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Displaying publications 941 - 960 of 3311 in total

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CD133: beyond a cancer stem cell biomarker

Barzegar Behrooz A, Syahir A, Ahmad S

J Drug Target, 2019 03;27(3):257-269.
PMID: 29911902 DOI: 10.1080/1061186X.2018.1479756

CD133 (prominin-1), a pentaspan membrane glycoprotein, is one of the most well-characterized biomarkers used for the isolation of cancer stem cells (CSCs). The presence of CSCs is one of the main causes of tumour reversal and resilience. Accumulating evidence has shown that CD133 might be responsible for CSCs tumourigenesis, metastasis and chemoresistance. It is now understood that CD133 interacts with the Wnt/β-catenin and PI3K-Akt signalling pathways. Moreover, CD133 can upregulate the expression of the FLICE-like inhibitory protein (FLIP) in CD133-positive cells, inhibiting apoptosis. In addition, CD133 can increase angiogenesis by activating the Wnt signalling pathway and increasing the expression of vascular endothelial growth factor-A (VEGF-A) and interleukin-8. Therefore, CD133 could be considered to be an 'Achilles' heel' for CSCs, because by inhibiting this protein, the signalling pathways that are involved in cell proliferation will also be inhibited. By understanding the molecular biology of CD133, we can not only isolate stem cells but can also utilise it as a therapeutic strategy. In this review, we summarise new insights into the fundamental cell biology of CD133 and discuss the involvement of CD133 in metastasis, metabolism, tumourigenesis, drug-resistance, apoptosis and autophagy.

Matched MeSH terms: Neoplastic Stem Cells/metabolism*
Fulltext Purification and differentiation of human adipose-derived stem cells by membrane filtration and membrane migration methods

Lin HR, Heish CW, Liu CH, Muduli S, Li HF, Higuchi A, et al.

Sci Rep, 2017 01 10;7:40069.
PMID: 28071738 DOI: 10.1038/srep40069

Human adipose-derived stem cells (hADSCs) are easily isolated from fat tissue without ethical concerns, but differ in purity, pluripotency, differentiation ability, and stem cell marker expression, depending on the isolation method. We isolated hADSCs from a primary fat tissue solution using: (1) conventional culture, (2) a membrane filtration method, (3) a membrane migration method where the primary cell solution was permeated through membranes, adhered hADSCs were cultured, and hADSCs migrated out from the membranes. Expression of mesenchymal stem cell markers and pluripotency genes, and osteogenic differentiation were compared for hADSCs isolated by different methods using nylon mesh filter membranes with pore sizes ranging from 11 to 80 μm. hADSCs isolated by the membrane migration method had the highest MSC surface marker expression and efficient differentiation into osteoblasts. Osteogenic differentiation ability of hADSCs and MSC surface marker expression were correlated, but osteogenic differentiation ability and pluripotent gene expression were not.

Matched MeSH terms: Stem Cells/physiology*
Humanizing glycosylation pathways in eukaryotic expression systems

Khan AH, Bayat H, Rajabibazl M, Sabri S, Rahimpour A

World J Microbiol Biotechnol, 2017 Jan;33(1):4.
PMID: 27837408

Glycosylation represents the most widespread posttranslational modifications, found in a broad spectrum of natural and therapeutic recombinant proteins. It highly affects bioactivity, site-specificity, stability, solubility, immunogenicity, and serum half-life of glycoproteins. Numerous expression hosts including yeasts, insect cells, transgenic plants, and mammalian cells have been explored for synthesizing therapeutic glycoproteins. However, glycosylation profile of eukaryotic expression systems differs from human. Glycosylation strategies have been proposed for humanizing the glycosylation pathways in expression hosts which is the main theme of this review. Besides, we also highlighted the glycosylation potential of protozoan parasites by emphasizing on the mammalian-like glycosylation potential of Leishmania tarentolae known as Leishmania expression system.

Matched MeSH terms: Eukaryotic Cells/metabolism*
Rapidly increasing liver progenitor cell numbers in human regenerating liver after portal vein ligation and liver partition

Lin KH, Hsu HT, Teng TH, Lin PY, Ko CJ, Hsieh CE, et al.

Malays J Pathol, 2017 Dec;39(3):289-291.
PMID: 29279592

BACKGROUND: Liver regeneration is dependent on the proliferation of hepatocytes. Hepatic progenitor cells are intra-hepatic precursor cells capable of differentiating into hepatocytes or biliary cells. Although liver progenitor cell proliferation during the regenerative process has been observed in animal models of severe liver injury, it has never been observed in vivo in humans because it is unethical to take multiple biopsy specimens for the purpose of studying the proliferation of liver progenitor cells and the roles they play in liver regeneration. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a staged procedure for inducing remnant liver hypertrophy so that major hepatectomy can be performed safely. This staged procedure allows for liver biopsy specimens to be taken before and after the liver begins to regenerate.
CASE PRESENTATION: The liver progenitor cell proliferation is observed in a patient undergoing ALPPS for a metastatic hepatic tumour. Liver biopsy is acquired before and after ALPPS for the calculation of average number of liver progenitor cell under high magnification examination by stain of immunomarkers. This is the first in vivo evidence of growing liver progenitor cells demonstrated in a regenerating human liver.

Matched MeSH terms: Stem Cells/cytology*
Nipah Virus Infection of Immature Dendritic Cells Increases Its Transendothelial Migration Across Human Brain Microvascular Endothelial Cells

Tiong V, Shu MH, Wong WF, AbuBakar S, Chang LY

Front Microbiol, 2018;9:2747.
PMID: 30483242 DOI: 10.3389/fmicb.2018.02747

Nipah virus (NiV) can infect multiple organs in humans with the central nervous system (CNS) being the most severely affected. Currently, it is not fully understood how NiV spreads throughout the body. NiV has been shown to infect certain leukocyte populations and we hypothesized that these infected cells could cross the blood-brain barrier (BBB), facilitating NiV entry into the CNS. Here, three leukocyte types, primary immature dendritic cells (iDC), primary monocytes (pMO), and monocytic cell line (THP-1), were evaluated for permissiveness to NiV. We found only iDC and THP-1 were permissive to NiV. Transendothelial migration of mock-infected and NiV-infected leukocytes was then evaluated using an in vitro BBB model established with human brain microvascular endothelial cells (HBMEC). There was approximately a threefold increase in migration of NiV-infected iDC across endothelial monolayer when compared to mock-infected iDC. In contrast, migration rates for pMO and THP-1 did not change upon NiV infection. Across TNF-α-treated endothelial monolayer, there was significant increase of almost twofold in migration of NiV-infected iDC and THP-1 over mock-infected cells. Immunofluorescence analysis showed the migrated NiV-infected leukocytes retained their ability to infect other cells. This study demonstrates for the first time that active NiV infection of iDC and THP-1 increased their transendothelial migration activity across HBMEC and activation of HBMEC by TNF-α further promoted migration. The findings suggest that NiV infection of leukocytes to disseminate the virus via the "Trojan horse" mechanism is a viable route of entry into the CNS.

Matched MeSH terms: Dendritic Cells; Endothelial Cells
Desmoplastic ameloblastoma in Indians: report of five cases and review of literature

Sivapathasundharam B, Einstein A, Syed RI

Indian J Dent Res, 2007 10 17;18(4):218-21.
PMID: 17938502

In the recent World Health Organization classification of odontogenic tumours, desmoplastic ameloblastoma has been characterized as a variant of ameloblastoma, with specific clinical, radiographical, and histological features. Till date, 145 cases have been reported in Japanese, Chinese, Malaysian, Western, and African populations, with very few cases described in Indians. Here, we report five cases in the Indian population. The male to female ratio was 3:2. The mean age at diagnosis was 33.2 years. Four of the tumours were located in the maxilla, in the anterior premolar region. The lone mandibular tumour was located anteriorly, crossing the midline. Three of the tumours had a mixed radiologic appearance with poorly defined borders. Unilocular change was seen in one of them. Two tumours presented as unilocular radiolucencies with specks of radiopacities and well-circumscribed borders. Histologically, irregular odontogenic islands, with a stretched-out 'kite-tail' appearance, were seen in a dense desmoplastic stroma. The peripheral layer of the epithelial islands was made up of flattened cells and the inner core was made up of spindle-shaped and, in some instances, squamous-shaped cells. In two cases, odontogenic epithelium in the form of follicles, typical of solid/multicystic ameloblastoma, was seen and these were typed as 'hybrid' variants. All the cases were treated by resection.

Matched MeSH terms: Epithelial Cells/pathology
BZD9L1 sirtuin inhibitor as a potential adjuvant for sensitization of colorectal cancer cells to 5-fluorouracil

Tan YJ, Lee YT, Petersen SH, Kaur G, Kono K, Tan SC, et al.

Ther Adv Med Oncol, 2019;11:1758835919878977.
PMID: 31632470 DOI: 10.1177/1758835919878977

Background: This study aims to investigate the combination effect of a novel sirtuin inhibitor (BZD9L1) with 5-fluorouracil (5-FU) and to determine its molecular mechanism of action in colorectal cancer (CRC).
Methods: BZD9L1 and 5-FU either as single treatment or in combination were tested against CRC cells to evaluate synergism in cytotoxicity, senescence and formation of micronucleus, cell cycle and apoptosis, as well as the regulation of related molecular players. The effects of combined treatments at different doses on stress and apoptosis, migration, invasion and cell death mechanism were evaluated through two-dimensional and three-dimensional cultures. In vivo studies include investigation on the combination effects of BZD9L1 and 5-FU on colorectal tumour xenograft growth and an evaluation of tumour proliferation and apoptosis using immunohistochemistry.
Results: Combination treatments exerted synergistic reduction on cell viability on HCT 116 cells but not on HT-29 cells. Combined treatments reduced survival, induced cell cycle arrest, apoptosis, senescence and micronucleation in HCT 116 cells through modulation of multiple responsible molecular players and apoptosis pathways, with no effect in epithelial mesenchymal transition (EMT). Combination treatments regulated SIRT1 and SIRT2 protein expression levels differently and changed SIRT2 protein localization. Combined treatment reduced growth, migration, invasion and viability of HCT 116 spheroids through apoptosis, when compared with the single treatment. In addition, combined treatment was found to reduce tumour growth in vivo through reduction of tumour proliferation and necrosis compared with the vehicle control group. This highlights the potential therapeutic effects of BZD9L1 and 5-FU towards CRC.
Conclusion: This study may pave the way for use of BZD9L1 as an adjuvant to 5-FU in improving the therapeutic efficacy for the treatment of colorectal cancer.

Matched MeSH terms: HT29 Cells; HCT116 Cells
Fulltext Elevated interleukin-25 and its association to Th2 cytokines in systemic lupus erythematosus with lupus nephritis

Selvaraja M, Abdullah M, Arip M, Chin VK, Shah A, Amin Nordin S

PLoS One, 2019;14(11):e0224707.
PMID: 31697750 DOI: 10.1371/journal.pone.0224707

Systemic lupus erythematosus (SLE) is an autoimmune disorder that is associated with lupus nephritis, initiated by the deposition of immune complexes in the kidney; subsequently, this induces the overexpression of cytokines. Lupus nephritis is known as one of the major clinical manifestations that affect the disease severity in SLE patients. An increased number of resident periglomerular and immune cells in the kidney has the potential to affect the equilibrium of different immune cell subsets, such as Th1, Th2, Th17, and Tregs, which may be central to the induction of tissue damage in kidney by exerting either proinflammatory or anti-inflammatory effects, or both. This equilibrium has yet to be confirmed, as new players such as IL-25 remain undiscovered. IL-25 is a cytokine of the IL-17 family, which stimulates Th2-mediated immune response when overly expressed. Thus, the aim of this research is to determine the plasma levels of IL-25 and Th2-associated cytokines (IL-4, IL-5, IL-6, IL-9, IL-10, IL-13) in SLE patients with (SLE-LN) and without lupus nephritis. Sixty-four (n = 64) SLE patients and fifteen (n = 15) healthy individuals were recruited. This study demonstrated that the IL-9, IL-10 and IL-25 had significantly increased expressions in SLE-LN, followed by SLE without LN, compared to healthy controls. Meanwhile, IL-5 and IL-6 had significantly reduced. No significant difference was observed with IL-13, while the level of IL-4 was undetectable. Furthermore, IL-9 and IL-10 were significantly correlated with the IL-25, and IL-25, IL-9 and IL-10 were positively correlated with the disease severity score, SLEDAI. In conclusion, IL-25 and its associated Th2 cytokines (IL-9 and IL-10) may be involved in SLE pathogenesis. These cytokines could be potential biomarkers in monitoring and predicting the disease severity during SLE pathogenesis.

Matched MeSH terms: Th2 Cells/immunology*
A level-set method for the evolution of cells and tissue during curvature-controlled growth

Alias MA, Buenzli PR

Int J Numer Method Biomed Eng, 2020 01;36(1):e3279.
PMID: 31724309 DOI: 10.1002/cnm.3279

Most biological tissues grow by the synthesis of new material close to the tissue's interface, where spatial interactions can exert strong geometric influences on the local rate of growth. These geometric influences may be mechanistic or cell behavioural in nature. The control of geometry on tissue growth has been evidenced in many in vivo and in vitro experiments, including bone remodelling, wound healing, and tissue engineering scaffolds. In this paper, we propose a generalisation of a mathematical model that captures the mechanistic influence of curvature on the joint evolution of cell density and tissue shape during tissue growth. This generalisation allows us to simulate abrupt topological changes such as tissue fragmentation and tissue fusion, as well as three dimensional cases, through a level-set-based method. The level-set method developed introduces another Eulerian field than the level-set function. This additional field represents the surface density of tissue-synthesising cells, anticipated at future locations of the interface. Numerical tests performed with this level-set-based method show that numerical conservation of cells is a good indicator of simulation accuracy, particularly when cusps develop in the tissue's interface. We apply this new model to several situations of curvature-controlled tissue evolutions that include fragmentation and fusion.

Matched MeSH terms: Cells/metabolism*
Fulltext Cytotoxic and apoptosis-inducing effects of wildtype and mutated Hydra actinoporin-like toxin 1 (HALT-1) on various cancer cell lines

Ng TJ, Teo MYM, Liew DS, Effiong PE, Hwang JS, Lim CSY, et al.

PeerJ, 2019;7:e6639.
PMID: 31106043 DOI: 10.7717/peerj.6639

Background: Hydra actinoporin like toxin -1 (HALT-1), is a small 18.5 kDa pore forming toxin derived from Hydra magnipapillata which has been shown to elicit strong haemolytic and cytolytic activity when in contact with cell membranes. Due to its cytotoxic potency, HALT-1 was further investigated for its potential as a toxin moiety candidate in immunotoxin developmental efforts, ideally as a form of targeted therapy against cancer.
Methods: In this study, wtHALT-1 (wild type) and its Y110A mutated binding domain counterpart (mHALT-1) were produced and evaluated for their cytotoxic and apoptotic effects on various cancer cell lines. A total of seven different tumour and non-tumour cell lines including HeLa, HepG2, SW-620, MCF-7, CCD841CoN, NHDF and HCT116 were used. Immunofluorescence assays were used to observe membrane binding and localization changes between both HALT-1 recombinant proteins based on 6xHis-tag detection.
Result: Based on MTT data, mHALT-1 demonstrated a significant reduction of 82% ± 12.21% in cytotoxic activity across all cell lines after the membrane recognition domain had been mutated in comparison to the wtHALT-1. Annexin V FITC/PI assay data also indicated that HeLa, HepG2 and MCF-7 demonstrated an apoptosis-mediated cell death after being treated with wtHALT-1. Additionally, a notable difference between wtHALT-1 and mHALT-1 binding affinity was clearly observed where emission of green fluorescence along the cell membrane was observed only in wtHALT-1 treated cells.
Discussion: These results suggest that mHALT-1 (Y110A) can be potentially developed as a toxin-moiety candidate for the development of future immunotoxins against various human cell-based diseases.

Matched MeSH terms: HeLa Cells; MCF-7 Cells
Fertility suppression in male sprague-dawley rats by administration of methanolic extract of hempedu bumi (Andrographis paniculata)

Mahanem M, Dayang Nurul Fatihah

Sains Malaysiana, 2015;44:1249-1255.

The recent expanding rat population is causing severe economic losses and diseases in human. The main objective of this study was to evaluate the antifertility effects of Andrographis paniculata (AP) methanol extract on the weight of testis, sexual behaviour, fertility, sperm quality and serum testosterone level in treated male rats compared with control rats. A total of 21 adult male rats Sprague-Dawley aged 12 weeks were divided into three groups; control group (distilled water), low dose group (800 mg/kg) and high dose group (1600 mg/kg) of AP methanol extracts given orally for 24 days. Body and testis weight, sexual behaviour test, fertility test, sperm quality and serum testosterone level were measured. Oral administration of AP methanol extract showed a significant decrease in testis weight, number of mountings, number of fetuses, sperm count, sperm motility and serum testosterone levels for all treatment group as compared with the control group, whereas mortality showed a significant increase. Observation on testis histology of treatment group exhibited features of degeneration in Sertoli cells and germinal cells in the seminiferous tubules, followed by the shrinkage of Leydig cells as compared with the control group, which showed characteristics of normal spermatogenesis. In conclusion, AP methanol extract exhibited antifertility effects in male rats, suggesting that AP is a potential herb to be applied as rodenticide.

Matched MeSH terms: Leydig Cells; Sertoli Cells
Genetic, epigenetic, and lineage-directed mechanisms in benzene-induced malignancies and hematotoxicity targeting hematopoietic stem cells niche

Dewi R, Hamid ZA, Rajab NF, Shuib S, Razak SA

Hum Exp Toxicol, 2020 May;39(5):577-595.
PMID: 31884827 DOI: 10.1177/0960327119895570

Benzene is a known hematotoxic and leukemogenic agent with hematopoietic stem cells (HSCs) niche being the potential target. Occupational and environmental exposure to benzene has been linked to the incidences of hematological disorders and malignancies. Previous studies have shown that benzene may act via multiple modes of action targeting HSCs niche, which include induction of chromosomal and micro RNA aberrations, leading to genetic and epigenetic modification of stem cells and probable carcinogenesis. However, understanding the mechanism linking benzene to the HSCs niche dysregulation is challenging due to complexity of its microenvironment. The niche is known to comprise of cell populations accounted for HSCs and their committed progenitors of lymphoid, erythroid, and myeloid lineages. Thus, it is fundamental to address novel approaches via lineage-directed strategy to elucidate precise mechanism involved in benzene-induced toxicity targeting HSCs and progenitors of different lineages. Here, we review the key genetic and epigenetic factors that mediate hematotoxicological effects by benzene and its metabolites in targeting HSCs niche. Overall, the use of combined genetic, epigenetic, and lineage-directed strategies targeting the HSCs niche is fundamental to uncover the key mechanisms in benzene-induced hematological disorders and malignancies.

Matched MeSH terms: Hematopoietic Stem Cells/drug effects*
Fulltext Induction of Apoptosis by Gluconasturtiin-Isothiocyanate (GNST-ITC) in Human Hepatocarcinoma HepG2 Cells and Human Breast Adenocarcinoma MCF-7 Cells

Arumugam A, Ibrahim MD, Kntayya SB, Mohd Ain N, Iori R, Galletti S, et al.

Molecules, 2020 Mar 09;25(5).
PMID: 32182965 DOI: 10.3390/molecules25051240

Gluconasturtiin, a glucosinolate present in watercress, is hydrolysed by myrosinase to form gluconasturtiin-isothiocyanate (GNST-ITC), which has potential chemopreventive effects; however, the underlying mechanisms of action have not been explored, mainly in human cell lines. The purpose of the study is to evaluate the cytotoxicity of GNST-ITC and to further assess its potential to induce apoptosis. GNST-ITC inhibited cell proliferation in both human hepatocarcinoma (HepG2) and human breast adenocarcinoma (MCF-7) cells with IC50 values of 7.83 µM and 5.02 µM, respectively. Morphological changes as a result of GNST-ITC-induced apoptosis showed chromatin condensation, nuclear fragmentation, and membrane blebbing. Additionally, Annexin V assay showed proportion of cells in early and late apoptosis upon exposure to GNST-ITC in a time-dependent manner. To delineate the mechanism of apoptosis, cell cycle arrest and expression of caspases were studied. GNST-ITC induced a time-dependent G2/M phase arrest, with reduction of 82% and 93% in HepG2 and MCF-7 cell lines, respectively. The same treatment also led to the subsequent expression of caspase-3/7 and -9 in both cells demonstrating mitochondrial-associated cell death. Collectively, these results reveal that GNST-ITC can inhibit cell proliferation and can induce cell death in HepG2 and MCF-7 cancer cells via apoptosis, highlighting its potential development as an anticancer agent.

Matched MeSH terms: Hep G2 Cells; MCF-7 Cells
Green synthesis of selenium-N-heterocyclic carbene compounds: Evaluation of antimicrobial and anticancer potential

Kamal A, Nazari V M, Yaseen M, Iqbal MA, Ahamed MBK, Majid ASA, et al.

Bioorg Chem, 2019 09;90:103042.
PMID: 31226469 DOI: 10.1016/j.bioorg.2019.103042

Three benzimidazolium salts (III-V) and respective selenium adducts (VI-VIII) were designed, synthesized and characterized by various analytical techniques (FT-IR and NMR 1H, 13C). Selected salts and respective selenium N-Heterocyclic carbenes (selenium-NHC) adducts were tested in vitro against Cervical Cancer Cell line (Hela), Breast Adenocarcinoma cell line (MCF-7), Retinal Ganglion Cell line (RGC-5) and Mouse Melanoma Cell line (B16F10) using MTT assay and the results were compared with standard drug 5-Fluorouracil. Se-NHC compounds and azolium salts showed significant anticancer potential. Molecular docking studies of compounds (VI, VII and VIII) showed strong binding energies and ligand affinity toward following angiogenic factors: VEGF-A (vascular endothelial growth factor A), EGF (human epidermal growth factor), HIF (Hypoxia-inducible factor) and COX-1 (Cyclooxygenase-1) suggesting that the anticancer activity of adducts (VI, VII and VIII) may be due to their strong anti-angiogenic effect. In addition, compounds III-VIII were screened for their antibacterial and antifungal potential. Adduct VI was found to be potent anti-fungal agent against A. Niger with zone of inhibition (ZI) value 27.01 ± 0.251 mm which is better than standard drug Clotrimazole tested in parallel.

Matched MeSH terms: Retinal Ganglion Cells; MCF-7 Cells
Effect of freeze-thaw cycles pretreatment on the vacuum freeze-drying process and physicochemical properties of the dried garlic slices

Feng Y, Ping Tan C, Zhou C, Yagoub AEA, Xu B, Sun Y, et al.

Food Chem, 2020 Sep 15;324:126883.
PMID: 32344350 DOI: 10.1016/j.foodchem.2020.126883

Freeze-thaw cycles (FTC) pretreatment was employed before the vacuum freeze-drying of garlic slices, aimed at improving the drying process and the quality of the end product. Cell viability, water status, internal structure, flavor, chemical composition and thermogravimetric of garlic samples were evaluated. The results indicated that FTC pretreatment reduced the drying time (22.22%-33.33%) and the energy consumption (14.25%-15.50%), owing to the water loss, the increase in free water, and the formation of porous structures. The FTC pretreatment improved thermal stability, flavor and chemical composition content of dried products. The antioxidant activity of polysaccharides extracted from FTC pretreated dried products was higher than that of the unpretreated dried product due to the reduction in polysaccharide molecular weight. This research could pave a route for future production of dried garlic slices having good quality by using the FTC pretreatment, with lower energy consumption and shorter drying time.

Matched MeSH terms: Plant Cells/physiology
Live-cell imaging and ultrastructural analysis reveal remarkable features of cultured porcine gonocytes

Awang-Junaidi AH, Fayaz MA, Kawamura E, Sobchishin L, MacPhee DJ, Honaramooz A

Cell Tissue Res, 2020 Aug;381(2):361-377.
PMID: 32388763 DOI: 10.1007/s00441-020-03218-5

Gonocytes in the neonatal testis have male germline stem cell potential. The objective of the present study was to examine the behavior and ultrastructure of gonocytes in culture. Neonatal porcine testis cells were cultured for 4 weeks and underwent live-cell imaging to explore real-time interactions among cultured cells. This included imaging every 1 h from day 0 to day 3, every 2 h from day 4 to day 7, and every 1 h for 24 h at days 14, 21, and 28. Samples also underwent scanning electron microscopy, transmission electron microscopy, morphometric evaluations, immunofluorescence, and RT-PCR. Live-cell imaging revealed an active amoeboid-like movement of gonocytes, assisted by the formation of extensive cytoplasmic projections, which, using scanning electron microscopy, were categorized into spike-like filopodia, leaf-like lamellipodia, membrane ruffles, and cytoplasmic blebs. In the first week of culture, gonocytes formed loose attachments on top of a somatic cell monolayer and, in week 2, formed grape-like clusters, which, over time, grew in cell number. Starting at week 3 of culture, some of the gonocyte clusters transformed into large multinucleated embryoid body-like colonies (EBLCs) that expressed both gonocyte- and pluripotent-specific markers. The number and diameter of individual gonocytes, the number and density of organelles within gonocytes, as well as the number and diameter of the EBLCs increased over time (P

Matched MeSH terms: Cells, Cultured; Germ Cells
Fulltext Asymptomatic neurotoxicity of amyloid β-peptides (Aβ1-42 and Aβ25-35) on mouse embryonic stem cell-derived neural cells

Mansor NI, Ntimi CM, Abdul-Aziz NM, Ling KH, Adam A, Rosli R, et al.

Bosn J Basic Med Sci, 2021 Feb 01;21(1):98-110.
PMID: 32156249 DOI: 10.17305/bjbms.2020.4639

One of the strategies in the establishment of in vitro oxidative stress models for neurodegenerative diseases, such as Alzheimer's disease (AD), is to induce neurotoxicity by amyloid beta (Aβ) peptides in suitable neural cells. Presently, data on the neurotoxicity of Aβ in neural cells differentiated from stem cells are limited. In this study, we attempted to induce oxidative stress in transgenic 46C mouse embryonic stem cell-derived neurons via treatment with Aβ peptides (Aβ1-42 and Aβ25-35). 46C neural cells were generated by promoting the formation of multicellular aggregates, embryoid bodies in the absence of leukemia inhibitory factor, followed by the addition of all-trans retinoic acid as the neural inducer. Mature neuronal cells were exposed to different concentrations of Aβ1-42 and Aβ25-35 for 24 h. Morphological changes, cell viability, and intracellular reactive oxygen species (ROS) production were assessed. We found that 100 µM Aβ1-42 and 50 µM Aβ25-35 only promoted 40% and 10%, respectively, of cell injury and death in the 46C-derived neuronal cells. Interestingly, treatment with each of the Aβ peptides resulted in a significant increase of intracellular ROS activity, as compared to untreated neurons. These findings indicate the potential of using neurons derived from stem cells and Aβ peptides in generating oxidative stress for the establishment of an in vitro AD model that could be useful for drug screening and natural product studies.

Matched MeSH terms: Mouse Embryonic Stem Cells/cytology*
Cytokine Induction in Nipah Virus-Infected Primary Human and Porcine Bronchial Epithelial Cells

Elvert M, Sauerhering L, Maisner A

J Infect Dis, 2020 05 11;221(Suppl 4):S395-S400.
PMID: 31665348 DOI: 10.1093/infdis/jiz455

During the Nipah virus (NiV) outbreak in Malaysia, pigs and humans were infected. While pigs generally developed severe respiratory disease due to effective virus replication and associated inflammation processes in porcine airways, respiratory symptoms in humans were rare and less severe. To elucidate the reasons for the species-specific differences in NiV airway infections, we compared the cytokine responses as a first reaction to NiV in primary porcine and human bronchial epithelial cells (PBEpC and HBEpC, respectively). In both cell types, NiV infection resulted in the expression of type III interferons (IFN-λ). Upon infection with similar virus doses, viral RNA load and IFN expression were substantially higher in HBEpC. Even if PBEpC expressed the same viral RNA amounts as NiV-infected HBEpC, the porcine cells showed reduced IFN- and IFN-dependent antiviral gene expression. Despite this inherently limited IFN response, the expression of proinflammatory cytokines (IL-6, IL-8) in NiV-infected PBEpC was not decreased. The downregulation of antiviral activity in the presence of a functional proinflammatory cytokine response might be one of the species-specific factors contributing to efficient virus replication and acute inflammation in the lungs of pigs infected with the Malaysian NiV strain.

Matched MeSH terms: Epithelial Cells/virology*
CD3-positive plasmablastic lymphoma reported in two cases: A potential diagnostic caveat

Wong YP, Masir N, Chew MX

Indian J Pathol Microbiol, 2021 8 4;64(3):579-583.
PMID: 34341278 DOI: 10.4103/IJPM.IJPM_616_20

Plasmablastic lymphoma (PBL) is a rare aggressive subtype of mature large B cell lymphoma involving almost exclusively the extranodal regions particularly the oral cavity, frequently described in immunocompromised patients. PBL is characterized histologically by diffuse proliferation of large neoplastic cells resembling B immunoblasts or plasmablasts. The diagnosis of PBL can be difficult due to its ambiguous histopathological features mimicking most large cell lymphomas and lacking a distinctive immunophenotypic pattern. They typically lack expression of CD20 and CD79a but may express plasma cell marker, CD138. Aberrant immunoexpression of CD3, a T-cell marker in PBL in the absence of other B-cell markers is exceptionally rare, may potentially lead to incorrect interpretation. Herein, we report a case series of CD3-positive PBL of oral cavity in two individuals, which were initially misdiagnosed as high-grade T-cell lymphomas including extranodal NK/T-cell lymphoma, nasal type. Useful distinguishing clinical settings, histomorphological features, immunohistochemistry and molecular expression profiles of PBL are discussed.

Matched MeSH terms: Plasma Cells/pathology
Rat full term amniotic fluid harbors highly potent stem cells

Mun-Fun H, Ferdaos N, Hamzah SN, Ridzuan N, Hisham NA, Abdullah S, et al.

Res Vet Sci, 2015 Oct;102:89-99.
PMID: 26412526 DOI: 10.1016/j.rvsc.2015.07.010

Amniotic fluid stem cells (AFSCs) are commonly isolated from mid-term amniotic fluid (AF) of animals and human collected via an invasive technique, amniocentesis. Alternatively, AFSCs could be collected at full-term. However, it is unclear whether AFSCs are present in the AF at full term. Here, we aimed to isolate and characterize stem cells isolated from AF of full term pregnant rats. Three stem cell lines have been established following immuno-selection against the stem cell marker, c-kit. Two of the new lines expressed multiple markers of pluripotency until more than passage 90. Further, they spontaneously differentiated into derivatives of the three primary germ layers through the formation of good quality embryoid bodies (EBs), and can be directly differentiated into neural lineage. Their strong stemness and potent neurogenic properties highlight the presence of highly potent stem cells in AF of full-term pregnancies, which could serve as a potential source of stem cells for regenerative medicine.

Matched MeSH terms: Stem Cells/physiology*

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