Core Cross-linked Micelles Made of Glycopolymers Bearing Dopamine and Cholic Acid Pendants

A series of block glycopolymers bearing galactose, dopamine, and cholic acid (CA) pendants have been synthesized by RAFT polymerization. These copolymers can self-assemble into micelles in water. The dopamine moieties, located near the interface of the core and shell of the micelles, can self-polymerize in a weakly basic solution, stabilizing the micelles in both water and organic solvent (DMSO). The cross-linked micelles are smaller in size than the uncross-linked precursors. Introducing more CA groups into the copolymers promotes the self-assembly to form larger aggregates, controls the cross-linking of the stabilized micelles, and facilitates the encapsulation of hydrophobic compounds such as Nile Red (NR). The amount of CA comonomers added also helps to control the cross-linking density, which affects the loading and release of NR. The core cross-linked micelles displayed a slow but sustained NR release and interact effectively with lectin (RCA₁₂₀), demonstrating their potential use as a biocompatible multifunctional platform for targeted release of drugs

Glycopolymeric Photosensitizers with Cholic Acid for HepG2-Targeted Chemo-Photodynamic Synergistic Therapy

The aggregation-caused quenching, premature drug release, and hypoxia-caused resistance of photodynamic therapy (PDT) are challenges in the design and preparation of novel porphyrin-containing photosensitizers. In this work, a series of block copolymers consisting of a hydrophilic glycopolymer block and a porphyrin-containing hydrophobic block were prepared via reversible addition–fragmentation chain transfer polymerization. The polymeric photosensitizers generate singlet oxygen and excellent PDT against HepG2, which can be strengthened by the addition of cholic acid. To combine with chemotherapy, doxorubicin (Dox) was successfully loaded into copolymers, which were observed to be more phototoxic, indicating that the therapeutic benefit of the synergistic effect of PDT and chemotherapy is better than their simple combination. The sugar-cell-specific interaction of galactose-containing photosensitizers results in a stronger mean fluorescent index (MFI) intracellular uptake in HepG2 cells in vitro compared to L929 and MCF-7 cells. These polymeric nanoplatforms present a versatile and effective avenue for developing synergistic therapy for cancer treatment

Enhancing Targeted Photodynamic Therapy: Star-Shaped Glycopolymeric Photosensitizers for Improved Selectivity and Efficacy

Targeted photodynamic therapy (PDT) offers advantages over nontargeted approaches, including improved selectivity, efficacy, and reduced side effects. This study developed star-shaped glycopolymeric photosensitizers using porphyrin-based initiators via ATRP. Incorporating a porphyrin core gave the polymers fluorescence and ROS generation, while adding fructose improved solubility and targeting capabilities. The photosensitizers had high light absorption, singlet oxygen production, specificity, low dark toxicity, and biocompatibility. The glycopolymers with longer sugar arms and higher density showed better uptake on MCF-7 and MDA-MB-468 cells compared to HeLa cells, indicating enhanced targeting capabilities. Inhibition of endocytosis confirmed the importance of the GLUT5 receptor. The resulting polymers exhibited good cytocompatibility under dark conditions and satisfactory PDT under light irradiation. Interestingly, the polymers containing fructose have a GLUT5-dependent elimination effect on the MCF-7 and MDA-MB-468 cells. The intracellular ROS production followed a similar pattern, indicating that the fructose polymer exhibits specific targeting toward cells with GLUT5 receptors

Data_Sheet_1_Association between Helicobacter pylori infection and non-alcoholic fatty liver disease for Asian and non-Asian population: A systematic review and meta-analysis.docx

BackgroundSeveral studies have revealed a positive correlation between a Helicobacter pylori (HP) infection and the risk of non-alcoholic fatty liver disease (NAFLD). This meta-analysis was conducted to explore further the relationship between HP infection and NAFLD in the Asian and non-Asian populations.MethodsRelevant studies published from inception to July 22, 2021, in the following databases: PubMed, EMBASE, the Cochrane library, and Web of Science were comprehensively searched. The odds ratio (OR) and hazard ratio (HR) with a 95% confidence interval (95%CI) were pooled by the random-effects model or fixed-effects model. Additionally, subgroup and sensitivity analyses were performed. The funnel plot and the Egger test were used to estimate publication bias.ResultsThis meta-analysis included 25 studies involving 107,306 participants. Positive associations between HP infection and NAFLD were found both for the Asian (OR = 1.30, 95% CI: 1.13–1.49, P 2 = 94.30%, P 2 = 44.90%, P = 0.09). Moreover, similar results were observed in the Asian female group (OR = 1.31, 95% CI: 1.17–1.46, P 2 = 46.30%, P = 0.07) but not for the Asian male group. Subgroup analyses for the Asian population showed that there were differences in the association among NAFLD diagnosis methods (P ConclusionsThe data obtained in this systematic review and meta-analysis suggested that an HP infection was associated with an increased risk of NAFLD for Asian and non-Asian populations. However, the association was not found for Asian males. Further studies are required to establish the causal association, especially for the non-Asian population.Systematic review registrationIdentifier: CRD42021266871.</p

Tunable Upper Critical Solution Temperatures for Acrylamide Copolymers with Bile Acid Pendants

Acrylamide derivatives of bile acids are chosen as a hydrophobic comonomer to copolymerize with acrylamide via reversible addition and fragmentation chain transfer (RAFT) polymerization to afford a series of copolymers of P­(AAm-<i>co</i>-CAA). These copolymers exhibit a sharp and reversible insoluble–soluble transition in water upon heating to a mixing temperature (<i>T</i>_mix) related to the upper critical solution temperature (UCST). <i>T</i>_mix of these copolymers can be conveniently tuned to a practical temperature range, around 37 °C for biomedical applications. <i>T</i>_mix rises with increasing molar fraction of the bile acid-based acrylamide and increasing concentration of the aqueous solution of the copolymers. The addition of a natural host molecule β-cyclodextrin lowered the <i>T</i>_mix. The insoluble–soluble transition of the copolymers was also evidenced by dynamic light scattering and transmission electron microscopy. The biocompatible nature of the bile acids and β-cyclodextrins may make these copolymers potentially useful for biomedical applications

Proposed model of the SV-associated fGAD65 cleavage mediated by calpain under sustained neuronal stimulation.

<p>Under sustained neuronal stimulation, SV-associated fGAD65 which is in association with VGAT via partnership with HSC70 and CSP is cleaved by hyper-active calpain to liberate the functional part of the enzyme. This resulted in the disruption of the fGAD65-VGAT functional coupling process, largely reducing the releasable pool of GABA loaded SVs. The GABA generated by SV-associated fGAD65 is shown in magenta; GABA generated by fGAD67 is shown in teal. The stars on GAD67 and GAD65 represent the active states of the enzymes. GAD67 is activated by dephosphorylation, whereas GAD65 is active in its phosphorylated state. Certain areas of the pathway which are directly affected by calpain-mediated cleavage of fGAD65 are shown in red crosses. The sequence of events leading to liberation of tGAD65 is discussed in the text.</p

Dual-Responsive Capsules with Tunable Low Critical Solution Temperatures and Their Loading and Release Behavior

Dual-responsive capsules sensitive to pH and temperature changes were successfully prepared by grafting random copolymer brushes of 2-(2-methoxyethoxy)­ethyl methacrylate (MEO₂MA) and oligo­(ethylene glycol) methacrylate (OEGMA) from polydopamine (Pdop)-coated SiO₂ via a surface-initiated atom-transfer radical polymerization (SI-ATRP) method with subsequent removal of the SiO₂ core. The uptake and release properties of the resulting capsules are highly affected by changes in the pH values and temperature of the solution. The capsules can take up cationic dye rhodamine 6G (Rh6G) at high pH and <i>T</i> < LCST but not at low pH and <i>T</i> > LCST. In contrast, the capsules can release Rh6G at pH < 7 and temperature below the LCST, but release is less efficient under the opposite conditions. This dual-responsive property was also observed for the anionic dye methyl orange

Time dependent differential expression of GAD65 and GAD67 mRNA upon exposure to 100 mM KCl in primary rat neuronal cell cultures.

<p>A. Representative gel image of GAD65 and GAD67 mRNA separated on a 1.5% agarose gel. Lane 1: Control; Lanes 2–5: 10 min, 1 hr, 4 hr and 8 hr exposure to 100 mM KCl respectively. GAD65 and GAD67 mRNA were differentially regulated under the same conditions of exposure to 100 mM KCl for different time points as indicated in lanes 2–5. B. Quantitative analyses of GAD65 and GAD67 mRNA expression shown as % of control (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033002#pone-0033002-g004" target="_blank">Fig. 4B</a>, Ctrl). Values are mean of ± SEM (n = 4); <i>^##P</i><0.05 statistically significant differences between GAD67 mRNA expression of 10 min exposure group and the control. <i>*P</i><0.05 statistically significant differences between GAD65 mRNA expression of 1 hr and 4 hr exposure groups with the control respectively. <i>**P</i><0.005 is the statistically significant difference between GAD65 mRNA expression between 8 hr exposure group and the control.</p

Time dependent cleavage of fGAD65 and corresponding cell viability upon exposure to 100 mM K⁺ stimulation in primary rat neuronal cultures.

<p>E17 primary rat neuronal cell cultures at 11 DIV were exposed to 100 mM KCl for different time intervals as shown. <b>A.</b> Representative immuno-blot analysis of fGAD65 cleavage post 100 mM KCl treatment (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033002#pone-0033002-g003" target="_blank">Fig. 3A</a>, lanes 2–5). Lane 1 represents the untreated control. <b>B.</b> Quantitative analysis of fGAD65 cleavage in primary rat neuronal cells expressed as % of control is shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033002#pone-0033002-g003" target="_blank">Fig. 3B</a>. Values are mean of ± SEM (n = 3); <i>*P</i><0.001 is the statistically significant differences between the levels of expression of fGAD65 in 1 hr, 4 hr and 8 hr treatment groups and the control group respectively; <i>^##P</i><0.005 and <i>^#P</i><0.05 are statistically significant differences between the levels of expression of tGAD65 in the 1 hr, 4 hr and 8 hr treatment groups with the control group respectively. <b>C.</b> Cell viability of rat primary neuronal cells in culture under similar conditions as in Expt. 3A, which promoted fGAD65 cleavage. Values are mean of ± SEM (n = 4); <i>*P</i><0.05 is the statistically significant difference between 10 min exposure and the control group. <i>*P</i><0.001 is the statistically significant differences between 1 hr, 4 hr and 8 hr treatment with the control group respectively.</p

Cleavage of SV-associated fGAD65 as a function of KCl concentration:

<p><b>A.</b> Representative immuno-blot demonstrating the isolation of enriched SVs, relatively free from any contaminating cytosolic fractions, other than that of Golgi and ER fractions, as indicated by immuno-blotting against synaptosophysin (SV marker), calnexin (ER marker) and 58K Protein (Golgi marker). <b>B.</b> Representative immuno-blot demonstrating cleavage of SV-associated fGAD65 directly on the SVs, on account of a dose-dependent KCl stimulation. <b>C.</b> Quantitative densitometric comparison, expressed as relative percentage with respect to SVs, of the levels of expression of fGAD65 and synaptophysin in SVs vs Cyt (cytosolic) fractions. Values are mean of ± SEM (n = 3). *<i>P</i><0.05 and <i>**P</i><0.001 are statistically significant differences in the levels of expression between fGAD65 and synaptophysin in the SV fractions when compared tocyt fractions. <b>D.</b> Densitometric analyses of the changes in the expressions of fGAD65 and tGAD65 in the SV fractions. Untreated SVs served as a control. Data points are mean of ± SEM (n = 3). <i>*P</i><0.05 and <i>^#P</i><0.05 are statistically significant differences between 50 mM KCl treatment group and the control group respectively. **P<0.005 and ##P<0.005 are statistically significant differences between 100 mM KCl group and the control group.</p