Dataset Information

Ocular Effects of Glycyrrhizin at Acidic and Neutral pH.

ABSTRACT:

Purpose

To test the effects of acidic vs. neutral pH glycyrrhizin (GLY) on the unwounded and wounded normal mouse cornea and after infection with Pseudomonas aeruginosa isolates KEI 1025 and multidrug-resistant MDR9.

Methods

Acidic or neutral GLY vs. phosphate-buffered saline (PBS) was topically applied to normal or wounded corneas of C57BL/6 mice. In unwounded corneas, goblet cells and corneal nerves were stained and quantitated. After wounding, corneas were fluorescein stained and photographed using a slit lamp. Mice also were infected with KEI 1025 or MDR9 and the protective effects of GLY pH evaluated comparatively.

Results

In the unwounded cornea, application of acidic or neutral GLY vs. PBS reduced the number of bulbar conjunctival goblet cells but did not alter corneal nerve density. Similar application of GLY to scarified corneas delayed wound closure. After KEI 1025 infection, none of the GLY vs. PBS-treated corneas perforated; GLY treatment also decreased plate count (neutral pH more effective) and reduced MPO and several cytokines. Similarly, for MDR9, GLY at either pH was protective and also enhanced the effects of moxifloxacin to which MDR9 is resistant.

Conclusion

Acidic or neutral pH GLY decreased goblet cell number but had no effect on nerve density. After corneal wounding, GLY at either pH (1) delayed wound closure and, (2) after infection, decreased keratitis when used alone or in combination with moxifloxacin. Neutral pH did not alter the therapeutic effect of GLY and would be preferred if used clinically.

SUBMITTER: Somayajulu M

PROVIDER: S-EPMC8814321 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Ocular Effects of Glycyrrhizin at Acidic and Neutral pH.

Somayajulu Mallika M McClellan Sharon A SA Bessert Denise A DA Pitchaikannu Ahalya A Hazlett Linda D LD

Frontiers in cellular and infection microbiology 20220121

<h4>Purpose</h4>To test the effects of acidic <i>vs</i>. neutral pH glycyrrhizin (GLY) on the unwounded and wounded normal mouse cornea and after infection with <i>Pseudomonas aeruginosa</i> isolates KEI 1025 and multidrug-resistant MDR9.<h4>Methods</h4>Acidic or neutral GLY <i>vs</i>. phosphate-buffered saline (PBS) was topically applied to normal or wounded corneas of C57BL/6 mice. In unwounded corneas, goblet cells and corneal nerves were stained and quantitated. After wounding, corneas were ...[more]

PMID: 35127554

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Project description:BackgroundChronic rhinosinusitis (CRS) increases the risk of developing nasopharyngeal carcinoma (NPC) while nasopharyngeal reflux is known to be one of the major aetiological factors of CRS. Bile acid (BA), the component of gastric duodenal contents, has been recognised as a carcinogen. BA-induced apoptosis was suggested to be involved in human malignancies. Cells have the potential and tendency to survive apoptosis. However, cells that evade apoptosis upon erroneous DNA repair may carry chromosome rearrangements. Apoptotic nuclease, caspase-activated deoxyribonuclease (CAD) has been implicated in mediating translocation in leukaemia. We hypothesised that BA-induced apoptosis may cause chromosome breaks mediated by CAD leading to chromosome rearrangement in NPC. This study targeted the AF9 gene located at 9p22 because 9p22 is one of the most common deletion sites in NPC.MethodsWe tested the ability of BA at neutral and acidic pH in inducing phosphatidylserine (PS) externalisation, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) disruption, and caspase 3/7 activity in normal nasopharyngeal epithelial (NP69) and NPC (TWO4) cells. Inverse-PCR (IPCR) was employed to detect AF9 gene cleavages. To investigate the role of CAD in mediating these cleavages, caspase inhibition was performed. IPCR bands representing AF9 cleaved fragments were sequenced.ResultsBA-treated cells showed higher levels of PS externalisation, ROS production, MMP loss and caspase 3/7 activity than untreated control cells. The effect of BA in the induction of these intracellular events was enhanced by acid. BA at neutral and acidic pH also induced significant cleavage of the AF9 gene. These BA-induced gene cleavages were inhibited by Z-DEVD-FMK, a caspase-3 inhibitor. Intriguingly, a few chromosome breaks were identified within the AF9 region that was previously reported to participate in reciprocal translocation between the mixed lineage leukaemia (MLL) and AF9 genes in an acute lymphoblastic leukaemia (ALL) patient.ConclusionsThese findings suggest a role for BA-induced apoptosis in mediating chromosome rearrangements in NPC. In addition, CAD may be a key player in chromosome cleavages mediated by BA-induced apoptosis. Persistent exposure of sinonasal tract to gastric duodenal refluxate may increase genomic instability in surviving cells.

Project description:A series of functionalized metal organic frameworks (MOFs) were synthesized by the post-synthetic modification (PSM) of Zr(iv)-containing UiO-66-NH2 MOFs using covalent grafting with various functional groups utilizing pendant -NH2 moieties. The tethering of amide (with/without pendant carboxylic acid), iminopyridine, phoshinic amide and sulphur-containing functionalities produced a library of eight different UiO-66-NH2 derivatives. The functionalized MOFs were characterized by FT-IR spectroscopy, NMR, PXRD, TGA, SEM-EDX and BET surface area analysis. Uranyl ion extraction with the functionalized MOFs was investigated in acidic/neutral/basic conditions (pH 1 to 9). This work presents a comprehensive study of different functionalized MOFs to investigate the effects of various analytical parameters, including pH, contact time, and desorption process. The MOFs as solid phase extractants (SPEs) provide a direct comparison of the sorption efficiencies of different functional groups on a common solid support. A phosphorous-functionalized material, UiO-66-PO-Ph, with enhanced thermal stability (∼500 °C) exhibits the best sorption capacity (∼96%) in an acidic medium (pH 3). The parent MOF UiO-66-NH2 (92%) and iminopyridine-functionalized UiO-66-IMP (90%) showed excellent sorption in neutral conditions (pH 7). Amide-containing MOFs UiO-66-AM1 (40%), UiO-66-AMMal (31%) and UiO-66-AMGlu (70%), sulfur-based MOFs UiO-66-SMA (65%) and UiO-66-SSA (27%), and phosphorous-functionalized UiO-66-PO-OPh (50%) displayed maximum sorption in basic conditions (pH 8). The kinetics studies revealed rapid uranium sorption in about 2 h due to the effective binding of uranyl ions with the anchored functional groups of MOFs; quantitative elution of uranyl ions from the MOF framework was carried out with 0.1/0.01 M HNO3. The MOFs also exhibit moderate recyclability for uranium sorption and can be regenerated by an acidic solution. The functionalized MOFs alter the stability in acidic/basic media; thus, UiO-66-NH2 is a versatile MOF material employed as an SPE for the extraction of radionuclides from aqueous media. This work also provides a platform for the development of new functionalized MOF materials for the efficient sorption of uranium as well as moderate recyclability for its removal, and the potential applications include the removal of uranium from aqueous waste streams.

Dataset Information

Ocular Effects of Glycyrrhizin at Acidic and Neutral pH.

Purpose

Methods

Results

Conclusion

Publications

Ocular Effects of Glycyrrhizin at Acidic and Neutral pH.

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