RUSI Journal最新文献

Introduction: In the fight against cancer, cisplatin is most widely used as a clinical mainstay for the chemotherapy of various human cancers. Meanwhile, its cytotoxic profile, as well as drug resistance, limits its widespread application. The goal of precision medicine is to tailor an optimized therapeutic program based on the biology of the disease. Recently, nanotechnology has been demonstrated to be promising in this scenario. Objective: The current work provides a rationale for the design of an alternative oncology trial for the treatment of hepatocarcinogenesis using a novel eco-friendly nanocomplex, namely gallic acid-coated gallium nanoparticles. Moreover, the study tests whether the antineoplastic efficacy of gallic acid-coated gallium nanoparticles could be enhanced or not when it is administrated together with cisplatin. Methods: The work comprised a series of both in vitro and in vivo investigations. The in vivo therapeutic efficacy of such treatments, against diethylnitrosamine-induced hepatocarcinogenesis, was strictly evaluated by tracking target genes expressions, iron homeostasis, diverse biomarkers alterations, and lastly, routine paraclinical investigations were also assessed. Results: The in vitro biological evaluation of gallic acid-coated gallium nanoparticles in a HepG-2 cancer cell line established its superior cytotoxicity. Else more, the results of the in vivo experiment highlighted that gallic acid-coated gallium nanoparticles could diminish key hallmarks of cancer by ameliorating most of the investigated parameters. This was well-appreciated with the histopathological findings of the liver architectures of the treated groups. Conclusions: Our findings suggest that novel biogenic Ga-based nanocomplexes may potentially present new hope for the development of alternative liver cancer therapeutics, which should attract further scientific interest.

Objective: To study obstetric and perinatal outcomes among pregnant women with Takayasu arteritis (TA), attending our hospital for pregnancy and childbirth between January 2011 to December 2016.

Material and methods: Retrospective study was carried out by abstracting clinical charts on all pregnant women with TA who underwent antenatal care and/or delivery in our hospital during this period. American College of Rheumatology criteria was used for diagnosis of TA. Sixteen women with TA were included in the study. Maternal demographic data, stage of disease, complications related to disease, details of treatment taken prior to pregnancy, pregnancy outcomes, and neonatal outcomes were studied.

Results: Forty-four percentage (7/16) belonged to type 5 angiographic type, however the same proportion (7/16) had undergone surgical corrections prior to pregnancy and the majority (15/16) were on medical management. Only three women (19%) were diagnosed during pregnancy. Most did not have active disease measured by Kerr’s criteria (n=12; 75%), and Indıan Takayasu clinical activity scores A. Chronic hypertension was the commonest antenatal complication (56.2%), nearly one-third had growth restricted babies and 25% had preterm labour. There were no cardiovascular events, no maternal deaths, nor fetal or neonatal deaths. Two-thirds of our women were delivered by caesarean section.

Conclusion: Preconceptional counselling is of paramount importance in women with TA. Good maternal and fetal outcomes are observed with close antenatal surveillance and multidisciplinary care. Pregnancy should be planned during disease remission, with good antenatal care, close monitoring of clinical symptoms, early diagnosis and treatment of complications.

The fidelity of signal transduction requires spatiotemporal control of the production of signaling agents. Phosphatidic acid (PA) is a pleiotropic lipid second messenger whose modes of action differ based on upstream stimulus, biosynthetic source, and site of production. How cells regulate the local production of PA to effect diverse signaling outcomes remains elusive. Unlike other second messengers, sites of PA biosynthesis cannot be accurately visualized with subcellular precision. Here, we describe a rapid, chemoenzymatic approach for imaging physiological PA production by phospholipase D (PLD) enzymes. Our method capitalizes on the remarkable discovery that bulky, hydrophilic trans-cyclooctene-containing primary alcohols can supplant water as the nucleophile in the PLD active site in a transphosphatidylation reaction of PLD's lipid substrate, phosphatidylcholine. The resultant trans-cyclooctene-containing lipids are tagged with a fluorogenic tetrazine reagent via a no-rinse, inverse electron-demand Diels-Alder (IEDDA) reaction, enabling their immediate visualization by confocal microscopy in real time. Strikingly, the fluorescent reporter lipids initially produced at the plasma membrane (PM) induced by phorbol ester stimulation of PLD were rapidly internalized via apparent nonvesicular pathways rather than endocytosis, suggesting applications of this activity-based imaging toolset for probing mechanisms of intracellular phospholipid transport. By instead focusing on the initial 10 s of the IEDDA reaction, we precisely pinpointed the subcellular locations of endogenous PLD activity as elicited by physiological agonists of G protein-coupled receptor and receptor tyrosine kinase signaling. These tools hold promise to shed light on both lipid trafficking pathways and physiological and pathological effects of localized PLD signaling.