Interaction of ovalbumin with lutein dipalmitate and their effects on the color stability of marigold lutein esters extracts.

In this study, the interaction of ovalbumin with lutein dipalmitate and the effect of ovalbumin on marigold lutein esters extracts were investigated. Lutein dipalmitate quenched the fluorescence of ovalbumin by static quenching. Binding and thermodynamic parameters proved that lutein dipalmitate bound to ovalbumin spontaneously by van der Waals force and hydrogen bond, and the complex stoichiometry was 1:1. Through three-dimensional fluorescence spectroscopy, Fourier transform infrared spectroscopy and circular dichroism experiments, the conformation of ovalbumin was unfolded, and alteration in the ovalbumin secondary structure induced by lutein dipalmitate was observed. The results of transmission electron microscopy and particle size revealed that there were spherical and nano-sized aggregates in the ovalbumin-lutein dipalmitate system, indicating the lutein dipalmitate not only could bind to ovalbumin at molecular level, but also promote the aggregation of ovalbumin. Additionally, the addition of ovalbumin had a positive effect on the stability of marigold lutein esters extracts.

Neferine Protects against Hypoxic-Ischemic Brain Damage in Neonatal Rats by Suppressing NLRP3-Mediated Inflammasome Activation.

Hypoxic-ischemic encephalopathy (HIE) is recognized as the main cause of neonatal death, and efficient treatment strategies remain limited. Given the prevalence of HIE and the associated fatality, further studies on its pathogenesis are warranted. Oxidative stress and neuroinflammatory injury are two important factors leading to brain tissue injury and nerve cell loss in HIE. Neferine, an alkaloid extracted from lotus seed embryo, exerts considerable effects against several diseases such as cancers and myocardial injury. In this study, we demonstrated the neuroprotective effect of neferine on HIE and hypothesized that it involves the inhibition of neuronal pyroptosis, thereby ameliorating neurological inflammation and oxidative stress. We demonstrated that the mRNA levels of proteins associated with pyroptosis including caspase-1, the caspase adaptor ASC, gasdermin D, interleukin- (IL-) 18, IL-1ß, and some inflammatory factors were significantly increased in neonatal HIBD model rats compared to those in the control group. The increase in these factors was significantly suppressed by treatment with neferine. We stimulated PC12 cells with CoCl2 to induce neuronal HIBD in vitro and investigated the relationship between neferine and pyroptosis by altering the expression of the NLRP3 inflammasome. The overexpression of NLRP3 partially reversed the neuroprotective effect of neferine on HIBD, whereas NLRP3 knockdown further inhibited caspase-1 activation and IL-1ß and IL18 expression. In addition, simultaneous alteration of NLRP3 expression induced changes in intracellular oxidative stress levels after HIBD. These findings indicate that neferine ameliorates neuroinflammation and oxidative stress injury by inhibiting pyroptosis after HIBD. Our study provides valuable information for future studies on neferine with respect to neuroinflammation and pyroptosis.

Multifunctional CuxS- and DOX-loaded AuNR@mSiO2 platform for combined melanoma therapy with inspired antitumor immunity.

Combined antitumor therapies based on nanomedicines have shown efficacy in various tumor models in recent years, overcoming the disadvantages of inefficiency and undesired toxicity of traditional therapies. Herein, we present a copper sulfide- and doxorubicin-loaded gold nanorods@mesoporous SiO2 multifunctional nanocomposite (AuNR@mSiO2@DOX-CuxS-PEG) to integrate chemotherapy, the photothermal properties of AuNRs, and the photodynamic properties of CuxS into a single nanoplatform based on hydrophobic interaction and electrostatic attraction. Upon near-infrared light irradiation, the AuNR@mSiO2@DOX-CuxS-PEG nanocomposites exhibit a synergistic therapeutic effect and inhibit the in situ tumor growth and lung metastasis in a melanoma model. This occurs because of the high photothermal conversion efficiency, boosted intracellular reactive oxygen species production, and excellent doxorubicin (DOX) release, as well as an induced tumor-specific immune response. The inspired antitumor immunity was confirmed by elevated infiltration of activated T cells in tumor tissues and improved maturation and activation of dendritic cells in tumor-draining lymph nodes. This study highlights the superior antitumor therapeutic effect elicited by a multifunctional nanoplatform for skin with in situ melanoma and lung metastasis inhibition, indicating its satisfactory clinical application prospects.

Polydopamine-Encapsulated Perfluorocarbon for Ultrasound Contrast Imaging and Photothermal Therapy.

Biomedical nanoplatforms have been widely investigated for ultrasound (US) imaging and cancer therapy. Herein, perfluorocarbon (PFC) is encapsulated into biocompatible polydopamine (PDA) to form a theranostic nanosystem, followed by the modification of polyethylene glycol (PEG) to stabilize the nanoparticle via a facile one-pot method. Under 808 nm near-infrared laser irradiation, PDA can generate hyperthermia to transform PFC droplets to bubbles with high US imaging sensitivity. The US imaging detection of the PFC-PDA-PEG nanosystem is achievable in a time span of up to 25 min in vitro at a low US frequency and mechanical index, manifesting a US imaging performance for in vivo application. Moreover, tumor cells incubated with the nanosystem are ablated effectively under laser irradiation at 808 nm. The results illustrate the potential of the PDA-based theranostic agent in US imaging-guided photothermal therapy of tumor.

Au Nanocage-Strengthened Dissolving Microneedles for Chemo-Photothermal Combined Therapy of Superficial Skin Tumors.

For superficial skin tumors (SST) with high incidence, surgery and systemic therapy are relatively invasive and possible to cause severe side effect, respectively. Yet, topical therapy is confronted with the limited transdermal capacity because of the stratum corneum barrier layer of skin. Therefore, it is crucial to develop a highly effective and minimally invasive alternative transdermal approach for treating SST. Here, we developed gold nanocage (AuNC)- and chemotherapeutic drug doxorubicin (DOX)-loaded hyaluronic acid dissolving microneedle (MN) arrays. The loaded AuNCs are not only reinforcers to enhance the mechanical strength of the MNs, but also effective agents for photothermal therapy to obtain effective transdermal therapy for SST. The resultant MNs can effectively penetrate the skin, dissolve in the skin and release cargoes within the tumor site. Photothermal effect of AuNCs initiated by near-infrared laser irradiation combined with the chemotherapy effect of DOX destroyed tumors synergistically. Moreover, we verified the potent antitumor effects of the DOX/AuNC-loaded MNs after four administrations to SST-bearing mice without obvious side effects. Therefore, the drug/AuNC-loaded dissolving MN system provides a promising platform for effective, safe, minimally invasive combined treatment of SST.

[Consideration about chemistry, manufacture and control (CMC) key problems in simplified registration of classical traditional Chinese medicine excellent prescriptions].

As an outstanding representative of traditional Chinese medicine(TCM) prescriptions accumulated from famous TCM doctors' clinical experiences in past dynasties, classical TCM excellent prescriptions (cTCMeP) are the most valuable part of TCM system. To support the research and development of cTCMeP, a series of regulations and measures were issued to encourage its simplified registration. There is still a long-way to go because many key problems and puzzles about technology, registration and administration in cTCMeP R&D process are not resolved. Based on the analysis of registration and management regulations of botanical drug products in FDA of USA and Japan, and EMA of Europe, the possible key problems and countermeasures in chemistry, manufacture and control (CMC) of simplified registration of cTCMeP were analyzed on the consideration of its actual situation. The method of "reference decoction extract by traditional prescription" (RDETP) was firstly proposed as standard to evaluate the quality and preparation uniformity between the new developing product under simplified registration and traditional original usages of cTCMeP, instead of Standard Decoction method in Japan. "Totality of the evidence" approach, mass balance and bioassay/biological assay of cTCMeP were emphatically suggested to introduce to the quality uniformity evaluation system in the raw drug material, drug substance and final product between the modern product and traditional decoction.