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Fulltext Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells

Munisvaradass R, Kumar S, Govindasamy C, Alnumair KS, Mok PL

Int J Mol Sci, 2017 Sep 08;18(9).
PMID: 28885562 DOI: 10.3390/ijms18091797

Breast cancer is a common malignancy among women. The innate and adaptive immune responses failed to be activated owing to immune modulation in the tumour microenvironment. Decades of scientific study links the overexpression of human epidermal growth factor receptor 2 (ERBB2) antigen with aggressive tumours. The Chimeric Antigen Receptor (CAR) coding for specific tumour-associated antigens could initiate intrinsic T-cell signalling, inducing T-cell activation, and cytotoxic activity without the need for major histocompatibility complex recognition. This renders CAR as a potentially universal immunotherapeutic option. Herein, we aimed to establish CAR in CD3+ T-cells, isolated from human peripheral blood mononucleated cells that could subsequently target and induce apoptosis in the ERBB2 overexpressing human breast cancer cell line, SKBR3. Constructed CAR was inserted into a lentiviral plasmid containing a green fluorescent protein tag and produced as lentiviral particles that were used to transduce activated T-cells. Transduced CAR-T cells were then primed with SKBR3 cells to evaluate their functionality. Results showed increased apoptosis in SKBR3 cells co-cultured with CAR-T cells compared to the control (non-transduced T-cells). This study demonstrates that CAR introduction helps overcome the innate limitations of native T-cells leading to cancer cell apoptosis. We recommend future studies should focus on in vivo cytotoxicity of CAR-T cells against ERBB2 expressing tumours.
Phthalates exposure and attention-deficit/hyperactivity disorder in children: a systematic review of epidemiological literature

Praveena SM, Munisvaradass R, Masiran R, Rajendran RK, Lin CC, Kumar S

Environ Sci Pollut Res Int, 2020 Dec;27(36):44757-44770.
PMID: 32895790 DOI: 10.1007/s11356-020-10652-z

Epidemiological studies have proven that children mental health can be affected by environmental pollutants which are believed to be visible in the form of psychological disorder later in their childhood. Moreover, the effects of children mental health are evidently clear in the case of phthalates which have been observed to increase psychological disorder, specifically attention-deficit hyperactivity disorder (ADHD). Hence, the present study aims to conduct a systematic review and provide an overview of the existing literature on the association between urinary phthalate metabolite concentrations and ADHD symptoms among children by emphasizing the confounding factors and limitations. Additionally, this review addressed the possible phthalate mechanism insights in human body including its impact on ADHD symptoms. In this case, 16 epidemiological studies (five cross-sectional, nine cohort and two case control studies) that met all the inclusion criteria were selected out of the total of 427 papers screened to show varying quantitative associations between phthalate exposure and ADHD symptoms among children with confounding factors and limitations in the existing studies in regard to the exposure and outcomes. This review also attempted to present possible explanation on phthalate mechanism in children body and its connection on neurodevelopment and ADHD symptom development which remains unclear in most of the studies. Finally, it is highly recommended for further research to carefully design cohort studies from prenatal to later childhood development with a complete sample size in order to understand phthalate impacts on children health.
Revisiting the role of erythropoietin for treatment of ocular disorders

Shirley Ding SL, Leow SN, Munisvaradass R, Koh EH, Bastion ML, Then KY, et al.

Eye (Lond), 2016 Oct;30(10):1293-1309.
PMID: 27285322 DOI: 10.1038/eye.2016.94

Erythropoietin (EPO) is a glycoprotein hormone conventionally thought to be responsible only in producing red blood cells in our body. However, with the discovery of the presence of EPO and EPO receptors in the retinal layers, the EPO seems to have physiological roles in the eye. In this review, we revisit the role of EPO in the eye. We look into the biological role of EPO in the development of the eye and the physiologic roles that it has. Apart from that, we seek to understand the mechanisms and pathways of EPO that contributes to the therapeutic and pathological conditions of the various ocular disorders such as diabetic retinopathy, retinopathy of prematurity, glaucoma, age-related macular degeneration, optic neuritis, and retinal detachment. With these understandings, we discuss the clinical applications of EPO for treatment of ocular disorders, modes of administration, EPO formulations, current clinical trials, and its future directions.
Morphological and genetical changes of endothelial progenitor cells after in-vitro conversion into photoreceptors

Qiang S, Alsaeedi HA, Yuhong C, Yang H, Tong L, Kumar S, et al.

J. Photochem. Photobiol. B, Biol., 2018 Jun;183:127-132.
PMID: 29704860 DOI: 10.1016/j.jphotobiol.2018.04.003

BACKGROUND: Retinal degeneration is a condition ensued by various ocular disorders such as artery occlusion, diabetic retinopathy, retrolental fibroplasia and retinitis pigmentosa which cause abnormal loss of photoreceptor cells and lead to eventual vision impairment. No efficient treatment has yet been found, however, the use of stem cell therapy such as bone marrow and embryonic stem cells has opened a new treatment modality for retinal degenerative diseases. The major goal of this study is to analyze the potential of endothelial progenitor cells derived from bone marrow to differentiate into retinal neural cells for regenerative medicine purposes.
METHODS: In this study, endothelial progenitor cells were induced in-vitro with photoreceptor growth factor (taurine) for 21 days. Subsequently, the morphology and gene expression of CRX and RHO of the photoreceptors-induced EPCs were examined through immunostaining assay.
FINDINGS: The results indicated that the induced endothelial progenitor cells demonstrated positive gene expression of CRX and RHO. Our findings suggested that EPC cells may have a high advantage in cell replacement therapy for treating eye disease, in addition to other neural diseases, and may be a suitable cell source in regenerative medicine for eye disorders.
Fulltext Stem Cell Therapy in Dengue Virus-Infected BALB/C Mice Improves Hepatic Injury

Sakinah S, Priya SP, Mok PL, Munisvaradass R, Teh SW, Sun Z, et al.

Front Cell Dev Biol, 2021;9:637270.
PMID: 34291043 DOI: 10.3389/fcell.2021.637270

Extensive clinical efforts have been made to control the severity of dengue diseases; however, the dengue morbidity and mortality have not declined. Dengue virus (DENV) can infect and cause systemic damage in many organs, resulting in organ failure. Here, we present a novel report showing a tailored stem-cell-based therapy that can aid in viral clearance and rescue liver cells from further damage during dengue infection. We administered a combination of hematopoietic stem cells and endothelial progenitor cells in a DENV-infected BALB/c mouse model and found that delivery of this cell cocktail had improved their liver functions, confirmed by hematology, histopathology, and next-generation sequencing. These stem and progenitor cells can differentiate into target cells and repair the damaged tissues. In addition, the regime can regulate endothelial proliferation and permeability, modulate inflammatory reactions, enhance extracellular matrix production and angiogenesis, and secrete an array of growth factors to create an enhanced milieu for cell reparation. No previous study has been published on the treatment of dengue infection using stem cells combination. In conclusion, dengue-induced liver damage was rescued by administration of stem cell therapy, with less apoptosis and improved repair and regeneration in the dengue mouse model.
Corrigendum: Stem Cell Therapy in Dengue Virus-Infected BALB/C Mice Improves Hepatic Injury

Sakinah S, Priya SP, Mok PL, Munisvaradass R, Teh SW, Sun Z, et al.

Front Cell Dev Biol, 2021;9:800659.
PMID: 35178398 DOI: 10.3389/fcell.2021.800659

[This corrects the article DOI: 10.3389/fcell.2021.637270.].