Displaying publications 121 - 140 of 2094 in total

Abstract:
Sort:
  1. A non-toxic recombinant protein rSUMO-CPBm4 as a potential vaccine candidate against Clostridium perfringens type C beta enterotoxemia
    Goa Y, Du JG, Jirapattharasate C, Galon E, Ji SW, Ran ZG, et al.
    Trop Biomed, 2023 Dec 01;40(4):400-405.
    PMID: 38308826 DOI: 10.47665/tb.40.4.004
    Beta toxin (CPB) is a lethal toxin and plays a key role in enterotoxemia of ruminants caused by Clostridium perfringens type C strain. The existing vaccines based on crude CPB need time-consuming detoxification and difficult quality control steps. In this study, we synthesized the rCPBm4 of C. perfringens type C strain and small ubiquitin-like modifier (SUMO)-tag CPBm4 (rSUMO-CPBm4) by introducing four amino acid substitutions: R212E, Y266A, L268G, and W275A. Compared with rCPBm4, rSUMO-CPBm4 was expressed with higher solubility in Escherichia coli BL21 (DE3). Neither rCPBm4 nor rSUMO-CPBm4 was lethal to mice. Although rCPBm4 and rSUMO-CPBm4 were reactogenic with polyclonal antibodies against crude CPB, rabbits vaccinated with rSUMO-CPBm4 developed significant levels of toxin-neutralizing antibody (TNA) titers that conferred protection against crude toxin challenge. These data suggest that genetically detoxified rSUMO-CPBm4 is a promising subunit vaccine candidate for C. perfringens type C beta enterotoxemia.
    Matched MeSH terms: Mice
  2. Purification of Plasmodium and Babesia- infected erythrocytes using a non-woven fabric filter
    Tao ZY, Liu WP, Dong J, Feng XX, Yao DW, Lv QL, et al.
    Trop Biomed, 2020 Dec 01;37(4):911-918.
    PMID: 33612745 DOI: 10.47665/tb.37.4.911
    The purification of parasite-infected erythrocytes from whole blood containing leucocytes is crucial for many downstream genetic and molecular assays in parasitology. Current methodologies to achieve this are often costly and time consuming. Here, we demonstrate the successful application of a cheap and simple Non-Woven Fabric (NWF) filter for the purification of parasitized red blood cells from whole blood. NWF filtration was applied to the malaria-parasitized blood of three strains of mice, and one strain of rat, and to Babesia gibsoni parasitized dog blood. Before and after filtration, the white blood cell (WBC) removal rates and red blood cell (RBC) recovery rates were measured. After NWF filter treatment of rodent malaria-infected blood, the WBC removal rates and RBC recovery rates were, for Kunming mice: 99.51%±0.30% and 86.12%±8.37%; for BALB/C mice: 99.61%±0.15% and 80.74%±7.11%; for C57 mice: 99.71%±0.12% and 84.87%±3.83%; for Sprague-Dawley rats: 99.93%±0.03% and 83.30%±2.96%. Microscopy showed WBCs were efficiently removed from infected dog blood samples, and there was no obvious morphological change of B. gibsoni parasites. NWF filters efficiently remove leukocytes from malaria parasite-infected mouse and rat blood, and are also suitable for filtration of B. gibsoni-infected dog blood.
    Matched MeSH terms: Mice, Inbred BALB C; Mice
  3. Electrophoretic profiles and biological activities: intraspecific variation in the venom of the Malayan pit viper (Calloselasma rhodostoma)
    Daltry JC, Ponnudurai G, Shin CK, Tan NH, Thorpe RS, Wüster W
    Toxicon, 1996 Jan;34(1):67-79.
    PMID: 8835335
    The Malayan pit viper (Calloselasma rhodostoma) is of major clinical significance both as a leading cause of snakebite and as the source of ancrod (Arvin). Although its venom has been extensively studied, the degree to which venom composition varies between individuals is poorly known. We individually analysed the venoms of over 100 C. rhodostoma using isoelectric focusing. In all populations, females produced an intense band that was absent from all males, and significant ontogenetic variation was detected. Principal components analysis of the banding profiles also revealed strong geographic variation, which was significantly congruent with variation in the biological activities of the venom (phosphodiesterase, alkalinephosphoesterase, L-amino acid oxidase, arginine ester hydrolase, 5'-nucleotidase, thrombin-like enzyme, haemorrhagic activity). Studies of captive-bred snakes indicate that the intraspecific variation in venom is genetically inherited rather than environmentally induced. The intraspecific variation in venom composition and biological activity could be of applied importance to snakebite therapy, both in correct diagnosis of the source of envenomation and in the development of a more effective antivenom. Greater attention should be given to the source of C. rhodostoma venom used in research to ensure reproducibility of results.
    Matched MeSH terms: Mice
  4. Fulltext Snake Venomics and Antivenomics of Cape Cobra (Naja nivea) from South Africa: Insights into Venom Toxicity and Cross-Neutralization Activity
    Tan CH, Wong KY, Huang LK, Tan KY, Tan NH, Wu WG
    Toxins (Basel), 2022 Dec 07;14(12).
    PMID: 36548757 DOI: 10.3390/toxins14120860
    Naja nivea (Cape Cobra) is endemic to southern Africa. Envenoming by N. nivea is neurotoxic, resulting in fatal paralysis. Its venom composition, however, has not been studied in depth, and specific antivenoms against it remain limited in supply. Applying a protein decomplexation approach, this study unveiled the venom proteome of N. nivea from South Africa. The major components in the venom are cytotoxins/cardiotoxins (~75.6% of total venom proteins) and alpha-neurotoxins (~7.4%), which belong to the three-finger toxin family. Intriguingly, phospholipase A2 (PLA2) was undetected-this is a unique venom phenotype increasingly recognized in the African cobras of the Uraeus subgenus. The work further showed that VINS African Polyvalent Antivenom (VAPAV) exhibited cross-reactivity toward the venom and immunorecognized its toxin fractions. In mice, VAPAV was moderately efficacious in cross-neutralizing the venom lethality with a potency of 0.51 mg/mL (amount of venom completely neutralized per milliliter of antivenom). In the challenge-rescue model, VAPAV prevented death in 75% of experimentally envenomed mice, with slow recovery from neurotoxicity up to 24 h. The finding suggests the potential para-specific utility of VAPAV for N. nivea envenoming, although a higher dose or repeated administration of the antivenom may be required to fully reverse the neurotoxic effect of the venom.
    Matched MeSH terms: Mice
  5. Fulltext Organ defects of the Usp7K444R mutant mouse strain indicate the essential role of K63-polyubiquitinated Usp7 in organ formation
    Wu HT, Lin YT, Chew SH, Wu KJ
    Biomed J, 2023 Feb;46(1):122-133.
    PMID: 35183794 DOI: 10.1016/j.bj.2022.02.002
    BACKGROUND: K63-linked polyubiquitination of proteins have nonproteolytic functions and regulate the activity of many signal transduction pathways. USP7, a HIF1α deubiquitinase, undergoes K63-linked polyubiquitination under hypoxia. K63-polyubiquitinated USP7 serves as a scaffold to anchor HIF1α, CREBBP, the mediator complex, and the super elongation complex to enhance HIF1α-induced gene transcription. However, the physiological role of K63-polyubiquitinated USP7 remains unknown.

    METHODS: Using a Usp7K444R point mutation knock-in mouse strain, we performed immunohistochemistry and standard molecular biological methods to examine the organ defects of liver and kidney in this knock-in mouse strain. Mechanistic studies were performed by using deubiquitination, immunoprecipitation, and quantitative immunoprecipitations (qChIP) assays.

    RESULTS: We observed multiple organ defects, including decreased liver and muscle weight, decreased tibia/fibula length, liver glycogen storage defect, and polycystic kidneys. The underlying mechanisms include the regulation of protein stability and/or modulation of transcriptional activation of several key factors, leading to decreased protein levels of Prr5l, Hnf4α, Cebpα, and Hnf1β. Repression of these crucial factors leads to the organ defects described above.

    CONCLUSIONS: K63-polyubiquitinated Usp7 plays an essential role in the development of multiple organs and illustrates the importance of the process of K63-linked polyubiquitination in regulating critical protein functions.

    Matched MeSH terms: Mice, Mutant Strains; Mice
  6. Structural Characterization and Immunomodulatory Activity of a Polysaccharide from Eurycoma longifolia
    He P, Dong Z, Wang Q, Zhan QP, Zhang MM, Wu H
    J Nat Prod, 2019 02 22;82(2):169-176.
    PMID: 30714735 DOI: 10.1021/acs.jnatprod.8b00238
    A polysaccharide, Ali-1, was isolated from the roots of Eurycoma longifolia, a popular traditional medicinal herb in Malaysia. The structure of Ali-1 was characterized by monosaccharide, methylation, and NMR data analyses. The average molecular weight of Ali-1 is 14.3 ku, and it is composed of arabinose (14.31%), xylose (57.69%), galacturonic acid (13.03%), and glucuronic acid (14.86%). The main chain comprises (1→4)-linked xylose residues. It has branch points in the main chain; (1→2,4)-linked xylose residues, 1,2-linked glucuronic acid residues, and 1,2-linked arabinose residues form the branches, and the branches are terminated with T-linked galacturonic acid residues and T-linked arabinose residues. Ali-1 significantly improves the pinocytic and phagocytic abilities of RAW264.7 cells and facilitates cytokine secretion according to an immunostimulation assay. These results demonstrate that Ali-1 has potential as a functional supplement for people with compromised immune systems.
    Matched MeSH terms: Mice
  7. Fucoidan Ameliorates Renal Injury-Related Calcium-Phosphorus Metabolic Disorder and Bone Abnormality in the CKD-MBD Model Rats by Targeting FGF23-Klotho Signaling Axis
    Liu BH, Chong FL, Yuan CC, Liu YL, Yang HM, Wang WW, et al.
    Front Pharmacol, 2020;11:586725.
    PMID: 33708111 DOI: 10.3389/fphar.2020.586725
    Background: Recently, chronic kidney disease (CKD)-mineral and bone disorder (MBD) has become one of common complications occurring in CKD patients. Therefore, development of a new treatment for CKD-MBD is very important in the clinic. In China, Fucoidan (FPS), a natural compound of Laminaria japonica has been frequently used to improve renal dysfunction in CKD. However, it remains elusive whether FPS can ameliorate CKD-MBD. FGF23-Klotho signaling axis is reported to be useful for regulating mineral and bone metabolic disorder in CKD-MBD. This study thereby aimed to clarify therapeutic effects of FPS in the CKD-MBD model rats and its underlying mechanisms in vivo and in vitro, compared to Calcitriol (CTR). Methods: All male rats were divided into four groups: Sham, CKD-MBD, FPS and CTR. The CKD-MBD rat models were induced by adenine administration and uninephrectomy, and received either FPS or CTR or vehicle after induction of renal injury for 21 days. The changes in parameters related to renal dysfunction and renal tubulointerstitial damage, calcium-phosphorus metabolic disorder and bone lesion were analyzed, respectively. Furthermore, at sacrifice, the kidneys and bone were isolated for histomorphometry, immunohistochemistry and Western blot. In vitro, the murine NRK-52E cells were used to investigate regulative actions of FPS or CTR on FGF23-Klotho signaling axis, ERK1/2-SGK1-NHERF-1-NaPi-2a pathway and Klotho deficiency. Results: Using the modified CKD-MBD rat model and the cultured NRK-52E cells, we indicated that FPS and CTR alleviated renal dysfunction and renal tubulointerstitial damage, improved calcium-phosphorus metabolic disorder and bone lesion, and regulated FGF23-Klotho signaling axis and ERK1/2-SGK1-NHERF-1-NaPi-2a pathway in the kidney. In addition, using the shRNA-Klotho plasmid-transfected cells, we also detected, FPS accurately activated ERK1/2-SGK1-NHERF-1-NaPi-2a pathway through Klotho loss reversal. Conclusion: In this study, we emphatically demonstrated that FPS, a natural anti-renal dysfunction drug, similar to CTR, improves renal injury-related calcium-phosphorus metabolic disorder and bone abnormality in the CKD-MBD model rats. More importantly, we firstly found that beneficial effects in vivo and in vitro of FPS on phosphorus reabsorption are closely associated with regulation of FGF23-Klotho signaling axis and ERK1/2-SGK1-NHERF-1-NaPi-2a pathway in the kidney. This study provided pharmacological evidences that FPS directly contributes to the treatment of CKD-MBD.
    Matched MeSH terms: Mice
  8. Investigating the addition of SiO₂-CaO-ZnO-Na₂O-TiO₂ bioactive glass to hydroxyapatite: Characterization, mechanical properties and bioactivity
    Yatongchai C, Placek LM, Curran DJ, Towler MR, Wren AW
    J Biomater Appl, 2015 Nov;30(5):495-511.
    PMID: 26116020 DOI: 10.1177/0885328215592866
    Hydroxyapatite (Ca10(PO4)6(OH)2) is widely investigated as an implantable material for hard tissue restoration due to its osteoconductive properties. However, hydroxyapatite in bulk form is limited as its mechanical properties are insufficient for load-bearing orthopedic applications. Attempts have been made to improve the mechanical properties of hydroxyapatite, by incorporating ceramic fillers, but the resultant composite materials require high sintering temperatures to facilitate densification, leading to the decomposition of hydroxyapatite into tricalcium phosphate, tetra-calcium phosphate and CaO phases. One method of improving the properties of hydroxyapatite is to incorporate bioactive glass particles as a second phase. These typically have lower softening points which could possibly facilitate sintering at lower temperatures. In this work, a bioactive glass (SiO2-CaO-ZnO-Na2O-TiO2) is incorporated (10, 20 and 30 wt%) into hydroxyapatite as a reinforcing phase. X-ray diffraction confirmed that no additional phases (other than hydroxyapatite) were formed at a sintering temperature of 560 ℃ with up to 30 wt% glass addition. The addition of the glass phase increased the % crystallinity and the relative density of the composites. The biaxial flexural strength increased to 36 MPa with glass addition, and there was no significant change in hardness as a function of maturation. The pH of the incubation media increased to pH 10 or 11 through glass addition, and ion release profiles determined that Si, Na and P were released from the composites. Calcium phosphate precipitation was encouraged in simulated body fluid with the incorporation of the bioactive glass phase, and cell culture testing in MC-3T3 osteoblasts determined that the composite materials did not significantly reduce cell viability.
    Matched MeSH terms: Mice
  9. Fulltext 3',4'-dihydroxyflavonol ameliorates endoplasmic reticulum stress-induced apoptosis and endothelial dysfunction in mice
    Lau YS, Mustafa MR, Choy KW, Chan SMH, Potocnik S, Herbert TP, et al.
    Sci Rep, 2018 01 29;8(1):1818.
    PMID: 29379034 DOI: 10.1038/s41598-018-19584-8
    Endoplasmic reticulum (ER) stress has been implicated in the development of hypertension 3 through the induction of endothelial impairment. As 3',4'-dihydroxyflavonol (DiOHF) 4 reduces vascular injury caused by ischaemia/reperfusion or diabetes, and flavonols have been demonstrated to attenuate ER stress, we investigated whether DiOHF can protect mice from ER stress-induced endothelial dysfunction. Male C57BLK/6 J mice were injected with tunicamycin to induce ER stress in the presence or absence of either DiOHF or tauroursodeoxycholic acid (TUDCA), an inhibitor of ER stress. Tunicamycin elevated blood pressure and impaired endothelium-dependent relaxation. Moreover, in aortae there was evidence of ER stress, oxidative stress and reduced NO production. This was coincident with increased NOX2 expression and reduced phosphorylation of endothelial nitric oxide synthase (eNOS) on Ser1176. Importantly, the effects of tunicamycin were significantly ameliorated by DiOHF or TUDCA. DiOHF also inhibited tunicamycin-induced ER stress and apoptosis in cultured human endothelial cells (HUVEC). These results provide evidence that ER stress is likely an important initiator of endothelial dysfunction through the induction of oxidative stress and a reduction in NO synthesis and that DiOHF directly protects against ER stress- induced injury. DiOHF may be useful to prevent ER and oxidative stress to preserve endothelial function, for example in hypertension.
    Matched MeSH terms: Mice, Inbred C57BL; Mice
  10. Fulltext Pathological findings in a mouse model of Japanese encephalitis infected via the footpad
    Fu, Tzeh Long, Ong, Kien Chai, Wong, Kum Thong
    Neurology Asia, 2015;20(4):349-354.
    MyJurnal
    We have developed and characterised a mouse model of Japanese encephalitis virus (JEV) infection via
    footpad inoculation in order to better mimic viral transmission by mosquito bites. Two-week-old and
    5-week-old mice consistently developed signs of infection such as ruffled fur, weight loss, hunchback
    posture, tremors, mask-like facies and occasionally, hindlimb paralysis at 4 days post infection (dpi)
    and 11-13 dpi, respectively. Most of the animals died within 24 to 48 hours following the onset of signs
    of infection, with mortalities of 100% and 33.3% in 2-week-old and 5-week-old mice, respectively.
    Mild meningitis and variable parenchymal inflammation with formation of microglial nodules, focal
    necrosis and neuronophagia, and perivascular cuffing by inflammatory cells were observed in the
    caudate nucleus, putamen, thalamus, cerebral cortex, brainstem, and spinal cord. Viral antigens/RNA
    were demonstrated by immunohistochemisty and in situ hybridization, respectively, in most of these
    areas as well as in the hippocampus and cerebellum, albeit more focally. The pathological findings in
    this mouse model were generally similar to human Japanese encephalitis (JE) and other established JE
    models but perhaps, compared to other JEV mouse models, it demonstrates lethal encephalitic infection
    more consistently. We believe that our mouse model should be useful to study the pathogenesis of JE,
    and for testing anti-viral drugs and vaccines
    Matched MeSH terms: Mice
  11. Fulltext Pathological findings in a mouse model for Coxsackievirus A16 infection
    Hooi, Yuan Teng, Ong, Kien Chai, Perera, David, Wong, Kum Thong
    Neurology Asia, 2015;20(4):343-347.
    MyJurnal
    Coxsackievirus A16 (CV-A16) is the leading cause of hand-foot-mouth disease (HFMD), which usually
    presents as mild and self-limiting symptoms in young children. Rarely, CV-A16 has been reported
    to cause severe and fatal neurological complications but little is known about these complications.
    In the present study, 1-day and 7-day old mouse models of CV-A16 were developed using a clinical
    strain via subcutaneous inoculation. All infected mice exhibited clinical signs of infection, including
    reduced mobility, limb weakness and paralysis between 3 to 6 days post-infection. Pathologically,
    the main organs involved were the central nervous system (CNS), skeletal muscles and brown fat. In
    the CNS, viral antigens as demonstrated by immunohistochemistry, were localized mainly to neurons
    in the brain stem and spinal cord, suggesting that CV-A16 is neurotropic although inflammation is
    very mild. The skeletal muscles showed necrosis and myositis due to viral infection as evidenced by
    the dense viral antigens. Focal viral antigens were also detected in the brown fat. These preliminary
    pathological findings indicate that our mouse models can be further developed to be useful models
    for pathogenesis studies, and vaccine and anti-viral drug evaluation.
    Matched MeSH terms: Mice
  12. Madecassoside activates anti‑neuroinflammatory mechanisms by inhibiting lipopolysaccharide‑induced microglial inflammation
    Sasmita AO, Ling APK, Voon KGL, Koh RY, Wong YP
    Int J Mol Med, 2018 May;41(5):3033-3040.
    PMID: 29436598 DOI: 10.3892/ijmm.2018.3479
    Neurodegeneration is typically preceded by neuroinflammation generated by the nervous system to protect itself from tissue damage, however, excess neuroinflammation may inadvertently cause more harm to the surrounding tissues. Attenuating neuroinflammation with non‑steroidal anti‑inflammatory drugs can inhibit neurodegeneration. However, such treatments induce chronic side effects, including stomach ulcers. Madecassoside, a triterpene derived from Centella asiatica, is considered to be an alternative treatment of inflammation. In the present study, the anti‑neuroinflammatory properties of madecassoside were assessed in BV2 microglia cells, which were pre‑treated with madecassoside at a maximum non‑toxic dose (MNTD) of 9.50 µg/ml and a ½ MNTD of 4.75 µg/ml for 3 h and stimulated with 0.1 µg/ml lipopolysaccharide (LPS). The effect of madecassoside was assessed by determining reactive oxygen species (ROS) levels in all groups. Furthermore, the expression of pro‑ and anti‑neuroinflammatory genes and proteins were analyzed using reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that ROS levels in cells treated with the MNTD of madecassoside were significantly reduced compared with cells treated with LPS alone (P<0.05). The expression of pro‑neuroinflammatory genes, including inducible nitric oxide synthase, cyclooxygenase‑2, signal transducer and activator of transcription 1 and nuclear factor‑κB, were significantly downregulated in a dose‑independent manner following treatment with madecassoside. Conversely, the anti‑neuroinflammatory component heme oxygenase 1 was significantly upregulated by 175.22% in the MNTD‑treated group, compared with cells treated with LPS alone (P<0.05). The gene expression profiles of pro‑ and anti‑inflammatory genes were also consistent with the results of western blotting. The results of the present study suggest that madecassoside may be a potent anti‑neuroinflammatory agent. The antioxidative properties of madecassoside, which serve a major role in anti‑neuroinflammation, indicate that this compound may be a functional natural anti‑neuroinflammatory agent, therefore, further in vivo or molecular studies are required.
    Matched MeSH terms: Mice
  13. Effect of an extract of Erioglossum edule on the central nervous system
    Sattar MA, Gan EK, Loke SE, Mah KF, Wong WH
    J Ethnopharmacol, 1989 Apr;25(2):217-20.
    PMID: 2747256
    Matched MeSH terms: Mice
  14. Fulltext Genome-Wide Transcription Study of Cryptococcus neoformans H99 Clinical Strain versus Environmental Strains
    Movahed E, Munusamy K, Tan GM, Looi CY, Tay ST, Wong WF
    PLoS One, 2015;10(9):e0137457.
    PMID: 26360021 DOI: 10.1371/journal.pone.0137457
    The infection of Cryptococcus neoformans is acquired through the inhalation of desiccated yeast cells and basidiospores originated from the environment, particularly from bird's droppings and decaying wood. Three environmental strains of C. neoformans originated from bird droppings (H4, S48B and S68B) and C. neoformans reference clinical strain (H99) were used for intranasal infection in C57BL/6 mice. We showed that the H99 strain demonstrated higher virulence compared to H4, S48B and S68B strains. To examine if gene expression contributed to the different degree of virulence among these strains, a genome-wide microarray study was performed to inspect the transcriptomic profiles of all four strains. Our results revealed that out of 7,419 genes (22,257 probes) examined, 65 genes were significantly up-or down-regulated in H99 versus H4, S48B and S68B strains. The up-regulated genes in H99 strain include Hydroxymethylglutaryl-CoA synthase (MVA1), Mitochondrial matrix factor 1 (MMF1), Bud-site-selection protein 8 (BUD8), High affinity glucose transporter 3 (SNF3) and Rho GTPase-activating protein 2 (RGA2). Pathway annotation using DAVID bioinformatics resource showed that metal ion binding and sugar transmembrane transporter activity pathways were highly expressed in the H99 strain. We suggest that the genes and pathways identified may possibly play crucial roles in the fungal pathogenesis.
    Matched MeSH terms: Mice
  15. Fulltext Suppression of cell division-associated genes by Helicobacter pylori attenuates proliferation of RAW264.7 monocytic macrophage cells
    Tan GM, Looi CY, Fernandez KC, Vadivelu J, Loke MF, Wong WF
    Sci Rep, 2015;5:11046.
    PMID: 26078204 DOI: 10.1038/srep11046
    Helicobacter pylori at multiplicity of infection (MOI ≥ 50) have been shown to cause apoptosis in RAW264.7 monocytic macrophage cells. Because chronic gastric infection by H. pylori results in the persistence of macrophages in the host's gut, it is likely that H. pylori is present at low to moderate, rather than high numbers in the infected host. At present, the effect of low-MOI H. pylori infection on macrophage has not been fully elucidated. In this study, we investigated the genome-wide transcriptional regulation of H. pylori-infected RAW264.7 cells at MOI 1, 5 and 10 in the absence of cellular apoptosis. Microarray data revealed up- and down-regulation of 1341 and 1591 genes, respectively. The expression of genes encoding for DNA replication and cell cycle-associated molecules, including Aurora-B kinase (AurkB) were down-regulated. Immunoblot analysis verified the decreased expression of AurkB and downstream phosphorylation of Cdk1 caused by H. pylori infection. Consistently, we observed that H. pylori infection inhibited cell proliferation and progression through the G1/S and G2/M checkpoints. In summary, we suggest that H. pylori disrupts expression of cell cycle-associated genes, thereby impeding proliferation of RAW264.7 cells, and such disruption may be an immunoevasive strategy utilized by H. pylori.
    Matched MeSH terms: Mice
  16. Influx of podoplanin-expressing inflammatory macrophages into the genital tract following Chlamydia infection
    Chan YT, Cheok YY, Cheong HC, Tan GMY, Seow SR, Tang TF, et al.
    Immunol Cell Biol, 2023 Apr;101(4):305-320.
    PMID: 36658328 DOI: 10.1111/imcb.12621
    Genital Chlamydia trachomatis infection remains a major health issue as it causes severe complications including pelvic inflammatory disease, ectopic pregnancy and infertility in females as a result of infection-associated chronic inflammation. Podoplanin, a transmembrane receptor, has been previously reported on inflammatory macrophages. Thus, strategies that specifically target podoplanin might be able to reduce local inflammation. This study investigated the expression level and function of podoplanin in a C. trachomatis infection model. C57BL/6 mice infected with the mouse pathogen Chlamydia muridarum were examined intermittently from days 1 to 60 using flow cytometry analysis. Percentages of conventional macrophages (CD11b+ CD11c- F4/80+ ) versus inflammatory macrophages (CD11b+ CD11c+ F4/80+ ), and the expression of podoplanin in these cells were investigated. Subsequently, a podoplanin-knockout RAW264.7 cell was used to evaluate the function of podoplanin in C. trachomatis infection. Our findings demonstrated an increased CD11b+ cell volume in the spleen at day 9 after the infection, with augmented podoplanin expression, especially among the inflammatory macrophages. A large number of podoplanin-expressing macrophages were detected in the genital tract of C. muridarum-infected mice. Furthermore, analysis of the C. trachomatis-infected patients demonstrated a higher percentage of podoplanin-expressing monocytes than that in the noninfected controls. Using an in vitro infection in a transwell migration assay, we identified that macrophages deficient in podoplanin displayed defective migratory function toward C. trachomatis-infected HeLa 229 cells. Lastly, using immunoprecipitation-mass spectrometry method, we identified two potential podoplanin interacting proteins, namely, Cofilin 1 and Talin 1 actin-binding proteins. The present study reports a role of podoplanin in directing macrophage migration to the chlamydial infection site. Our results suggest a potential for reducing inflammation in individuals with chronic chlamydial infections by targeting podoplanin.
    Matched MeSH terms: Mice, Inbred C57BL; Mice
  17. Vitexin and isovitexin from the Leaves of Ficus deltoidea with in-vivo α-glucosidase inhibition
    Choo CY, Sulong NY, Man F, Wong TW
    J Ethnopharmacol, 2012 Aug 1;142(3):776-81.
    PMID: 22683902 DOI: 10.1016/j.jep.2012.05.062
    The leaves of Ficus deltoidea are used as a traditional medicine by diabetes patients in Malaysia.
    Matched MeSH terms: Mice
  18. 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
  19. Fulltext The in vitro and in vivo anti-cancer activities of a standardized quassinoids composition from Eurycoma longifolia on LNCaP human prostate cancer cells
    Tong KL, Chan KL, AbuBakar S, Low BS, Ma HQ, Wong PF
    PLoS One, 2015;10(3):e0121752.
    PMID: 25826409 DOI: 10.1371/journal.pone.0121752
    Quassinoids are a group of diterpenoids found in plants from the Simaroubaceae family. They are also the major bioactive compounds found in Eurycoma longifolia which is commonly used as traditional medicine in South East Asia to treat various ailments including sexual dysfunction and infertility. These uses are attributed to its ability to improve testosterone level in men. Chronic consumption of E. longifolia extracts has been reported to increase testosterone level in men and animal model but its effect on prostate growth remains unknown. Therefore, the present study investigates the effects of a standardized total quassinoids composition (SQ40) containing 40% of the total quassinoids found in E. longifolia on LNCaP human prostate cancer cell line. SQ40 inhibited LNCaP cell growth at IC50 value of 5.97 μg/mL while the IC50 on RWPE-1 human prostate normal cells was 59.26 μg/mL. SQ40 also inhibited 5α-dihydrotestosterone-stimulated growth in LNCaP cells dose-dependently. The inhibitory effect of SQ40 in anchorage-independent growth of LNCaP cells was also demonstrated using soft agar assay. SQ40 suppressed LNCaP cell growth via G0/G1 phase arrest which was accompanied by the down-regulation of CDK4, CDK2, Cyclin D1 and Cyclin D3 and up-regulation of p21Waf1/Cip1 protein levels. SQ40 at higher concentrations or longer treatment duration can cause G2M growth arrest leading to apoptotic cell death as demonstrated by the detection of poly(ADP-ribose) polymerase cleavage in LNCaP cells. Moreover, SQ40 also inhibited androgen receptor translocation to nucleus which is important for the transactivation of its target gene, prostate-specific antigen (PSA) and resulted in a significant reduction of PSA secretion after the treatment. In addition, intraperitoneal injection of 5 and 10 mg/kg of SQ40 also significantly suppressed the LNCaP tumor growth on mouse xenograft model. Results from the present study suggest that the standardized total quassinoids composition from E. longifolia promotes anti-prostate cancer activities in LNCaP human prostate cancer cells.
    Matched MeSH terms: Mice, Nude; Mice
  20. Fulltext Synergistic inhibition of melanoma xenografts by Brequinar sodium and Doxorubicin
    Dorasamy MS, Ab A, Nellore K, Wong PF
    Biomed Pharmacother, 2019 Feb;110:29-36.
    PMID: 30458345 DOI: 10.1016/j.biopha.2018.11.010
    Malignant melanoma continues to be a fatal disease for which novel and long-term curative breakthroughs are desired. One such innovative idea would be to assess combination therapeutic treatments - by way of combining two potentially effective and very different therapy. Previously, we have shown that DHODH inhibitors, A771726 and Brequinar sodium (BQR) induced cell growth impairment in melanoma cells. Similar results were seen with DHODH RNA interference (shRNA). In the present study, we showed that combination of BQR with doxorubicin resulted in synergistic and additive cell growth inhibition in these cells. In addition, in vivo studies with this combination of drugs demonstrated an almost 90% tumor regression in nude mice bearing melanoma tumors. Cell cycle regulatory proteins, cyclin B1 and its binding partner pcdc-2 and p21 were significantly downregulated and upregulated respectively following the combined treatment. Given that we have observed synergistic effects with BQR and doxorubicin, both in vitro and in vivo, these drugs potentially represent a new combination in the targeted therapy of melanoma.
    Matched MeSH terms: Mice, Nude; Mice
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links