https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 In vitro comparison of liposomal drug delivery systems targeting the oxytocin receptor: a potential novel treatment for obstetric complications https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45259 sn-glycero-2-phosphocholine and cholesterol were prepared according to the method of dried lipid film hydration. Ligands were conjugated with the surface of liposomes using optimized methods to maximize conjugation efficiency. The liposomes were characterized for particle size, ligand conjugation, drug encapsulation, liposome stability, specificity of binding, cellular internalization, mechanistic pathway of cellular uptake, and cellular toxicity. Results: Both OTR-Lipo and ATO-Lipo showed significant and specific binding to OTRs in a concentration-dependent manner compared to all control groups. There was no significant difference in binding values between OTR-Lipo and ATO-Lipo across all concentrations evaluated. In addition, OTR-Lipo (81.61%±7.84%) and ATO-Lipo (85.59%±8.28%) demonstrated significantly increased cellular internalization in comparison with rabbit IgG immunoliposomes (9.14%±1.71%) and conventional liposomes (4.09%±0.78%) at 2.02 mM phospholipid concentration. Cellular association following liposome incubation at 4.05 mM resulted in similar findings. Evaluation of the mechanistic pathway of cellular uptake indicated that they undergo internalization through both clathrin- and caveolin-mediated mechanisms. Furthermore, cellular toxicity studies have shown no significant effect of both liposomal platforms on cell viability. Conclusion: This study further supports OTRs as a novel pharmaceutical target for drug delivery. OTR-targeted liposomal platforms may provide an effective way to deliver existing therapies directly to myometrial tissue and avoid adverse effects by circumventing non-target tissues.]]> Wed 26 Oct 2022 19:46:49 AEDT ]]> Mechanotransduction mechanisms for coordinating uterine contractions in human labor https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29643 Wed 11 Apr 2018 14:32:15 AEST ]]> Phasic contractions of the mouse vagina and cervix at different phases of the estrus cycle and during late pregnancy https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:16822 2+ release from sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) -dependent intracellular Ca2+ stores; and 3) c-Kit and/or vimentin immunoreactive ICs have a role in pacemaking. Methodology/Principal Findings: Vaginal and cervical contractions were measured in vitro, as was the distribution of c-Kit and vimentin positive interstitial cells (ICs). Cervical smooth muscle was spontaneously active in estrus and metestrus but quiescent during proestrus and diestrus. Vaginal smooth muscle was normally quiescent but exhibited phasic contractions in the presence of oxytocin or the K+ channel blocker tetraethylammonium (TEA) chloride. Spontaneous contractions in the cervix and TEA-induced phasic contractions in the vagina persisted in the presence of cyclopiazonic acid (CPA), a blocker of the SERCA that refills intracellular SR Ca2+ stores, but were inhibited in low Ca2+ solution or in the presence of nifedipine, an inhibitor of L-type Ca2+channels. ICs were found in small numbers in the mouse cervix but not in the vagina. Conclusions/Significance: Cervical smooth muscle strips taken from mice in estrus, metestrus or late pregnancy were generally spontaneously active. Vaginal smooth muscle strips were normally quiescent but could be induced to exhibit phasic contractions independent on phase of the estrus cycle or late pregnancy. Spontaneous cervical or TEA-induced vaginal phasic contractions were not mediated by ICs or intracellular Ca2+ stores. Given that vaginal smooth muscle is normally quiescent then it is likely that increases in hormones such as oxytocin, as might occur through sexual stimulation, enhance the effectiveness of such pacemaking until phasic contractile activity emerges.]]> Wed 11 Apr 2018 13:40:08 AEST ]]> Female reproductive tract pain: targets, challenges, and outcomes https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18783 Wed 11 Apr 2018 12:33:36 AEST ]]> Elucidating the role of myosin phosphatase in the contractility of myometrial smooth muscle https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27510 Wed 11 Apr 2018 11:48:28 AEST ]]> Molecular analysis of early-stage ovarian cancer https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51462 Wed 06 Mar 2024 14:35:39 AEDT ]]> A hypothesis for self-organization and symmetry reduction in the synchronization of organ-level contractions in the human uterus during labor https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23393 Tue 24 Apr 2018 11:33:54 AEST ]]> The endometrial transcriptome transition preceding receptivity to embryo implantation in mice https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53503 Thu 30 Nov 2023 15:57:23 AEDT ]]> 3D cell culturing and possibilities for myometrial tissue engineering https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32097 Thu 28 Oct 2021 12:37:05 AEDT ]]> Development and characterization of human fetal female reproductive tract organoids to understand Müllerian duct anomalies https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53981 Thu 25 Jan 2024 12:57:12 AEDT ]]> Interferon-gamma inhibits seminal plasma induction of colony-stimulating factor 2 in mouse and human reproductive tract epithelial cells https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37555 TGFBR2 encoding TGFB receptor 2. Conversely, TGFB1 suppressed IFNG receptor 1 and 2 genes IFNGR1 and IFNGR2. These data identify IFNG as a potent inhibitor of the TGFB-mediated seminal fluid interaction with relevant reproductive tract epithelia in mice and human. These findings raise the prospect that IFNG in the male partner's seminal fluid impairs immune adaptation for pregnancy following coitus in women.]]> Thu 18 Feb 2021 09:50:20 AEDT ]]> Role of mitochondria in contraction and pacemaking in the mouse uterus https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:11410 Sat 24 Mar 2018 08:11:11 AEDT ]]> Role of Wnt signalling in endometrial homeostasis and cancer https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32344 Mon 23 Sep 2019 12:47:41 AEST ]]> Exploring novel application of tissue engineering strategies to human myometrium https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32223 Mon 23 Sep 2019 12:01:01 AEST ]]> Synthesis and in vitro characterization of oxytocin receptor targeted PEGylated immunoliposomes for drug delivery to the uterus https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47748 in vivo in a murine model of preterm labour. The aim of this study was to report the pharmaceutical synthesis and characterization of the OTR-PEG-ILs and investigate their specific cellular interaction with OTR-expressing myometrial cells in vitro. Immunoliposomes composed of 1,2-distearoyl-sn-glycero-2-phosphocholine (DSPC) and cholesterol were prepared using an optimized method for the coupling of low concentrations of antibody to liposomes. The liposomes were characterized for particle size, antibody conjugation, drug encapsulation, liposome stability, specificity of binding, cellular internalization, mechanistic pathway of cellular uptake, and cellular toxicity. Cellular association studies demonstrated specific binding of OTR-PEG-ILs to OTRs and significant cellular uptake following binding. Evaluation of the mechanistic pathway of cellular uptake indicated that they undergo internalization through both clathrin- and caveolin-mediated mechanisms. Furthermore, cellular toxicity studies have shown no significant effect of OTR-PEG-ILs or the endocytotic inhibitors on cell viability. This study further supports oxytocin receptors as a novel pharmaceutical target for drug delivery to the uterus.]]> Fri 27 Jan 2023 09:49:49 AEDT ]]> Resveratrol restores uterine contractions during hypoxia by blockade of ATP-sensitive potassium channels https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34698 75% of its contraction capability. The effects of resveratrol on uterine contractions under hypoxia were attenuated by tetraethylammonium (10 mM) and almost abolished by glibenclamide (10 µM). Our results show regenerative and protective effects of resveratrol in non-pregnant murine uteri under hypoxia and describes for the first time that these effects are mediated by blockade of ATP-sensitive potassium channels.]]> Fri 12 Apr 2019 15:45:10 AEST ]]> Proteomic analysis identifies tenascin-C expression is upregulated in uterine fibroids https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45565 1.5-fold) with a confidence corresponding to false discovery rate (FDR) <1% in small-, medium-, and large-sized fibroid samples regardless of MED12 mutation status. The TNC was validated on additional patient samples using Western blotting (WB) and immunohistochemistry (IHC) and confirmed significant overexpression of this protein in fibroids compared to matched ANM. Proteomic analyses have identified the increased ECM protein expression, TNC, as a hallmark of uterine fibroids regardless of MED12 mutations. Further functional studies focusing on the upregulated ECM proteins in leiomyogenesis will lead to the identification of novel ECM drug targets for fibroid treatment.]]> Fri 04 Nov 2022 14:44:56 AEDT ]]> Bovine and human endometrium-derived hydrogels support organoid culture from healthy and cancerous tissues https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51354 Fri 01 Sep 2023 13:44:28 AEST ]]>