Cleavage and Noncleavage Chemistry in Reactive Oxygen Species (ROS)-Responsive Materials for Smart Drug Delivery.

The design and development of advanced drug delivery systems targeting reactive oxygen species (ROS) have gained significant interest in recent years for treating various diseases, including cancer, psychiatric diseases, cardiovascular diseases, neurological diseases, metabolic diseases, and chronic inflammations. Integrating specific chemical bonds capable of effectively responding to ROS and triggering drug release into the delivery system is crucial. In this Review, we discuss commonly used conjugation linkers (chemical bonds) and categorize them into two groups: cleavable linkers and noncleavable linkers. Our goal is to clarify their unique drug release mechanisms from a chemical perspective and provide practical organic synthesis approaches for their efficient production. We showcase numerous significant examples to demonstrate their synthesis routes and diverse applications. Ultimately, we strive to present a comprehensive overview of cleavage and noncleavage chemistry, offering insights into the development of smart drug delivery systems that respond to ROS.

STING-Targeted PET Imaging for Specific Detection and Therapeutic Monitoring of Myocarditis.

Imaging strategies for the specific detection and therapeutic monitoring of myocarditis are still lacking. Stimulator of interferon genes (STING) is a signal transduction molecule involved in an innate immune response. Here, we evaluated the feasibility of the recently developed STING-targeted radiotracer [18F]FBTA for positron emission tomography (PET) imaging to detect myocardial inflammation and monitor treatment in myocarditis mice. [18F]FBTA-PET imaging was performed in myocarditis mice and normal mice to verify the specificity of [18F]FBTA for the diagnosis of myocarditis. We also performed PET imaging in mice with myocarditis treated to verify the ability of [18F]FBTA in therapeutic monitoring. The expression of STING and inflammatory cell types was confirmed by flow cytometry and immunohistochemistry. [18F]FDG-PET imaging of myocarditis was used as a contrast. [18F]FBTA-PET imaging showed that the average radioactive uptake was significantly higher in the hearts of the myocarditis group than in the control group. STING was highly overexpressed in cardiac inflammatory cells, including macrophages, dendritic cells (DCs), and T cells. However, there was no significant difference in cardiac radiotracer uptake of [18F]FDG between the myocarditis group and the control group. Moreover, cardiac uptake of [18F]FBTA was significantly reduced in cyclosporin A-treated myocarditis mice and myocardial STING expression was also significantly reduced after the treatment. Overall, we showed that a STING-targeted PET tracer [18F]FBTA can be used to monitor changes in the inflammatory microenvironment in myocarditis. Besides, [18F]FBTA-PET is also suitable for real-time monitoring of myocarditis treatment, representing a promising diagnostic and therapeutic monitoring approach for myocarditis.

Harnessing antimicrobial peptides in endodontics.

Endodontic therapy includes various procedures such as vital pulp therapy, root canal treatment and retreatment, surgical endodontic treatment and regenerative endodontic procedures. Disinfection and tissue repair are crucial for the success of these therapies, necessitating the development of therapeutics that can effectively target microbiota, eliminate biofilms, modulate inflammation and promote tissue repair. However, no current endodontic agents can achieve these goals. Antimicrobial peptides (AMPs), which are sequences of amino acids, have gained attention due to their unique advantages, including reduced susceptibility to drug resistance, broad-spectrum antibacterial properties and the ability to modulate the immune response of the organism effectively. This review systematically discusses the structure, mechanisms of action, novel designs and limitations of AMPs. Additionally, it highlights the efforts made by researchers to overcome peptide shortcomings and emphasizes the potential applications of AMPs in endodontic treatments.

Efficacy of peptide-based enamel coatings in the prevention of demineralization using fixed orthodontic brackets in a rat model.

INTRODUCTION: White spot lesions (WSLs) represent a prominent pathology encountered during orthodontic treatment, originating from enamel demineralization induced by the accumulation of bacterial biofilms. The previously developed bioinspired enamel coating form of self-assembling antimicrobial peptide D-GL13K exhibited antimicrobial activity and enhanced acid impermeability, offering a potential solution to prevent demineralization. The primary aim of this investigation is to assess the in vivo anti-demineralization properties and biocompatibility of the D-GL13K coating. METHODS: A rat model was developed to assess the antimicrobial enamel coating during fixed orthodontic treatment. The anti-demineralization efficacy attributed to the D-GL13K coating was evaluated by employing optical coherence tomography, Vickers microhardness testing, and scanning electron microscopy. The biocompatibility of the D-GL13K coating was investigated through histologic observations of vital organs and tissues using hematoxylin and eosin. RESULTS: The D-GL13K coating demonstrated significant anti-demineralization effects, evidenced by reduced demineralization depth analyzed through optical coherence tomography and enhanced Vickers hardness than in the noncoated control group, showcasing the coating's potential to protect teeth from WSLs. Scanning electron microscopy analysis further elucidated the diminished enamel damage observed in the group treated with D-GL13K. Importantly, histologic examination of vital organs and tissues using hematoxylin and eosin staining revealed no overt disparities between the D-GL13K coated group and the noncoated control group. CONCLUSIONS: The D-GL13K enamel coating demonstrated promising anti-demineralization and biocompatibility properties in a rat model, thereby suggesting its potential for averting WSLs after orthodontic interventions. Further research in human clinical settings is needed to evaluate the coating's long-term efficacy.

Evaluation of 1,2-diacyl-3-acetyl triacylglycerol production in Yarrowia lipolytica.

Plants produce many high-value oleochemical molecules. While oil-crop agriculture is performed at industrial scales, suitable land is not available to meet global oleochemical demand. Worse, establishing new oil-crop farms often comes with the environmental cost of tropical deforestation. The field of metabolic engineering offers tools to transplant oleochemical metabolism into tractable hosts while simultaneously providing access to molecules produced by non-agricultural plants. Here, we evaluate strategies for rewiring metabolism in the oleaginous yeast Yarrowia lipolytica to synthesize a foreign lipid, 3-acetyl-1,2-diacyl-sn-glycerol (acTAG). Oils made up of acTAG have a reduced viscosity and melting point relative to traditional triacylglycerol oils making them attractive as low-grade diesels, lubricants, and emulsifiers. This manuscript describes a metabolic engineering study that established acTAG production at g/L scale, exploration of the impact of lipid bodies on acTAG titer, and a techno-economic analysis that establishes the performance benchmarks required for microbial acTAG production to be economically feasible.

Effects of bepridil on early cardiac development of zebrafish.

Bepridil is a commonly used medication for arrhythmia and heart failure. It primarily exerts hemodynamic effects by inhibiting Na+/K+ movement and regulating the Na+/Ca2+ exchange. In comparison to other Ca2+ inhibitors, bepridil has a long half-life and a complex pharmacology. Additionally, it is widely used in antiviral research and the treatment of various diseases. However, the toxicity of this compound and its other possible effects on embryonic development are unknown. In this study, we investigated the toxicity of bepridil on rat myocardial H9c2 cells. After treatment with bepridil, the cells became overloaded with Ca2+ and entered a state of cytoplasmic vacuolization and nuclear abnormality. Bepridil treatment resulted in several morphological abnormalities in zebrafish embryo models, including pericardium enlargement, yolk sac swelling, and growth stunting. The hemodynamic effects on fetal development resulted in abnormal cardiovascular circulation and myocardial weakness. After inhibiting the Ca2+ transmembrane, the liver of zebrafish larvae also displayed an ectopic and deficient spatial location. Additionally, the results of the RNA-seq analysis revealed the detailed gene expression profiles and metabolic responses to bepridil treatment in zebrafish embryonic development. Taken together, our study provides an important evaluation of antiarrhythmic agents for clinical use in prenatal heart patients.

Transient and Dissipative Host-Guest Hydrogels Regulated by Consumption of a Reactive Chemical Fuel.

The transient self-assembly of molecules under the direction of a consumable fuel source is fundamental to biological processes such as cellular organization and motility. Such biomolecular assemblies exist in an out-of-equilibrium state, requiring continuous consumption of high energy molecules. At the same time, the creation of bioinspired supramolecular hydrogels has traditionally focused on associations occurring at the thermodynamic equilibrium state. Here, hydrogels are prepared from cucurbit[7]uril host-guest supramolecular interactions through transient physical crosslinking driven by the consumption of a reactive chemical fuel. Upon action from this fuel, the affinity and dynamics of CB[7]-guest recognition are altered. In this way, the lifetime of transient hydrogel formation and the dynamic modulus obtained are governed by fuel consumption, rather than being directed by equilibrium complex formation.

USP53 activated by H3K27 acetylation regulates cell viability, apoptosis and metabolism in esophageal carcinoma via the AMPK signaling pathway.

Esophageal carcinoma (ESCA) is a leading cause of cancer death worldwide, despite an overall decline in the incidence of new cases. However, knowledge of gene expression signatures for risk and prognosis stratification of ESCA is inadequate. Thus, identifying novel molecular biomarkers and therapeutic targets for ESCA might improve its prognosis and treatment. The current study investigated the role of ubiquitin-specific peptidase 53 (USP53), a member of the USP family that exhibits deubiquitinating activity, in ESCA and showed that USP53 is downregulated in ESCA tissues, indicating poor prognosis. USP53 suppresses the proliferation and growth of ESCA cells in vitro and in vivo, whereas its knockdown exerts opposite effects. AMP-activated protein kinase inhibitor reverses the effects of USP53 knockdown. USP53 also inhibits glycolysis, oxidative metabolism and mitochondrial dynamics. H3K27 acetylation increases USP53 expression by binding to its promoter region. Our study reveals that USP53 is activated by H3K27 acetylation and suppresses ESCA progression by regulating cell growth and metabolism. USP53 is therefore a promising target for ESCA treatment.

Polymeric Microneedle Arrays with Glucose-Sensing Dynamic-Covalent Bonding for Insulin Delivery.

The ongoing rise in diabetes incidence necessitates improved therapeutic strategies to enable precise blood glucose control with convenient device form factors. Microneedle patches are one such device platform capable of achieving therapeutic delivery through the skin. In recent years, polymeric microneedle arrays have been reported using methods of in situ polymerization and covalent crosslinking in microneedle molds. In spite of promising results, in situ polymerization carries a risk of exposure to toxic unreacted precursors remaining in the device. Here, a polymeric microneedle patch is demonstrated that uses dynamic-covalent phenylboronic acid (PBA)-diol bonds in a dual role affording both network crosslinking and glucose sensing. By this approach, a pre-synthesized and purified polymer bearing pendant PBA motifs is combined with a multivalent diol crosslinker to prepare dynamic-covalent hydrogel networks. The ability of these dynamic hydrogels to shear-thin and self-heal enables their loading to a microneedle mold by centrifugation. Subsequent drying then yields a patch of uniformly shaped microneedles with the requisite mechanical properties to penetrate skin. Insulin release from these materials is accelerated in the presence of glucose. Moreover, short-term blood glucose control in a diabetic rat model following application of the device to the skin confirms insulin activity and bioavailability. Accordingly, dynamic-covalent crosslinking facilitates a route for fabricating microneedle arrays circumventing the toxicity concerns of in situ polymerization, offering a convenient device form factor for therapeutic insulin delivery.

Antibody-Targeted Liposomes for Enhanced Targeting of the Blood-Brain Barrier.

The blood-brain barrier (BBB) hinders therapeutic delivery to the central nervous system (CNS), thereby impeding the development of therapies for brain injury and disease. Receptor-mediated transcytosis (RMT) systems are a promising way to shuttle a targeted therapeutic into the brain. Here, we developed and evaluated an RMT antibody-targeted liposomal system. A previously identified antibody, scFv46.1, that binds to the human and murine BBB and can pass through the murine BBB by transcytosis after intravenous injection was used to decorate the surface of liposomes. Using an in vitro BBB model, we demonstrated the cellular uptake of scFv46.1-modified liposomes (46.1-Lipo). Next, the biodistribution and brain uptake capacity of 46.1-targeted liposomes were assessed after intravenous administration. Our results showed that 46.1-Lipo can lead to increased brain accumulation through targeting of the brain vasculature. Initial rate pharmacokinetic experiments and biodistribution analyses indicated that 46.1-Lipo loaded with pralidoxime exhibited a 10-fold increase in brain accumulation compared with a mock-targeted liposomal group, and this increased accumulation was brain-specific. These studies indicate the potential of this 46.1-Lipo system as a synthetic vehicle for the targeted transport of therapeutic molecules into the CNS.

Efficacy and safety of ligation-assisted endoscopic submucosal resection combined with endoscopic ultrasonography for treatment of rectal neuroendocrine tumors.

OBJECTIVE: Rectal neuroendocrine tumors (R-NETs) usually invade the submucosa, and so complete resection is difficult. The treatment of choice for R-NETs ≤10 mm in size is endoscopic resection, but there is still controversy concerning the best endoscopic method. This study evaluated the efficacy and safety of ligation-assisted endoscopic submucosal resection combined with endoscopic ultrasonography (ESMR-LUS) for treatment of R-NETs. METHODS: We retrospectively analyzed the data of 101 patients with R-NETs ≤10 mm in size who underwent ESMR-LUS (n = 48) or conventional ligation-assisted endoscopic submucosal resection (ESMR-L; n = 53) between May 2019 and September 2021 at the 900th Hospital of Joint Logistics Support Force. Complete resection rate, pathological complete resection rate, procedure time, and adverse events were compared between the two groups of patients. RESULTS: The endoscopic complete resection rate was slightly higher in the ESMR-LUS group than in the ESMR-L group (100 vs. 96.2%, p = .496). The pathological complete resection rate was also slightly higher in the ESMR-LUS group (97.9 vs. 88.7%, p = .152), these findings, though statistically non-significant, have practical clinical significance. Margin involvement was less common in ESMR-LUS patients than in ESMR-L patients (1 vs. 6). Involvement of the lateral resection margin was found one patient in the ESMR-LUS group versus two patients in the ESMR-L group, and deep resection margin involvement in no patient in the ESMR-LUS group versus four patients in the ESMR-L group. Mean procedure time was longer in the ESMR-LUS group than in the ESMR-L group (11.08 ± 1.89 min vs. 9.38 ± 2.09 min, p = .061). Immediate bleeding occurred in two patients in the ESMR-LUS group vs. seven patients in the ESMR-L group. Two patients in the ESMR-L group also suffered perforation; both patients were successfully treated by endoscopy. CONCLUSIONS: ESMR-LUS appears to be a safe and effective technique for removal of small rectal NETs confined to the submucosal layer without metastasis. Further studies are warranted to compare the efficacy and safety of different methods.

Interactions of two enantiomers of a designer antimicrobial peptide with structural components of the bacterial cell envelope.

Antimicrobial peptides (AMPs) have great potential in treating multi-drug resistant bacterial infections. The antimicrobial activity of d-enantiomers is significantly higher than l-enantiomers and sometimes selectively enhanced against Gram-positive bacteria. Unlike phospholipids in the bacterial plasma membrane, the role of other bacterial cell envelop components is often overlooked in the mode of action of AMPs. In this work, we explored the structural interactions between the main different structural components in Gram-negative/Gram-positive bacteria and the two enantiomers of a designer AMP, GL13K. We observed that both l-GL13K and d-GL13K formed self-assembled amyloid-like nanofibrils when the peptides interacted with lipopolysaccharide and lipoteichoic acid, components of the outer membrane of Gram-negative bacteria and cell wall of Gram-positive bacteria, respectively. Another cell wall component, peptidoglycan, showed strong interactions exclusively with d-GL13K and formed distinct laminar structures. This specific interaction between peptidoglycans and d-GL13K might contribute to the enhanced activity of d-GL13K against Gram-positive bacteria as they have a much thicker peptidoglycan layer than Gram-negative bacteria. A better understanding of the specific role of bacterial cell envelop components in the AMPs mechanism of action can guide the design of more effective Gram-selective AMPs.

NEDD4L inhibits cell viability, cell cycle progression, and glutamine metabolism in esophageal squamous cell carcinoma via ubiquitination of c-Myc.

Esophageal squamous cell carcinoma (ESCC) is a common subtype of esophageal cancer with high incidence. Surgery remains the main strategy for treatment of ESCC at early stage. However, the treatment outcome is unsatisfactory. Therefore, finding new therapeutics is of great importance. In the present study, we measured the level of NEDD4L, an ubiquitin protein ligase, in clinical samples and investigated the effects of NEDD4L on cell viability, cell cycle progression, and glutamine metabolism in TE14 cells determined by CCK-8 assay, flow cytometry and biochemical analysis, respectively. The results show that NEDD4L is significantly decreased in ESCC specimens, and its decreased expression is associated with a poor clinical outcome. Overexpression of NEDD4L significantly inhibits cell viability, cell cycle progression, and glutamine metabolism in TE14 cells. Mechanistic study indicates that NEDD4L regulates tumor progression through ubiquitination of c-Myc and modulation of glutamine metabolism. NEDD4L inhibits cell viability, cell cycle progression, and glutamine metabolism in ESCC by ubiquitination of c-Myc to decrease the expressions of GLS1 and SLC1A5. Our findings highlight the importance of NEDD4L/c-Myc signaling in ESCC.

Present status and future directions of intracanal medicaments.

Two fundamental goals of endodontic treatment are to prevent or treat apical periodontitis. From a predictive perspective, several variables can affect the outcome of root canal treatment. Some of these variables depend on intraoperative factors, which include irrigation technique, size of the apical preparation, use of intracanal medicaments or the number of appointments necessary to complete the treatment. However, the outcome may also be affected by host and microbial factors. The intensity of periradicular bone loss or tissue damage, the presence of preoperative pain and associated conditions such as mechanical allodynia and central sensitization, the anatomical complexity of the apical portion of the canal, and the virulence and longevity of the bacterial infection can all have a profound influence on the outcome. Furthermore, numerous medical conditions have been reported to decrease the capability of the immune system to heal the periapical tissues. It is the clinician's responsibility to analyse these variables and incorporate them into the disinfection strategy to maximize the chances of healing. This narrative review will focus on the present status of intracanal medicaments, the clinical indications for their use and future directions for research.

Effects of concentration of sodium hypochlorite as an endodontic irrigant on the mechanical and structural properties of root dentine: A laboratory study.

AIM: The use of high-concentration sodium hypochlorite (NaOCl) as an endodontic irrigant remains controversial because of its potential impact on the fracture strength of endodontically treated teeth. This study evaluated the effects of using different NaOCl concentrations, with 2-min-ethylenediaminetetraacetic acid (EDTA) as the final active irrigant, on the biomechanical and structural properties of root dentine. METHODOLOGY: A new test method, which is more clinically relevant, was utilized to calculate the fracture strength of root dentine. Bovine incisors were used to obtain root dentine discs. The root canals were enlarged to mean diameter of 2.90 mm with a taper of 0.06. The resulting discs were divided into five groups (n = 20) and treated with different concentrations of NaOCl (5.25%, 2.5%, and 1.3%) for 30 min plus 17% EDTA for 2 min. The discs were then loaded to fracture by a steel rod with the same taper through the central hole. The fractured specimens were examined by scanning electron microscopy to evaluate changes in the dimensions of the remaining intertubular dentine and the tubular radius. Micro-hardness was also measured with a Knoop diamond indenter along a radius to determine the depth of dentine eroded by the irrigation. Results were analysed by one-way anova and the Tukey test. The level of significance was set at α = 0.05. RESULTS: The damage by NaOCl increased with its concentration. 5.25% NaOCl greatly reduced the fracture strength of root dentine from 172.10 ± 30.13 MPa to 114.58 ± 26.74 MPa. The corresponding reduction in micro-hardness at the root canal wall was 34.1%. The damages reached a depth of up to 400 µm (p < .05). Structural changes involved the degradation of the intratubular wall leading to enlarged dentinal tubules and the loss of intertubular dentine. Changes in the microstructural parameters showed positive linear relationships with the fracture strength. CONCLUSIONS: With the adjunctive use of EDTA, NaOCl caused destruction to the intratubular surface near the root canal and, consequently, reduced the root dentine's mechanical strength. The higher the concentration of NaOCl, the greater the effect. Therefore, endodontists should avoid using overly high concentration of NaOCl for irrigation to prevent potential root fracture in endodontically treated teeth.

Glucose-Fueled Peptide Assembly: Glucagon Delivery via Enzymatic Actuation.

Nature achieves remarkable function from the formation of transient, nonequilibrium materials realized through continuous energy input. The role of enzymes in catalyzing chemical transformations to drive such processes, often as part of stimuli-directed signaling, governs both material formation and lifetime. Inspired by the intricate nonequilibrium nanostructures of the living world, this work seeks to create transient materials in the presence of a consumable glucose stimulus under enzymatic control of glucose oxidase. Compared to traditional glucose-responsive materials, which typically engineer degradation to release insulin under high-glucose conditions, the transient nanofibrillar hydrogel materials here are stabilized in the presence of glucose but destabilized under conditions of limited glucose to release encapsulated glucagon. In the context of blood glucose control, glucagon offers a key antagonist to insulin in responding to hypoglycemia by signaling the release of glucose stored in tissues so as to restore normal blood glucose levels. Accordingly, these materials are evaluated in a prophylactic capacity in diabetic mice to release glucagon in response to a sudden drop in blood glucose brought on by an insulin overdose. Delivery of glucagon using glucose-fueled nanofibrillar hydrogels succeeds in limiting the onset and severity of hypoglycemia in mice. This general strategy points to a new paradigm in glucose-responsive materials, leveraging glucose as a stabilizing cue for responsive glucagon delivery in combating hypoglycemia. Moreover, compared to most fundamental reports achieving nonequilibrium and/or fueled classes of materials, the present work offers a rare functional example using a disease-relevant fuel to drive deployment of a therapeutic.

Analysis of Triterpenoid Saponins Reveals Insights into Structural Features Associated with Potent Protein Drug Enhancement Effects.

Plant-based saponins are amphipathic glycosides composed of a hydrophobic aglycone backbone covalently bound to one or more hydrophilic sugar moieties. Recently, the endosomal escape activity of triterpenoid saponins has been investigated as a potentially powerful tool for improved cytosolic penetration of protein drugs internalized by endocytic uptake, thereby greatly enhancing their pharmacological effects. However, only a few saponins have been studied, and the paucity in understanding the structure-activity relationship of saponins imposes significant limitations on their applications. To address this knowledge gap, 12 triterpenoid saponins with diverse structural side chains were screened for their utility as endosomolytic agents. These compounds were used in combination with a toxin (MAP30-HBP) comprising a type I ribosome-inactivating protein fused to a cell-penetrating peptide. Suitability of saponins as endosomolytic agents was assessed on the basis of cytotoxicity, endosomal escape promotion, and synergistic effects on toxins. Five saponins showed strong endosomal escape activity, enhancing MAP30-HBP cytotoxicity by more than 106 to 109 folds. These saponins also enhanced the apoptotic effect of MAP30-HBP in a pH-dependent manner. Additionally, growth inhibition of MAP30-HBP-treated SMMC-7721 cells was greater than that of similarly treated HeLa cells, suggesting that saponin-mediated endosomolytic effect is likely to be cell-specific. Furthermore, the structural features and hydrophobicity of the sugar side chains were analyzed to draw correlations with endosomal escape activity and derive predictive rules, thus providing new insights into structure-activity relationships of saponins. This study revealed new saponins that can potentially be exploited as efficient cytosolic delivery reagents for improved therapeutic drug effects.

Dual Self-Assembled Nanostructures from Intrinsically Disordered Protein Polymers with LCST Behavior and Antimicrobial Peptides.

Antimicrobial peptides (AMPs) have attracted great interest as they constitute one of the most promising alternatives against drug-resistant infections. Their amphipathic nature not only provides them antimicrobial and immunomodulatory properties but also the ability to self-assemble into supramolecular nanostructures. Here, we propose their use as self-assembling domains to drive hierarchical organization of intrinsically disordered protein polymers (IDPPs). Using a modular approach, hybrid protein-engineered polymers were recombinantly produced, thus combining designer AMPs and a thermoresponsive IDPP, an elastin-like recombinamer (ELR). We exploited the ability of these AMPs and ELRs to self-assemble to develop supramolecular nanomaterials by way of a dual-assembly process. First, the AMPs trigger the formation of nanofibers; then, the thermoresponsiveness of the ELRs enables assembly into fibrillar aggregates. The interplay between the assembly of AMPs and ELRs provides an innovative molecular tool in the development of self-assembling nanosystems with potential use for biotechnological and biomedical applications.

Dual Oral Tissue Adhesive Nanofiber Membranes for pH-Responsive Delivery of Antimicrobial Peptides.

Bioadhesive membranes with controllable and reversible underwater adhesion are desirable for several biomedical applications ranging from biosensing, drug/therapeutic delivery, and tissue regeneration. Here, we present dual soft mucosal and hard bone/enamel tissue adhesive nanofiber membranes composed of chitosan and pectin derivatives for pH-controlled delivery of antimicrobial peptides (AMPs) in the oral cavity. Ex vivo testing with porcine esophagus (soft mucosal mimic) indicated a 2-fold increase in the mucoadhesion of chitosan membranes with 0.05 wt % oxidized pectin coating, while the uncoated membranes exhibited 3-4-fold stronger adhesion to hydroxyapatite discs (enamel/hard bone mimic) compared to the coated membranes. The former is attributed to a synergistic interaction of surface nanofiber topography, intermolecular hydrogen bonding, and aldehyde-amine chemistry between surface polar groups and mucosal proteins, while the latter may arise from electrostatic interactions between cationic amines (-NH3+) in chitosan and anionic phosphates (-PO43-) in hydroxyapatite. Further, the dual hard-soft oral tissue adhesive nanofiber membranes loaded with cationic amphipathic AMPs (D-GL13K and IDR-1018) elicited pH-responsive AMP delivery and antimicrobial action comparable to chlorhexidine (CHX) against oral streptococci. Concurrently, the AMP loaded membranes were cytocompatible to both soft epithelial tissue-derived human oral keratinocytes and hard calvarial murine pre-osteoblast cells. We envision these membranes to function as adhesive gingival grafts and guided bone regeneration (GBR) membranes at the hard-soft tissue interface while simultaneously protecting against oral infections.

Efficacy and safety of three different endoscopic methods in treatment of 6-20 mm colorectal polyps.

Objective: Endoscopic resection of colorectal polyps is widely established as the optimal method to manage precancerous lesions. But the optimal technique for removal of the polyps is uncertain. The aim of this study was to compare the efficacy and safety of three methods for the management of 6-20mm colorectal polyps.Methods: A prospective, randomised controlled trial was conducted at the 900TH Hospital of Joint Logistics Support Force in Fujian, China. Endoscopically diagnosed colorectal polyps, 6-20 mm in size, were randomly assigned to the cold snare polypectomy (CSP), cold snare endoscopic mucosal resection (CS-EMR) or endoscopic mucosal resection (EMR) group. After polypectomy, additional 3-5 forceps biopsies by leading narrow-band imaging (NBI) were performed at the base and margins of polypectomy sites to assess the presence of residual polyp tissue and all samples were sent for histopathological analysis to assess completeness of resection. Polypectomy timing, tissue retrieval and complications were recorded at the time of the procedure.Results: A total of 781 polyps in 404 patients were assessed and randomly assigned to each group. Of these, 763 polyps were finally analyzed based on the pathology results. The complete resection rates with CSP, CS-EMR and EMR were 81.6%, 94.1% and 95.5%, respectively (p < .001). The intraprocedural bleeding rate, immediately after polypectomy, was significantly higher in the CSP group than in the CS-EMR and EMR group (9.4% vs. 4.4% vs. 1.9%; p < .001). However,delayed bleeding was higher in the EMR group than in the CSP and CS-EMR group (2.6% vs. 1.2% vs. 0.8%, respectively; p = .215). In the multivariate analysis showed that the operation method, lesion size, morphology and the number of resection were independent risk factors for complete resection rate (CRR) (p < .05), but the location and pathological classification of polyps had no significant influence on CRR.Conclusions: CS-EMR is safe and effective in the treatment of 6-20 mm colorectal polyps. Especially for 6-15 mm non-pedunculated polyps, CS-EMR has a high histological complete resection rate comparable to EMR, and retains the low risk of delayed complications after polypectomy with cold snare. CS-EMR is expected to become a more valuable new cold-cutting technique after cold snare polypectomy.