Acid-sensing ion channel 1a modulation of apoptosis in acidosis-related diseases: implications for therapeutic intervention.

Acid-sensing ion channel 1a (ASIC1a), a prominent member of the acid-sensing ion channel (ASIC) superfamily activated by extracellular protons, is ubiquitously expressed throughout the human body, including the nervous system and peripheral tissues. Excessive accumulation of Ca2+ ions via ASIC1a activation may occur in the acidified microenvironment of blood or local tissues. ASIC1a-mediated Ca2+­induced apoptosis has been implicated in numerous pathologies, including neurological disorders, cancer, and rheumatoid arthritis. This review summarizes the role of ASIC1a in the modulation of apoptosis via various signaling pathways across different disease states to provide insights for future studies on the underlying mechanisms and development of therapeutic strategies.

Loading drugs into liposomes by temperature up-down cycle procedure with controllable results fitting prediction by mathematical and thermodynamic process.

Liposomes are a useful carrier for delivering drugs but rarely make a poorly water-soluble drug (PWSD) realize its therapeutic potential. A key barrier lies in that, by conventional methods, PWSD is mainly loaded just in liposome bilayer membranes, which rarely provide sufficient room to accommodate drugs satisfying clinical therapy. In this investigation, a novel procedure of temperature up-down cycle (TUDC) was developed for loading PWSDs into the liposome interiors instead of bilayer membranes to hold enough agents. In particular, the TUDC procedure renders PWSDs such as curcumin (Cur) entrapment purposely controllable, as evidenced by the encapsulation efficiency (EE) of Cur varies nearly from 0% to 100% in response to changes the determinant factors of the procedure. In addition, several mathematical equations that could calculate the loading efficiency by TUDC were established and proved, when combined with thermodynamic process, able to successfully predict the loading results through including thermodynamic parameters, such as temperature and deduced drug solubility, thus remarkably cutting down the laborious experiments and enhancing liposome development efficiency. Cryo-TEM, SAXS, XRD and DSC tests proved that TUDC is feasible to load a PWSD into PEG-liposomes but rendering the drug in the amorphous state. Thus, the novel TUDC procedure and the established mathematical and thermodynamic process may provide a useful tool to promote the development of liposome products.

Preparation of Nested g-C3N4 Fiber Surrounding Graphene Oxide and Its Photocatalytic Degradation of Rhodamine B.

g-C3N4 and graphene oxide (GO) are simultaneously introduced into electrospun polyacrylonitrile (PAN) nanofibers to form a nested structure. By Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS), g-C3N4 has been perfectly introduced into the PAN@GO nanofiber membrane and affects the porosity of the fiber itself. Comparison of nested electrospinning PAN/PAN@GO and different proportions of PAN@g-C3N4/PAN@GO nanofibers has a different effect on reducing the concentration and absorption of rhodamine B (RhB) dye in the visible region. Combined with the advantages of g-C3N4 and GO and the performance of fibers in the photocatalytic process, the optimal nested PAN@g-C3N4/PAN@GO nanofibers were selected. These results indicate that the nested PAN@g-C3N4/PAN@GO nanofibers with high photocatalytic activity have great potential in the treatment of printing and dyeing wastewater.

Covering Aluminum Oxide Nanoparticles with Biocompatible Materials to Efficiently Deliver Subunit Vaccines.

Subunit vaccines have advantages of good safety, minimal reactogenicity, and high specificity. However, subunit vaccines also show a crucial disadvantage of poor immunogenicity and, therefore, are often formulated with an adjuvant carrier to form a vaccine adjuvant-delivery system (VADS) to enhance their efficacies. Alums, the coarse aggregates of the insoluble aluminum salts, are the conventional adjuvants and have been widely used in clinical vaccines for a long time. Unfortunately, alums also show two main drawbacks of low potency in eliciting cellular immunity, and high reactogenicity to cause unwanted inflammations. Therefore, herein the phospholipid bilayer-coated aluminum oxide nanoparticles (PLANs) and the PEGylated PLANs (PEG-PLANs) were engineered as a VADS to overcome the drawbacks of both subunit vaccines and coarse alums, while synergizing their functions. In vitro experiments demonstrated that, unlike the micron-sized alums, the nanosized PLANs and PEG-PLANs loaded with model antigen of ovalbumin (OVA) showed a high safety profile and were able to promote APC (antigen-presenting cell) uptake and engender lysosome escape for enhancing the MHC (major histocompatibility complex)-I-antigen display. Subcutaneously administered to mice, PLANs and, especially, PEG-PLANs smoothly trafficked into the draining lymph nodes, wherein the densely clustered immune cells were activated in substantial numbers, leading to robust immunoresponses and efficient production of the anti-antigen antibodies and CD8+ T cells. Thus, the aluminum-based nanocarriers, especially the PEG-PLANs, are a promising VADS possessing the potential of eliciting strong and comprehensive immunity against pathogens.

Deciphering the Adsorption Behavior of Volatile Organic Compounds with Electrospun Polyacrylonitrile/Molecular Sieve Nanocomposites.

In this study, a new type of molecular sieve/polyacrylonitrile fiber (M-PAN) was prepared by electrospinning to adsorb atmospheric volatile organic compounds (VOCs). The suitable content of molecular sieve in nanocomposites was also determined for achieving maximum VOCs adsorption capacity. SEM, TEM and N2 adsorption/desorption analyzer were performed for characterization of the surface morphology, structural properties, surface area and pore size. A part of molecular sieve is exposed on the fiber surface where VOCs can be adsorbed efficiently in a short time. Acetone was used as a challenge pollutant to evaluate the adsorption of VOCs at different recycling times and types of electrospinning nanofibers. The adsorption capacity of 6M-PAN (60% weight of molecular sieve) nanofiber reached 58.2 µg g-1 and the reused nanofibers nearly had the same adsorption capacity as the newly prepared nanofibers after several times of recirculation.

Liposomes used as a vaccine adjuvant-delivery system: From basics to clinical immunization.

Liposomes are widely utilized as a carrier to improve therapeutic efficacy of agents thanks to their merits of high loading capacity, targeting delivery, reliable protection of agents, good biocompatibility, versatile structure modification and adjustable characteristics, such as size, surface charge, membrane flexibility and the agent loading mode. In particular, in recent years, through modification with immunopotentiators and targeting molecules, and in combination with innovative immunization devices, liposomes are rapidly developed as a multifunctional vaccine adjuvant-delivery system (VADS) that has a high capability in inducing desired immunoresponses, as they can target immune cells and even cellular organelles, engender lysosome escape, and promote Ag cross-presentation, thus enormously enhancing vaccination efficacy. Moreover, after decades of development, several products developed on liposome VADS have already been authorized for clinical immunization and are showing great advantages over conventional vaccines. This article describes in depth some critical issues relevant to the development of liposomes as a VADS, including principles underlying immunization, physicochemical properties of liposomes as the immunity-influencing factors, functional material modification to enhance immunostimulatory functions, the state-of-the-art liposome VADSs, as well as the marketed vaccines based on a liposome VADS. Therefore, this article provides a comprehensive reference to the development of novel liposome vaccines.

Improved immunogenicity of a self tumor antigen by covalent linkage to CD40 ligand.

The interaction between the CD40 ligand (CD40L) and CD40 on antigen-presenting cells (APCs) is critical in promoting humoral and cellular immune responses. Agonistic anti-CD40 monoclonal antibody and soluble CD40L can act as powerful adjuvants to promote vaccination, but usually require repeated high-dose treatment. In this study, we demonstrate that the adjuvant effect of CD40L can be greatly improved by directly linking the antigen to CD40L. We constructed a fusion protein (Id-CD40L) consisting of the extracellular domain of CD40L and the idiotype (Id) protein, a weakly immunogenic tumor-specific antigen derived from the murine 38C13 B-cell lymphoma. The soluble Id-CD40L fusion protein retained CD40 binding activity and stimulated CD80 and CD86 upregulation and interleukin (IL)-12 production by macrophages. Immunization of mice with Id-CD40L without adjuvants resulted in high titers of anti-Id Abs dominated by the IgG1 isotype and protected the mice from subsequent lethal tumor challenge. In a dose-response study, we demonstrated that Id-CD40L elicited anti-Id antibody (Ab) responses in all immunized animals, even at a dose as low as 0.5 microg. Immunization with free Id and an IgG-CD40L fusion protein, which was identical in structure to Id-CD40L but lost the Id determinant, resulted in significant lower anti-Id responses, indicating that physical linkage between the tumor antigen and CD40L was required for the optimal immune response. These results demonstrate that fusing CD40L to a candidate antigen can greatly improve the adjuvant activity of CD40L. This approach may be useful in developing vaccines for a variety of malignant and infectious diseases.