Self-Assembled Core-Shell Nanoscale Coordination Polymer Nanoparticles Carrying a Sialyltransferase Inhibitor for Cancer Metastasis Inhibition.

Despite hypersialylation of cancer cells together with a significant upregulation of sialyltransferase (ST) activity contributes to the metastatic cascade at multiple levels, there are few dedicated tools to interfere with their expression. Although transition state-based ST inhibitors are well-established, they are not membrane permeable. To tackle this problem, herein, we design and construct long-circulating, self-assembled core-shell nanoscale coordination polymer (NCP) nanoparticles carrying a transition state-based ST inhibitor, which make the inhibitor transmembrane and potently strip diverse sialoglycans from various cancer cells. In the experimental lung metastasis and metastasis prevention models, the nanoparticle device (NCP/STI) significantly inhibits metastases formation without systemic toxicity. This strategy enables ST inhibitors to be applied to cells and animals by providing them with a well-designed nanodelivery system. Our work opens a new avenue to the development of transition state-based ST inhibitors and demonstrates that NCP/STI holds great promise in achieving metastases inhibition for multiple cancers.

Effect of polymerized human placenta hemoglobin on hemodynamic parameter and cardiac function in a rat hemorrhagic shock model.

To investigate whether polymerized human placenta hemoglobin (PolyPHb) improved hemodynamic parameter recovery and cardiac function after hemorrhagic shock, a mean arterial pressure (MAP) of 30 mmHg was maintained for 60min. Then, all the rats were randomly resuscitated with hetastarch (HES), shed blood (Whole Blood), or PolyPHb (PolyPHb). The MAP was greatly improved by PolyPHb, but it was still lower than that of the Whole Blood group. Meanwhile, the cardiac function and enzyme releases in the PolyPHb group were similar to the HES group. Therefore, our findings suggest that PolyPHb moderately improved hemodynamic recovery and provided little cardioprotective effect in hemorrhagic shock.

Biomechanical analysis of effective mandibular en-masse retraction using Class II elastics with a clear aligner: a finite element study.

BACKGROUND: This study aimed to evaluate the displacement and stress distribution of mandibular dentition by various positions of the Class II elastics during en-masse retraction in clear aligner therapy. METHODS: Models including a mandibular dentition (without first premolars), periodontal ligament (PDL), mandible, as well as attachments, aligners and buttons were constructed and imported into Ansys Workbench 2019 (ANSYS, USA) to generate the three-dimensional (3D) finite element model. Six combinations were created: (1) aligner alone (control), (2)-(5) Class II elastics with buttons placed on the mesiobuccal (MB), distobuccal (DB), mesiolingual (ML) and distolingual (DL) surface of the mandibular first molar, and (6) Class II elastics with a button on the aligner corresponding to the mesiobuccal surface of the mandibular first molar (AMB). The elastic force was set to 2 N for simulations. RESULTS: The central incisors appeared lingual tipping in the six models. The lingual crown movement of the central incisors was 0.039 mm, 0.034 mm, 0.034 mm, 0.042 mm, 0.041 mm, and 0.034 mm for control model, MB model, DB model, ML model, DL model, and AMB model, respectively. The first molars showed mesial tipping in the six models. The mesial movement of the mesiobuccal cusps of the first molars was 0.045 mm, 0.060 mm, 0.063 mm, 0.048 mm, 0.051 mm, and 0.055 mm for control model, MB model, DB model, ML model, DL model, and AMB model, respectively. CONCLUSIONS: Class II elastics reduced lingual tipping of anterior teeth but aggravated mesial tipping of posterior teeth. Mesiolingual elastics developed minimum mesial tipping of the posterior teeth. When Class II elastics are required, attaching elastics on the mesiolingual surface of the mandibular first molar is recommended to prevent mandibular anchorage loss.

Construction of multilayer films with bactericidal and long-term antitumor drug release properties as a non-vascular stent coating for therapy in obstruction.

The construction of antibacterial and antitumor coatings could offer effective routes to improve the therapeutic effects of non-vascular stents for unresectable obstructions caused by malignant tumours. Herein, polyelectrolyte multilayers have been explored as bactericidal coatings with controlled antitumor drug release. To solve the challenges of loading and controlled release of small-molecule chemotherapeutic drugs in polyelectrolyte multilayers, the antitumor drug doxorubicin (DOX) was chemically conjugated onto polyethylenimine via cis aconitic anhydride (pH-sensitive linker), thus obtaining the polycation prodrug PEI-CA-DOX. Alginate sodium was oxidized (O-Alg) and mixed with DOX to prepare the O-Alg-DOX complex as a polyanion. QCM-D and contact angle tests were used to monitor and verify the progressive build-up of the PEI-CA-DOX/O-Alg-DOX multilayer films, which show a linear growth. The in vitro antibacterial tests indicated that the PEI-CA-DOX-terminated PEI-CA-DOX/O-Alg-DOX multilayers could kill the bacteria effectively. As-such multilayers also presented a long-term sustained DOX release behaviour in PBS due to the combination of slow release in PEI-CA-DOX and fast release in the O-Alg-DOX complex. The as-designed PEI-CA-DOX/O-Alg-DOX multilayers with combined antibacterial and antitumor properties may have great potential for applications in non-vascular stent coatings for palliative treatment of obstruction caused by malignant tumours.