Displaying publications 41 - 60 of 2140 in total

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  1. Failure to infect congenitally immunodeficient SCID and NUDE mice with Rhinosporidium seeberi
    Arseculeratne SN, Hussein FN, Atapattu DN, Pathmanathan R
    Med Mycol, 2000 Oct;38(5):393-5.
    PMID: 11092388
    Congenitally T and B cell-deficient SCID mice and T cell-deficient NUDE mice, with BALB/c mice as immunologically normal controls, were inoculated with Rhinosporidium seeberi. At 3 and 16 weeks after inoculation, no evidence of rhinosporidiosis was detected. The reasons for the failure to establish rhinosporidiosis in immunodeficient or normal mice remain obscure.
    Matched MeSH terms: Mice, Inbred BALB C; Mice, Nude; Mice, SCID; Mice
  2. Influence of natural convection on gold nanorods-assisted photothermal treatment of bladder cancer in mice
    Ooi EH, Popov V, Alfano M, Cheong JKK
    Int J Hyperthermia, 2020;37(1):634-650.
    PMID: 32538190 DOI: 10.1080/02656736.2020.1771437
    Background: The thermally-induced urine flow can generate cooling that may alter the treatment outcome during hyperthermic treatments of bladder cancer. This paper investigates the effects of natural convection inside the bladder and at skin surface during gold nanorods (GNR) - assisted photothermal therapy (PTT) of bladder cancer in mice. Methods: 3D models of mouse bladder at orientations corresponding to the mouse positioned on its back, its side and its abdomen were examined. Numerical simulations were carried out for GNR volume fractions of 0.001, 0.005 and 0.01% and laser power of 0.2 and 0.3 W. Results: The obtained results showed that cooling due to natural convection inside the bladder and above the skin depends on the mouse orientation. For a mouse positioned on its back, on its side or on its abdomen, the maximum temperature achieved inside the tumour at 0.001% GNR volume fraction and 0.2 W laser power was 55.2°C, 50.0°C and 52.2°C, respectively compared to 56.8°C when natural convection was not considered. The average thermal gradients when natural convection was considered were also lower, suggesting a more homogenous temperature distribution. Conclusions: Natural convection inside the bladder can be beneficial but also detrimental to GNR-assisted PTT depending on the level of heating. At low levels of heating due to low GNR volume fraction and/or laser power, flow inside the bladder may dissipate heat from the targeted tissue; making the treatment ineffective. At high levels of heating due to high GNR volume fraction and/or laser power, cooling may prevent excessive thermal damage to surrounding tissues.
    Matched MeSH terms: Mice
  3. Immunoreactivity and neutralization capacity of Philippine cobra antivenom against Naja philippinensis and Naja samarensis venoms
    Tan CH, Palasuberniam P, Blanco FB, Tan KY
    Trans R Soc Trop Med Hyg, 2021 01 07;115(1):78-84.
    PMID: 32945886 DOI: 10.1093/trstmh/traa087
    BACKGROUND: The Philippine cobra (Naja philippinensis) and Samar cobra (Naja samarensis) are two WHO Category 1 medically important venomous snakes in the Philippines. Philippine cobra antivenom (PCAV) is the only antivenom available in the country, but its neutralization capacity against the venoms of N. philippinensis and hetero-specific N. samarensis has not been reported. This knowledge gap greatly hinders the optimization of antivenom use in the region.

    METHODS: This study examined the immunological binding and neutralization capacity of PCAV against the two cobra venoms using WHO-recommended protocols.

    RESULTS: In mice, both venoms were highly neurotoxic and lethal with a median lethal dose of 0.18 and 0.20 µg/g, respectively. PCAV exhibited strong and comparable immunoreactivity toward the venoms, indicating conserved venom antigenicity between the two allopatric species. In in vivo assay, PCAV was only moderately effective in neutralizing the toxicity of both venoms. Its potency was even lower against the hetero-specific N. samarensis venom by approximately two-fold compared with its potency against N. philippinensis venom.

    CONCLUSION: The results indicated that PCAV could be used to treat N. samarensis envenomation but at a higher dose, which might increase the risk of hypersensitivity and worsen the shortage of antivenom supply in the field. Antivenom manufacturing should be improved by developing a low-dose, high-efficacy product against cobra envenomation.

    Matched MeSH terms: Mice
  4. A study of the flame cell pattern of Echinostomum malayanum cercariae
    Kruatrachue M, Chesdapan C
    Med J Malaya, 1968 Mar;22(3):231-2.
    PMID: 4234367
    Matched MeSH terms: Mice
  5. Venom proteome of Bungarus sindanus (Sind krait) from Pakistan and in vivo cross-neutralization of toxicity using an Indian polyvalent antivenom
    Oh AMF, Tan CH, Tan KY, Quraishi NH, Tan NH
    J Proteomics, 2019 02 20;193:243-254.
    PMID: 30385415 DOI: 10.1016/j.jprot.2018.10.016
    The proteome of the Pakistani B. sindanus venom was investigated with reverse-phase HPLC and nano-ESI-LCMS/MS analysis. At least 36 distinct proteins belonging to 8 toxin protein families were identified. Three-finger toxin (3FTx), phospholipase A2 (including β-bungarotoxin A-chains) and Kunitz-type serine protease inhibitor (KSPI) were the most abundant, constituting ~95% of total venom proteins. The other toxin proteins of low abundance are snake venom metalloproteinase (SVMP), L-amino acid oxidase (LAAO), acetylcholinesterase (AChE), vespryn and cysteine-rich secretory protein (CRiSP). The venom was highly lethal to mice with LD50 values of 0.04 μg/g (intravenous) and 0.15 μg/g (subcutaneous). The 3FTx proteins are diverse, comprising kappa-neurotoxins, neurotoxin-like protein, non-conventional toxins and muscarinic toxin-like proteins. Kappa-neurotoxins and β-bungarotoxins represent the major toxins that mediate neurotoxicity in B. sindanus envenoming. Alpha-bungarotoxin, commonly present in the Southeast Asian krait venoms, was undetected. The Indian VINS Polyvalent Antivenom (VPAV) was immunoreactive toward the venom, and it moderately cross-neutralized the venom lethality (potency = 0.25 mg/ml). VPAV was able to reverse the neurotoxicity and prevent death in experimentally envenomed mice, but the recovery time was long. The unique toxin composition of B. sindanus venom may be considered in the formulation of a more effective pan-regional, polyspecific antivenom. BIOLOGICAL SIGNIFICANCE: Bungarus sindanus, an endemic krait species distributed mainly in the Sindh Province of Pakistan is a cause of snake envenomation. Its specific antivenom is, however, lacking. The proteomic study of its venom revealed a substantial presence of κ-bungarotoxins and β-bungarotoxins. The toxin profile corroborates the potent neurotoxicity and lethality of the venom tested in vivo. The heterologous Indian VINS polyvalent antivenom (VPAV) cross-reacted with B. sindanus venom and cross-neutralized the venom neurotoxicity and lethality in mice, albeit the efficacy was moderate. The findings imply that B. sindanus and the phylogenetically related B. caeruleus of India share certain venom epitopes. Research should be advanced to improve the efficacy spectrum of a pan-regional polyspecific antivenom.
    Matched MeSH terms: Mice
  6. Fulltext ClicO FS: an interactive web-based service of Circos
    Cheong WH, Tan YC, Yap SJ, Ng KP
    Bioinformatics, 2015 Nov 15;31(22):3685-7.
    PMID: 26227146 DOI: 10.1093/bioinformatics/btv433
    : We present ClicO Free Service, an online web-service based on Circos, which provides a user-friendly, interactive web-based interface with configurable features to generate Circos circular plots.
    Matched MeSH terms: Mice
  7. Fulltext Potential role of microRNAs in selective hepatic insulin resistance: From paradox to the paradigm
    Palihaderu PADS, Mendis BILM, Premarathne JMKJK, Dias WKRR, Yeap SK, Ho WY, et al.
    Front Endocrinol (Lausanne), 2022;13:1028846.
    PMID: 36479211 DOI: 10.3389/fendo.2022.1028846
    The paradoxical action of insulin on hepatic glucose metabolism and lipid metabolism in the insulin-resistant state has been of much research interest in recent years. Generally, insulin resistance would promote hepatic gluconeogenesis and demote hepatic de novo lipogenesis. The underlying major drivers of these mechanisms were insulin-dependent, via FOXO-1-mediated gluconeogenesis and SREBP1c-mediated lipogenesis. However, insulin-resistant mouse models have shown high glucose levels as well as excess lipid accumulation. As suggested, the inert insulin resistance causes the activation of the FOXO-1 pathway promoting gluconeogenesis. However, it does not affect the SREBP1c pathway; therefore, cells continue de novo lipogenesis. Many hypotheses were suggested for this paradoxical action occurring in insulin-resistant rodent models. A "downstream branch point" in the insulin-mediated pathway was suggested to act differentially on the FOXO-1 and SREBP1c pathways. MicroRNAs have been widely studied for their action of pathway mediation via suppressing the intermediate protein expressions. Many in vitro studies have postulated the roles of hepato-specific expressions of miRNAs on insulin cascade. Thus, miRNA would play a pivotal role in selective hepatic insulin resistance. As observed, there were confirmations and contradictions between the outcomes of gene knockout studies conducted on selective hepatic insulin resistance and hepato-specific miRNA expression studies. Furthermore, these studies had evaluated only the effect of miRNAs on glucose metabolism and few on hepatic de novo lipogenesis, limiting the ability to conclude their role in selective hepatic insulin resistance. Future studies conducted on the role of miRNAs on selective hepatic insulin resistance warrant the understanding of this paradoxical action of insulin.
    Matched MeSH terms: Mice
  8. iSegMSI: An Interactive Strategy to Improve Spatial Segmentation of Mass Spectrometry Imaging Data
    Guo L, Liu X, Zhao C, Hu Z, Xu X, Cheng KK, et al.
    Anal Chem, 2022 Oct 25;94(42):14522-14529.
    PMID: 36223650 DOI: 10.1021/acs.analchem.2c01456
    Spatial segmentation is a critical procedure in mass spectrometry imaging (MSI)-based biochemical analysis. However, the commonly used unsupervised MSI segmentation methods may lead to inappropriate segmentation results as the MSI data is characterized by high dimensionality and low signal-to-noise ratio. This process can be improved by the incorporation of precise prior knowledge, which is hard to obtain in most cases. In this study, we show that the incorporation of partial or coarse prior knowledge from different sources such as reference images or biological knowledge may also help to improve MSI segmentation results. Here, we propose a novel interactive segmentation strategy for MSI data called iSegMSI, which incorporates prior information in the form of scribble-regularization of the unsupervised model to fine-tune the segmentation results. By using two typical MSI data sets (including a whole-body mouse fetus and human thyroid cancer), the present results demonstrate the effectiveness of the iSegMSI strategy in improving the MSI segmentations. Specifically, the method can be used to subdivide a region into several subregions specified by the user-defined scribbles or to merge several subregions into a single region. Additionally, these fine-tuned results are highly tolerant to the imprecision of the scribbles. Our results suggest that the proposed iSegMSI method may be an effective preprocessing strategy to facilitate the analysis of MSI data.
    Matched MeSH terms: Mice
  9. Fulltext Gold nanorods assisted photothermal therapy of bladder cancer in mice: A computational study on the effects of gold nanorods distribution at the centre, periphery, and surface of bladder cancer
    Cheong JK, Ooi EH, Chiew YS, Menichetti L, Armanetti P, Franchini MC, et al.
    Comput Methods Programs Biomed, 2023 Mar;230:107363.
    PMID: 36720181 DOI: 10.1016/j.cmpb.2023.107363
    BACKGROUND AND OBJECTIVES: Gold nanorod-assisted photothermal therapy (GNR-PTT) is a cancer treatment whereby GNRs incorporated into the tumour act as photo-absorbers to elevate the thermal destruction effect. In the case of bladder, there are few possible routes to target the tumour with GNRs, namely peri/intra-tumoural injection and intravesical instillation of GNRs. These two approaches lead to different GNR distribution inside the tumour and can affect the treatment outcome.

    METHODOLOGY: The present study investigates the effects of heterogeneous GNR distribution in a typical setup of GNR-PTT. Three cases were considered. Case 1 considered the GNRs at the tumour centre, while Case 2 represents a hypothetical scenario where GNRs are distributed at the tumour periphery; these two cases represent intratumoural accumulation with different degree of GNR spread inside the tumour. Case 3 is achieved when GNRs target the exposed tumoural surface that is invading the bladder wall, when they are delivered by intravesical instillation.

    RESULTS: Results indicate that for a laser power of 0.6 W and GNR volume fraction of 0.01%, Case 2 and 3 were successful in achieving complete tumour eradication after 330 and 470 s of laser irradiation, respectively. Case 1 failed to form complete tumour damage when the GNRs are concentrated at the tumour centre but managed to produce complete tumour damage if the spread of GNRs is wider. Results from Case 2 also demonstrated a different heating profile from Case 1, suggesting that thermal ablation during GNR-PTT is dependant on the GNRs distribution inside the tumour. Case 3 shows similar results to Case 2 whereby gradual but uniform heating is observed. Cases 2 and 3 show that uniformly heating the tumour can reduce damage to the surrounding tissues.

    CONCLUSIONS: Different GNR distribution associated with the different methods of introducing GNRs to the bladder during GNR-PTT affect the treatment outcome of bladder cancer in mice. Insufficient spreading during intratumoural injection of GNRs can render the treatment ineffective, while administered via intravesical instillation. GNR distribution achieved through intravesical instillation present some advantages over intratumoural injection and is worthy of further exploration.

    Matched MeSH terms: Mice
  10. Fulltext In Vivo Toxicological Analysis of MnFe2O4@poly(tBGE-alt-PA) Composite as a Hybrid Nanomaterial for Possible Biomedical Use
    Kumar R, Bauri S, Sahu S, Chauhan S, Dholpuria S, Ruokolainen J, et al.
    ACS Appl Bio Mater, 2023 Mar 20;6(3):1122-1132.
    PMID: 36757355 DOI: 10.1021/acsabm.2c00983
    Nanocomposites have significantly contributed to biomedical science due to less aggregation behavior and enhanced physicochemical properties. This study synthesized a MnFe2O4@poly(tBGE-alt-PA) nanocomposite for the first time and physicochemically characterized it. The obtained hybrid nanomaterial was tested in vivo for its toxicological properties before use in drug delivery, tissue engineering fields, and environmental applications. The composite was biocompatible with mouse fibroblast cells and hemocompatible with 2% RBC suspension. This nanocomposite was tested on Drosophila melanogaster due to its small size, well-sequenced genome, and low cost of testing. The larvae's crawling speed and direction were measured after feeding. No abnormal path and altered crawling pattern indicated the nonappearance of abnormal neurological disorder in the larva. The gut organ toxicity was further analyzed using DAPI and DCFH-DA dye to examine the structural anomalies. No apoptosis and necrosis were observed in the gut of the fruit fly. Next, adult flies were examined for phenotypic anomalies after their pupal phases emerged. No defects in the phenotypes, including the eye, wings, abdomen, and bristles, were found in our study. Based on these observations, the MnFe2O4@poly(tBGE-alt-PA) composite may be used for various biomedical and environmental applications.
    Matched MeSH terms: Mice
  11. Role of non-coding RNAs in tuberculosis and their potential for clinical applications
    Jumat MI, Sarmiento ME, Acosta A, Chin KL
    J Appl Microbiol, 2023 Jun 01;134(6).
    PMID: 37197901 DOI: 10.1093/jambio/lxad104
    Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains the leading cause of mortality due to infectious diseases, only surpassed in 2020 by COVID-19. Despite the development in diagnostics, therapeutics, and evaluation of new vaccines for TB, this infectious disease remains uncontrollable due to the emergence of multidrug-resistant (MDR) and extremely drug-resistant (XDR) TB, among other factors. The development in transcriptomics (RNomics) has enabled the study of gene expression in TB. It is considered that non-coding RNAs (ncRNAs) from host [microRNAs (miRNAs)] and Mtb [small RNAs (sRNAs)] are important elements in TB pathogenesis, immune resistance, and susceptibility. Many studies have shown the importance of host miRNAs in regulating immune response against Mtb via in vitro and in vivo mice models. The bacterial sRNAs play a major role in survival, adaptation, and virulence. Here, we review the characterization and function of host and bacteria ncRNAs in TB and their potential use in clinical applications as diagnostic, prognostic, and therapeutic biomarkers.
    Matched MeSH terms: Mice
  12. Fulltext Impact of Gut Recolonization on Liver Regeneration: Hepatic Matrisome Gene Expression after Partial Hepatectomy in Mice
    Amin AR, Hairulhisyam NM, Aqilah RNF, Nur Fariha MM, Mallard BL, Shanahan F, et al.
    Int J Mol Sci, 2023 Jun 28;24(13).
    PMID: 37445951 DOI: 10.3390/ijms241310774
    The hepatic matrisome is involved in the remodeling phase of liver regeneration. As the gut microbiota has been implicated in liver regeneration, we investigated its role in liver regeneration focusing on gene expression of the hepatic matrisome after partial hepatectomy (PHx) in germ-free (GF) mice, and in GF mice reconstituted with normal gut microbiota (XGF). Liver mass restoration, hepatocyte proliferation, and immune response were assessed following 70% PHx. Hepatic matrisome and collagen gene expression were also analyzed. Reduced liver weight/body weight ratio, mitotic count, and hepatocyte proliferative index at 72 h post PHx in GF mice were preceded by reduced expression of cytokine receptor genes Tnfrsf1a and Il6ra, and Hgf gene at 3 h post PHx. In XGF mice, these indices were significantly higher than in GF mice, and similar to that of control mice, indicating normal liver regeneration. Differentially expressed genes (DEGs) of the matrisome were lower in GF compared to XGF mice at both 3 h and 72 h post PHx. GF mice also demonstrated lower collagen expression, with significantly lower expression of Col1a1, Col1a2, Col5a1, and Col6a2 compared to WT mice at 72 h post PHx. In conclusion, enhanced liver regeneration and matrisome expression in XGF mice suggests that interaction of the gut microbiota and matrisome may play a significant role in the regulation of hepatic remodeling during the regenerative process.
    Matched MeSH terms: Mice
  13. Fulltext Fezf2-positive fork cell-like neurons in the mouse insular cortex
    Taniguchi M, Iwahashi M, Oka Y, Tiong SYX, Sato M
    PLoS One, 2022;17(9):e0274170.
    PMID: 36067159 DOI: 10.1371/journal.pone.0274170
    The fork cell and von Economo neuron, which are found in the insular cortex and/or the anterior cingulate cortex, are defined by their unique morphologies. Their shapes are not pyramidal; the fork cell has two primary apical dendrites and the von Economo neurons are spindle-shaped (bipolar). Presence of such neurons are reported only in the higher animals, especially in human and great ape, indicating that they are specific for most evolved species. Although it is likely that these neurons are involved in higher brain function, lack of results with experimental animals makes further investigation difficult. We here ask whether equivalent neurons exist in the mouse insular cortex. In human, Fezf2 has been reported to be highly expressed in these morphologically distinctive neurons and thus, we examined the detailed morphology of Fezf2-positive neurons in the mouse brain. Although von Economo-like neurons were not identified, Fezf2-positive fork cell-like neurons with two characteristic apical dendrites, were discovered. Examination with electron microscope indicated that these neurons did not embrace capillaries, rather they held another cell. We here term such neurons as holding neurons. We further observed several molecules, including neuromedin B (NMB) and gastrin releasing peptide (GRP) that are known to be localized in the fork cells and/or von Economo cells in human, were localized in the mouse insular cortex. Based on these observations, it is likely that an equivalent of the fork cell is present in the mouse.
    Matched MeSH terms: Mice
  14. Fulltext Calretinin-expressing islet cells are a source of pre- and post-synaptic inhibition of non-peptidergic nociceptor input to the mouse spinal cord
    Davis OC, Dickie AC, Mustapa MB, Boyle KA, Browne TJ, Gradwell MA, et al.
    Sci Rep, 2023 Jul 18;13(1):11561.
    PMID: 37464016 DOI: 10.1038/s41598-023-38605-9
    Unmyelinated non-peptidergic nociceptors (NP afferents) arborise in lamina II of the spinal cord and receive GABAergic axoaxonic synapses, which mediate presynaptic inhibition. However, until now the source of this axoaxonic synaptic input was not known. Here we provide evidence that it originates from a population of inhibitory calretinin-expressing interneurons (iCRs), which correspond to lamina II islet cells. The NP afferents can be assigned to 3 functionally distinct classes (NP1-3). NP1 afferents have been implicated in pathological pain states, while NP2 and NP3 afferents also function as pruritoceptors. Our findings suggest that all 3 of these afferent types innervate iCRs and receive axoaxonic synapses from them, providing feedback inhibition of NP input. The iCRs also form axodendritic synapses, and their targets include cells that are themselves innervated by the NP afferents, thus allowing for feedforward inhibition. The iCRs are therefore ideally placed to control the input from non-peptidergic nociceptors and pruritoceptors to other dorsal horn neurons, and thus represent a potential therapeutic target for the treatment of chronic pain and itch.
    Matched MeSH terms: Mice
  15. Fulltext Paramyxoviruses in rodents: A review
    Mohd-Qawiem F, Nawal-Amani AR, Faranieyza-Afiqah F, Yasmin AR, Arshad SS, Norfitriah MS, et al.
    Open Vet J, 2022;12(6):868-876.
    PMID: 36650879 DOI: 10.5455/OVJ.2022.v12.i6.14
    Paramyxoviruses have been shown to infect a wide range of hosts, including rodents, and humans. Several novel murine paramyxoviruses have been discovered in the last several decades. Although these viruses are unclassified, they are recognized as Beilong virus, Mojiang virus (MojV), and Tailam virus in rats, Jeilongvirus, Nariva, Paju Apodemus paramyxovirus-1 and -2 in mice, and Pentlands paramyxovirus-1, -2, and -3 in squirrels. These paramyxoviruses were reported mainly in China and a few other countries like Australia, the Republic of Korea, Trinidad, and France. In June 2012, it becomes a great concern in China whereby, three miners were reported dead potentially caused by a novel zoonotic MojV, a henipa-like virus isolated from tissue samples of rats from the same cave. Rats are considered to be natural hosts for the MojV from the literature research. The classified paramyxovirus, Sendai virus in rodents is also reviewed. Paramyxoviruses infection in rodents leads to respiratory distress such as necrotizing rhinitis, tracheitis, bronchiolitis, and interstitial pneumonia. Infections caused by paramyxoviruses often spread between species, manifesting disease in spillover hosts, including humans. This review focuses on the paramyxoviruses in rodents, including the epidemiological distributions, transmission and pathogenesis, clinical manifestations, diagnostic methods, and control and prevention of paramyxoviruses infection to provide a better understanding of these highly mutating viruses.
    Matched MeSH terms: Mice
  16. Phillyrin: an adipose triglyceride lipase inhibitor supported by molecular docking, dynamics simulation, and pharmacological validation
    Zhou C, Yan L, Xu J, Hamezah HS, Wang T, Du F, et al.
    J Mol Model, 2024 Feb 13;30(3):68.
    PMID: 38347278 DOI: 10.1007/s00894-024-05875-7
    CONTEXT: Adipose triglyceride lipase (ATGL), a key enzyme responsible for lipolysis, catalyzes the first step of lipolysis and converts triglycerides to diacylglycerols and free fatty acids (FFA). Our previous work suggested that phillyrin treatment improves insulin resistance in HFD-fed mice, which was associated with ATGL inhibition. In this study, using docking simulation, we explored the binding pose of phillyrin and atglistatin (a mouse ATGL inhibitor) to ATGL in mouse. From the docking results, the interactions with Ser47 and Asp166 were speculated to have caused phillyrin to inhibit ATGL in mice. Further, molecular dynamics simulation of 100 ns and MM-GBSA were conducted for the protein-ligand complex, which indicated that the system was stable and that phillyrin displayed a better affinity to ATGL than did atglistatin throughout the simulation period. Moreover, the results of pharmacological validation were consistent with those of the in silico simulations. In summary, our study illustrates the potential of molecular docking to accurately predict the binding protein produced by AlphaFold and suggests that phillyrin is a potential small molecule that targets and inhibits ATGL enzymatic activity.

    METHODS: The ATGL-predicted protein structure, verified by PROCHECK, was determined using AlphaFold. Molecular docking, molecular dynamics simulation, and prime molecular mechanic-generalized born surface area were performed using LigPrep, Desmond, and prime MM-GBSA modules of Schrödinger software release 2021-2, respectively. For pharmacological validation, immunoblotting was performed to assess ATGL protein expression. The fluorescence intensity and glycerol concentration were quantified to evaluate the efficiency of phillyrin in inhibiting ATGL.

    Matched MeSH terms: Mice
  17. Fulltext Mesenchymal stem cells: angels or demons?
    Wong RS
    J Biomed Biotechnol, 2011;2011:459510.
    PMID: 21822372 DOI: 10.1155/2011/459510
    Mesenchymal stem cells (MSCs) have been used in cell-based therapy in various disease conditions such as graft-versus-host and heart diseases, osteogenesis imperfecta, and spinal cord injuries, and the results have been encouraging. However, as MSC therapy gains popularity among practitioners and researchers, there have been reports on the adverse effects of MSCs especially in the context of tumour modulation and malignant transformation. These cells have been found to enhance tumour growth and metastasis in some studies and have been related to anticancer-drug resistance in other instances. In addition, various studies have also reported spontaneous malignant transformation of MSCs. The mechanism of the modulatory behaviour and the tumorigenic potential of MSCs, warrant urgent exploration, and the use of MSCs in patients with cancer awaits further evaluation. However, if MSCs truly play a role in tumour modulation, they can also be potential targets of cancer treatment.
    Matched MeSH terms: Mice
  18. Immune-stealth VP28-conjugated heparin nanoparticles for enhanced and reversible anticoagulation
    Hussein HR, Chang CY, Zheng Y, Yang CY, Li LH, Lee YT, et al.
    Nanotechnology, 2024 Feb 09;35(17).
    PMID: 38262054 DOI: 10.1088/1361-6528/ad21a2
    Heparins are a family of sulfated linear negatively charged polysaccharides that have been widely used for their anticoagulant, antithrombotic, antitumor, anti-inflammatory, and antiviral properties. Additionally, it has been used for acute cerebral infarction relief as well as other pharmacological actions. However, heparin's self-aggregated macrocomplex may reduce blood circulation time and induce life-threatening thrombocytopenia (HIT) complicating the use of heparins. Nonetheless, the conjugation of heparin to immuno-stealth biomolecules may overcome these obstacles. An immunostealth recombinant viral capsid protein (VP28) was expressed and conjugated with heparin to form a novel nanoparticle (VP28-heparin). VP28-heparin was characterized and tested to determine its immunogenicity, anticoagulation properties, effects on total platelet count, and risk of inducing HIT in animal models. The synthesized VP28-heparin trimeric nanoparticle was non-immunogenic, possessed an average hydrodynamic size (8.81 ± 0.58 nm) optimal for the evasion renal filtration and reticuloendothelial system uptake (hence prolonging circulating half-life). Additionally, VP28-heparin did not induce mouse death or reduce blood platelet count when administered at a high dosein vivo(hence reducing HIT risks). The VP28-heparin nanoparticle also exhibited superior anticoagulation properties (2.2× higher prothrombin time) and comparable activated partial thromboplastin time, but longer anticoagulation period when compared to unfractionated heparin. The anticoagulative effects of the VP28-heparin can also be reversed using protamine sulfate. Thus, VP28-heparin may be an effective and safe heparin derivative for therapeutic use.
    Matched MeSH terms: Mice
  19. Photoactive imaging and therapy for colorectal cancer using a CEA-Affimer conjugated Foslip nanoparticle
    Khaled YS, Khot MI, Aiyappa-Maudsley R, Maisey T, Pramanik A, Tiernan J, et al.
    Nanoscale, 2024 Apr 04;16(14):7185-7199.
    PMID: 38506227 DOI: 10.1039/d3nr04118b
    Theranostic nanoparticles hold promise for simultaneous imaging and therapy in colorectal cancer. Carcinoembryonic antigen can be used as a target for these nanoparticles because it is overexpressed in most colorectal cancers. Affimer reagents are synthetic proteins capable of binding specific targets, with additional advantages over antibodies for targeting. We fabricated silica nanoparticles using a water-in-oil microemulsion technique, loaded them with the photosensitiser Foslip, and functionalised the surface with anti-CEA Affimers to facilitate fluorescence imaging and photodynamic therapy of colorectal cancer. CEA-specific fluorescence imaging and phototoxicity were quantified in colorectal cancer cell lines and a LS174T murine xenograft colorectal cancer model. Anti-CEA targeted nanoparticles exhibited CEA-specific fluorescence in the LoVo, LS174T and HCT116 cell lines when compared to control particles (p < 0.0001). No toxicity was observed in LS174T cancer mouse xenografts or other organs. Following photo-irradiation, the anti-CEA targeted particles caused significant cell death in LoVo (60%), LS174T (90%) and HCT116 (70%) compared to controls (p < 0.0001). Photodynamic therapy (PDT) at 24 h in vivo showed a 4-fold reduction in tumour volume compared to control mouse xenografts (p < 0.0001). This study demonstrates the efficacy of targeted fluorescence imaging and PDT using Foslip nanoparticles conjugated to anti-CEA Affimer nanoparticles in in vitro and in vivo colorectal cancer models.
    Matched MeSH terms: Mice
  20. Identification and Validation of Peptides Specifying SARS-CoV-2 B-Cell Epitopes Eliciting Neutralizing Antibodies
    Poh CL, Yahaya AAAB, Cheong HT, Lim HX
    Methods Mol Biol, 2024;2821:165-177.
    PMID: 38997488 DOI: 10.1007/978-1-0716-3914-6_13
    Vaccination is an effective means of inducing immune protection to prevent transmissible diseases. During the Covid-19 pandemic, immunizations using traditional and novel vaccine platforms such as the inactivated SARSCo-V-2 vaccine, adenoviral-vectored, and nucleic acid-based mRNA vaccines have been relatively successful in controlling the rates of infection and hospitalizations. Nevertheless, the danger posed by the emergence of SARS-CoV-2 variants would set the stage for the design of next generation vaccines. To overcome the lack of efficacy of current vaccines against emerging SARS-CoV-2 variants, new vaccines must be able to overcome the reduced effectiveness of the current vaccines. Since the current Covid-19 vaccines are dependent on the whole S-protein of Wuhan strain as the antigen, mutations have rendered the current Covid-19 vaccines less effective against variants of concern (VoCs). Instead of using the whole S-protein, peptide-based epitopes could be predicted using immunoinformatic approaches, simulation of the 3D structures, overlapping peptides covering the whole length of the S-protein or peptide arrays based on synthetic peptide combinatorial libraries comprising peptides recognizable by monoclonal antibodies. B-cell epitopes were predicted, and immunogenicity of peptides was validated in mice by immunizing mice with peptides conjugated to keyhole limpet hemocyanin (KLH) mixed with Montanide 51 as an adjuvant. The immunogenicity of epitopes that could elicit peptide specific IgGs was determined by peptide-based ELISA. Neutralizing activities were determined by cPass and pseudovirus-based neutralization assays.
    Matched MeSH terms: Mice
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