Bo Wang

In this nanotechnology era, nanostructures play a crucial role in the investigation of novel functional nanomaterials. Complex nanostructures and their corresponding fabrication techniques provide powerful tools for the development of high-performance functional materials. In this study, advanced micro-nanomanufacturing technologies and composite micro-nanostructures were applied to the development of a new type of pharmaceutical formulation, aiming to achieve rapid hemostasis, pain relief, and antimicrobial properties. Briefly, an approach combining a electrohydrodynamic atomization (EHDA) technique and reversed-phase solvent was employed to fabricate a novel beaded nanofiber structure (BNS), consisting of micrometer-sized particles distributed on a nanoscale fiber matrix. Firstly, Zein-loaded Yunnan Baiyao (YB) particles were prepared using the solution electrospraying process. Subsequently, these particles were suspended in a co-solvent solution containing ciprofloxacin (CIP) and hydrophilic polymer polyvinylpyrrolidone (PVP) and electrospun into hybrid structural microfibers using a handheld electrospinning device, forming the EHDA product E3. The fiber-beaded composite morphology of E3 was confirmed through scanning electron microscopy (SEM) images. Fourier-transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) analysis revealed the amorphous state of CIP in the BNS membrane due to the good compatibility between CIP and PVP. The rapid dissolution experiment revealed that E3 exhibits fast disintegration properties and promotes the dissolution of CIP. Moreover, in vitro drug release study demonstrated the complete release of CIP within 1 min. Antibacterial assays showed a significant reduction in the number of adhered bacteria on the BNS, indicating excellent antibacterial performance. Compared with the traditional YB powders consisting of Chinese herbs, the BNS showed a series of advantages for potential wound dressing. These advantages include an improved antibacterial effect, a sustained release of active ingredients from YB, and a convenient wound covering application, which were resulted from the integration of Chinese herbs and Western medicine. This study provides valuable insights for the development of novel multiscale functional micro-/nano-composite materials and pioneers the developments of new types of medicines from the combination of herbal medicines and Western medicines.

Thioredoxin (Trx) plays a critical role in maintaining redox balance in various cells and exhibits anti-oxidative, anti-apoptotic, and anti-inflammatory effects. However, whether exogenous Trx can inhibit intracellular oxidative damage has not been investigated. In previous study, we have identified a novel Trx from the jellyfish Cyanea capillata, named CcTrx1, and confirmed its antioxidant activities in vitro. Here, we obtained a recombinant protein, PTD-CcTrx1, which is a fusion of CcTrx1 and protein transduction domain (PTD) of HIV TAT protein. The transmembrane ability and antioxidant activities of PTD-CcTrx1, and its protective effects against H₂O₂-induced oxidative damage in HaCaT cells were also detected. Our results revealed that PTD-CcTrx1 exhibited specific transmembrane ability and antioxidant activities, and it could significantly attenuate the intracellular oxidative stress, inhibit H₂O₂-induced apoptosis, and protect HaCaT cells from oxidative damage. The present study provides critical evidence for application of PTD-CcTrx1 as a novel antioxidant to treat skin oxidative damage in the future.

Vibrio vulnificus (V. vulnificus) infection-associated multiple antibiotic resistance has raised serious public health concerns. Recently, nanosponges (NSs) have been expected to provide innovative platforms for addressing antibacterial and drug-resistant challenges by targeting various pore-forming toxins (PFTs). In the present study, we constructed NSs to explore the effects and possible mechanism of recombinant V. vulnificus hemolysin (rVvhA)-induced injuries. In vitro, NSs significantly reversed rVvhA-induced apoptosis and necrosis, and improved toxin-induced intracellular reactive oxygen species (ROS) production, adenosine triphosphate (ATP) depletion, and apoptosis signaling pathway disruption. To explore the clinical translation potential of NSs, we established VvhA-induced septicemia and wound infection mouse models, respectively, and further found NSs could notably attenuate rVvhA-induced acute toxicity and septicemia-associated inflammation, as well as local tissue damage. In a conclusion, NSs showed excellent protective effects against rVvhA-induced toxicity, thus providing useful insights into addressing the rising threats of severe V. vulnificus infections.

Sea snake venom is extremely toxic, and it can induce severe respiratory failure and cause high mortality. The most effective first aid treatment for sea snake bites is to inject antivenom as soon as possible. However, in China, there are only four types of terrestrial snake antivenoms, none of which are effective in the treatment of sea snake bites. In order to develop an antivenom for the dominant species of sea snakes in Chinese seas, Hydrophis curtus venom (HcuV) was chosen as the antigen to immunize horses. From immune plasma, a high-titer Hydrophis curtus antivenom (HcuAV) was prepared. In vitro assessment showed that HcuAV had a cross-neutralizing capacity against HcuV and Hydrophis cyanocinctus venom (HcyV). In vivo assessment indicated that HcuAV injection could significantly improve the survival rates of the HcuV and HcyV envenomated mice (0% to 100% and 87.5%, respectively) when it was injected at a sufficient amount within the shortest possible time. In addition, HcuAV could also effectively alleviate multiple organ injuries caused by HcuV. These results provide experimental support for the future clinical application of HcuAV.

In this study, for the first time, we reported a jellyfish-derived Kazal-type serine protease inhibitor, named CcKPI1, from Cyanea capillata. CcKPI1 has a calculated molecular mass of 19.02 kDa and contains three typical Kazal domains. The soluble recombinant CcKPI1 (rCcKPI1) was successfully purified. rCcKPI1 exhibited significant inhibitory activities against elastase, subtilisin A and proteinase K, but not against trypsin or chymotrypsin. The kinetic studies showed that all of the inhibitory effects of rCcKPI1 were competitive, indicating that it may be a microbial serine protease inhibitor and can exhibit antimicrobial activity. As predicted, rCcKPI1 directly bound to various microorganisms, including the Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis, Gram-negative bacteria Escherichia coli, marine pathogenic vibrios Vibrio vulnificus, Vibrio cholerae, Vibrio natriegens, Vibrio mimicus, Vibrio alginolyticus and Vibrio parahaemolyticus, and fungi Candida albicans, Candida parapsilokis and Candida glabrata. In addition, rCcKPI1 inhibited the growth of most of the tested microorganisms that it bound to. These findings indicate that CcKPI1 possesses marked antibacterial and antifungal activities and may play an important role in the immune defence of C. capillata, providing a novel view for the understanding of the immune system of jellyfish and also facilitating future research on antimicrobial agents from marine natural products.