Prodigiosin Inhibits Transforming Growth Factor ß Signaling by Interfering Receptor Recycling and Subcellular Translocation in Epithelial Cells.

Prodigiosin (PG) is a naturally occurring polypyrrole red pigment produced by numerous microorganisms including some Serratia and Streptomyces strains. PG has exhibited promising anticancer activity; however, the molecular mechanisms of action of PG on malignant cells remain ambiguous. Transforming growth factor-ß (TGF-ß) is a multifunctional cytokine that governs a wide array of cellular processes in development and tissue homeostasis. Malfunctions of TGF-ß signaling are associated with numerous human cancers. Emerging evidence underscores the significance of internalized TGF-ß receptors and their intracellular trafficking in initiating signaling cascades. In this study, we identified PG as a potent inhibitor of the TGF-ß pathway. PG blocked TGF-ß signaling by targeting multiple sites of this pathway, including facilitating the sequestering of TGF-ß receptors in the cytoplasm by impeding the recycling of type II TGF-ß receptors to the cell surface. Additionally, PG prompts a reduction in the abundance of receptors on the cell surface through the disruption of the receptor glycosylation. In human Caucasian lung carcinoma cells and human hepatocellular cancer cell line cells, nanomolar concentrations of PG substantially diminish TGF-ß-triggered phosphorylation of Smad2 protein. This attenuation is further reflected in the suppression of downstream target gene expression, including those encoding fibronectin, plasminogen activator inhibitor-1, and N-cadherin. SIGNIFICANCE STATEMENT: Prodigiosin (PG) emerges from this study as a potent TGF-ß pathway inhibitor, disrupting receptor trafficking and glycosylation and reducing TGF-ß signaling and downstream gene expression. These findings not only shed light on PG's potential therapeutic role but also present a captivating avenue towards future anti-TGF-ß strategies.

Oral health self-management barriers among rural older adults in Guangxi, China: A qualitative study.

BACKGROUND: Objective: To understand the barriers associated with self-management of oral health among rural older adults in Guangxi, and to explore the high incidence of oral problems. This information will assist in the formulation of relevant strategies to solve the oral health problems in this population. METHODS: Taking a phenomenological approach, the current status of, and barriers to, oral health self-management in rural older adults from different regions of Guangxi were explored. Participants were purposively selected and interviewed face-to-face. RESULTS: The interviews yielded four overarching themes and six corresponding sub-themes pertaining to barriers in oral health self-management. These included: (1) Older adults' understanding of oral health and disease, perceptions of oral health and their oral health behaviours; (2) Problems in accessing oral health information; (3) Role of family support; and (4) Barriers to healthcare that included access to dental services, oral treatment experience and financial burden of access to dental care. CONCLUSION: Rural older adults in Guangxi face oral health self-management barriers. Improving access to oral healthcare services and changing existing oral health perceptions and habits may assist them in overcoming self-management challenges.

Hierarchical Nanomaterials Assembled from Peptoids and Other Sequence-Defined Synthetic Polymers.

In nature, the self-assembly of sequence-specific biopolymers into hierarchical structures plays an essential role in the construction of functional biomaterials. To develop synthetic materials that can mimic and surpass the function of these natural counterparts, various sequence-defined bio- and biomimetic polymers have been developed and exploited as building blocks for hierarchical self-assembly. This review summarizes the recent advances in the molecular self-assembly of hierarchical nanomaterials based on peptoids (or poly-N-substituted glycines) and other sequence-defined synthetic polymers. Modern techniques to monitor the assembly mechanisms and characterize the physicochemical properties of these self-assembly systems are highlighted. In addition, discussions about their potential applications in biomedical sciences and renewable energy are also included. This review aims to highlight essential features of sequence-defined synthetic polymers (e.g., high stability and protein-like high-information content) and how these unique features enable the construction of robust biomimetic functional materials with high programmability and predictability, with an emphasis on peptoids and their self-assembled nanomaterials.

Invisible Bactericidal Coatings on Generic Surfaces through a Convenient Hand Spray.

Robust antimicrobial coatings featuring high transparency, strong bactericidal activity, and an easy application procedure on generic surfaces can be widely accepted by the public to prevent pandemics. In this work, we demonstrated the hand-sprayer-based approach to deposit complex oxide coatings composed of Co-Mn-Cu-Zn-Ag on screen protectors of smartphones through acidic redox-assisted deposition (ARD). The as-obtained coatings possess high transparency (99.74% transmittance at 550 nm) and long-lasting durability against swiping (for 135 days of average use) or wet cleaning (for a routine of 3 times/day for 33 days). The spray coating enabling 3.14% Escherichia coli viability can further be reduced to 0.21% through a consistent elemental composition achieved via the immersion method. The high intake of Cu2+ in the coating is majorly responsible for the bactericidal activity, and the presence of Ag+ and Zn2+ is necessary to achieve almost complete eradication. The success of extending the bactericidal coatings on other typical hand-touched surfaces (e.g., stainless steel railings, rubber handrails, and plastic switches) in public areas has been demonstrated.

Hierarchical Self-Assembly Pathways of Peptoid Helices and Sheets.

Peptoids (N-substituted glycines) are a class of tailorable synthetic peptidomic polymers. Amphiphilic diblock peptoids have been engineered to assemble 2D crystalline lattices with applications in catalysis and molecular separations. Assembly is induced in an organic solvent/water mixture by evaporating the organic phase, but the assembly pathways remain uncharacterized. We conduct all-atom molecular dynamics simulations of Nbrpe6Nc6 as a prototypical amphiphilic diblock peptoid comprising an NH2-capped block of six hydrophobic N-((4-bromophenyl)ethyl)glycine residues conjugated to a polar NH3(CH2)5CO tail. We identify a thermodynamically controlled assembly mechanism by which monomers assemble into disordered aggregates that self-order into 1D chiral helical rods then 2D achiral crystalline sheets. We support our computational predictions with experimental observations of 1D rods using small-angle X-ray scattering, circular dichroism, and atomic force microscopy and 2D crystalline sheets using X-ray diffraction and atomic force microscopy. This work establishes a new understanding of hierarchical peptoid assembly and principles for the design of peptoid-based nanomaterials.

Engineered resistance to Zika virus in transgenic Aedes aegypti expressing a polycistronic cluster of synthetic small RNAs.

Recent Zika virus (ZIKV) outbreaks have highlighted the necessity for development of novel vector control strategies to combat arboviral transmission, including genetic versions of the sterile insect technique, artificial infection with Wolbachia to reduce population size and/or vectoring competency, and gene drive-based methods. Here, we describe the development of mosquitoes synthetically engineered to impede vector competence to ZIKV. We demonstrate that a polycistronic cluster of engineered synthetic small RNAs targeting ZIKV is expressed and fully processed in Aedes aegypti, ensuring the formation of mature synthetic small RNAs in the midgut where ZIKV resides in the early stages of infection. Critically, we demonstrate that engineered Ae. aegypti mosquitoes harboring the anti-ZIKV transgene have significantly reduced viral infection, dissemination, and transmission rates of ZIKV. Taken together, these compelling results provide a promising path forward for development of effective genetic-based ZIKV control strategies, which could potentially be extended to curtail other arboviruses.

Two-thirds anteroposterior ramus length is the preferred osteotomy point for intraoral vertical ramus osteotomy.

OBJECTIVES: This study aimed to investigate the mandibular canal of ramus and design a suitable osteotomy line for intraoral vertical ramus osteotomy (IVRO) using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: Ninety patients were classified into class I, II, and III skeletal pattern groups. When extended from the horizontal base plane (0 mm, mandibular foramen [MF]), with a 2-mm section interval, to 10 mm above and 10 mm below the MF, the following landmarks were identified: external oblique ridge (EOR), posterior border of the ramus (PBR), and posterior lateral cortex of ramus (PLC): IVRO osteotomy point. RESULTS: In the base plane (0-mm plane), the EOR-PBR distance of class III (34.78 mm) and the IOR-PBR distance of class II (32.72 mm) were significantly higher than those of class I (32.95 mm and 30.03 mm). Compared to the EOR-PLC distance, the designed osteotomy point (two-thirds EOR-PBR length) has a 3.49-mm safe zone at the base plane and ranging from 0.89 mm (+ 10-mm plane) to 8.37 mm (- 10-mm plane). CONCLUSIONS: The position at two-thirds EOR-PBR length (anteroposterior diameter of the ramus) can serve as a reference distance for the IVRO osteotomy position. CLINICAL RELEVANCE: Mandibular setback operations for treating mandibular prognathism mainly include sagittal split ramus osteotomy (SSRO) and IVRO. IVRO has a markedly lower incidence of postoperative lower lip paraesthesia than SSRO. Our design presented a reference point for identification during IVRO, to prevent damage to the inferior alveolar neurovascular bundle.

Clinical significance of postoperative skeletal relapse in the treatment of mandibular prognathism: Receiver operating characteristic curve analysis.

BACKGROUND/PURPOSE: Postoperative skeletal relapse is the most important issue in patients undergoing orthognathic surgery. This study aimed to investigate clinical skeletal relapse (≥2 mm) after mandibular setback surgery (intraoral vertical ramus osteotomy: IVRO) using receiver operating characteristic curve (ROC curve) analysis. METHODS: Serial cephalograms of 40 patients with mandibular prognathism were obtained at different time points: (1) before surgery (T1), (2) immediately after surgery (T2), and (3) at least with a 2-year follow-up postoperatively (T3). The menton (Me) was used as the landmark for measuring the amount of mandibular setback and postoperative skeletal relapse. Postoperative stability (T32) was divided into groups A and B by skeletal relapse ≥2 mm and <2 mm, respectively. The area under the ROC curve (AUC) was used to determine the cut-off point for mandibular setback. RESULTS: At the immediate surgical setback (T21), the amount of setback in group A (15.55 mm) was significantly larger than in group B (10.97 mm). Group A (T32) showed a significant relapse (4.07 mm), while group B showed a significant posterior drift (1.23 mm). The amount of setback had the highest AUC area (0.788). The cut-off point was 14.1 mm (T21) that would lead to a clinical relapse of 2 mm (T32). CONCLUSION: In IVRO, the postoperative mandibular positions reveal posterior drift and anterior displacement (relapse). The experience of clinical observation and patient perception of postoperative skeletal relapse was ≥2 mm. In the ROC curve analysis, the cut-off point of setback was 14.1 mm.

Management of Mandibular Subcondylar Fracture Through an Intraoral Approach Using a Trans-Buccal Trocar With Ramus Buccal Decortication.

PURPOSE: The aim of this study was to review retrospectively the functional recoveries of subcondylar fracture patients that underwent open reduction surgery using an extraoral approach or an intraoral approach using a trans-buccal trocar and involving ramus buccal decortication. MATERIALS AND METHODS: Of 47 patients with mandibular condyle fracture who visited Pusan National University Dental Hospital Department of Oral and Maxillofacial Surgery between May 2015 and November 2020, 38 patients underwent open reduction and were classified according to the surgical method used. Preauricular, submandibular, and retro-mandibular approaches were all classified as extraoral approaches condyle fractures were classified as described by Spiessl and Schroll (1972). Distances between bone fragments on panorama radiographs before and after surgery were measured. RESULTS: Thirty-eight patients were included in this study, 9 patients received subcondylar fracture surgery. Open reduction surgery using an extraoral approach had a greater mean operation time than the intraoral approach using a trocar. Of the 17 patients treated with an intraoral approach, the average distance between bone fragments right after surgery was 1.27 ± 1.41mm, which was significantly greater than that of the extraoral approach (0.72 ± 0.35 mm). CONCLUSIONS: Favorable results can be obtained by mandibular condylar fracture surgery through an intraoral approach using a trans-buccal trocar with ramus buccal decortication. This technique minimizes scarring, secures accessibility using a trocar, and sufficiently secures the field of view through buccal cortical bone reduction.

Correlation Between Sports-Related Maxillofacial Injuries and Head Injuries: A Five-Year Retrospective Study.

PURPOSE: As sports have become more diverse and demanding, the number of patients with a maxillofacial injury accompanied by a cranial injury or neurological symptoms has increased. This study examined the correlation between sports-related maxillofacial injuries and head injuries. PATIENTS AND METHODS: Among the patients who visited the emergency department of Pusan National University Dental Hospital due to a maxillofacial injury from sporting activities between 2014 and 2018, those who additionally had head injuries were retrospectively examined. Sporting activities were classified according to the American Academy of Pediatrics classification, and severity of injuries was determined using the Facial Injury Severity Scale (FISS). Patients whose medical records showed neurological symptoms and who underwent brain computed tomography for concomitant head injury were selected. The association between each of these variables, including age and gender, was statistically analyzed. RESULTS: A total of 95 patients were included in this study, most of whom were male teenagers, and cycling was the most common cause of injuries. The meanFISS score was 0.79. Brain computed tomography was conducted for 91 patients, and 28 patients reported neurological symptoms. Only 11 patients underwent advanced evaluation in the neurology or neurosurgery department. Most patients were diagnosed with contusion and concussion and were monitored without any treatment. CONCLUSIONS: Higher FISS values did not reflect the severity of maxillofacial and head injury. In this study, there were some patients with cranial fracture and cerebral hemorrhage with mild neurosurgical symptoms of facial trauma. Although the incidence of head trauma is not high, the necessity of wearing protective equipment cannot be overemphasized because severe trauma is permanent. Neurological signs and symptoms of patients with maxillofacial trauma should not be overlooked and require a thorough evaluation.

[Integration and Promotion of a Care Model for Chewing and Swallowing Reconstruction Teams].

Eating with the mouth is one of the basic joys of life. However, some 450,000 people currently live with nasogastric tubes in Taiwan. The causes of dysphagia disorders are complicated. Caring effectively for these cases requires interdisciplinary medical cooperation. Taiwan is expected to become a super-aged society in 2025. In Taiwan, people over 65 years old, residents of long-term care institutions, and stroke cases experience high rates of dysphagia. Every case of dysphagia has a potential risk of aspiration pneumonia, with pneumonia ranking as the third leading cause of death in people over 65 years old. Therefore, this issue demands the attention and assistance of medical care personnel. The integrated care model used at Kaohsiung Siaogang Hospital to promote the reconstruction of dysphagia functions is introduced in this article to help give medical teams interested in assisting cases a deeper understanding of this model. Integrating the resources and manpower of multiple disciplines helps cases improve dysphagia functions and reduces the need for indwelling nasogastric tubes and the incidence of aspiration pneumonia. Let us protect the everyday happiness of eating and improve quality of life.

Dendronized Arm Snowflake Polymer as a Highly Branched Scaffold for Cellular Imaging and Delivery.

Incorporation of branched structures is a major pathway to build macromolecules with desired three-dimensional (3D) structures, which are of high importance in the rational design of functional polymeric scaffolds. Dendrimers and hyperbranched polymers have been extensively studied for this purpose, but proper gain-of-function for these structures usually requires large enough molecular weights and a highly branched interior so that a spherical 3D core-shell architecture can be obtained, yet it is generally challenging to achieve precise control over the structure, high molecular weight, and high degree of branching (DoB) simultaneously. In this article, we present a set of snowflake-shaped star polymers with functional cores and dendronized arms, which ensure a high DoB and an overall globular conformation, thus facilitating the introduction of functional moieties onto the easily achieved scaffold without the need for high-generation dendrons. Using a polyglycerol dendron (PGD) as a proof of concept, we propose that this dendronized arm snowflake polymer (DASP) structure can serve as a better performing alternative to high-generation PGDs. DASPs with molecular weights of 750, 1220, 2120, and 3740 kDa were prepared with >85% yields in all cases, and we show that these DASPs have high encapsulating efficiency of Nile Red due to their high DoB and high biocompatibility due to their hydroxyl-rich nature after ketal removal, as well as high cell permeability that is molecular-weight-dependent. Introduced fluorophores such as fluorescein and difluoroboron 1,3-diphenylaminophenyl ß-diketonate with suitable excitation wavelengths may turn the DASPs into stable, endosome-staining fluorophores with ultra-large Stokes shifts, narrowed emission bands, and suitability for long-term cellular tracing. Moreover, the scaffold can encapsulate antibiotic molecules and deliver them into phagolysosomes for efficient elimination of intracellular Staphylococcus aureus, which is insensitive toward many antibiotics but is a key target for the clinical success of methicillin-resistant Staphylococcus aureus infection treatment. Elimination of Staphylococcus aureus could be improved to >99.9% for chloramphenicol at 32 µg/mL with 450 µg/mL DASP.

Comparison of lesion characteristics between conventional and high-power short-duration ablation using contact force-sensing catheter in patients with paroxysmal atrial fibrillation.

BACKGROUND: Transmural lesion creation is essential for effective atrial fibrillation (AF) ablation. Lesion characteristics between conventional energy and high-power short-duration (HPSD) setting in contact force-guided (CF) ablation for AF remained unclear. METHODS: Eighty consecutive AF patients who received CF with conventional energy setting (power control: 25-30 W, force-time integral = 400 g s, n = 40) or with HPSD (power control: 40-50 W, 10 s, n = 40) ablation were analyzed. Of them, 15 patients in each conventional and HPSD group were matched by age and gender respectively for ablation lesions analysis. Type A and B lesions were defined as a lesion with and without significant voltage reduction after ablation, respectively. The anatomical distribution of these lesions and ablation outcomes among the 2 groups were analyzed. RESULTS: 1615 and 1724 ablation lesions were analyzed in the conventional and HPSD groups, respectively. HPSD group had a higher proportion of type A lesion compared to conventional group (P < 0.01). In the conventional group, most type A lesions were at the right pulmonary vein (RPV) posterior wall (50.2%) whereas in the HPSD group, most type A lesions were at the RPV anterior wall (44.0%) (P = 0.04). The procedure time and ablation time were significantly shorter in the HPSD group than that in the conventional group (91.0 ± 12.1 vs. 124 ± 14.2 min, P = 0.03; 30.7 ± 19.2 vs. 57.8 ± 21 min, P = 0.02, respectively). At a mean follow-up period of 11 ± 1.4 months, there were 13 and 7 patients with recurrence in conventional and HPSD group respectively (P = 0.03). CONCLUSION: Optimal ablation lesion characteristics and distribution after conventional and HPSD ablation differed significantly. HPSD ablation had shorter ablation time and lower recurrence rate than did conventional ablation.

Er:YAG laser promotes proliferation and wound healing capacity of human periodontal ligament fibroblasts through Galectin-7 induction.

BACKGROUND/PURPOSE: Among various dental lasers, the erbium-doped yttrium-aluminum-garnet (Er:YAG) laser has great potential for periodontal treatment including soft and hard tissue ablation with minimal thermal side effects under suitable energy densities and it has multiple effects on tissues for wound-healing benefits. In the present study, we sought to reveal the molecular mechanism underlying the impact of Er:YAG laser on PDL fibroblasts. METHODS: Cells were irradiated by a Er:YAG laser with various energy densities (3.6-6.3 J/cm2). MTT assay was used for cell proliferation, and the transwell system was employed for migration and invasion abilities. The wound healing capacity was evaluated by a scratch assay. After confirming these effects, qRT-PCR and western blotting analysis was applied to identify the differentially galectin-7 expression in the irradiated cells. Knockdown experiments were conducted to reveal the functional role of galectin-7 in the modulation of Er:YAG laser-mediated effects. RESULTS: 4.2 J/cm2 was the lowest energy density to induce the optimal cell proliferation, migration and invasion abilities. In the group of upregulated genes, galectin-7 was selected for further examination and its elevation after Er:YAG laser treatment was validated by RT-PCR and Western blot. We demonstrated that silence of galectin-7 abrogated the effects of Er:YAG laser on cell proliferation, migration ad invasion, suggesting the Er:YAG laser promoted these effects through induction of galectin-7. CONCLUSION: These findings indicated that Er:YAG laser may accelerate the regeneration process in periodontal tissues through enhancement of their proliferative and mobile activities. Additionally, the significance of galectin-7 in the Er:YAG laser-elicited benefits was demonstrated.

Importance in the occurrence rate of shortest buccal bone marrow distance (<1 mm) for sagittal split ramus osteotomy.

BACKGROUND/PURPOSE: The neurosensory disturbance is a common complication following sagittal split ramus osteotomy (SSRO) whereas the shortest buccal bone marrow (SBM) is an important risk factor. The present study aimed to investigate the relationship between the occurrence rates of SBM among three skeletal patterns. METHODS: The cone-beam computed tomography (CBCT) images of 90 participants were divided into skeletal Class I, II, and III. There were six horizontal planes separated apart by a 2 mm interval; it started with plane 0 (original intact mandibular canal) to plane 5 which was 10 mm below. The data of SBM were divided into two groups (SBM ≥ 1 mm and SBM < 1 mm). With an SBM value < 1 mm, we defined a high occurrence rate of postoperative neurosensory abnormality or unfavorable split. RESULTS: The Class III patients had the smallest SBM value (1.31-1.75 mm) whereas the Class II patients had the largest SBM value (1.57-2.09 mm). For the Class III patients, the highest and lowest occurrence rates of SBM were 56.5% and 43.5% respectively. For the Class II patients, the highest and lowest occurrence rates of SBM were 37.1% and 17.7% respectively. The patients with Class III malocclusion had higher occurrence rates of SBM than the patients with Class II malocclusion. CONCLUSION: Class III had a significantly higher occurrence of probability (SBM < 1 mm) than Class II. Therefore, patients with Class III were more likely to experience postoperative neurosensory abnormalities and unfavorable split than patients with Class II.

Recommendations for treating stage I-III periodontitis in the Taiwanese population: A consensus report from the Taiwan Academy of Periodontology.

BACKGROUND/PURPOSE: Based on the fundamental of the S3-level clinical practice guideline (CPG) for treating stage I-III periodontitis developed by the European Federation of Periodontology (EFP), this consensus report aimed to develop treatment recommendations for treating periodontitis in the Taiwanese population. METHODS: The report was constructed by experts from the Taiwan Academy of Periodontology. The following topics were reviewed: (a) the prevalence of periodontitis in Asia and current status of treatment in Taiwan; (b) specific anatomical considerations for treating periodontitis in Asians; (d) educational and preventive interventions and supragingival plaque control; (d) subgingival instrumentation and adjunctive treatment; (e) surgical periodontal therapy; and (f) maintenance and supportive periodontal care. Recommendations were made according to the evidences from the EFP CPG, the published literature and clinical studies in Asians, and the expert opinions. RESULTS: The treatment recommendations for the Taiwanese population were generally in parallel with the EFP CPG, and extra cautions during treatment and maintenance phases were advised due to the anatomical variations, such as shorter root trunk, higher prevalence of supernumerary distolingual root and lingual bony concavity in mandibular posteriors, and thinner anterior labial plate, of the Asian population. CONCLUSION: The EFP CPG could be adopted for treating periodontitis and maintaining periodontal health of the Taiwanese population, and anatomical variations should be cautious when the treatment is delivered.

Farnesol-Loaded Liposomes Protect the Epidermis and Dermis from PM2.5-Induced Cutaneous Injury.

Particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5) increases oxidative stress through free radical generation and incomplete volatilization. In addition to affecting the respiratory system, PM2.5 causes aging- and inflammation-related damage to skin. Farnesol (Farn), a natural benzyl semiterpene, possesses anti-inflammatory, antioxidative, and antibacterial properties. However, because of its poor water solubility and cytotoxicity at high concentrations, the biomedical applications of Farn have been limited. This study examined the deleterious effects of PM2.5 on the epidermis and dermis. In addition, Farn-encapsulated liposomes (Lipo-Farn) and gelatin/HA/xanthan gel containing Lipo-Farn were prepared and applied in vivo to repair and alleviate PM2.5-induced damage and inflammation in skin. The prepared Lipo-Farn was 342 ± 90 nm in diameter with an encapsulation rate of 69%; the encapsulation significantly reduced the cytotoxicity of Farn. Lipo-Farn exhibited a slow-release rate of 35% after 192 h of incubation. The half-maximal inhibitory concentration of PM2.5 was approximately 850 µg/mL, and ≥400 µg/mL PM2.5 significantly increased IL-6 production in skin fibroblasts. Severe impairment in the epidermis and hair follicles and moderate impairment in the dermis were found in the groups treated with post-PM2.5 and continuous subcutaneous injection of PM2.5. Acute and chronic inflammation was observed in the skin in both experimental categories in vivo. Treatment with 4 mM Lipo-Farn largely repaired PM2.5-induced injury in the epidermis and dermis, restored injured hair follicles, and alleviated acute and chronic inflammation induced by PM2.5 in rat skin. In addition, treatment with 4 mM pure Farn and 2 mM Lipo-Farn exerted moderate reparative and anti-inflammatory effects on impaired skin. The findings of the current study indicate the therapeutic and protective effects of Lipo-Farn against various injuries caused by PM2.5 in the pilosebaceous units, epidermis, and dermis of skin.

Fluoroquinolones Suppress TGF-ß and PMA-Induced MMP-9 Production in Cancer Cells: Implications in Repurposing Quinolone Antibiotics for Cancer Treatment.

BACKGROUND: Fluoroquinolones (FQs) are potent antimicrobials with multiple effects on host cells and tissues. Although FQs can attenuate cancer invasion and metastasis, the underlying molecular mechanisms remain unclear. Matrix metalloproteinase-9 (MMP-9) has functional roles in tumor angiogenesis, invasion, and metastasis, and is associated with cancer progression and poor prognosis, suggesting that inhibitors of MMP-9 activity and transcription are prime candidates for cancer therapy. Despite numerous preclinical data supporting the use of MMP-9 inhibitors as anticancer drugs, the few available examples are not therapeutically useful due to low specificity and off-target effects. We examined the effects of FQs on MMP-9 production in cancer cells following transforming growth factor beta (TGF-ß) and phorbol 12-myristate 13-acetate (PMA) stimulation. EXPERIMENTAL APPROACHES: Using confluent cultures of HepG2 and A549 cells, the effects of FQs (ciprofloxacin, levofloxacin, clinafloxacin, gatifloxacin, and enrofloxacin) on TGF-ß and PMA-induced MMP-9 mRNA expression and production were studied in RNA extracts and culture supernatants, respectively. FQs specifically abrogated TGF-ß and PMA-induced MMP-9 levels and activity in a concentration and time-dependent manner, without affecting other MMPs or proteins involved in epithelial-mesenchymal transition. Additionally, FQs inhibited TGF-ß and PMA-induced cell migration via p38 and cyclic AMP signaling pathways. CONCLUSIONS AND IMPLICATIONS: Overall, we demonstrated that FQs inhibit cancer cell migration and invasion by downregulating MMP-9 expression and revealed the cellular mechanisms underlying their potential value in cancer treatment.

Randomized clinical trial of a conventional and a digital workflow for the fabrication of interim crowns: An evaluation of treatment efficiency, fit, and the effect of clinician experience.

STATEMENT OF PROBLEM: Limited information is available regarding the fabrication of tooth-supported interim single crowns (SCs) with either a digital or a conventional workflow. PURPOSE: The purpose of this randomized clinical trial was to compare the time efficiency and fit of interim crowns fabricated by using either a digital or a conventional workflow. MATERIAL AND METHODS: Forty participants in need of posterior tooth-supported SCs were enrolled and randomly allocated to either the digital or conventional group. In the digital group, the interim SCs were fabricated by using digital sextant scans and computer-aided design and computer-aided manufacturing (CAD-CAM) technology without definitive casts. The conventional group included conventional impressions and direct fabrication of the interim restorations intraorally. Five experienced and 5 less experienced clinicians were randomly assigned to fabricate the interim SCs. The total fabrication time (laboratory and clinical) was recorded for time efficiency. The fit assessment included marginal fit, proximal contact, occlusal contact, and crown morphology. The evaluated parameters were analyzed with the Mann-Whitney U Test (α=.05). RESULTS: The digital workflow required significantly less total fabrication time (laboratory and clinical) than the conventional workflow (P<.001). The less-experienced clinicians needed longer clinical time with the conventional workflow than the experienced ones (P=.023). In contrast, the laboratory time and total fabrication time were shorter for less-experienced clinicians using the digital workflow (P=.005 and P=.015). The interim SCs fabricated with the digital workflow had significantly better fit and occlusal contacts than those fabricated with the conventional workflow (P=.005 and P<.001). With the digital workflow, the interim SCs made by less-experienced clinicians were of the same quality as those made by experienced clinicians. When using the conventional workflow, the fit of the experienced clinicians was significantly better than that of the less-experienced clinicians. CONCLUSIONS: The interim SCs fabricated with a digital workflow required a shorter fabrication time and resulted in better fit than those fabricated with a conventional workflow, especially for less-experienced clinicians.

Using Guided Imagery to Relieve the Anxiety of Preschool Children Undergoing Dental Procedures.

PURPOSE: Negative experiences in dental clinics can induce anxiety in patients, and the effects are particularly pronounced in children. When behavior guidance methods (eg, direct observation, tell-show-do, and ask-tell-ask) fail, general anesthesia is an important alternative; however, the procedure of anesthesia can also induce fear and anxiety. This study assessed the effectiveness of guided imagery in relieving the anxiety associated with dental surgery in children and caregivers. DESIGN: A prospective randomized trial with two groups. METHODS: The guided imagery in this study was meant to establish a rapport between the medical team and the patient, by encouraging the child to imagine having an adventure while riding in a spacecraft. Anxiety levels and behavior were measured using five well-established scales: the modified Yale Preoperative Scale-Short Form, the State-Trait Anxiety Inventory-6 items, the Watcha score, the Pediatric Anesthesia Emergent Delirium scale, and the Posthospitalization Behavioral Questionnaire-Ambulatory Surgery. FINDINGS: The results indicate that the guided imagery had no significant effects on anxiety levels. CONCLUSIONS: Guided imagery is a low-cost, easy-to-implement, interesting exercise capable of enhancing interactions between nursing staff and children. It may also help to condition children to the environment and thereby assist them in overcoming their fears.