A Mendelian randomization study between chronic periodontitis and non-alcoholic fatty liver disease.

BACKGROUND AND OBJECTIVE: Observational studies have suggested a potential association between non-alcoholic fatty liver disease (NAFLD) and chronic periodontitis (CP). However, these studies are prone to confounding factors. The aim of this study was to assess the causal relationship between NAFLD and CP using a two-sample bidirectional Mendelian randomization (MR) analysis method. METHODS: Datasets of CP and NAFLD were retrieved from the European database, and instrumental variables (IVs) related to exposure were selected for the MR analysis. Sensitivity tests, including heterogeneity and horizontal pleiotropy tests, were conducted to ensure the consistency of the selected IVs, following which the analysis results were visualized. RESULTS: Genetic variants associated with CP and NAFLD were identified as IVs, and the MR assessment was performed using the summary data (CP: 3046 cases and 195 395 controls; NAFLD: 894 cases and 217 898 controls). CP increased the risk of NAFLD (inverse variance weighted [IVW], b = 0.132 > 0, p = .006 < .05), whereas the reverse was not observed (IVW, b = -0.024 < 0, p = .081 > .05). The sensitivity analysis indicated no heterogeneity or horizontal pleiotropy. CONCLUSION: The MR analysis suggested that CP could increase the risk of NAFLD among European populations.

DLX6-AS1 regulates odonto/osteogenic differentiation in dental pulp cells under the control of BMP9 via the miR-128-3p/MAPK14 axis: A laboratory investigation.

AIM: The regenerative capacity of dental pulp relies on the odonto/osteogenic differentiation of dental pulp cells (DPCs), but dynamic microenvironmental changes hinder the process. Bone morphogenetic protein 9 (BMP9) promotes differentiation of DPCs towards an odonto/osteogenic lineage, forming dentinal-like tissue. However, the molecular mechanism underlying its action remains unclear. This study investigates the role of DLX6 antisense RNA 1 (DLX6-AS1) in odonto/osteogenic differentiation induced by BMP9. METHODOLOGY: Custom RT2 profiler PCR array, quantitative Real-Time PCR (qRT-PCR) and western blots were used to investigate the expression pattern of DLX6-AS1 and its potential signal axis. Osteogenic ability was evaluated using alkaline phosphatase and alizarin red S staining. Interactions between lncRNA and miRNA, as well as miRNA and mRNA, were predicted through bioinformatic assays, which were subsequently validated via RNA immunoprecipitation and dual luciferase reporter assays. Student's t-test or one-way ANOVA with post hoc Tukey HSD tests were employed for data analysis, with a p-value of less than .05 considered statistically significant. RESULTS: DLX6-AS1 was upregulated upon BMP9 overexpression in DPCs, thereby promoting odonto/osteogenic differentiation. Additionally, miR-128-3p participated in BMP9-induced odonto/osteogenic differentiation by interacting with the downstream signal MAPK14. Modifying the expression of miR-128-3p and transfecting pcMAPK14/siMAPK14 had a rescue impact on odonto/osteogenic differentiation downstream of DLX6-AS1. Lastly, miR-128-3p directly interacted with both MAPK14 and DLX6-AS1. CONCLUSIONS: DLX6-AS1 could regulate the odonto/osteogenic differentiation of DPCs under the control of BMP9 through the miR-128-3p/MAPK14 axis.

Metagenomic analysis of oral and intestinal microbiome of patients during the initial stage of orthodontic treatment.

INTRODUCTION: This prospective study analyzed changes in the oral and intestinal microbiomes in patients before and after fixed orthodontic treatment, elucidating the impacts of fixed orthodontic treatment on patient health and metabolism. METHODS: Metagenomic analysis was conducted on stool, dental plaque, and saliva samples from 10 fixed orthodontic patients. All the samples were sequenced with Illumina NovaSeq 6000 with a paired-end sequencing length of 150 bp. Identification of taxa in metagenomes and functional annotation of genes of the microbiota were performed using the data after quality control. Clinical periodontal parameters, including the gingiva index, plaque index, and pocket probing depth, were examined at each time point in triplicates. Patients also received a table to record their oral hygiene habits of brushing, flossing, and dessert consumption frequency over 1 month. RESULTS: The brushing and flossing times per day of patients were significantly increased after treatment compared with baseline. The number of times a patient ate dessert daily was also fewer after treatment than at baseline. In addition, the plaque index decreased significantly, whereas the pH value of saliva, gingiva index, and pocket probing depth did not change. No significant differences were observed between the participants before and after orthodontic treatment regarding alpha-diversity analysis of the gut, dental plaque, or saliva microbiota. However, on closer analysis, periodontal disease-associated bacteria levels in the oral cavity remain elevated. Alterations in gut microbiota were also observed after orthodontic treatment. CONCLUSIONS: The richness and diversity of the microbiome did not change significantly during the initial stage of fixed orthodontic treatment. However, the levels of periodontal disease-associated bacteria increased.

Network analysis of three-dimensional hard-soft tissue relationships in the lower 1/3 of the face: skeletal Class I-normodivergent malocclusion versus Class II-hyperdivergent malocclusion.

BACKGROUND: The determining effect of facial hard tissues on soft tissue morphology in orthodontic patients has yet to be explained. The aim of this study was to clarify the hard-soft tissue relationships of the lower 1/3 of the face in skeletal Class II-hyperdivergent patients compared with those in Class I-normodivergent patients using network analysis. METHODS: Fifty-two adult patients (42 females, 10 males; age, 26.58 ± 5.80 years) were divided into two groups: Group 1, 25 subjects, skeletal Class I normodivergent pattern with straight profile; Group 2, 27 subjects, skeletal Class II hyperdivergent pattern with convex profile. Pretreatment cone-beam computed tomography and three-dimensional facial scans were taken and superimposed, on which landmarks were identified manually, and their coordinate values were used for network analysis. RESULTS: (1) In sagittal direction, Group 2 correlations were generally weaker than Group 1. In both the vertical and sagittal directions of Group 1, the most influential hard tissue landmarks to soft tissues were located between the level of cemento-enamel junction of upper teeth and root apex of lower teeth. In Group 2, the hard tissue landmarks with the greatest influence in vertical direction were distributed more forward and downward than in Group 1. (2) In Group 1, all the correlations for vertical-hard tissue to sagittal-soft tissue position and sagittal-hard tissue to vertical-soft tissue position were positive. However, Group 2 correlations between vertical-hard tissue and sagittal-soft tissue positions were mostly negative. Between sagittal-hard tissue and vertical-soft tissue positions, Group 2 correlations were negative for mandible, and were positive for maxilla and teeth. CONCLUSION: Compared with Class I normodivergent patients with straight profile, Class II hyperdivergent patients with convex profile had more variations in soft tissue morphology in sagittal direction. In vertical direction, the most relevant hard tissue landmarks on which soft tissue predictions should be based were distributed more forward and downward in Class II hyperdivergent patients with convex profile. Class II hyperdivergent pattern with convex profile was an imbalanced phenotype concerning sagittal and vertical positions of maxillofacial hard and soft tissues.

Orthodontic retreatment need and related self-perceived factors among contemporary college freshmen in China.

Given that an increasing number of patients who received orthodontic treatment during their childhood or adolescence are seeking retreatment in contemporary China, it is of great necessity to comprehensively understand their motivations. A valid and reliable self-designed questionnaire, based on the Index of complexity, outcome and need (ICON), was distributed online to college freshmen who received orthodontic treatment during their childhood or adolescence. After collecting their basic information and orthodontic retreatment needs data from the survey, the participants' general self-perception of front facial appearance, lateral facial appearance and tooth alignment, as well as their self-perceived dental alignment, occlusal status, oral function and psychological status, were assessed. Correlation analysis, Chi-square test, Kruskal-Wallis test and logistic regression were performed. Reliability was evaluated for 20 paired questionnaires, and all questions were found to be reliable (intraclass correlation coefficient, >0.70). Among the 1609 participants with a history of orthodontic treatment, 45.56% were males and 54.44% were females. Their mean age was 18.48 ± 0.91 years. Our results showed that self-perceived front facial appearance, lateral facial profile, tooth alignment, occlusal status, oral function and psychological status were significantly correlated with orthodontic retreatment needs. Both appearance and psychological status affected their self-perceived dental alignment and occlusal status. In conclusion, patients who received orthodontic treatment during their childhood or adolescence in contemporary China seek orthodontic retreatment because they desire better aesthetics of their front facial appearance and tooth alignment, especially the anterior region of the tooth, the lower part of the face and a decent pronunciation. Additionally, psychological concerns should be viewed as an urge, while intraoral factors should be viewed as the foundation during future clinical practice regarding orthodontic retreatment in this age group.

Radiographic adjacent segment degeneration and risk factors for osteoporotic vertebral compression fractures treated with percutaneous kyphoplasty.

PURPOSE: In this study, we aimed to clarify whether osteoporotic vertebral compression fracture (OVCF) following percutaneous kyphoplasty (PKP) was associated with a high risk for radiographic adjacent segment degeneration (ASD) and to identify the risk factors for radiographic ASD in these individuals. METHODS: We retrospectively reviewed consecutive patients with OVCFs who underwent PKP at our institution between November 2015 and January 2021. The incidence of radiographic ASD was calculated and specific subgroups of ASD were identified. Univariate and multivariate analyses of demographic, clinical baseline, and radiologic data were performed to identify risk factors associated with radiographic ASD. RESULTS: With a mean follow-up time of 27.3 months, a total of 95 eligible patients were enrolled. The incidence of radiographic ASD distinguished from natural degeneration was 52.6%. Patients with OVCFs who underwent PKP had a high risk of developing radiographic ASD, particularly disc degeneration. Intradiscal cement leakage (odds ratio [OR], 5.706; 95% confidence interval [CI], 2.039-15.970; P = 0.001) and preoperative disc height (OR, 0.681; 95% CI, 0.518-0.895; P = 0.006) were identified as independent risk factors. CONCLUSION: Patients with OVCFs who underwent PKP were more likely to develop radiographic ASD, and their progression was distinguished from natural degeneration. Disc degeneration was the most common type of degeneration. Intradiscal cement leakage and preoperative disc height were identified as independent risk factors for developing radiographic ASD in these patients. Further validation through prospective multicenter studies is required.

A survey regarding orthodontic treatment among contemporary college freshmen in China.

BACKGROUND: A growing number of Chinese residents are seeking orthodontic treatment. The aim of the study was to investigate rates of orthodontic publicity, orthodontic treatment history and related factors among college freshmen in China, to preliminarily understand the current situation of orthodontic publicity and treatment in China, especially after the 2020s. METHODS: Referred to previous studies, a self-designed online questionnaire of Chinese college freshmen was conducted. The questionnaire was divided into two parts, after collecting basic information, we investigated orthodontic publicity rate and orthodontic treatment history with starting age, relapse phenomenon, satisfaction score and willingness to re-treatment. Factors hindering first-time and second-time treatment were also collected. The statistical analysis was performed using the Chi-square test, t-test, Kruskal-Wallis test and logistic regression analysis. RESULTS: The response rate was 100% and 3308 responses were included. The male to female ratio was 1524:1784 with a mean age of 18.43 years (SD 0.91 years). Statistically significant of economic administrative regions, age, major and orthodontics engagement of relatives or friends were found on prevalence and rate of orthodontic treatment (P < 0.05). Average opinion on orthodontic treatment was "satisfied" and most claimed a phenomenon of relapse (slight relapse: 38.22%, obvious relapse: 23.12%), where age, major and orthodontics engagement of relatives or friends showed statistically significant. Retreatment willingness was correlation with start age and relapse phenomenon. For those who refused first-time treatment, except for good tooth arrangement condition, pain, long-time span, and cost weighted, while for those who refused re-treatment, the fair of discomfort and long-time span ranked at the top. CONCLUSIONS: In contemporary China, the prevalence and rate of orthodontic treatment had been greatly promoted. Earlier age for receiving orthodontic treatment was also discovered. Subjective factors regarding psychology, self-requirement affected the need of orthodontic treatment. Contemporary Chinese college freshmen had a high ability of judging dental alignment, while improve of overall orthodontic care level is still required.

Clinical observation of postoperative warfarin anticoagulation in 300 patients undergoing mitral valve replacement with a carbomedics mechanical valve.

OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of low-intensity warfarin treatment in Chinese patients after mitral valve replacement as well as the rationality of the INR standards of the hospital (The First People's Hospital of Jining City). METHODS: We retrospectively analyzed 270 cases in our hospital from January 2009 to December 2013; 239 patients completed the 5-year follow-up. There were 192 male and 78 female subjects, age 32-65 years old with a mean age 51.51 ± 12.12 years old. All eligible candidates received a Carbomedics artificial mechanical valve replacement and were anticoagulated under this hospital's current guidelines for postoperative anticoagulant therapy mitral valve replacement (INR 1.8-2.5). We analyzed the patient's regularly recorded prothrombin times (PTs) and the occurrence of anticoagulation-related complications, such as bleeding, thrombosis, and embolism. RESULTS: A follow-up for 239 of 300 patients was performed for 3-60 months. Within this group, one patient died from cerebral hemorrhage, there was 1 case of subcutaneous bleeding, 1 case of epistaxis, 12 cases of gingival bleeding, in 15 menstrual quantity increased, and in 1 case we found cerebral infarction. CONCLUSIONS: In conclusion, low-intensity anticoagulation after mitral Carbomedics valve replacement is therapeutically effective and safe. There is room to improve the anticoagulation standard currently used, perhaps at a slightly lower level than this standard suggests. From our research we can formulate individualized treatment plans and effectively reduce the occurrence of complications.

Nitrogen-doped carbon dots derived from polyvinyl pyrrolidone and their multicolor cell imaging.

Nitrogen-doped carbon dots (N-CDs) with a high quantum yield of 19.6% were prepared by calcining polyvinyl pyrrolidone (PVP, K-30), and then modified with 4,7,10-trioxa-1,13-tridecanediamine. The as-prepared N-CDs exhibited excitation-dependent and pH-sensitive photoluminescence. Transmission electron microscopy and Raman spectra demonstrated the graphitic structure of the N-CDs. Fourier transform infrared spectroscopy and x-ray diffraction studies revealed successful passivation and the presence of hydrophilic groups on the surface. Importantly, such modified quantum dots acted as good multicolor cell imaging probes due to their excellent fluorescent properties, low cytotoxicity and fine dispersity.

The Host Response to Autogenous, Allogeneic, and Xenogeneic Treated Dentin Matrix/Demineralized Dentin Matrix-Oriented Tissue Regeneration.

Dentin is a bone-like matrix that forms the bulk of the tooth. By fabricating dentin with protocols involving demineralization, sterilization, and preservation, treated dentin matrix (TDM)/demineralized dentin matrix (DDM) could be obtained, which is considered as a useful tool for bone and tooth-tissue regeneration. Non-negligible inflammatory and immune responses are reviewed in this article of autogenous, allogeneic, and xenogeneic TDM/DDM for the first time. Both autogenous and allogeneic TDM/DDM showed good biocompatibility in original and clinical studies, while a few cases reported the observation of inflammatory cells around tissue samples. As for xenogeneic TDM/DDM, multiple immune responses were revealed. Immune cells, including eosinocytes, macrophages, lymphocytes, mutinucleated giant cell, M1/M2 macrophages, and Th1-type CTL responses were involved. To avoid these adverse inflammatory responses caused by TDM/DDM implantation, some of the effective fabricating methods are discussed to reduce host immune responses to TDM/DDM.

Applications of hydrogels in tissue-engineered repairing of temporomandibular joint diseases.

Epidemiological studies reveal that symptoms of temporomandibular joint disorders (TMDs) occur in 60-70% of adults. The inflammatory damage caused by TMDs can easily lead to defects in the articular disc, condylar cartilage, subchondral bone and muscle of the temporomandibular joint (TMJ) and cause pain. Despite the availability of various methods for treating TMDs, few existing treatment schemes can achieve permanent recovery. This necessity drives the search for new approaches. Hydrogels, polymers with high water content, have found widespread use in tissue engineering and regeneration due to their excellent biocompatibility and mechanical properties, which resemble those of human tissues. In the context of TMD therapy, numerous experiments have demonstrated that hydrogels show favorable effects in aspects such as articular disc repair, cartilage regeneration, muscle repair, pain relief, and drug delivery. This review aims to summarize the application of hydrogels in the therapy of TMDs based on recent research findings. It also highlights deficiencies in current hydrogel research related to TMD therapy and outlines the broad potential of hydrogel applications in treating TMJ diseases in the future.

Jaw osteoporosis: Challenges to oral health and emerging perspectives of treatment.

Osteoporosis is a prevalent bone metabolic disease that poses a significant challenge to global human health. Jaw osteoporosis, characterized by microstructural damage of the jaw resulting from various factors, is one of the common manifestations of this condition. Recent studies have demonstrated that jaw osteoporosis has multifaceted effects on oral health and can negatively impact conditions such as periodontitis, oral implantation, orthodontic treatment, and wound healing. However, there are still some limitations in the conventional treatment of osteoporosis. For instance, while bisphosphonates can enhance bone quality, they may also lead to osteonecrosis of the jaw, which poses a potential safety hazard in oral diagnosis and treatment. In recent years, considerable attention has been focused on improving the pathological condition of jaw osteoporosis. Treatment strategies such as gut microbial regulation, extracellular vesicles, molecular targeted therapy, herbal medicine, mechanical stimulation are expected to enhance efficacy and minimize adverse reactions. Therefore, understanding these effects and exploring novel treatments for jaw osteoporosis may provide new insights for oral health maintenance and disease treatment. This article reviews the impact of jaw osteoporosis on oral health and describes the limitations associated with current methods. It also discusses emerging perspectives on treatment, offering a comprehensive overview of the challenges and future directions in managing jaw osteoporosis.

Human apolipoprotein E peptides inhibit hepatitis C virus entry by blocking virus binding.

UNLABELLED: Hepatitis C virus (HCV) entry is a multiple-step process involving a number of host factors and hence represents a promising target for new antiviral drug development. In search of novel inhibitors of HCV infection, we found that a human apolipoprotein E (apoE) peptide, hEP, containing both a receptor binding fragment and a lipid binding fragment of apoE specifically blocked the entry of cell culture grown HCV (HCVcc) at submicromolar concentrations. hEP caused little cytotoxicity in vitro and remained active even if left 24 hours in cell culture. Interestingly, hEP inhibited neither human immunodeficiency virus (HIV)-HCV pseudotypes (HCVpp) nor HIV and Dengue virus (DENV) infection. Further characterization mapped the anti-HCV activity to a 32-residue region that harbors the receptor binding domain of apoE, but this fragment must contain a cysteine residue at the N-terminus to mediate dimer formation. The anti-HCV activity of the peptide appears to be dependent on both its length and sequence and correlates with its ability to bind lipids. Finally, we demonstrated that the apoE-derived peptides directly blocked the binding of both HCVcc and patient serum-derived virus to hepatoma cells as well as primary human hepatocytes. CONCLUSION: apoE peptides potently inhibit HCV infection and suggest a direct role of apoE in mediating HCV entry. Our findings also highlight the potential of developing apoE mimetic peptides as novel HCV entry inhibitors by targeting HCV-host interactions.

Reactive Oxygen Species-Responsive Polymeric Prodrug Nanoparticles for Selective and Effective Treatment of Inflammatory Diseases.

It is challenging to manage inflammatory diseases using traditional anti-inflammatory drugs due to their limited efficacy and systemic side effects, which are a result of their lack of selectivity, poor stability, and low solubility. Herein, it reports the development of a novel nanoparticle system, called ROS-CA-NPs, which is formed using polymer-cinnamaldehyde (CA) conjugates and is responsive to reactive oxygen species (ROS). ROS-CA-NPs exhibit excellent drug stability, tissue selectivity, and controlled drug release upon oxidative stress activation. Using mouse models of chronic rheumatoid arthritis and acute ulcerative colitis, this study demonstrates that the systemic administration of ROS-CA-NPs results in their accumulation at inflamed lesions and leads to greater therapeutic efficacy compared to traditional drugs. Furthermore, ROS-CA-NPs present excellent biocompatibility. The findings suggest that ROS-CA-NPs have the potential to be developed as safe and effective nanotherapeutic agents for a broad range of inflammatory diseases.

The investigation on polyion complex micelles composed of diammonium glycyrrhizinate/poly(ethylene glycol)-glycidyltrimethylammonium chloride-grafted polyasparthydrazide.

To prepare stable polyion complex (PIC) micelles, polyasparthydrazide (PAHy) modified with glycidyltrimethylammonium groups and methoxy poly(ethylene glycol) (mPEG) (mPEG-g-PAHy-GTA) was synthesized. The cytotoxicity of the polymer was evaluated by the methyl tetrazolium assay. The polymer entrapped the diammonium glycyrrhizinate (DG) and formed polyion complexes. The effect of pH value, grafting degree of mPEG, copolymer and drug concentration on the micelle formation was investigated by means of measuring entrapment efficiency and micelle size. In vitro DG release from the PIC micelles was detected by dialysis in various media of different ionic strengths. To examine the pharmacokinetic behavior of micelles in vivo, the time course of the drug in plasma was evaluated. The cytotoxicity of the polymer was very low. The results showed that entrapment efficiency can reach about 93%, and the mean particle size was almost 50 nm. The drug release rate decreased with a decrease in ionic strength of the release medium or an increase in the PEG grafting degree. Compared with DG solution, the AUC of DG micelles had a twofold increase. The smaller clearance and longer mean residence time of the DG micelles group compared with DG solution group showed that the DG loaded in PIC micelles can reduce drug elimination and prolong the drug residence time in the blood circulation. The results indicated that PIC micelles composed of mPEG-g-PAHy-GTA would be prospective as a drug carrier to the drugs which can be ionized in solution.

Associations between serum lipids and hepatitis C antiviral treatment efficacy.

UNLABELLED: Approximately one half of patients who undergo antiviral therapy for chronic hepatitis C virus (HCV) genotype 1 infection do not respond to treatment. African Americans (AAs) are less responsive to treatment than Caucasian Americans (CAs), but the reasons for this disparity are largely unknown. Recent studies suggest that serum lipids may be associated with treatment response. The aims of this study were to evaluate baseline and changes in serum lipids during therapy, determine whether serum lipids are associated with virological response, and assess whether these measures explain the racial difference in efficacy. The study participants were from Virahep-C, a prospective study of treatment-naïve patients with genotype 1 HCV infection who received peginterferon (PEG-IN) alfa-2a plus ribavirin therapy for up to 48 weeks. Fasting serum lipids were analyzed at baseline and during and after therapy in 160 AAs and 170 CAs. A relative risk (RR) model was employed to evaluate characteristics associated with sustained virological response (SVR). Antiviral therapy was associated with changes in serum lipids during and after antiviral therapy, with the changes differing by race and the amount of PEG-IFN taken. Baseline lipid measures independently associated with higher rates of SVR were lower triglyceride and higher low-density lipoprotein cholesterol, with an interaction between high-density lipoprotein cholesterol (HDLc) and gender. Lipid measures did not contribute significantly to an explanation of the racial difference in SVR. CONCLUSION: Serum lipids are associated with SVR, although these paramaters did not explain the racial difference in treatment response. The results of this study are compatible with proposed biological mechanisms of HCV entry, replication, and secretion, and may underscore new potential therapeutic targets for HCV eradication.

Investigation of nanosized crystalline form to improve the oral bioavailability of poorly water soluble cilostazol.

PURPOSE: The aim of this study was to develop cilostazol (CLT) nanocrystals intended to improve its dissolution rate and enhance its bioavailability. METHODS: In this study, CLT nanosuspension was prepared by the anti-solvent and high-pressure homogenization method. The effects of the production parameters, such as the stabilizer concentration, pressure and number of cycles, were investigated. Characterization of the product was performed by scanning electron microscopy (SEM), Nitrogen adsorption, differential scanning calorimetry (DSC), X-ray powder diffraction analysis (XRPD), X-ray Photoelectron Spectroscopy (XPS), particle size analysis and dissolution testing. Additionally, the comparison studies of oral bioavailability in beagle dogs of three type tables were performed. RESULTS: The images of SEM showed a spherical smooth CLT powder, and Nitrogen adsorption test revealed spray dried powder were porous with high BET surface area compared with that of raw CLT. DSC and XRPD results demonstrated that the combination of preferred polymorph B and C of CLT were prepared successfully, the saturation solubility of the nanosized crystalline powder is about 5 fold greater than that of raw CLT, and the dissolution rate was enhanced 4 fold than that of raw CLT. The Cmax and AUC0-48h of CLT nanosized crystalline tablets were 2.1 fold and 1.9 fold, and 3.0 fold and 2.3 fold compared with those of the nanosized tablets and commercial tablets, respectively. CONCLUSION: The anti-solvent-high-pressure homogenization technique was employed successfully to produce cilostazol nanosuspensions. The bioavailability of CLT tablets prepared using spray dried nanosized crystalline powder after oral administration to dogs was markedly increased compared with that produced by nanosized tablets and commercial tablets, because of its greater dissolution rate owing to its transition of the crystalline state to form C and form B, reduced particle size and porous structure with increased surface area.

A kinetic study of the polymorphic transformation of nimodipine and indomethacin during high shear granulation.

The objective of the present study was to investigate the mechanism, kinetics, and factors affecting the polymorphic transformation of nimodipine (NMD) and indomethacin (IMC) during high shear granulation. Granules containing active pharmaceutical ingredient, microcrystalline cellulose, and low-substituted hydroxypropylcellulose were prepared with ethanolic hydroxypropylcellulose solution, and the effects of independent process variables including impeller speed and granulating temperature were taken into consideration. Two polymorphs of the model drugs and granules were characterized by X-ray powder diffraction analysis and quantitatively determined by differential scanning calorimetry. A theoretical kinetic method of ten kinetic models was applied to analyze the polymorphic transformation of model drugs. The results obtained revealed that both the transformation of modification I to modification II of NMD and the transformation of the α form to the γ form of IMC followed a two-dimensional nuclei growth mechanism. The activation energy of transformation was calculated to be 7.933 and 56.09 kJ·mol(-1) from Arrhenius plot, respectively. Both the granulating temperature and the impeller speed affected the transformation rate of the drugs and, in particular, the high shear stress significantly accelerated the transformation process. By analyzing the growth mechanisms of granules in high-shear mixer, it was concluded that the polymorphic transformation of NMD and IMC took place in accordance with granule growth in a high-shear mixer.

Comprehensive Analysis of Differentially Expressed Genes in Clinically Diagnosed Irreversible Pulpitis by Multiplatform Data Integration Using a Robust Rank Aggregation Approach.

INTRODUCTION: Molecular diagnosis may overcome the limitations of clinical and histologic diagnosis in pulpitis, thereby benefiting many treatment techniques, such as vital pulp therapies. In this study, integrated microarray data on pulpitis were used to obtain a list of normalized differentially expressed (DE) genes for analyzing the molecular mechanisms underlying pulpitis and identifying potential diagnostic biomarkers. METHODS: A systematic search of public microarray and sequencing databases was performed to obtain expression data of pulpitis. Robust rank aggregation (RRA) was used to obtain DE gene lists (RRA_DEmRNAs and RRA_DElncRNAs) between inflamed pulp and normal samples. DE genes were evaluated by functional enrichment analyses, correlation analyses for inflammation-related RRA_DEmRNAs, and protein-protein interaction and competing endogenous RNA network construction. Quantitative real-time polymerase chain reaction validation was applied in snap-frozen pulp tissues. RESULTS: Using the GSE77459 and GSE92681 data sets, 280 RRA_DEmRNAs and 90 RRA_DElncRNAs were identified. RRA_DEmRNAs were significantly enriched in inflammation-related biological processes and osteoclast differentiation and tumor necrosis factor, chemokine, and B-cell receptor signaling pathways. The molecular complex detection and cytoHubba methods identified 2 clusters and 10 hub genes in the protein-protein interaction network. The competing endogenous RNA network was composed of 2 long noncoding RNAs (ADAMTS9-AS2 and LINC00290), 2 microRNAs (hsa-miR-30a-5p and hsa-miR-128-3p), and 3 messenger RNAs (ABCA1, FBLN5, and SOCS3). The expression between most top inflammation-related RRA_DEmRNAs in pulpitis showed positive correlations. Quantitative real-time polymerase chain reacation validated the expression trends of selected genes, including ITGAX, TREM1, CD86, FCGR2A, ADAMTS9-AS2, LINC00290, hsa-miR-30a-5p, hsa-miR-128-3p, RASGRP3, IL3RA, CCDC178, CRISPLD1, LINC01857, AC007991.2, ARHGEF26-AS1, and AL021408.1. CONCLUSIONS: The identified biomarkers provide insight into the pathology and may aid in the molecular diagnosis of pulpitis.

Micropatterning of polymer substrates for cell culture.

The cell microenvironment such as substrate topology plays an important role in biological processes. In this study, microgrooves were successfully produced on surfaces of both thermoplastic and thermoset polymers using cost-effective techniques for mass production. The micropatterning of thermoplastic polystyrene (PS) petri dish was accomplished efficiently using an in-house developed low-cost hot embossing system. The high replication fidelity of the microgroove with depth and width of 2 µm and spacing of 2 µm was achieved by using silicone rubber as a soft counter mold. This patterned petri dish subsequently served as the cast to replicate the micropattern onto thermoset polydimethylsiloxane (PDMS). It was found that the micropattern increased the hydrophobicity of both PS and PDMS surfaces. The effect of the substrate micropattern on cellular behaviors was preliminarily investigated with untreated and treated PS petri dish as well as PDMS. The results show that the micropattern significantly improved cell adhesion and proliferation for cells cultured on untreated PS petri dish and PDMS substrates. Moreover, the micropattern induced obvious cell alignment along the microgrooves for culturing on all substrates which were studied.