed the link between the severity of insomnia and the severity of depression among UPM students studying health sciences. The percentage of students with depression and insomnia was rather high (54.9% and 33.9%, respectively), and this occurred during the second wave of Covid-19 cases in Malaysia.
Fulltext Biocompatibility Study of Curcumin-Loaded Pluronic F127 Nanoformulation (NanoCUR) against the Embryonic Development of Zebrafish (Danio rerio)

Abdullah SNS, Subramaniam KA, Muhamad Zamani ZH, Sarchio SNE, Md Yasin F, Shamsi S

Molecules, 2022 Jul 14;27(14).
PMID: 35889367 DOI: 10.3390/molecules27144493

Curcumin (CUR) has been studied for its biomedical applications due to its active biological properties. However, CUR has limitations such as poor solubility, low bioavailability, and rapid degradation. Thus, CUR was nanoformulated with the application of polymeric micelle. Previous studies of CUR-loaded Pluronic F127 nanoformulation (NanoCUR) were generally prioritized toward cancer cells and its therapeutic values. There are reports that emphasize the toxicity of CUR, but reports on the toxicity of NanoCUR on embryonic developmental stages is still scarce. The present study aims to investigate the toxicity effects of NanoCUR on the embryonic development of zebrafish (Danio rerio). NanoCUR was synthesized via thin film hydration method and then characterized using DLS, UV-Vis, FTIR, FESEM, and XRD. The toxicity assessment of NanoCUR was conducted using zebrafish embryos, in comparison to native CUR, as well as Pluronic F127 (PF) as the controls, and ROS assay was further carried out. It was revealed that NanoCUR showed an improved toxicity profile compared to native CUR. NanoCUR displayed a delayed toxicity response and showed a concentration- and time-dependent toxicity response. NanoCUR was also observed to generate a significantly low reactive oxygen species (ROS) compared to native CUR in ROS assay. Overall, the results obtained highlight the potential of NanoCUR to be developed in clinical settings due to its improved toxicity profile compared to CUR.
Fulltext A persistent antimicrobial resistance pattern and limited methicillin-resistance-associated genotype in a short-term Staphylococcus aureus carriage isolated from a student population

Mat Azis N, Pung HP, Abdul Rachman AR, Amin Nordin S, Sarchio SNE, Suhaili Z, et al.

J Infect Public Health, 2017 Mar-Apr;10(2):156-164.
PMID: 27033676 DOI: 10.1016/j.jiph.2016.02.013

The aim of the present study was to assess and compare the antimicrobial susceptibility pattern against a panel of antibiotics and molecular and methicillin resistance-associated genotypes of 120 carriage S. aureus isolates previously isolated from a student population at two isolation events within a one-month interval. The antibiotic susceptibility of isolates was determined using the Kirby-Bauer disc-diffusion method (cefoxitin by Etest). The MRSA was screened using polymerase chain reaction for the presence of the mecA gene. The mecA-positive isolates were subjected to staphylococcal cassette chromosome (SCC) mec typing, multilocus sequence typing (MLST) and eBURST analysis. All isolates were characterized for the presence of the Panton-Valentine leukocidin (PVL) gene, an enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) pattern and the spa type. For the two occasions where S. aureus was isolated, the highest frequency of resistance was observed for penicillin (70% and 65%, respectively), with a lower rate against erythromycin and tetracycline (<12%). All isolates were susceptible to ciprofloxacin and gentamycin. As for methicillin resistance, eight isolates had minimum inhibitory concentrations (MIC) of resistant categories, but 10 isolates (8.33%) were positive for the mecA gene. The mecA-positive isolates belonged to SCCmec types I (n=9) and V (n=1). MLST was resolved for only three MRSAs, ST508 (n=1), ST88 (n=1) and ST96 (n=1). The results of the eBURST analysis showed that the MRSA isolates analyzed in the present study were potentially related to MRSA identified in other countries. Approximately half of the persistent S. aureus carriers harbored S. aureus of a similar spa type in the respective individuals during both isolation events. A persistent antimicrobial pattern and limited distinct MRSAs were observed over the short study period. The latter frequently exhibited SCCmec type I, commonly associated with hospital-acquired (HA) characteristics, but further delineation is needed to justify the origins of these bacteria.
Fulltext Stability, Toxicity, and Antibacterial Potential of Gallic Acid-Loaded Graphene Oxide (GAGO) Against Methicillin-Resistant Staphylococcus aureus (MRSA) Strains

Shamsi S, Abdul Ghafor AAH, Norjoshukrudin NH, Ng IMJ, Abdullah SNS, Sarchio SNE, et al.

Int J Nanomedicine, 2022;17:5781-5807.
PMID: 36474524 DOI: 10.2147/IJN.S369373

BACKGROUND: The impetuous usage of antibiotics has led to the perpetual rise of methicillin-resistant Staphylococcus aureus (MRSA), which has garnered the interest of potential drug alternatives, including nanomaterials.
PURPOSE: The present study investigates the stability, toxicity, and antibacterial potential of gallic acid-loaded graphene oxide (GAGO) on several MRSA strains.
METHODS: The stability of a synthesized and characterized GAGO was monitored in different physiological media. The toxicity profile of GAGO was evaluated in 3T3 murine fibroblast cells and the embryonic zebrafish model. The antibacterial activity of GAGO against MRSA, methicillin-susceptible S. aureus (MSSA), and community-acquired MRSA; with or without Panton-valentine leucocidin gene (MRSA-pvl+ and MRSA-pvl-) was investigated through disk diffusion, CFU counting method, time-kill experiment, and high-resolution transmission electron microscopy (HRTEM) observation.
RESULTS: A stable GAGO nanocomposite has shown an improved toxicity profile in 3T3 murine fibroblast cells and zebrafish embryos, besides exhibiting normal ROS levels than graphene oxide (GO) and GA (gallic acid). The nanocomposite inhibited the growth of all bacterial strains employed. The effectiveness of the GAGO nanocomposite was comparable to cefoxitin (CFX), at ≥150 µg/mL in MRSA and MSSA. GAGO exhibited a significantly delayed response towards MRSA-pvl+ and MRSA-pvl-, with increased inhibition following 8 to 24 h of exposure, while comparable activity to native GA was only achieved at 24 h. Meanwhile, for MRSA and MSSA, GAGO had a comparable activity with native GA and GO as early as 2 h of exposure. HRTEM observation further reveals that GAGO-exposed cells were membrane compromised.
CONCLUSION: In summary, the present study indicates the antibacterial potential of GAGO against MRSA strains, but further study is warranted to understand the mechanism of action of GAGO and its resistance in MRSA strains.