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Fertilized Sea Urchin Eggs as a Model for Detecting Cell Division Inhibitors
Published in Adorjan Aszalos, Modern Analysis of Antibiotics, 2020
Robert S. Jacobs, Leslie Wilson
A group of cyclic polysulfides from C. californica obtained from the Pacific at Isla San Jose, Mexico, were isolated and purified when crude fractions were found to have antibiotic activity against V. anguillarium [71]. One of these compounds (JF-23) was shown to have weak inhibiting activity in both the cell division assay (Figure 1) and the microtubule assembly assay (Table 3). These types of structures are relatively rare in nature, and the compound was included in this study primarily because of its novel structure.
Nutraceuticals for Hypertension Control
Published in Nilanjana Maulik, Personalized Nutrition as Medical Therapy for High-Risk Diseases, 2020
Balázs Varga, Mariann Bombicz, Andrea Kurucz, Béla Juhász
The major components of alliums, including onion, are organopolysulfides. The preventive potency of polysulfides in different chronic diseases including cancer, obesity, metabolic syndrome, gastric ulcer and cardiovascular disorders are well-known. The mechanism of polysulfides in cardioprotection are based on its hydrogen sulfide (H2S) donor property. H2S, next to nitric oxide (NO) and carbon monoxide (CO), is the third gasotransmitter and synthesized enzymatically from l-cysteine or l-homocysteine. H2S exerts its endotheliumdependent vasorelaxation by three main mechanisms: 1) activating NO synthase and inhibiting cGMP degradation by phosphodiesterase 5 (PDE5), thus potentiating the effect of NO-cGMP pathway; 2) H2S-derived polysulfides directly activate protein kinase G; and finally 3) H2S interacts with NO to form nitroxyl (HNO)-a potent vasorelaxant (Beltowski and Jamroz-Wisniewska 2014). Sakai et al. support this with their in vivo experiment on NO synthase inhibitor-induced hypertensive rats and spontaneously hypertensive rats (2003).
Characterization of Epidermal Langerhans Cells
Published in Francis N. Marzulli, Howard I. Maibach, Dermatotoxicology Methods: The Laboratory Worker’s Vade Mecum, 2019
Marie Cumberbatch, Rebecca J. Dearman, Ian Kimber
Membrane adenosine triphosphatase (ATPase) activity has been used extensively for identification of LC both in situ and in cell suspensions (Hanau et al., 1989). Epidermal sheets are fixed in cacodylate/formaldehyde fixative (100 ml, 13.7% sucrose; 80 ml, 3.2% sodium cacodylate; 20 ml formaldehyde) for 1 hr at 4°C. Excess fixative is removed by thorough washing in three changes of PBS for a total of 30 min. The tissue is then stained with ATP-lead for 70 min at 37°C. To prepare ATP-lead, 10 ml 1.2% MgSO4 and 5 g D-glucose in 50 ml distilled water are added to 40ml Tris/mal buffer (24.4g Tris, 23.3 g maleic acid, 8 g sodium hydroxide; pH 7.3). Immediately prior to use, 12 mg ATP and 1.8 ml of 2% PbNO3 are added to 20 ml buffer and warmed to 37°C. Following incubation of epidermal sheets in ATP-lead, the tissue is washed three times in Tris/mal buffer (2:3) and exposed to 2% ammonium polysulphide in distilled water for 20 min. The final wash is carried out in water prior to mounting of epidermal sheets on microscope slides in glycerol/saline (9:1) and sealing with nail varnish.
Role of nanotechnology in the prolonged release of drugs by the subcutaneous route
Published in Expert Opinion on Drug Delivery, 2023
At the EMA, nanosystems are classified based on their biological or nonbiological origins. For approval, a comparison with the reference formulation in terms of bioequivalence, safety, quality, and efficacy is needed [118]. However, because the interplay between nanosystem physicochemical characteristics and pharmacokinetic properties is not understood, replacing traditional animal models with more adequate models may allow extrapolation with greater certainty and safety. Nevertheless, the EMA has already published several reflection papers to help the industry develop its nanosystems and expedite its market entry [116]. Assessing the immunostimulatory profile of every nanosystem more precisely to determine whether the loaded drug plays a major role may avoid interference from background immunostimulation due to the nanosystem. Unloaded blank PEG-polysulfide nanosystems elicit low immunomodulatory activity [26], whereas comparable PLGA nanosystems [119] lead to alterations in immune cell populations and coreceptor expression and changes in the inflammatory status.
Glutathione Trisulfide Prevents Lipopolysaccharide-induced Inflammatory Gene Expression in Retinal Pigment Epithelial Cells
Published in Ocular Immunology and Inflammation, 2022
Hiroshi Tawarayama, Noriyuki Suzuki, Maki Inoue-Yanagimachi, Noriko Himori, Satoru Tsuda, Kota Sato, Tomoaki Ida, Takaaki Akaike, Hiroshi Kunikata, Toru Nakazawa
Glutathione, the principal in vivo antioxidant in animals, can directly quench intracellular reactive oxygen species (ROS) during thiol-dependent redox reactions mediated by glutathione disulfide reductase (GSR) and glutathione peroxidase (GPX)1.16 Increasing evidence demonstrates in vivo biosynthesis of sulfane sulfur-containing glutathiones (glutathione polysulfides and persulfides), and their physiological functions under normal and pathological conditions.17–25 Glutathione polysulfides, including glutathione trisulfide (GSSSG), exert stronger ROS-quenching activities than glutathione disulfide (GSSG) in the presence of GSR via conversion to their reduced forms, which are highly reactive.18,19 We have previously found that the GSSSG concentration in the aqueous humor of diabetic retinopathy patients, who suffer from excessive oxidative stress and inflammation, is significantly increased relative to that in the control patients.19 This observation suggests that GSSSG counteracts the increased oxidative stress in diabetic retinopathy patients. ROS function as secondary messengers that regulate immune responses and the expression of inflammatory genes by modulating the activities of nuclear factor-kappa B (NF-κB), mitogen-activated protein kinases (MAPKs), and inflammasomes.26–33 Therefore, GSSSG might be useful for attenuating cellular inflammation since this compound is more effective than GSSG in quenching ROS.
Non-surgical osteoarthritis therapy, intra-articular drug delivery towards clinical applications
Published in Journal of Drug Targeting, 2021
Yujie Liang, Xiao Xu, Limei Xu, Indira Prasadam, Li Duan, Yin Xiao, Jiang Xia
Affinity peptides are selected as target ligands for cell-specific drug delivery. Previously, a peptide was identified with a high affinity for collagen II α1 that also showed a high affinity for collagen II α1. Then, the short peptide, with the sequence WYRGRL, was conjugated to polysulphide propylene nanoparticles' surface. In vivo experiments showed that this functional nanoparticle successfully targeted the cartilage matrix with a retention time of 71-fold that of none targeted nanoparticles [42]. Affinity selection with a phage display of a peptide library was used to determine the cartilage-targeting polypeptide (CAP, sequence: DWRVIIPPRPSA). The CAP-modified drug delivery vector showed perfect cartilage-targeting properties; for example, CAP-PEI nanoparticles specifically facilitated hypoxia-inducible factor-2a (HIF-2) siRNA delivery to chondrocytes with high local concentrations in the cartilage seven days after injection [18], indicating that the CAP-PEI targeted drug-loading system may be suitable for OA gene therapy.