Virtual Planning and Rapid 3D Prototyping Surgical Guide for Anterior Crown Lengthening Surgery: A Clinical Case Report.

Progress with additive 3D printing is revolutionizing biomaterial manufacturing, including clinical dentistry and prosthodontics. Among the several 3D additive printing technologies, stereolithography is very popular as it utilizes light-activated resin for precise resolution. A simplified digital technique was used to fabricate two designs of a surgical guide for crown lengthening. Two cases are presented that utilized digital imaging and communications in medicine (DICOM) files obtained with computed tomography (CT) imaging and processed using four CAD software (Blue Sky Plan, Exocad, Meshmixer and 3D Slicer). The final models were converted to standard tessellation (STL) files and the guides were 3D printed with an additive stereolithography (SLA) printer. The first case was fabricated with a bone model from cone beam computed tomography (CBCT) data, and the second case was generated with intraoral and wax-up scans alone. Both methods appear to be equally effective compared to using a conventional method of guide frabication. However, proximal bone reduction was a concern with both designs. Digitally fabricated 3D printed surgical guide for crown lengthening has merit and a practical design is needed for future clinical validation.

EpCAM Aptamer-Functionalized Cationic Liposome-Based Nanoparticles Loaded with miR-139-5p for Targeted Therapy in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common cancers worldwide. MicroRNAs (miRNAs) play a vital role in a variety of biology processes. Our previous work identified miR-139-5p as a tumor suppressor gene overexpressed in CRC that assisted in inhibiting progression of cancer. The main challenge of miRNAs as therapeutic agents is their rapid degradation in plasma, poor uptake, and off-target effects. Therefore, the development of miRNA-based therapies is necessary. In this study, we developed a cationic liposome-based nanoparticle loaded with miR-139-5p (miR-139-5p-HSPC/DOTAP/Chol/DSPE-PEG2000-COOH nanoparticles, MNPs) and surface-decorated with epithelial cell adhesion molecule (EpCAM) aptamer (Apt) (miR-139-5p-EpCAM Apt-HSPC/DOTAP/Chol/DSPE-PEG2000-COOH nanoparticles, MANPs) for the targeted treatment of CRC. The size of MANPs was 150.3 ± 8.8 nm, which had a round-shaped appearance and functional dispersion capabilities. It also showed negligible hemolysis in the blood. MANPs markedly inhibited the proliferation, migration, and invasion of one or more CRC cell lines in vitro. Furthermore, we demonstrated the uptake and targeting ability of MANPs in vivo and in vitro. MANPs inhibit the growth of HCT8 cells in vitro and have a significant tumor suppressive effect on subcutaneous HCT8 colorectal tumor mice. Our results demonstrated that MANPs were an effective carrier approach to deliver therapeutic miRNAs to CRC.

Cytotoxic Alkaloids from Leaves of Pilea aff. martinii.

Two new phenanthroquinolizidine alkaloids (1: and 2: ) and a new piperidine derivative (3: ) were isolated from the leaves of Pilea aff. martinii together with 3 known alkaloids: julandine (4: ), cryptopleurine (5: ), and 1,3,6,6-tetramethyl-5,6,7,8-tetrahydro-isoquinolin-8-one (6: ). Their structures were determined by spectral data analyses including mass spectrometry and 2-dimensional nuclear magnetic resonance data. The absolute configurations of 1: -3: were established by comparison of their experimental circular dichroism data with the calculated electronic circular dichroism spectra. The isolated compounds were evaluated for their cytotoxicity against 4 cancer cell lines: KB (mouth epidermal carcinoma cells), HepG-2 (human liver hepatocellular carcinoma cells), LU-1 (human lung adenocarcinoma cells), and MCF-7 (human breast cancer cells). The new phenanthroquinolizidine pileamartine D (2: ) showed strong and selective proliferation inhibition toward KB and HepG-2 cells with IC50 values of 25 and 27 nM, respectively. Pileamartine C (1: ), julandine (4: ), and cryptopleurine (5: ) exhibited cytotoxicity against 4 tested cancer cell lines with IC50 values less than 1 µM.

Development and evaluation of a non-ribosomal random PCR and next-generation sequencing based assay for detection and sequencing of hand, foot and mouth disease pathogens.

BACKGROUND: Hand, foot and mouth disease (HFMD) has become a major public health problem across the Asia-Pacific region, and is commonly caused by enterovirus A71 (EV-A71) and coxsackievirus A6 (CV-A6), CV-A10 and CV-A16. Generating pathogen whole-genome sequences is essential for understanding their evolutionary biology. The frequent replacements among EV serotypes and a limited numbers of available whole-genome sequences hinder the development of overlapping PCRs for whole-genome sequencing. We developed and evaluated a non-ribosomal random PCR (rPCR) and next-generation sequencing based assay for sequence-independent whole-genome amplification and sequencing of HFMD pathogens. A total of 16 EV-A71/CV-A6/CV-A10/CV-A16 PCR positive rectal/throat swabs (Cp values: 20.9-33.3) were used for assay evaluation. RESULTS: Our assay evidently outperformed the conventional rPCR in terms of the total number of EV-A71 reads and the percentage of EV-A71 reads: 2.6 % (1275/50,000 reads) vs. 0.1 % (31/50,000) and 6 % (3008/50,000) vs. 0.9 % (433/50,000) for two samples with Cp values of 30 and 26, respectively. Additionally the assay could generate genome sequences with the percentages of coverage of 94-100 % of 4 different enterovirus serotypes in 73 % of the tested samples, representing the first whole-genome sequences of CV-A6/10/16 from Vietnam, and could assign correctly serotyping results in 100 % of 24 tested specimens. In all but three the obtained consensuses of two replicates from the same sample were 100 % identical, suggesting that our assay is highly reproducible. CONCLUSIONS: In conclusion, we have successfully developed a non-ribosomal rPCR and next-generation sequencing based assay for sensitive detection and direct whole-genome sequencing of HFMD pathogens from clinical samples.

Modeling and Optimization for a New Compliant 2-dof Stage for Locating Biomaterial Samples by an Efficient Approach of a Kinetostatic Analysis-Based Method and Neural Network Algorithm.

The nanoindentation technique is employed to characterize the behaviors of biomaterials. Nevertheless, there is a lack of development of a miniaturized precise positioner for in situ nanoindentation. Besides, modeling behaviors of the positioner are restricted due to its complex kinematic characteristics. Therefore, this paper proposes a novel compliant two degrees of freedom (dof) stage for positioning a biomaterial sample in in situ nanoindentation. In addition, a new modeling and dimensional optimization synthesis method of the stage is developed. The proposed effective methodology is developed based on a kinetostatic analysis-based calculation method, the Lagrange approach, and a neural network algorithm. With an increased advance in artificial intelligence, a neural network algorithm is proposed to extend the applicability of artificial neural networks in optimizing the parameters of the stage. First, the 2-dof stage is built via a combination of an eight-lever displacement amplifier and a symmetric parallelogram mechanism. Second, a chain of mathematical equations of the 2-dof stage is constructed using a kinetostatic analysis-based method to calculate the ratio of displacement amplification and the input stiffness of the 2-dof stage. Then, the Lagrange method is utilized to formulate the dynamic equation of the 2-dof stage. Finally, a neural network algorithm is adopted to maximize the natural first frequency of the proposed stage. The optimal results determined that the frequency of the stage can achieve a high value of 112.0995 Hz. Besides, the formed mathematical models were relatively precise by comprising the simulation verifications.

Formulation and characterization of hydroxyethyl cellulose-based gel containing metronidazole-loaded solid lipid nanoparticles for buccal mucosal drug delivery.

Local delivery of drug is a promising strategy to manage periodontitis characterized by chronic inflammation of the soft tissue surrounding the teeth. An optimized system should prolong the drug retention time and exhibit controlled drug permeation through the buccal mucosal layer. This study was aimed to develop hydroxyethyl cellulose (HEC)-based gel containing metronidazole (MTZ) loaded in solid lipid nanoparticles (SLNs), and to enhance the antimicrobial activity of MTZ. SLNs were prepared using a combination method of solvent evaporation and hot homogenization. The results showed that the fabricated SLNs, comprising of Precirol (2.93%, w/v), Tween 80 (1.8%, w/v), and the drug:lipid ratio of 19.3% (w/w), were approximately 200 nm in size, with a narrow distribution. The HEC (3%, w/w)-based gel formed a smooth, homogeneous structure and had preferable mechanical and rheological properties. Moreover, the MTZ-loaded SLNs-based HEC gel (equivalent to 1% of MTZ, w/w) exhibited a sustained in vitro drug release pattern, optimal ex vivo permeability, and enhanced in vitro antimicrobial activity after 24 h of treatment. These findings indicate the potential of the MTZ-loaded SLNs-based HEC formulation for local drug delivery at the buccal mucosa in managing periodontal disease.

Urban drainage channels as microplastics pollution hotspots in developing areas: A case study in Da Nang, Vietnam.

This study provides information on the current situation of microplastics contamination in inland freshwater bodies in Vietnam. An urban drainage channel in Da Nang City was selected as a case study. Receiving mainly domestic wastewater and landfill leachate, the channel itself is becoming a microplastic pollution hotspot with a microplastic concentration of 1482.0 ± 1060.4 items m-3 in waters and 6120.0 ± 2145.7 items kg-1 in sediments. The dominant shapes of microplastics were fibers and fragments, in which the polymer types were mainly polyethylene, polypropylene, and polyethylene terephthalate. Microplastics with sizes ranging from 1000 to 5000 µm tended to be distributed primarily in surface waters, whereas particles from 300 to 1000 µm accumulated in sediments. The channel places Da Nang Bay at a high risk for microplastic pollution, with an estimated pollution load of approximately 623 × 106 items d-1 in dry weather.

Temporalis Muscle Flap for the Immediate Reconstruction of Oral Defects after Oncologic Resection.

An oral defect after oncologic resection, especially in the upper jaw, is an extremely complex problem in terms of reconstructive surgery. Herein, we report 2 patients who were diagnosed with oral mucosal squamous cell carcinoma. In one patient, the lesion was present on the right side of the hard palate, invading the maxillary bone. In the other patient, the lesion was present in the left retromolar trigone region. Reconstruction of the postsurgical defects was successfully done using a temporalis muscle flap. Both patients were discharged after ensuring the absence of any postsurgical complications. Furthermore, the postoperative functional and esthetic outcomes were adequate. These case reports highlight the usefulness and reliability of a temporalis muscle flap for the immediate reconstruction of oral and maxillary defects after oncologic resection.

Cleft Lip/Nasal Deformities After Plastic Surgery for Unilateral Cleft Lip/Palate: A Prospective Study at a Large Hospital in Vietnam.

INTRODUCTION: Congenital cleft lip, with or without cleft palate, is the most common deformity of the face. Primary plastic surgery for rehabilitation and esthetics is important for patients and their parents; however, secondary deformities of the lip and nose can occur after the primary surgery. Therefore, we performed assessment of secondary cleft lip/nasal deformities to aid in planning of surgical repair of these deformities. MATERIALS AND METHODS: Forty-six patients with unilateral cleft lip, with or without cleft palate, were operated with different techniques and examined post-surgery at the Department of Maxillofacial Surgery, University of Medicine and Pharmacy Hospital and Center of Odonto-Stomatology, Hue Central Hospital. They were assessed according to Motier's post-operative evaluation scale (1997), including the red lip, white lip, scars, and nose. RESULTS: V notch and defect on the shift line were the most common deformities on the red lip (52.2%). About 34.8% of the patients had a short white lip on the cleft side. Straight and prominent scars were observed in 52.2% of the patients. The most common deformities of the nose were septal deviation (78.3%), followed by defects in the upper part of the nostril contour (78.3%), narrow sill (52.2%), and low position of the ala (47.8%). CONCLUSION: Secondary cleft lip/nasal deformities are unavoidable. It is necessary to develop a plan for surgical repair of these deformities. There is no single method of cleft lip surgery that gives perfect results. Therefore, clinicians choose a combination of methods to bring optimal results for each patient.

Formation of the upper digestive tract by the ileum - right colon for patient with concurrent cancers of the esophagus and the stomach: A case report.

INTRODUCTION AND IMPORTANCE: A very rare case with presence of both esophageal and gastric cancers raised questions on how to perform optimal surgery for such cases. To date, reports on experimental surgery strategies for these rare cases remained sparse in the literatures. CASE PRESENTATION: A 61-year-old male patient having epigastric abdominal pain and swallowing difficulties for a month prior to the hospital. Esophagoscopy and gastroscopy results showed a 2-cm lesion in the esophagus, located around 25 cm away from the teeth arch; and a 2-cm ulcer lesion with high ridge line at the corner of the lesser curvature of stomach. Biopsy results revealed esophageal squamous epithelium carcinoma and poorly differentiated gastric adenocarcinoma. The surgery was esophago-gastrectomy with curettage of the lymph nodes and reconstruction of the upper gastrointestinal tract with the ileum - right colon in the left side of the neck. CLINICAL DISCUSSION: We did not remain the stomach and performed thoracoscopic Ivor Lewis esophagectomy with chest anastomosis, as in previous studies to prevent cancer recurrence. Here, we performed a new surgical method of reconstruct the upper gastrointestinal tract by connecting the upper part of the esophagus at the neck, to the ileum - right colon. CONCLUSIONS: This case could suggest an effective surgical strategy that the ileum - right colon was an organ to be used in replacing the upper gastrointestinal tract in cases of removing the entire stomach and thoracic esophagus, which could serve as a valuable reference for similar rare cases in the future.

Cytotoxic phenolic compounds isolated from the fruits of Macaranga denticulata.

A new modified geranylated flavonoid, 3'-dehydroxy-solophenol C (1), along with 17 known compounds (2-18) were isolated from the fruits of Macaranga denticulata. Their structures were established by spectral analysis, such as mass spectrometry, 1D-NMR and 2D-NMR. The new geranylated flavonoid 1 showed a moderate cytotoxic activity against the A549 cell line with IC50 value of 16.0 µM. Compound 9 showed the highest cytotoxic activities against KB, HepG2, Lu-1 and MCF7 cell lines with IC50 values of 0.6, 0.8, 1.3 and 1.2 µM, respectively.

Characteristics of microplastics in shoreline sediments from a tropical and urbanized beach (Da Nang, Vietnam).

Microplastics in shoreline sediments were investigated from Da Nang beach for the first time. Sediment samples at the two depth strata (0-5 cm and 5-10 cm) at eight sites along the entire coast were collected for identifying the characteristics of microplastics, including their concentration, size, shape, color, and nature. The synthetic fiber was the predominant type of microplastics, accounting for 99.2% of the total items. Blue (59.9%) and white (22.9%) were the most common colors of the fibers. Synthetic fibers showed a homogenous distribution at all sampling sites with a mean concentration of 9238 ± 2097 items kg-1 d.w. Meanwhile, the fibers tended to concentrate much more at the surface stratum than the deeper stratum. A large number of synthetic fibers (81.9%) were in the size range of 300-2600 µm, which might pose a threat to marine biota and human health.

A Novel Liposomal S-Propargyl-Cysteine: A Sustained Release of Hydrogen Sulfide Reducing Myocardial Fibrosis via TGF-ß1/Smad Pathway.

PURPOSE: S-propargyl-cysteine (SPRC; alternatively known as ZYZ-802) is a novel modulator of endogenous tissue H2S concentrations with known cardioprotective and anti-inflammatory effects. However, its rapid metabolism and excretion have limited its clinical application. To overcome these issues, we have developed some novel liposomal carriers to deliver ZYZ-802 to cells and tissues and have characterized their physicochemical, morphological and pharmacological properties. METHODS: Two liposomal formulations of ZYZ-802 were prepared by thin-layer hydration and the morphological characteristics of each liposome system were assessed using a laser particle size analyzer and transmission electron microscopy. The entrapment efficiency and ZYZ-802 release profiles were determined following ultrafiltration centrifugation, dialysis tube and HPLC measurements. LC-MS/MS was used to evaluate the pharmacokinetic parameters and tissue distribution profiles of each formulation via the measurements of plasma and tissues ZYZ-802 and H2S concentrations. Using an in vivo model of heart failure (HF), the cardio-protective effects of liposomal carrier were determined by echocardiography, histopathology, Western blot and the assessment of antioxidant and myocardial fibrosis markers. RESULTS: Both liposomal formulations improved ZYZ-802 pharmacokinetics and optimized H2S concentrations in plasma and tissues. Liposomal ZYZ-802 showed enhanced cardioprotective effects in vivo. Importantly, liposomal ZYZ-802 could inhibit myocardial fibrosis via the inhibition of the TGF-ß1/Smad signaling pathway. CONCLUSION: The liposomal formulations of ZYZ-802 have enhanced pharmacokinetic and pharmacological properties in vivo. This work is the first report to describe the development of liposomal formulations to improve the sustained release of H2S within tissues.

An investigation of antitumor efficiency of novel sustained and targeted 5-fluorouracil nanoparticles.

Traditional chemotherapeutic drugs remain the major treatment for advanced colorectal cancer. However, due to the lack of tumor specificity these drug also destroy healthy tissue and organs, which has been the main reason for treatment failure and mortality. Folate-based drug delivery systems for improving nanoparticle endocytosis have been used to address these problems. Here, folic acid (FA) conjugated mPEG-b-P(CABCL-co-ACL) diblock copolymers were synthesized and characterized by TEM and NMR. Drug loaded nanoparticles were prepared using dialysis method and was obtained with a mean diameter of 45.2 nm with sustained in vitro release profile. In vitro cytotoxicity assay indicated that the cytotoxicity of folate modified nanoparticles were significantly increased compared to free drug and non-folate nanoparticles. In addition, results of hemolytic and histopathologic study suggested that the non-loaded nanoparticle (NL/NP) was non-toxic and biocompatible at the testing concentration. Moreover, in vivo results showed that FA/5-FU/NP effectively inhibited growth of HCT-8 cell-based xenograft tumors in BALB/c mice and revealed stronger antitumor efficacy than other treated groups. Thus, both in vitro and in vivo results exhibited that the folate conjugated mPEG-b-P(CABCL-co-ACL) copolymers have great potential to be used as sustainable and specific colon cancer targeting delivery system for anticancer agents.

Overcoming multidrug resistance in 2D and 3D culture models by controlled drug chitosan-graft poly(caprolactone)-based nanoparticles.

The principal limitations of chemotherapy are dose-limiting systemic toxicity and the development of multidrug-resistant phenotypes. The aim of this study was to investigate the efficiency of a new sustained drug delivery system based on chitosan and ε-caprolactone to overcome multidrug resistance in monolayer and drug resistance associated with the three-dimensional (3D) tumor microenvironment in our established 3D models. The 5-fluorouracil (5-FU)-loaded nanoparticles (NPs) were characterized by transmission electron microscope and dynamic light scattering, and its released property was determined at different pH values. 5-FU/NPs exhibited well-sustained release properties and markedly enhanced the cytotoxicity of 5-FU against HCT116/L-OHP or HCT8/VCR MDR cells in two-dimensional (2D) and its parental cells in 3D collagen gel culture with twofold to threefold decrease in the IC50 values, as demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Hoechst/propidium iodide staining and flow cytometry analysis. Furthermore, the possible mechanism was explored by high-performance liquid chromatography and rhodamine 123 accumulation experiment. Overall, the results demonstrated that 5-FU/NPs increase intracellular concentration of 5-FU and enhance its anticancer efficiency by inducing apoptosis. It was suggested that this novel NPs are a promising carrier to decrease toxic of 5-FU and has the potential to reverse the forms of both intrinsic and acquired drug resistance in 2D and 3D cultures.

Chemical components of Ardisia splendens leaves and their activity against coxsackie A16 viruses.

Using a combination of chromatographic methods, one new flavonol glycoside, myricetin 3,7-di-O-alpha-L-rhamnopyranoside (1), and nine known compounds myricitrin (2), quercetin 3,7-di-O-alpha-L-rhamnopyranoside (3), quercitrin (4), desmanthin-l (5), myricetin 3-O-(3"-O-galloyl)-alpha-L-rhamnopyranoside (6), (+)-catechin (7), benzyl O-1-D-glucopyranoside (8), 2-phenylethyl O-beta-D-glucopyranoside (9), and corilagin (10) were isolated from the leaves of Ardisia splendens Pit. Based on an in vitro test against Coxsackie viruses A16 by SRB assay, only compounds 2, 5, and 10 exhibited activity against Coxsackie viruses A16 with IC50 values of 40.1, 32.2, and 30.5 microM, respectively. This result suggested that compounds 2, 5, and 10 might be potential agents for treating hand, foot and mouth diseases.