The Anti-Biofilm Properties of Phloretin and Its Analogs against Porphyromonas gingivalis and Its Complex Flora.

Porphyromonas gingivalis is crucial for the pathogenesis of periodontitis. This research investigated the effects of the fruit-derived flavonoid phloretin and its analogs on the growth of pure P. gingivalis and the flora of P. gingivalis mixed with the symbiotic oral pathogens Fusobacterium nucleatum and Streptococcus mitis. The results showed that the tested flavonoids had little effect on the biofilm amount of pure P. gingivalis, but significantly reduced the biofilm amount of mixed flora to 83.6~89.1%. Biofilm viability decreased to 86.7~92.8% in both the pure- and mixed-bacterial groups after naringenin and phloretin treatments. SEM showed that phloretin and phlorizin displayed a similar and remarkable destructive effect on P. gingivalis and the mixed biofilms. Transcriptome analysis confirmed that biofilm formation was inhibited by these flavonoids, and phloretin significantly regulated the transcription of quorum sensing. Phlorizin and phloretin reduced AI-2 activity to 45.9% and 55.4%, respectively, independent of the regulation of related gene transcription. This research marks the first finding that these flavonoids possess anti-biofilm properties against P. gingivalis and its intricate bacterial community, and the observed performance variations, driven by structural differences, underscore the existence of intriguing structure-activity relationships.

The Effect of Conjunctival Flap Transplantation, Pterygium Excision, and Scleral Fixation Surgery in Treating Pterygium Combined with Conjunctival Laxity and Its Impact on Postoperative Complications.

Objective: Pterygium and conjunctival laxity are common ocular conditions that can significantly affect visual comfort and quality of life. Therefore, it is essential to investigate ways to treat these problems. This study aimed to compare the effectiveness of same-stage trapezoidal conjunctival flap transplantation, pterygium excision, and scleral fixation surgery versus staged pterygium excision, crescentic conjunctiva excision, and scleral fixation surgery in treating pterygium combined with conjunctival laxity. The study also aimed to evaluate the impact of these surgical techniques on postoperative complications. Methods: From June 2019 to May 2021, 90 patients (90 eyes) with pterygium combined with conjunctival laxity were included in this study and were randomly divided into two groups (A and B) using a simple number table method. Group A underwent same-stage trapezoidal conjunctival flap transplantation, pterygium excision, and scleral fixation surgery, while group B underwent staged pterygium excision, crescentic conjunctiva excision, and scleral fixation surgery. The International Ocular Surface Disease Index (OSDI), degree of conjunctival laxity excision, changes in ocular tear film dynamics, recurrence rate, and postoperative complications were compared between the two groups. Results: The results showed that different surgical methods for pterygium and conjunctivochalasis did not significantly improve the symptoms and quality of life of patients. This suggests that more intensive research is needed to find more effective treatments. Therefore, the risks and benefits should be carefully considered when selecting ophthalmologic surgery, OSDI scores and fluorescein staining results of both groups were trending downward after surgery, while the breakup time of the tear film and height of the tear meniscus was increasing but there was no significant difference in the above indicators (P > .05). However, there was no significant difference in the above indicators between the two groups before surgery, at 1, 3, and 6 months, and at 1 year after surgery (P > .05). There was also no significant difference in the degree of conjunctival laxity excision between the two groups at 1 and 3 months after surgery (P > .05). Finally, there was no significant difference in the healing time of the conjunctiva and recurrence rates between the two groups (P > .05). The results showed that different surgical methods for pterygium and conjunctivochalasis did not significantly improve the symptoms and quality of life of patients. This suggests that more intensive research is needed to find more effective treatments. Therefore, the risks and benefits should be carefully considered when selecting ophthalmologic surgery. Conclusion: The results of this study showed no significant differences between surgical techniques, making monitoring and management of complications after surgery even more critical. Patients need to be carefully watched for possible complications such as infection, discomfort, and inflammation. Doctors and medical teams should be alert in advance and take appropriate measures to deal with these problems in a timely manner to ensure the success of the operation and the comfort of the patient. By monitoring and proactively managing potential complications, unnecessary pain and complexity can be reduced, thereby improving patient experience and outcomes. Additionally, the study had several limitations, including a small sample size, a limited study period, and failure to consider other potential factors. These limitations need to be addressed in future studies to validate and extend the results of this study. In conclusion, same-stage trapezoidal conjunctival flap transplantation, pterygium excision, and scleral fixation surgery is an effective treatment for patients with pterygium combined with conjunctival laxity, which can improve their visual function and ocular tear film dynamics. However, careful monitoring and management of postoperative complications are necessary.

Highly efficient whole-cell biosynthesis and cytotoxicity of esculin esters.

Esculin is a polyphenol with multiple bioactivities and poor lipophilicity. Therefore, a whole-cell catalytic strategy for esculin acylation was developed to improve its lipophilicity. A total of 12 strains were tested, among which Pseudomonas stutzeri exhibited the highest catalytic activity and mono-acylated regioselectivity. The conversion reached the highest level of 92.7 % at 24 h under the optimal conditions, when vinyl acetate was used as an acyl donor. The catalytic ability of P. stutzeri remained above 60 % after three cycles. Subsequently, five esculin esters with different lengths of fatty chains were synthesized and structurally identified. Of them, esculin-6'-O-octanoate, esculin-6'-O-laurate, and esculin-6'-O-myristate exhibited cytotoxicity on LO2 cells by inducing apoptosis and necrosis. The cytotoxicity of these three esters may attribute to their membrane-disrupting properties. This study provides a novel whole-cell biocatalytic strategy for the acylation of esculin and insight for application of esculin esters as a food additive or drug.

Transformable nanoparticles triggered by cancer-associated fibroblasts for improving drug permeability and efficacy in desmoplastic tumors.

Cancer-associated fibroblasts (CAFs) are important barriers for nanoparticles (NPs) to deeply penetrate into tumors and severely limit the antitumor efficacy of nanomedicines. Herein, we proposed a CAF-triggered transformable drug delivery system based on a cleavable peptide responsive to fibroblast activation protein-α (FAP-α) specifically overexpressed on the surface of CAFs. The NPs were composed of cationic poly(amidoamine) (PAMAM) dendrimers cross-linked by our designed peptide, a chemotherapeutical drug was incorporated onto PAMAM using disulfide bonds and finally, hyaluronic acid (HA) was conjugated to improve the tumor targetability as well as biocompatibility through electrostatic interactions. These NPs had an initial size of ∼200 nm and negative zeta potential favorable for stable blood circulation; however, after docking with CAFs, they dissociated into smaller NPs and exposed the relative positive surface charge to facilitate penetration and enter the tumor cells together with CAFs. An interesting finding was that this system intracellularly released different levels of drugs in these two kinds of cells, which was beneficial for the disruption of the stromal barrier and increasing the local drug accumulation. Our investigation confirmed that the constructed system could alleviate the biological barriers and hold promising therapeutic efficiency for desmoplastic solid tumors.

Copper sulfide nanoparticle-based localized drug delivery system as an effective cancer synergistic treatment and theranostic platform.

Localized cancer treatment with combination therapy has attracted increasing attention for effective inhibition of tumor growth. In this work, we introduced diffusion molecular retention (DMR) tumor targeting effect, a new strategy that employed transferrin (Tf) modified hollow mesoporous CuS nanoparticles (HMCuS NPs) to undergo extensive diffuse through the interstitium and tumor retention after a peritumoral (PT) injection. Herein, HMCuS NPs with strong near-infrared (NIR) absorption and photothermal conversion efficiency could serve as not only a drug carrier but also a powerful contrast agent for photoacoustic imaging to guide chemo-phototherapy. The iron-dependent artesunate (AS), which possessed profound cytotoxicity against tumor cell, was used as model drug. As a result, this AS loaded Tf-HMCuS NPs (AS/Tf-HMCuS NPs) system could specially target to tumor cells and synchronously deliver AS as well as irons into tumor to achieve enhanced antitumor activity. It was found that AS/Tf-HMCuS NPs was taken up by MCF-7 cells via Tf-mediated endocytosis, and could effectively convert NIR light into heat for photothermal therapy as well as generated high levels of reactive oxygen species (ROS) for photodynamic therapy. In addition, in vivo antitumor efficacy studies showed that tumor-bearing mice treated with AS/Tf-HMCuS NPs through peritumoral (PT) injection under NIR laser irradiation displayed the strongest inhibition rate of about 74.8%, even with the reduced frequency of administration. Furthermore, to demonstrate DMR, the optical imaging, photoacoustic tomography and immunofluorescence after PT injection were adopted to track the behavior of AS/Tf-HMCuS NPs in vivo. The results exhibited that Tf-HMCuS NPs prolonged the local accumulation and retention together with slow vascular uptake and extensive interstitial diffusion, which was consistent with the biodistribution studies of AS/Tf-HMCuS NPs. Therefore, the approach of localized delivery through DMR combined with multi-mechanism therapy may be a promising method for cancer treatment. STATEMENT OF SIGNIFICANCE: In recent years, localized cancer treatment using different biomaterials has attracted increasing attention for effective inhibition of tumor growth. However, it is still challenging for this kind of system to achieve a high drug loading, overcome biological barriers from the site of injection to the site of action, and combine synergetic therapy with diagnosis without adversely affecting the formation process. This study provides a localized diffusion molecular retention (DMR) tumor targeting drug delivery system based on hollow mesoporous copper sulfide nanoparticles (HMCuS NPs) entrapment of anticancer drug for the first time, which can achieve high drug loading, improve local drug accumulation and retention, accomplish synergistic combination of chemo-phototherapy, and finally enhance antitumor effect. In addition, HMCuS NPs also possesses the property suitable for photoacoustic imaging, which could offer us a theranostic platform.