RESUMEN

The spin-orbit charge transfer intersystem crossing (SOCT-ISC) photophysical process has shown great potential for constructing heavy-atom-free photosensitizers (PSs) for photodynamic therapy (PDT) of tumors. However, for almost all such PSs reported to date, the SOCT-ISC is driven by the acceptor-excited photoinduced electron transfer (a-PeT). In this work, for the first time the donor-excited photoinduced electron transfer (d-PeT)-driven SOCT-ISC mechanism is utilized to construct the heavy-atom-free PSs for PDT of tumors by directly installing the electron-deficient N-alkylquinolinium unit (as an electron acceptor) into the meso-position of the near-infrared (NIR) distyryl Bodipy chromophore (as an electron donor). In the less polar environment, the PSs exist as the monomer and promote the production of singlet oxygen (1O2) (Type-II) relying on the d-PeT-driven population of the triplet excited state via SOCT-ISC, whereas in the aqueous environment, they exist as nanoaggregates and induce the generation of superoxides (O2-•) and hydroxyl radicals (HO•) (Type-I) via the d-PeT-driven formation of the delocalized charge-separated state. The PSs could rapidly be internalized into cancer cells and induce the simultaneous production of intracellular 1O2, O2-•, and HO• upon NIR light irradiation, endowing the PSs with superb photocytotoxicity with IC50 values up to submicromolar levels whether under normoxia or under hypoxia. Based on the PSs platform, a tumor-targetable PS is developed, and its abilities in killing cancer cells and in ablating tumors without damage to normal cells/tissues under NIR light irradiation are verified in vitro and in vivo. The study expands the design scope of PSs by introducing the d-PeT conception, thus being highly valuable for achieving novel PSs in the realm of tumor PDT.

Asunto(s)

Fotoquimioterapia , Fármacos Fotosensibilizantes , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/efectos de la radiación , Humanos , Ratones , Animales , Transporte de Electrón/efectos de los fármacos , Oxígeno Singlete/metabolismo , Oxígeno Singlete/química , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Compuestos de Boro/química , Compuestos de Boro/farmacología , Compuestos de Boro/efectos de la radiación , Línea Celular Tumoral , Rayos Infrarrojos , Supervivencia Celular/efectos de los fármacos , Hipoxia Tumoral/efectos de los fármacos , Ratones Endogámicos BALB C

RESUMEN

Anoectochilus roxburghii is a well-known and valuable traditional Chinese herb due to various medicinal and functional benefits. In-depth investigation is necessary to discover active ingredients and expand its application. In this study, four new compounds (1-4) along with ten known compounds (5-14) were isolated from the ethanol extract of A.roxburghii. Their structures were elucidated by spectroscopic data interpretation. The isolates were screened for their inhibitory activities on the production of NO in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Among them, compounds 5, 6, 9, 10, 12, 13 and 14 exhibited significant anti-inflammatory activity through inhibiting the release of NO.

RESUMEN

The one-pot immobilization of halophilic phenylalanine dehydrogenase from marine microorganism with metal ions modified reduced graphene oxide (CRGO) material was studied. Phenylalanine dehydrogenase was from Bacillus nanhaiensi and expressed with a C-terminal His-tag. Investigation of CRGO, CRGO-PEI, CRCO-Mn, and CRGO-PEI-Mn for one-pot purification and immobilization of phenylalanine dehydrogenase from crude enzyme solution was carried out. Enzyme activity yield rate achieved 80.0% by immobilization with CRCO-Mn, and the loading capacity was 6.7 mg/mg. Manganese ion coordination greatly improved the selectivity of the CRGO for the target His-tagged enzyme. Furthermore, the effect of NaCl concentration on the immobilization was investigated, which the loading capacity of CRGO-PEI and CRGO-Mn-PEI was increased by 10.7% and 30.6% with 1 M NaCl, respectively. The adsorption curves of crude enzyme one-pot immobilized by CRGO-Mn and purified enzyme immobilized by CRGO-Mn were similar. Therefore, one-pot immobilization strategy is promising for industrial application with advantages such as high efficiency and low cost, which shorten the pipelines for enzyme discovery towards industrial applications through the establishing of marine enzyme collections.

Asunto(s)

Bacillus , Enzimas Inmovilizadas , Aminoácido Oxidorreductasas , Bacillaceae , Bacillus/metabolismo , Estabilidad de Enzimas , Enzimas Inmovilizadas/metabolismo , Grafito , Concentración de Iones de Hidrógeno , Cloruro de Sodio

RESUMEN

Based on spin-orbit charge transfer intersystem crossing mechanism, two heavy-atom-free photosensitizers (PSs) BDP1/BDP2 with absorption maxima at 506 nm/660 nm were constructed for photodynamic therapy (PDT). The long triplet state lifetimes and large singlet oxygen quantum yields, coupled with the mitochondria-targeted feature, made them highly phototoxic toward cancer cells. Moreover, the PDT-promoted cell apoptosis could be monitored by an obvious fluorescence off-on response of the two PSs due to the concomitant activation of extensive mitophagy, thus facilitating timely therapeutic feedback to avoid under- or over-treatment. Importantly, such design allows the activatable PSs Glu-BDP1/Glu-BDP2 to be fabricated by attaching γ-glutamyl, a substrate of γ-glutamyltranspeptidase, to the alkoxyaniline unit of BDP1/BDP2, and their ability in either selectively killing cancer cells over normal cells or in ablating implanted tumour without damage to healthy tissue was demonstrated.

Asunto(s)

Fotoquimioterapia , Fármacos Fotosensibilizantes , Fluorescencia , Mitocondrias , Fármacos Fotosensibilizantes/farmacología , Oxígeno Singlete

RESUMEN

Objective: The study aims to investigate the functional outcome of the lateral approach for insertional Achilles tendinitis (IAT) with Haglund deformity. Methods: From January 2016 to September 2019, 14 cases of IAT with Haglund deformity that resisted conservative treatment received surgery in our department. A lateral approach was used to debride the bony and soft tissue and reattach the insertion of the Achilles tendon. The Visual Analog Scale (VAS), American Orthopedic Foot and Ankle Score (AOFAS), and Victorian Institute of Sport Tendon Study Group-Achilles Tendinopathy score (VISA-A) were used to evaluate clinical outcomes. Result: The mean patient age was 39.57 years at the time of surgery. The mean follow-up was 14.74 months. The mean VAS score significantly decreased from 4.86 ± 0.86 preoperatively to 1.21 ± 1.58 postoperatively (P < 0.001). The mean AOFAS score significantly improved from 66.64 ± 6.23 preoperatively to 90.21 ± 11.50 postoperatively (P < 0.001). The mean preoperative and the last follow-up VISA-A were 66 (range 56.75-69.25) and 86 (range 75.75-97.00) points, respectively (P < 0.05). Conclusion: The lateral approach was effective and safe for IAT with Haglund deformity. Moreover, the mid-term functional outcome was promising. Level of Clinical Evidence: IV.

RESUMEN

Graphene oxide-based nanomaterials are promising for enzyme immobilization due to the possibilities of functionalizing surface. Polyethylenimine-grafted graphene oxide was constructed as a novel scaffold for immobilization of formate dehydrogenase. Compared with free formate dehydrogenase and graphene oxide adsorbed formate dehydrogenase, thermostability, storage stability, and reusability of polyethylenimine-grafted graphene oxide-formate dehydrogenase were enhanced. Typically, polyethylenimine-grafted graphene oxide-formate dehydrogenase remained 47.4% activity after eight times' repeat reaction. The immobilized capacity of the polyethylenimine-grafted graphene oxide was 2.4-folds of that of graphene oxide. Morphological and functional analysis of polyethylenimine-grafted graphene oxide-formate dehydrogenase was performed and the assembling mechanism based on multi-level interactions was studied. Consequently, this practical and facile strategy will likely find applications in biosynthesis, biosensing, and biomedical engineering.