Novel BODIPY-based nano-biomaterials with enhanced D-A-D structure for NIR-triggered photodynamic and photothermal therapy.

Near-infrared (NIR) responsive nanoparticles are an important platform for multimodal phototherapy. Importantly, the simultaneous NIR-triggered photodynamic (PDT) and photothermal (PTT) therapy is a powerful approach to increase the antitumor efficiency of phototherapic nanoparticles due to the synergistic effect. Herein, a boron dipyrromethene (BODIPY)-based amphiphilic dye with enhanced electron donor-acceptor-donor (D-A-D) structure (BDP-AP) was designed and synthesized, which could self-assemble into stable nanoparticles (BDP-AP NPs) for the synergistic NIR-triggered PDT/PTT therapy. BDP-AP NPs synchronously generated singlet oxygen (1O2) and achieved preeminent photothermal conversion efficiency (61.42%). The in vitro and in vivo experiments showed that BDP-AP NPs possessed negligible dark cytotoxicity and infusive anticancer performance. BDP-AP NPs provide valuable guidance for the construction of PDT/PTT-synergistic NIR nanoagents to improve the efficiency of photoinduced cancer therapy in the future.

Thyrotropin inhibits osteogenic differentiation of human periodontal ligament stem cells.

BACKGROUND AND OBJECTIVE: Periodontal ligament stem cells (PDLSCs) are derived from the periodontal ligament and have the characteristics of pluripotent differentiation, including osteogenesis, and are one of the important seed cells in oral tissue engineering. Thyrotropin (TSH) has been shown to regulate bone metabolism independently of thyroid hormone, including the fate of osteoblasts and osteoclasts, but whether it affects osteogenic differentiation of PDLSCs is unknown. MATERIALS AND METHODS: PDLSCs were isolated and cultured from human periodontal ligament and grown in osteogenic medium (containing sodium ß-glycerophosphate, ascorbic acid, and dexamethasone). Recombinant human TSH was added to the culture medium. Osteogenic differentiation of PDLSCs was assessed after 14 days by staining with alkaline phosphatase and alizarin red and by detection of osteogenic differentiation genes. Differentially expressed genes (DEGs) in PDLSCs under TSH were detected by high-throughput sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyzed the biological functions and signaling pathways involved in DEGs. RESULTS: We found that osteogenic differentiation of PDLSCs was significantly inhibited in the presence of TSH: including decreased calcium nodule formation, decreased alkaline phosphatase levels, and decreased collagen synthesis. Using high-throughput sequencing, we found changes in the expression of some osteogenesis-related genes, which may be the reason that TSH inhibits osteogenic differentiation of PDLSCs. CONCLUSION: Unless TSH is ≥10 mU/L, patients with subclinical hypothyroidism usually do not undergo thyroxine supplementation therapy. However, in this work, we found that elevated TSH inhibited the osteogenic differentiation of PDLSCs. Therefore, correction of TSH levels in patients with subclinical hypothyroidism may be beneficial to improve orthodontic, implant, and periodontitis outcomes in these patients.

Cementum protein 1 gene-modified adipose-derived mesenchymal stem cell sheets enhance periodontal regeneration in osteoporosis rat.

BACKGROUND AND OBJECTIVES: Osteoporosis (OP) and periodontitis are both diseases with excessive bone resorption, and the number of patients who suffer from these diseases is expected to increase. OP has been identified as a risk factor that accelerates the pathological process of periodontitis. Achieving effective and safe periodontal regeneration in OP patients is a meaningful challenge. This study aimed to assess the efficacy and biosecurity of human cementum protein 1 (hCEMP1) gene-modified cell sheets for periodontal fenestration defect regeneration in an OP rat model. MATERIALS AND METHODS: Rat adipose-derived mesenchymal stem cells (rADSCs) were isolated from Sprague-Dawley rats. After primary culture, rADSCs were subjected to cell surface analysis and multi-differentiation assay. And rADSCs were transduced with hCEMP1 by lentiviral vector, and hCEMP1 gene-modified cell sheets were generated. The expression of hCEMP1 was evaluated by reverse transcription polymerase chain reaction and immunocytochemistry staining, and transduced cell proliferation was evaluated by Cell Counting Kit-8. The hCEMP1 gene-modified cell sheet structure was detected by histological analysis and scanning electron microscopy. Osteogenic and cementogenic-associated gene expression was evaluated by real-time quantitative polymerase chain reaction. In addition, an OP rat periodontal fenestration defect model was used to evaluate the regeneration effect of hCEMP1 gene-modified rADSC sheets. The efficacy was assessed with microcomputed tomography and histology, and the biosecurity of gene-modified cell sheets was evaluated by histological analysis of the spleen, liver, kidney and lung. RESULTS: The rADSCs showed a phenotype of mesenchymal stem cells and possessed multi-differentiation capacity. The gene and protein expression of hCEMP1 through lentiviral transduction was confirmed, and there was no significant effect on rADSC proliferation. Overexpression of hCEMP1 upregulated osteogenic and cementogenic-related genes such as runt-related transcription factor 2, bone morphogenetic protein 2, secreted phosphoprotein 1 and cementum attachment protein in the gene-modified cell sheets. The fenestration lesions in OP rats treated with hCEMP1 gene-modified cell sheets exhibited complete bone bridging, cementum and periodontal ligament formation. Furthermore, histological sections of the spleen, liver, kidney and lung showed no evident pathological damage. CONCLUSION: This pilot study demonstrates that hCEMP1 gene-modified rADSC sheets have a marked ability to enhance periodontal regeneration in OP rats. Thus, this approach may represent an effective and safe strategy for periodontal disease patients with OP.

Endoscopic visualization of the inferior alveolar nerve associated with somatosensory changes after impacted mandibular third molar extraction.

The aim of this study is to assess the relationship between somatosensory functional changes and inferior alveolar nerve (IAN) exposure after impacted mandibular third molars (M3M) removal. We recruited 35 patients who underwent impacted M3M extraction near the IAN. The M3Ms were extracted by combined endoscopy, piezosurgery, and contra-angle high-speed turbine handpiece. All IAN canal perforations and exposed regions were recorded and measured by endoscopy after extraction and on cone-beam computed tomography (CBCT) images before extraction. The patients were followed up 1, 7, and 35 days after surgery. A standardized quantitative sensory testing (QST) battery was performed on the lower lip skin. All of 35 cases had exposed IAN on CBCT images, 5 of which had no exposed IAN under endoscopy. For the other 30 cases, the endoscopy-measured IAN length and width were shorter than the CBCT measurements (P < 0.001). The warm and mechanical detection thresholds (MDT) on the operation side were significantly higher than the contralateral side after surgery (P < 0.05). Thermal sensory limen, MDT, and cold pain threshold were strongly correlated with the exposed IAN length and MDT also with the exposed IAN width one day after surgery. In conclusion, it was found that not all exposed IAN in CBCT images were real exposure after surgery. The intraoperative exposed IAN endoscopic measurements were smaller than by CBCT and strongly correlated with some QST parameters.

Drug-Coated Balloons for Acute Myocardial Infarction: A Metaanalysis of Randomized Clinical Trials.

Background: The role of a drug-coated balloon (DCB) in the treatment of acute myocardial infarction (AMI) is not well established. Methods: Five databases were searched for randomized controlled trials that compared DCB with stents in the treatment of AMI from their inception to 30 July 2021. The primary clinical endpoint was major adverse cardiac events (MACEs). Summary estimations were conducted using fixed-effects analysis complemented by several subgroups. The protocol was registered with PROSPERO (https://clinicaltrials.gov/ct2/show/CRD42021272886). Results: A total of 4 randomized controlled trials with 485 patients were included. On routine clinical follow-up, DCB was associated with no difference in the incidence of MACEs compared with control (risk ratio [RR] 0.59 [0.31 to 1.13]; P=0.11). DCB was associated with similar MACEs compared with drug-eluting stent and lower MACEs compared with bare-metal stent. There was no difference between DCB and control in terms of all-cause mortality, cardiovascular mortality, stent thrombosis, target lesion revascularization, and minimal lumen diameter during follow-up. However, DCB was associated with a lower incidence of myocardial infarction (RR 0.16 [0.03 to 0.90]; P=0.04) and lower late lumen loss (mean difference -0.20 [-0.27 to -0.13]; P < 0.00001). Conclusions: In treatment of patients with AMI, DCB might be a feasible interventional strategy versus control as it associated with comparable clinical outcomes. Future large-volume, well-designed randomized controlled trials to evaluating the role of the DCB in this setting are warranted.

A randomized comparison of two paclitaxel-coated balloons for the treatment of in-stent restenosis: The LONGTY ISR China randomized trial (LONGTY DCB vs. SeQuent Please DCB).

OBJECTIVES: This study sought to compare the efficacy and clinical safety of the LONGTY drug-coated balloon (DCB) with those of SeQuent Please DCB in patients with in-stent restenosis (ISR). BACKGROUND: Although DCB technologies have evolved, little is known about the clinical efficacy of the new-generation LONGTY DCB. METHODS: This was a prospective, multicenter, randomized, noninferiority trial comparing LONGTY DCB with SeQuent Please DCB in patients with ISR. The primary endpoint was target lesion late lumen loss at 9 months' follow-up. RESULTS: A total of 211 patients with ISR from 13 Chinese sites were included (LONGTY DCB, n = 105; SeQuent Please DCB, n = 106). Device success was achieved in all patients. At the 9 month angiographic follow-up, target lesion late lumen loss was 0.35 ± 0.42 mm with LONGTY and 0.38 ± 0.45 mm with SeQuent Please (p for noninferiority <.001). The target lesion revascularization rates at 1 year were similar in both DCB groups (15.24 vs. 13.21%; p = .673). Over an extended follow-up of 2 years, the clinical endpoints, including cardiac death, myocardial infarction, and thrombus rate, were extremely low and similar in both groups. CONCLUSIONS: In this multicenter, head-to-head, randomized trial, the new-generation LONGTY DCB was noninferior to the SeQuent Please DCB for the primary endpoint of target lesion late lumen loss at 9 months.

Self-powered portable melt electrospinning for in situ wound dressing.

BACKGROUND: Electrospun (e-spun) nanofibers for wound dressing have attracted wide attention due to its large specific surface area, large porosity and breathability. Compared with solution electrospinning (e-spinning), melt e-spinning is more bio-friendly without toxic solvent participation, which provides the possibility of in situ e-spinning on wounds directly. However, previously reported melt e-spinning devices were usually bulky and cumbersome due to their necessary heating unit, and different components were separated to avoid electrostatic interference. RESULTS: In this article, we report on a self-powered hand-held melt e-spinning gun which can work without any external power supply (outdoors). The problem of electrostatic interference for this integrated device was solved by using a special high heat transfer insulation unit. The apparatus is easy and safe to operate by a single hand due to its small volume (24 × 6 × 13 cm3) and light weight (about 450 g). Some biodegradable polymers, for example, polycaprolactone (PCL) fibers were successful e-spun onto wounds directly by using this dressing gun. CONCLUSIONS: PCL fibrous membrane has good biocompatibility and can be in situ electrospun to wound surface as a wound dressing by the portable melt e-spinning gun. Besides wound dressing, this hand-held melt e-spinning gun may be used in 3D printing and experimental teaching demonstration aids.

Chiral polymer modified nanoparticles selectively induce autophagy of cancer cells for tumor ablation.

BACKGROUND: Autophagy regulation through exogenous materials has aroused intensive attention to develop treatment protocols according to diverse human diseases. However, to the best of our knowledge, few examples have been reported to selectively control autophagy process and ultimately achieve efficient therapeutic potential. RESULTS: In this study, monolayers of poly (acryloyl-L, D and racemic valine) (L-PAV-AuNPs, D-PAV-AuNPs and L/D-PAV-AuNPs) chiral molecules were anchored on the surfaces of gold nanoparticles (PAV-AuNPs), and the subsequent chirality-selective effects on autophagy activation were thoroughly studied. The cytotoxicity induced by PAV-AuNPs towards MDA-MB-231 cells (Breast cancer cells) was achieved mainly through autophagy and showed chirality-dependent, with D-PAV-AuNPs exhibiting high autophagy-inducing activity in vitro and in vivo. In contrast, the PAV-AuNPs exhibited autophagy inactivation for normal cells, e.g., 3T3 fibroblasts and HBL-100 cells. The chirality-selective autophagy activation effect in MDA-MB-231 cells was likely attributed to the chirality-variant ROS generation, cellular uptake and their continuous autophagy stimulus. Furthermore, the intratumoral injection of D-PAV-AuNPs could largely suppress the tumor growth but exhibit negligible toxicity in vivo. CONCLUSIONS: As the first exploration on stereospecific NPs for autophagy induction, this work not only substantiates that chiral polymer coated NPs can selective induce autophagy-specific in cancer cells and achieve a high tumor eradication efficiency in vivo, but also opens up a new direction in discovering unprecedented stereospecific nanoagents for autophagy-associated tumor treatment.

Effect of local hIL-10 gene therapy on experimental periodontitis in ovariectomized rats.

OBJECTIVE: To investigate the effect of local hIL-10 gene therapy on experimental periodontitis in rats and to elucidate the mechanism underlying this effect. MATERIAL AND METHODS: Experimental periodontitis was induced in ovariectomized (OVX) rats using a silk ligature. We then injected 5 µg of hIL-10 plasmid with 5 µl of liposomes or 5 µg of vector plasmid with 5 µl of liposomes into the palatal side of the gingival mucosa of the upper left second molar once every two days. The rats were killed 48 hours after the seventh injection. The body weight; bone mineral density of the whole body, pelvis and spine; resorption of the alveolar bone; and number of cytokine-positive cells were measured to determine the effects of hIL-10 on the periodontal tissue. RESULTS: hIL-10 was expressed in periodontal tissues after local gene delivery. The expressed hIL-10 protein inhibited alveolar bone resorption and downregulated IL-1ß, IL-6, TNF-α, RANKL and MMP-8 in the periodontal ligament in the root furcation region. CONCLUSIONS: Local hIL-10 gene transfer suppressed alveolar bone resorption in OVX rats, and this effect was probably associated with the decline in the expression of pro-inflammatory cytokines in the periodontal tissues.

In Vivo Molecular MRI Imaging of Prostate Cancer by Targeting PSMA with Polypeptide-Labeled Superparamagnetic Iron Oxide Nanoparticles.

The prostate specific membrane antigen (PSMA) is broadly overexpressed on prostate cancer (PCa) cell surfaces. In this study, we report the synthesis, characterization, in vitro binding assay, and in vivo magnetic resonance imaging (MRI) evaluation of PSMA targeting superparamagnetic iron oxide nanoparticles (SPIONs). PSMA-targeting polypeptide CQKHHNYLC was conjugated to SPIONs to form PSMA-targeting molecular MRI contrast agents. In vitro studies demonstrated specific uptake of polypeptide-SPIONs by PSMA expressing cells. In vivo MRI studies found that MRI signals in PSMA-expressing tumors could be specifically enhanced with polypeptide-SPION, and further Prussian blue staining showed heterogeneous deposition of SPIONs in the tumor tissues. Taken altogether, we have developed PSMA-targeting polypeptide-SPIONs that could specifically enhance MRI signal in tumor-bearing mice, which might provide a new strategy for the molecular imaging of PCa.

Oligomeric hydrogels self-assembled from reduction-controlled condensation.

Polymer hydrogels and small-molecule-based (SMB) supramolecular hydrogels have been widely explored. But oligomeric hydrogels have remained a challenge because synthetic difficulties of the oligomers and control of their amphiphilicities. Reported herein is the rational design of two precursors Cys(SEt)-Lys-CBT (1) and (Cys-Lys-CBT)2 (2) (CBT=2-cyano-6-aminobenzothiazole) and the use of a biocompatible condensation to prepare oligomeric hydrogels. Glutathione reduction of 1 or 2 yields the same gelator Cys-Lys-CBT (3) which condenses with each other to yield amphiphilic cyclic oligomers. The oligomers instantly self-assemble into nanofibers and form oligomeric hydrogels with similar mechanic properties. Chemical analyses indicated that the major condensation product in both two hydrogels is a cyclic dimer. Considering its biocompatibility, optimal mechanical strength, and biodegradability, we believe that our oligomeric hydrogel might be useful for long-term drug delivery in the future.

Moisture loss inhibition with biopolymer films for preservation of fruits and vegetables: A review.

In cold storage, fruits and vegetables still keep a low respiratory rate. Although cold storage is beneficial to maintain the quality of some fruits and vegetables, several factors (temperature and humidity fluctuations, heat inflow, air velocity, light, etc.) will accelerate moisture loss. Biopolymer films have attracted great attention for fruits and vegetables preservation because of their biodegradable and barrier properties. However, there is still a certain amount of water transfer occurring between storage environment/biopolymer films/fruits and vegetables (EFF). The effect of biopolymer films to inhibit moisture loss of fruits and vegetables and the water transfer mechanism in EFF system need to be studied systematically. Therefore, the moisture loss of fruits and vegetables, crucial properties, major components, fabrication methods, and formation mechanisms of biopolymer films were reviewed. Further, this study highlights the EFF system, responses of fruits and vegetables, and water transfer in EFF. This work aims to clarify the characteristics of EFF members, their influence on each other, and water transfer, which is conducive to improving the preservation efficiency of fruits and vegetables purposefully in future studies. In addition, the prospects of studies in EFF systems are shown.

Targeting of focal adhesion kinase enhances the immunogenic cell death of PEGylated liposome doxorubicin to optimize therapeutic responses of immune checkpoint blockade.

BACKGROUNDS: Immune checkpoint blockade (ICB) is widely considered to exert long-term treatment benefits by activating antitumor immunity. However, many cancer patients show poor clinical responses to ICB due in part to the lack of an immunogenic niche. Focal adhesion kinase (FAK) is frequently amplified and acts as an immune modulator across cancer types. However, evidence illustrates that targeting FAK is most effective in combination therapy rather than in monotherapy. METHODS: Here, we used drug screening, in vitro and in vivo assays to filter out that doxorubicin and its liposomal form pegylated liposome doxorubicin (PLD) showed synergistic anti-tumor effects in combination with FAK inhibitor IN10018. We hypothesized that anti-tumor immunity and immunogenic cell death (ICD) may be involved in the treatment outcomes through the data analysis of our clinical trial testing the combination of IN10018 and PLD. We then performed cell-based assays and animal studies to detect whether FAK inhibition by IN10018 can boost the ICD of PLD/doxorubicin and further established syngeneic models to test the antitumor effect of triplet combination of PLD, IN10018, and ICB. RESULTS: We demonstrated that the combination of FAK inhibitor IN10018, and PLD/doxorubicin exerted effective antitumor activity. Notably, the doublet combination regimen exhibited response latency and long-lasting treatment effects clinically, outcomes frequently observed in immunotherapy. Our preclinical study confirmed that the 2-drug combination can maximize the ICD of cancer cells. This approach primed the tumor microenvironment, supplementing it with sufficient tumor-infiltrating lymphocytes (TILs) to activate antitumor immunity. Finally, different animal studies confirmed that the antitumor effects of ICB can be significantly enhanced by this doublet regimen. CONCLUSIONS: We confirmed that targeting FAK by IN10018 can enhance the ICD of PLD/doxorubicin, further benefiting the anti-tumor effect of ICB. The animal tests of the triplet regimen warrant further discovery in the real world.

Detection of human enterovirus 71 and Coxsackievirus A16 in an outbreak of hand, foot, and mouth disease in Henan Province, China in 2009.

During 2009, an outbreak of hand, foot, and mouth disease (HFMD) enrolled 490 people in Henan Province, causing the death of two children. In order to investigate the pathogens responsible for this outbreak and characterize their genetic characteristics, a total of 508 clinical specimens (stool, throat swab, and vesicle fluid) were collected from the Center for Disease Control and Prevention of Henan Province. Virological investigations (virus isolation, conventional reverse transcription PCR, and real-time reverse transcription PCR) and phylogenetic analysis were performed. It was found that human enterovirus 71 (EV71) was the main pathogen causing this outbreak, while Coxsackievirus A16 (CoxA16) played only a subsidiary role. Phylogenetic analysis of 24 EV71 isolates collected during the period from March 11 to July 24, 2009 showed that they belonged to subgenotypes C4 and C5. Our study for the first time characterizes the epidemiology of HFMD and EV71 infection in Henan Province in 2009 and provides the first direct evidence of the genotype of EV71 circulating in Henan Province at that time. Our study should facilitate the development of public health measures for the control and prevention of HFMD and EV71 infection in at-risk individuals in China.

[Osteotomy for severe thoracolumbar kyphosis in advanced ankylosing spondylitis: skipping two-level pedicle subtraction osteotomy].

OBJECTIVE: To explore the feasibility of single-stage skipping two-level pedicle subtraction osteotomy (PSO) for severe thoracolumbar kyphosis (Cobb > 100°) in advanced ankylosing spondylitis (AS). METHODS: Ten AS patients with thoracolumbar kyphosis undergoing skipping two-level PSO were retrospectively reviewed. The most frequent levels of osteotomy was L1 and L4 (n = 7), followed by T12 and L3 (n = 2) and L2 and L5 (n = 1). All patients were males with a mean age of 28.5 ± 9.1 years (range: 17 - 47). The pre- and post-operative values of thoracic kyphosis (TK), lumbar lordosis (LL), globe kyphosis (GK), local kyphosis of osteotomized vertebra (LK1, LK2) and sagittal imbalance (SVA) were measured. RESULTS: Significant differences were observed with respects to the improvements of LL, GK, LK1, LK2 and SVA (P < 0.01). LL, GK, LK1, LK2 and SVA improved from 41.9°, 113.4°, 40.5°, -0.3° and 25.2 cm preoperatively to -44.1°, 71.6°, 13.5°,-26.8° and 5.8 cm postoperatively respectively. The mean operative duration was 370 minutes (range: 290 - 420) and the estimated volume of blood loss 2600 ml (range: 1700 - 3800). Dural tear occurred intra-operatively in 1 patient. One had a transient brachial plexus paralysis and resolved after 1 week postoperatively. One had transient radiculopathy in right lower extremity and recovered completely 3 weeks postoperatively. CONCLUSION: As a safe and effective technique for correction of severe thoracolumbar kyphosis (Cobb > 100°) secondary to AS, single-stage skipping two-level PSO osteotomy can achieve larger correction and better sagittal alignment with a mean correction of 86°in terms of LL.

Effect mechanism of steel slag on CO2 capture in hydraulic lime.

Steel slag (SS) inhibits the early hydration of cement, limiting its application in cement-based materials. In this study, SS was used to prepare hydraulic lime (HL), and the effect of SS on CO2 capture in HL was investigated. SS inhibited the carbonation of HL in the early stages but promoted carbonation in the later stages. Adding more than 10% SS inhibited the formation of hydration products, and the reduction of hydration products inhibited the carbonation product content, increased the porosity of the hydration mortar, promoted the later stage carbonation rate, and reduced the compressive strength. The carbonation area and captured CO2 content of the mortars in SS-HL increased exponentially with an increasing carbonation curing age. With an increasing SS content, the carbonation area and the degree of CO2 capture decreased then increased after 1 day and after 3 days of accelerated carbonation curing, respectively.

First Ultrathin Pure Polyoxometalate 2D Material as a Peroxidase-Mimicking Catalyst for Detecting Oxidative Stress Biomarkers.

Although two-dimensional (2D) materials with ultrathin geometry and extraordinary electrical attributes have attracted substantial concern, exploiting new-type 2D materials is still a great challenge. In this work, an unprecedented single-layer pure polyoxometalate (POM) 2D material (2D-1) was prepared by ultrasonically exfoliating a one-dimensional (1D)-chain heterometallic crystalline germanotungstate Na4[Ho(H2O)6]2[Fe4(H2O)2(pic)6Ge2W20O72]·16H2O (1) (Hpic = picolinic acid). The 1D polymeric chain of 1 is assembled from particular {Ge2W20}-based [Fe4(H2O)2(pic)6Ge2W20O72]10- segments through bridging [Ho(H2O)6]3+ cations. 2D-1 is formed by π-π interaction driving force among adjacent 1D polymeric chains of 1. Also, the peroxidase-mimicking properties of 2D-1 toward detecting H2O2 were evaluated and good detection result was observed with a limit of detection (LOD) of 58 nM. Density functional theory (DFT) calculation further confirms that 2D-1 displays outstanding catalytic activity and active sites are located on Fe centers and Hpic ligands. Under the catalysis of uricase, uric acid can be transformed to allantoin and H2O2, and then, H2O2 oxidizes TMB to its blue ox-TMB in the presence of 2D-1 as a catalyst. Then, we utilized this cascade reaction to detect uric acid, which also exhibits prominent results. This research opens a door to prepare ultrathin pure POM 2D materials and broadens the scope of potential applications of POMs in biology and iatrology.

The role of tracheal wall injury in the development of benign airway stenosis in rabbits.

To investigate the role of tracheal wall injury in the development of benign airway stenosis in rabbits. Prospective study. We injured the tracheal walls of 28 New Zealand white rabbits using four different methods. Experimental group: Group A (n = 7, mild injury of tracheal mucosa by ordinary brush under bronchoscopy); Group B (n = 7, severe injury of tracheal mucosa by nylon brush under tracheotomy); Group C (n = 7, tracheal cartilage was injured by vascular clamp after tracheotomy); Group D (n = 7, the tracheal cartilage was injured with vascular forceps and the tracheal mucosa was injured with a nylon brush after tracheotomy). Bronchoscopy was performed on each experimental rabbit at 1, 2, 3 and 4 weeks after operation. High-resolution computed tomography (HRCT) and endobronchial optical coherence tomography (EB-OCT) were performed at 4 weeks, and the rabbits were sacrificed after the examination. Their gross and histological findings were comparatively determined whether the experimental rabbit stenosis was established. No airway stenosis was observed in group A. In group B, 28.57% of experimental rabbits developed tracheal stenosis (granulation tissue proliferation was observed in rabbits No. 2 and No. 6 at 1, 2 and 3 weeks after operation, and the tracheal scar contracture was observed in No.6 rabbit at 4 weeks after operation). Fourteen rabbits in group C and group D had tracheal stenosis caused by granulation tissue proliferation at 1, 2 and 3 weeks after operation. At the fourth week after operation, 71.43% of experimental rabbits had tracheal stenosis due to granulation tissue hyperplasia, 7.14% of experimental rabbits had tracheal stenosis due to scar contracture and granulation hyperplasia, and 21.43% of experimental rabbits had tracheal stenosis due to scar contracture. EB-OCT scan showed that the cartilage layer with low signal reflection band was discontinuous. The injury of cartilage is the key factor of benign airway stenosis. Acute injury of airway mucosa alone is unlikely to cause airway stenosis, but combined with cartilage injury may aggravate airway stenosis. EB-OCT can clearly identify the airway layers of rabbits, which is helpful to evaluate the damage of tracheal cartilage and mucosa. The diagnostic potential of this technique makes EB-OCT a promising approach for the study and monitoring of airway diseases.

Biomineral-binding liposomes with dual antibacterial effects for preventing and treating dental caries.

Dental caries is a chronic oral disease that results from the demineralization of dental hard tissues caused by the long-term interaction of various pathogenic factors in the human oral cavity. Although magnolol (Mag) and fluconazole (FLC) have shown promising antibacterial activity against Candida albicans (C. albicans) and Streptococcus mutans (S. mutans), their clinical application is limited due to hydrophobicity. In this study, we constructed biomineral-binding liposomes co-loaded with Mag and FLC (PPi-Mag/FLC-LPs) to overcome the hydrophobicity and achieve a dual antibacterial activity in the acidic microenvironment of caries. PPi-Mag/FLC-LPs were characterized by laser particle size analysis, transmission electron microscopy, and high-performance liquid chromatography (HPLC). The ability of PPi-Mag/FLC-LPs to bind hydroxyapatite was assessed in vitro using fluorescence microscopy and HPLC, while the antibacterial activity was examined by measuring drug effects on the acidogenicity, acid resistance, biofilm formation and survival of C. albicans and S. mutans. The pharmacodynamics of PPi-Mag/FLC-LPs was also evaluated in vivo in a rat model of dental caries. Mag and FLC were released rapidly from PPi-Mag/FLC-LPs in a pH-sensitive manner, and they bound effectively to hydroxyapatite, leading to a better antibacterial effect on C. albicans and S. mutans compared to free drugs or liposomes loaded with a single drug. PPi-Mag/FLC-LPs improved the medicinal properties of Mag and FLC and provided a rapid, pH-sensitive release of both drugs in vitro. PPi-Mag/FLC-LPs displayed good antibacterial activity in vivo, showing promise as a dual-drug delivery system for the prevention and treatment of caries.

Ureteral reconstruction using autologous tubular grafts for the management of ureteral strictures and defects: an experimental study.

OBJECTIVE: To investigate whether the peritoneal cavity could function as a bioreactor to produce autologous tubular grafts for ureteral reconstruction in beagles. MATERIALS AND METHODS: 8-Fr Silastic tubes were implanted into the peritoneal cavities of 6 female beagles. At 3 weeks, the tubes were harvested and the tubular tissue covering the tubes was gently everted. A segment 3 cm in length of the right mid-ureter, involving two thirds of its diameter, was removed parallel to the ureteral axis, leaving a third of the ureteral wall. A 5-Fr double-J stent was inserted into the ureter through the created defect, and two thirds of the graft were anastomosed to both edges of the ureteral defect. One third of the graft was overlapped with the retained normal ureter and anastomosed to the external surface of the lumens. Thus, the graft was partly encapsulated by the remainder of ureteral wall. The stent was maintained for 6 weeks and removed. Excretory urography was performed at 8 (n = 3) and 12 weeks (n = 3), postoperatively. Meanwhile, the neoureter was harvested and analyzed. The left ureter served as the control and a simple intubated ureterotomy was performed. RESULTS: Histological analysis of the tubular tissue demonstrated transversely arranged myofibroblasts and an outer layer of mesothelium. The tissue was easily everted and transplanted as a ureteral graft. Eight weeks postoperatively, the neoureter demonstrated normal ureteral architecture, composed of multilayers of urothelium surrounded by smooth muscle bundles, which became increasingly organized with time. Excretory urography indicated no stenosis or hydronephrosis. CONCLUSIONS: These results show that autologous tubular tissue grown within the recipients' peritoneal cavity can be used for ureteral reconstruction in the beagle model.