The structure of a self-assembly formed from a cationic azobenzene derivative, 4-cholesterocarbonyl-4'-(N,N,N-triethylamine butyloxyl bromide) azobenzene (CAB) and surfactant sodium dodecyl sulfate ...(SDS) in aqueous solution was studied by cryo-TEM and synchrotron radiation small-angle X-ray scattering (SAXS). Both unilamellar and multilamellar vesicles could be observed. CAB in vesicles were capable to undergo reversible trans-to-cis isomerization upon UV or visible light irradiation. The structural change upon UV light irradiation could be catched by SAXS, which demonstrated that the interlamellar spacing of the cis-multilamellar vesicles increased by 0.2-0.3 nm. Based on this microstructural change, the release of rhodamine B (RhB) and doxorubicin (DOX) could be triggered by UV irradiation. When incubated NIH 3T3 cells and Bel 7402 cells with DOX-loaded CAB/SDS vesicles, UV irradiation induced DOX release decreased the viability of both cell lines significantly compared with the non-irradiated cells. The in vitro experiment indicated that CAB/SDS vesicles had high efficiency to deliver loaded molecules into cells. The in vivo experiment showed that CAB/SDS vesicles not only have high drug delivery efficiency into rat retinas, but also could maintain high drug concentration for a longer time. CAB/SDS catanionic vesicles may find potential applications as a smart drug delivery system for controlled release by light.
Intracellular tau accumulation forming neurofibrillary tangles is hallmark pathology of Alzheimer's disease (AD), but how tau accumulation induces synapse impairment is elusive. By overexpressing ...human full‐length wild‐type tau (termed hTau) to mimic tau abnormality as seen in the brain of sporadic AD patients, we find that hTau accumulation activates JAK2 to phosphorylate STAT1 (signal transducer and activator of transcription 1) at Tyr701 leading to STAT1 dimerization, nuclear translocation, and its activation. STAT1 activation suppresses expression of N‐methyl‐D‐aspartate receptors (NMDARs) through direct binding to the specific GAS element of GluN1, GluN2A, and GluN2B promoters, while knockdown of STAT1 by AAV‐Cre in STAT1flox/flox mice or expressing dominant negative Y701F‐STAT1 efficiently rescues hTau‐induced suppression of NMDAR expression with amelioration of synaptic functions and memory performance. These findings indicate that hTau accumulation impairs synaptic plasticity through JAK2/STAT1‐induced suppression of NMDAR expression, revealing a novel mechanism for hTau‐associated synapse and memory deficits.
Synopsis
Tau accumulation, one hallmark of Alzheimer's disease, induces synaptic impairment by activating JAK2/STAT1 signaling, which transcriptionally suppresses N‐methyl‐D‐aspartate receptors. Downregulation of STAT1 ameliorates synaptic function and memory performance in mice.
Accumulation of hTau triggers JAK2‐dependent STAT1 dimerization, activation and nuclear translocation.
STAT1 activation directly suppresses N‐methyl‐D‐aspartate receptor expression.
Downregulation of STAT1 rescues hTau‐induced N‐methyl‐D‐aspartate receptor suppression.
Tau accumulation, one hallmark of Alzheimer's disease, induces synaptic impairment by activating JAK2/STAT1 signaling, which transcriptionally suppresses N‐methyl‐D‐aspartate receptors. Downregulation of STAT1 ameliorates synaptic function and memory performance in mice.
To investigate the molecular etiology of low sperm quality in patients with intractable spermatocystitis, spermatozoa samples from patients with persistent hematospermia undergoing transurethral ...seminal vesiculoscopy and healthy volunteers were utilized. Spermatozoa samples were collected from the seminal vesicles through transurethral seminal vesiculoscopy or by masturbation ejaculation. Sperm quality was analyzed by a WLJY-9000 color semen analysis system. Measurement of tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) in the seminal plasma was performed using enzyme-linked immunosorbent assay (ELISA). Measurement of H2O2 in the seminal plasma was performed with a hydrogen peroxide kit. The protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and phosphorylated-Nrf2 (p-Nrf2) were measured by western blot analysis and immunofluorescence assays. Low sperm quality parameters and increased levels of inflammatory cytokines (TNFα, IL-6, and H2O2) in the seminal plasma were detected among the semen samples from the patients with persistent hematospermia. Nrf2 and p-Nrf2 were strongly expressed in the nucleus and periphery of human sperm cells, according to the results of the immunofluorescence assays. The protein levels of Nrf2 and p-Nrf2 were significantly lower in the spermatozoa samples from patients with persistent hematospermia than in those from healthy volunteers with normal sperm motility. The results suggested that Nrf2 signaling might play a role in the low sperm quality of patients with intractable spermatocystitis.
A novel microsphere drug delivery system of ivermectin (IVM) using hydrophobic protein zein was prepared by the phase separation method and characterized by a scanning electron microscope and laser ...light scattering particle size analyzer. Releases of model drug IVM from zein microspheres, tabletted microspheres and pepsin degradation of tabletted microspheres were also performed in vitro to investigate the mechanism of model drug release. The results show that the zein microspheres and tabletted microspheres are suitable for use as a sustained-release form of IVM. The microspheres may also be useful in drug targeting system since the diameter of the microspheres is appropriate for phagocytosis by macrophages. Moreover, the release of IVM from enzymatic degraded tabletted microspheres shows a zero-order release, implying a potential application in tissue engineering for preparing scaffold, which is composed of microspheres encapsulating bioactive components for stimulating cell differentiation and proliferation.
A new aporphine, 3-hydroxyhernandonine (
) and a new lignin, 4'-
-demethyl-7-
-methyldehydropodophyllotoxin (
), have been isolated from the root wood of
, together with thirteen known compounds (
⁻
...). The structures of these compounds were determined through mass spectrometry (MS) and spectroscopic analyses. The known isolate, 2-
-methyl-7-oxolaetine (
), was first isolated from natural sources. Among the isolated compounds, 3-hydroxyhernandonine (
), 4'-
-demethyl-7-
-methyldehydropodophyllotoxin (
), hernandonine (
), oxohernangerine (
), and oxohernagine (
) displayed inhibition (IC
values ≤5.72 μg/mL) of superoxide anion production by human neutrophils in response to formyl-l-methionyl-l-leucyl-l-phenylalanine/cytochalasin B (fMLP/CB). In addition, 3-hydroxyhernandonine (
), 4'-
-demethyl-7-
-methyldehydropodophyllotoxin (
), oxohernangerine (
), and oxohernagine (
) suppressed fMLP/CB-induced elastase release with IC
values ≤5.40 μg/mL.
α-Zein, a storage protein in corn endosperm, could be purified easily and in large amounts. In this study, α-zein was incorporated into phospholipid–cholesterol (PC–Chol) liposomes. The maximal ...amount of α-zein incorporated in the liposome was 0.05% (mol/mol) and the PC:Zein molar ratio was near 2400. At this level of zein insertion, the phase transition temperature of the lipid bilayer was little affected, but the leakage of doxorubicin (DOX) from the PC–Chol liposome became obviously slower when α-zein was added at a higher temperature than the phase transition temperature. Cryogenic transmission electron micrographs of the PC–Chol–Zein liposome showed that adjacent membranes in multilamellar vesicles were often aligned at a regular interval of about 7 nm. Data from synchrotron small-angle X-ray scattering of the PC–Chol–Zein liposome indicated the formation of the multilamellar structure with an intermembrane interval of 7.2 nm, whereas no homogeneous membrane alignment was observed in the absence of zein. The present observation can be well explained by supposing that α-zein takes on such an elongated conformation that it penetrates through two adjacent membrane layers. This feature seems to be compatible with a recently proposed superhelical structural model of α-zein. Meanwhile, experiments with the fluorescent-labeled α-zein showed that the PC–Chol–Zein liposome could be uptaken by an intact cell and localized in some specialized area (possibly endosomes) within the cell instead of being diffusely distributed in the cell. Thus, the PC–Chol–Zein liposome seems to act as an interesting biomembrane model and may be applicable as a drug delivery system.
Exposure to UV radiation may cause harmful effects to the skin such as damage, aging and cancer, which can be prevented by using sunscreens. Here, two azobenzene derivatives, ...4-cholesterocarbonyl-4'-(
,
,
-triethylaminebutyloxyl bromide) azobenzene (CAB) and 4-cholesterocarbonyl-4'-(
,
-diethylaminebutyloxyl) azobenzene (ACB) were studied as reusable sunscreen candidates. Biocompatibility studies including apoptosis, cytotoxicity and
phototoxicity revealed that the two compounds were rather safe, except ACB, which showed a weak phototoxicity
. Both CAB and ACB have good UV absorption capacity not only in their solution state (dimethylsulfoxide, DMSO) but also in the cosmetic cream state. A commercial sunscreen, avobenzone was decomposed upon UV irradiation and lost its UV protection ability, while that of CAB and ACB could be quickly recovered upon visible light irradiation, implying that they can serve as a new type of reusable sunscreen.
The zein films, were prepared for culturing human liver cells (HL-7702) and mice fibroblast cells (NIH3T3), while the Corning microplate and polylactic acid (PLA) were chosen as controls. The surface ...morphology of zein films prepared by two different methods was studied by scanning electron microscope (SEM), which revealed that the zein films were composed of particles of diameter 100–500 and 500–2500
nm, respectively. The biocompatibility of zein films was assessed by attachment, extensibility and proliferation of cells on them. Our study indicated that over 60% of both HL-7702 cells and NIH3T3 cells could attach to the Corning microplate, zein films and PLA at 3
h after seeding. The concentration and particle sizes for preparing zein films did not seem to affect the proliferation of the cells tested. There were no significant differences in the proliferation of both HL-7702 cells and NIH3T3 cells between the Corning microplate and two kinds of zein films, except that the zein film composed of smaller particles at the lowest concentration exhibited a very good ability for proliferation of both the cells, while PLA was a poor matrix in the latter period of the cell proliferation. This preliminary study demonstrates that zein is a promising biomaterial with good biocompatibility for the development of tissue engineering.
Four-dimensional (4D) printing is a promising technology that provides solutions for compelling needs in various fields. Most of the reported 4D printed systems are based on the temporal shape ...transformation of printed subjects. Induction of temporal heterogenicity in functions in addition to shape may extend the scope of 4D printing. Herein, we report a 4D printing approach using plant protein (zein) gel inspired by the amyloid fibrils formation mechanism. The printing of zein gel in a specialized layered-Carbopol supporting bath with different water concentrations in an ethanol-water mixture modulates hydrophobic and hydrogen bonding that causes temporal changes in functions. The part of the construct printed in a supporting bath with higher water content exhibits higher drug loading, faster drug release and degradation than those printed in the supporting bath with lower water content. Tri-segment conduit and butterfly-shaped construct with two asymmetrical wings are printed using this system to evaluate biomedical function as nerve conduit and drug delivery system. 4D printed conduits are also effective as a drug-eluting urethral stent in the porcine model. Overall, this study extends the concept of 4D printing beyond shape transformation and presents an approach of fabricating specialized baths for 4D printing that can also be extended to other materials to obtain 4D printed medical devices with translational potential.
Display omitted
•Expanding scope of 4D printing beyond shape morphing.•Preparation of printable amyloid-inspired zein gel.•Preparation of specialized layered supporting bath with gradient water concentration to tune molecular interactions of zein.•Temporal control over drug loading, drug release rate, porosity, and degradation rate of printed constructs.
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