Peg-IFNα combined with hepatitis B vaccination contributes to HBsAg seroconversion and improved immune function.

PURPOSE: The purpose of this study was to investigate immunological variations between a group that received the hepatitis B vaccine and a non-vaccine group. We focused on a cohort that achieved HBsAg seroclearance after Peg-IFNα treatment of CHB. METHODS: We enrolled twenty-eight individuals who achieved HBsAg seroclearance after Peg-IFNα treatment. They were divided into two groups: a vaccine group (n = 14) and a non-vaccine group (n = 14). We assessed lymphocyte subpopulations, B cell- and T cell-surface costimulatory/inhibitory factors, cytokines and immunoglobulin levels were detected at different time points to explore immune-function differences between both groups. RESULTS: The seroconversion rate in the vaccine group at 24 weeks post-vaccination was 100%, which was significantly higher (p = 0.006) than that of the non-vaccine group (50%). Additionally, more individuals in the vaccine group exhibited anti-HBs levels exceeding 100 IUs/L and 300 IUs/L compared to the non-vaccine group (p < 0.05). The vaccine group demonstrated significantly increase total B cells and class-switched B cells at 24 weeks and plasma cells, CD80+B cells, Tfh cells, and ICOS+Tfh cell at 12 weeks, compared with baseline levels (p < 0.05). Conversely, Bregs (CD24+CD27+ and CD24+CD38high) decreased significantly at 24 weeks (p < 0.05). None of the above changes were statistically significance in the non-vaccine group (p > 0.05). Total IgG increased significantly in the vaccine group, and IL-2, IL-5, and IL-6 concentrations increased significantly at week 24 (p < 0.05). Differences in various types of cytokines and immunoglobulins in the plasma of the non-vaccine group were not significant (p > 0.05). Anti-HBs titers positively correlated with Th1/Th2 cells at 24 weeks (r = 0.448 and 0.458, respectively, p = 0.022 and 0.019, respectively), and negatively with CD24+CD38highBreg cells (r = -0.402, p = 0.042). CONCLUSIONS: After achieving HBsAg seroclearance through Peg-IFNα treatment for CHB, administering the hepatitis B vaccine significantly increased anti-HBs-seroconversion rates and antibody levels. We also observed significant immunological differences between the vaccine and non-vaccine groups. Specifically, the vaccine group exhibited significant increases in B cells, plasma cells, and Tfh cells, while Breg levels was significantly lower. These immunological changes are likely conducive to the production of anti-HBs antibodies. However, in the non-vaccine group, the observed changes were not significantlly significant.

Feasibility evaluation of a Zn-Cu alloy for intrauterine devices: In vitro and in vivo studies.

The comprehensively adopted copper-containing intrauterine devices (Cu-IUDs) present typical adverse effects such as bleeding and pain at the initial stage of post-implantation. The replacement of Cu material is demanded. Zinc and its alloys, the emerging biodegradable materials, exhibited contraceptive effects since 1969. In this work, we evaluated the feasibility of bulk Zn alloys as IUD active material. Using pure Cu and pure Zn as control groups, we investigated the contraceptive performance of Zn-0.5Cu and Zn-1Cu alloys via in vitro and in vivo tests. The results showed that the main corrosion product of Zn-Cu alloys is ZnO from both in vitro and in vivo studies. CaZn2(PO4)2·2H2O is formed atop after long-term immersion in simulated uterine fluid, whereas CaCO3 is generally formed atop after implantation in the rat uterine environment. The cytocompatibility of the Zn-1Cu alloy was significantly higher than that of the pure Zn and pure Cu to the human endometrial epithelial cell lines. Furthermore, the in vivo results showed that the Zn-1Cu alloy presented much improved histocompatibility, least damage and the fastest recovery on endometrium structure in comparison to pure Zn, Zn-0.5Cu and pure Cu. The systematic and comparing studies suggest that Zn-1Cu alloy can be considered as a possible candidate for IUD with great biochemical and biocompatible properties as well as high contraceptive effectiveness. STATEMENT OF SIGNIFICANCE: The existing adverse effects with the intrinsic properties of copper materials for copper-containing intrauterine devices (Cu-IUD) are of concerns in their employment. Such as burst release of cupric ions (Cu2+) at the initial stage of the Cu-IUD. Zinc and its alloys which have been emerging as a potential biodegradable material exhibited contraceptive effects since 1969. In this study, Zn-1Cu alloys displayed significantly improved biocompatibility with human uterus cells and a decreased inflammatory response within the uterus. Therefore, high antifertility efficacy of the Zn-1Cu alloy was well maintained, while the adverse effects are significantly eased, suggesting that the Zn-1Cu alloy is promising for IUD.

Intracellular Self-Immolative Polyprodrug with Near-Infrared Light Guided Accumulation and in Vivo Visualization of Drug Release.

The selective accumulation and real-time monitoring of drug release at tumor site are the key bottlenecks to the clinical translation of polyprodrug. Herein, an intracellular self-immolative polyprodrug (PMTO) is exploited, which not only shows the enhanced cellular internalization and selective accumulation in tumor site under the mild hyperthermia triggered by laser irradiation, but also possesses the self-monitoring drug release ability in vivo. The polyprodrug amphiphiles are synthesized by sequential esterification reaction, and hydrophilic poly(ethylene glycol) serves as blocking agent. On account of the mild hyperthermia produced by PMTO under the laser irradiation at tumor site, the cell membranous permeability increases, resulting in the enhanced cellular internalization and drug accumulation in tumor. After internalized by cells, the self-immolative PMTO nanoparticles can release free mitoxantrone (MTO) in intracellular reductive environment, and ratiometric photoacoustic imaging based on distinct signals between MTO and PMTO is presented to trace the drug release in vivo. Finally, this self-monitoring polyprodrug presents significant tumor suppression efficacy, which exhibits great potential for guiding the clinical medication in cancer treatment.

Feasibility evaluation of a Cu-38 Zn alloy for intrauterine devices: In vitro and in vivo studies.

The existing adverse effects of copper in copper-containing intrauterine devices (Cu-IUDs) have raised concerns regarding their use. These adverse effects include burst release of cupric ions (Cu2+) at the initial stage and an increasingly rough surface of the Cu-IUDs. In this study, we investigated the use of two copper alloys, Cu-38 Zn and H62 as the new upgrading or alternative material for IUDs. Their corrosive properties were studied in simulated uterine fluid (SUF) by using electrochemical methods, with pure Cu as a control. We studied the in vitro long-term corrosion behaviors in SUF, cytotoxicity to uterine cells (human endometrial epithelial cells and human endometrial stromal cells), in vivo biocompatibility and contraceptive efficacy of pure Cu, H62, and Cu-38 Zn. In the first month, the burst release rate of Cu2+ in the Cu-38 Zn group was significantly lower than those in the pure Cu and H62 groups. The in vitro cytocompatibility Cu-38 Zn was better than that of pure Cu and H62. Moreover, Cu-38 Zn showed improved tissue biocompatibility in vivo experiments. Therefore, the contraceptive efficacy of the Cu-38 Zn is still maintained as high as the pure Cu while the adverse effects are significantly eased, suggesting that Cu-38 Zn can be a suitable potential candidate material for IUDs. STATEMENT OF SIGNIFICANCE: The existing adverse effects associated with the intrinsic properties of copper materials for copper-containing intrauterine devices (Cu-IUD) are of concern in their employment. Such as, burst release of cupric ions (Cu2+) at the initial stage and an increasingly rough surface of the Cu-IUD. In this work, Cu alloyed with a high amount of bioactive Zn was used for a Cu-IUD. The Cu-38 Zn alloy exhibited reduced burst release of Cu2+ within the first month compared with the pure Cu and H62. Furthermore, the Cu-38 Zn alloy displayed significantly improved biocompatibility and a much smoother surface. Therefore, high antifertility efficacy of the Cu-38 Zn alloy was well maintained, while the adverse effects are significantly eased, suggesting that the Cu-38 Zn alloy is promising for a Cu-IUD.

Effective easing of the side effects of copper intrauterine devices using ultra-fine-grained Cu-0.4Mg alloy.

Copper intrauterine device is one of the most adopted contraceptive methods with high effectiveness (over 99 %), low cost, spontaneous reversibility and long-lasting usage. However, the side effects induced from the initial burst release of copper ions (Cu2+) hinder the continuation of the Cu-IUD made of Coarse-Grained Copper (CG Cu). We proposed to tailor the bio-corrosion behaviors of better control of Cu2+ release via the addition of bioactive Mg into the Ultra-Fine Grained (UFG) Bulk Cu. Thus, UFG bulk Cu with 0.4 wt.% Mg was produced via equal-channel angular pressing. The microstructures of the UFG Cu-0.4Mg was observed using electron backscatter diffraction and transmission electron microscopy techniques. The in vitro long-term corrosion behaviors in simulated uterine fluid, cytotoxicity to four cell lines, in vivo biocompatibility and contraceptive efficacy were all studied on CG Cu, UFG Cu and UFG Cu-0.4Mg materials. The results demonstrate that both the ultrafine grains and the addition of bioactive Mg into Cu contribute to the suppression of the burst release of Cu2+ in the initial stage and the maintenance of high level Cu2+ in long-term release. Moreover, the UFG Cu-0.4Mg also exhibited much improved cell and tissue biocompatibility from both the in vitro and in vivo evaluations. Therefore, the contraceptive efficacy of UFG Cu-0.4Mg is still maintained as high as the CG Cu and UFG Cu while the side effects are significantly eased, suggesting the high potential of the UFG Cu-0.4Mg alloy as a new upgrading or alternative material for Cu-IUD. STATEMENT OF SIGNIFICANCE: The side effects from burst release of Cu2+ at the initial implantation stage of Cu-containing intrauterine devices (Cu-IUD) is one of the main drawbacks of these devices. In this work, an ultra-fine-grained Cu (UFG Cu) alloyed with a low amount of bioactive Mg was used for a Cu-IUD. The UFG Cu-0.4Mg alloy exhibited suppressed burst release of Cu2+ at initial implantation, while active Cu2+ release for long-term usage was maintained, comparable to coarse-grained pure Cu. Furthermore, the UFG Cu-0.4Mg alloy displayed significantly improved biocompatibility with human uterus cells and a much decreased inflammatory response within the uterus. Therefore, the side effects from Cu-IUD were eased, while high antifertility efficacy of the UFG Cu-0.4Mg alloy was maintained. The UFG Cu-0.4Mg alloy is promising for Cu-IUD.

Aligned Nanofibers from Polypyrrole/Graphene as Electrodes for Regeneration of Optic Nerve via Electrical Stimulation.

The damage of optic nerve will cause permanent visual field loss and irreversible ocular diseases, such as glaucoma. The damage of optic nerve is mainly derived from the atrophy, apoptosis or death of retinal ganglion cells (RGCs). Though some progress has been achieved on electronic retinal implants that can electrically stimulate undamaged parts of RGCs or retina to transfer signals, stimulated self-repair/regeneration of RGCs has not been realized yet. The key challenge for development of electrically stimulated regeneration of RGCs is the selection of stimulation electrodes with a sufficient safe charge injection limit (Q(inj), i.e., electrochemical capacitance). Most traditional electrodes tend to have low Q(inj) values. Herein, we synthesized polypyrrole functionalized graphene (PPy-G) via a facile but efficient polymerization-enhanced ball milling method for the first time. This technique could not only efficiently introduce electron-acceptor nitrogen to enhance capacitance, but also remain a conductive platform-the π-π conjugated carbon plane for charge transportation. PPy-G based aligned nanofibers were subsequently fabricated for guided growth and electrical stimulation (ES) of RGCs. Significantly enhanced viability, neurite outgrowth and antiaging ability of RGCs were observed after ES, suggesting possibilities for regeneration of optic nerve via ES on the suitable nanoelectrodes.