Changes in patient peripheral blood cell microRNAs after total body irradiation during hematopoietic stem cell transplantation.

Background: Ionizing radiation exposure is a great threat to human health. MicroRNAs (miRNAs) have been shown to play an important role in radiation-induced biological effects. Here, we investigated plasma miRNA expression changes and differentially expressed miRNAs in radiotherapy patients exposed to cobalt-60 (60Co) gamma rays to provide an experimental basis for human plasma miRNAs as an estimation indicator for ionizing radiation injury. Methods: Six patients with acute lymphoblastic leukemia (ALL) received continuous 5 gray (Gy) total body irradiation (TBI) twice. At 12 hours after irradiation, miRNA microarray was applied to screen for differentially expressed miRNAs, with some miRNAs confirmed by real-time polymerase chain reaction (RT-PCR) assay. Bioinformatic analysis was carried out to identify the relevant target genes and biological function of the differentially expressed miRNAs. Results: After radiotherapy patients were exposed to 5 Gy gamma radiation, the expression of 9 plasma miRNAs was significantly upregulated, and the expression of 2 miRNAs was downregulated. After irradiation with 10 Gy gamma radiation, the blood plasma of radiotherapy patients contained 18 differentially expressed miRNAs, of which 17 were upregulated and 1 was downregulated (P<0.05). The expression of miR-4532, miR-4634, miR-4655-5p, miR-4763-3p, miR-4785, miR-6087, miR-6850-5p, and miR-6869-5p were significantly upregulated in both the 5-Gy and 10-Gy dose groups, showing a certain dose-response relationship. The RT-PCR results were consistent with the findings of high-throughput sequencing. In addition, the target genes of the differentially expressed miRNAs were mainly involved in RNA transcription and DNA damage. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that these miRNAs participated in phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), Ras, mitogen-activated protein kinase (MAPK), and other signaling pathways. Conclusions: The expression of differential plasma miRNAs of radiotherapy patients was associated with irradiation injury and showed a certain dose-effect relationship. These differentially coexpressed plasma miRNAs could be used as an early indicator for estimating radiation injury.

The effects of hyperglycemia on the biological behavior of human gingival fibroblasts on a titanium surface.

BACKGROUND: It is well known that diabetes mellitus is one of the high-risk factors for periodontitis and also for the failure of implant restorations. Usually, the success of an implant restoration depends on both the good osseointegration and the stable soft tissue interface on the implant neck. A good gingival interface of the implant neck is the barrier that enables implant to resist oral microorganisms and the site of initiation of peri-implantitis. This study sought to investigate the effects of hyperglycemia on the attachment and proliferation of human gingival fibroblasts (HGFs) on pure titanium surfaces. METHODS: HGFs were cultured in cell culture mediums with different glucose concentrations (i.e., 5.5, 8. 8, 10, and 15 mmol/L) for 7 d and seeded on pure titanium surfaces. The cells that were seeded on the titanium surfaces had been cultured in cell culture mediums with different glucose concentrations for 3 and 7 d. The attached HGFs on the titanium surfaces were counted for all groups using a blood cell counting plate, and the results were statistically analyzed. The morphologies of the attached HGFs on the titanium surfaces were observed for all the groups using a scanning electronic microscope. RESULTS: As the glucose concentrations increased, the number of attached HGFs on the titanium surfaces decreased. The numbers of attached cells in Groups A and B 7 d after being seeded on the titanium surfaces were more than those 3 d after being seeded (P<0.05). The numbers of attached cells in Groups C and D 3 d after being seeded on the titanium were more than those 7 d after being seeded (P<0.05). The scanning electronic microscope showed that the attached cells in Groups A and B proliferated well, and most cells grew one on top of another. Conversely, the attached cells in Groups C and D proliferated sparsely and the cell morphologies were not good. CONCLUSIONS: The attachment and proliferation of HGFs on pure titanium surfaces were inhibited by increases in glucose concentrations, and the inhibition was further enhanced by the passage of time.

Numerical simulation and analysis of midfacial impacts and traumatic brain injuries.

BACKGROUNDS: The maxillofacial region is the exposed part of the human body and is susceptible to injury due to the limited protective equipment. Due to anatomic proximity of the maxillofacial skeleton and cranium, the force can be transmitted directly to the brain in case of maxillofacial impact, maxillofacial injuries are often accompanied with craniocerebral trauma. Therefore, it is necessary to study the biomechanical response mechanism of trauma to improve prevention of traumatic brain injury (TBI). METHODS: To investigate the biomechanical mechanism between the two injuries, a finite element (FE) head model including skull, midfacial bones and detailed anatomical intracranial features was successfully developed based on CT/MRI data. The model was validated by comparing it with one classical cadaver experiment. During the simulations, three different load forces were used to simulate common causes of injury seen in the clinic including boxing-type impact injury and car accident-type impact injury, and four locations on the model were considered as common injury sites in the midface. RESULTS: Twelve common impact scenarios were reproduced by FE simulation successfully. Simulations showed that there was a linear relationship between the severity of TBI and the collision energy. The location of TBI was directly related to the location of the impact site, and a lateral impact was more injurious to the brain than an anterior-posterior impact. The relative movement between the skull and brain could cause physical damage to the brain. The study indicated that the midfacial bones acted as a structure capable of absorbing energy and protecting the brain from impact. CONCLUSIONS: This biomechanical information may assist surgeons better understand and diagnose brain injuries accompanied by midfacial fractures.

Clinical application and accuracy analysis of 3D printing guide plate based on polylactic acid in mandible reconstruction with fibula flap.

BACKGROUND: Due to the special anatomy morphology and physiological function of the mandible, it has always become a challenge to accurately reconstruct the mandibular defect in maxillofacial surgery. Digital three dimensions (3D) printing surgical guide, as the effective method for individual and accurate surgery, is a hotspot of clinical research at present. In this study, 3D printing PLA surgical guide plate was applied to reconstruct the mandibular defect with fibula flap, its clinical effect and accuracy were evaluated, which aimed to improve the accurate reconstruction of mandibular defects. METHODS: After sterilization, the dimension deformation of the PLA standard specimen were measured. Eighteen patients diagnose with mandibular tumor were collected as observation objects. Then partial mandible resection and simultaneous mandible reconstruction with fibula graft were implemented according to the computer-aided design plan. The clinical effects of 3D printing PLA guide plates application were evaluated by facial contours, occlusal stability and chewing function. Through registering the postoperative computed images reconstruction with preoperative designed shape, the reconstruction accuracy was evaluated by detecting the maximum difference including the distance between lateral convex point of the condyles, the distance between medial convex point of the condyles and the horizontal contained angle between long axis of the condyles. RESULTS: After high temperature steam sterilization, the curvature of the PLA specimen with 100% filling rate and 4.8 mm thickness were the smallest and their dimension deformation had no statistical significance (P>0.05). The minimally deformed 3D printing PLA guide plate were smoothly placed in the right place during the operation. After surgery, the face was symmetrical, the occlusal relationship was restored well and no deviation of the mandibular movement were found. The spiral computed tomography (SCT) scanning showed that the distance between lateral/medial convex points of the condyle and the horizontal contained angle were 128.34±8.68 mm, 88.69±6.75 mm and 145.87°±12.01°. Compared with preoperative design, the maximum deviation of the actual postoperative registration was 1.67±0.63, and the difference was not statistically significant (P>0.05). CONCLUSIONS: The application of 3D printing PLA guide plate in the segmental section and reconstruction of the mandible can effectively simplify the operation, and better reconstruct the continuity of the mandible. The surgical accuracy can fully meet clinical needs with relatively low prices.

Efficacy and safety of the long-acting fusion inhibitor albuvirtide in antiretroviral-experienced adults with human immunodeficiency virus-1: interim analysis of the randomized, controlled, phase 3, non-inferiority TALENT study.

BACKGROUND: Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. METHODS: We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. RESULTS: At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. CONCLUSIONS: The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.

[Morphological change analysis based on cone beam CT of the upper airway for obstructive sleep apnea syndrome patients treated with oral appliance in skeletal class ⠡ malocclusion with different vertical patterns].

OBJECTIVE: To analyze the morphological changes in the upper airway of obstructive sleep apnea syndrome (OSAS) patients treated with oral appliance in skeletal class Ⅱ malocclusion with different vertical features by using cone beam CT (CBCT). METHODS: Thirty-six patients diagnosed with OSAS by polysomnography and daytime sleepiness scale and skeletal class Ⅱ malocclusion were treated with oral appliance for 4 months. The changes based on CBCT in the morphology of glossopharyngeal and palatopharyngeal before and after treatment in OSAS patients with different vertical features were compared. RESULTS: After treatment with oral appliance, the glossopharyngeal and palatopharyngeal morphologies of patients with mild OSAS showed significant changes. After treatment with oral appliance, the glossopharyngeal morphology of all patients showed significant changes (P<0.05). The palatopharyngeal morphology of patients in the lower and average groups also exhibited significant changes (P<0.05). Sagittal changes in the glossopharyngeal measurements of high-angle patients demonstrated significant difference, whereas the other measured values showed no significant difference. CONCLUSIONS: The morphological changes in the upper airway were significant in OSAS patients with lower and average vertical patterns when treated with oral appliance, but the changes in high vertical patterns were not significant.

Antibacterial peptides inhibit MC3T3-E1 cells apoptosis induced by TNF-α through p38 MAPK pathway.

BACKGROUND: Antimicrobial peptides (AMP), as a small molecular polypeptide with a broad antibacterial spectrum and high efficiency, have attracted more and more attention. Few pieces of research on the effect of the antimicrobial peptide on osteoblast under inflammatory conditions have so far been reported. The main aim of this work was to investigate the antiapoptosis effect of the antimicrobial peptide on MC3T3-E1 cells induced by TNF-α and its related mechanism. METHODS: Rat MC3T3-E1 cells were co-cultured with different concentrations of antibacterial peptide DP7 and TNF-α.MTS assay, cell scratch test, alkaline phosphatase activity, and alizarin red staining assay were used to determine osteoblast viability in this experiment. Annexin V-FITC/PI double staining cells and flow cytometry were used to analyze apoptosis and Western blot assay detection to show mitogen-activated protein kinase (MAPK) protein expression in rat MC3T3-E1 cells. Then, Realtime polymerase chain reaction (PCR) was used to examine the caspase-3 gene expression. Also, ELISA detection was used to clarify the anti-apoptotic effect of the p38 MAPK inhibitor, SB203580, on cells' apoptosis. RESULTS: Antimicrobial peptide could promote the proliferation, migration, and osteogenic ability of MC3T3-E1 cells induced by TNF-α, but inhibit cell apoptosis rate (P<0.05), and the effect was concentration-dependent. Western blot results showed after TNF-αtreatment, the expression of p-p38 MAPK in the MC3T3-E1 cells increased after TNF-α and antimicrobial peptide cotreatment, TNF-α induced p-p38 MAPK phosphorylation was inhibited, and the difference was statistically significant (P<0.05). Realtime PCR results showed that the gene expression of caspase-3 mRNA was up-regulated after TNF-α treatment, while their expression was down-regulated after cultured with TNF-α and antimicrobial peptide. Elisa's analysis showed that cell apoptosis increased after TNF-α treatment alone, and cell apoptosis was reduced to the normal levels when combined with antimicrobial peptide, and cell apoptosis induced by TNF-α was partially abolished when combined with SB203580. CONCLUSIONS: Antimicrobial peptide DP7 could inhibit MC3T3-E1 cells apoptosis induced by TNF-α, and the effect was concentration-dependent. The antiapoptosis activation of the antimicrobial peptide on MC3TE-E1 cells may be related to the inhibition of the p38 MAPK pathway.

The effectiveness of adjustable oral appliance for older adult patients with obstructive sleep apnea syndrome.

BACKGROUND: Oral appliance (OA) treatment for obstructive sleep apnea syndrome (OSAS) has attracted more and more attention due to its low price, comfort, portable and non-invasion. This study aimed to investigate the clinical effectiveness of adjustable oral appliance on older adult patients with OSAS. METHODS: Thirty older adult patients diagnosed with OSAS were chosen as the study participants and received an adjustable OA for 6 months. Then, the patients were subjected to a polysomnographic examination, Berlin Questionnaire (BQ) scale questionnaire, and cone beam computer tomography (CBCT) analytical measurement to evaluate their symptom improvement and the morphologic changes of the upper airway. RESULTS: After treatment with adjustable oral appliance for six months, the results showed that there was an improvement of different degrees in the subjective symptoms. Apnea hypopnea index (AHI) had decreased from (27.65±1.31) per hour to (6.74±0.75) per hour (P<0.05); the maximum apnea time (MAT) had decreased from 43.82±2.69 to 21.37±3.18 s (P<0.05); the average oxygen saturation (MSaO2) had increased from (89.24±7.27)% to (92.69±4.46)%; the lowest oxygen saturation (LSaO2) from (81.85±8.31)% to (86.93±4.45)%. Moreover, the CBCT scanning analysis showed that the minimal sagittal diameter, sectional area, and the volume of the palatopharynx, as well as the sagittal diameter and volume of the glossopharynx significantly increased. CONCLUSIONS: The adjustable OA had considerable clinical efficacy and comfort in older adult OSAS patients by enlarging the palatopharynx and glossopharynx.

Tantalum-incorporated hydroxyapatite coating on titanium implants: its mechanical and in vitro osteogenic properties.

OBJECTIVE: The fabrication of bioactive coatings on metallic implants to enhance osseointegration has become a topic of general interest in orthopedics and dentistry. Hydroxyapatite (HA) coating has been shown to induce bone formation and promote bone-implant integration. Unfortunately, poor mechanical performance has hindered this from becoming a favorable coating material. The majority of present studies have focused in incorporating different elements into HA coatings to improve mechanical properties. In recent years, tantalum (Ta) has received increasing attention due to its excellent biocompatibility and corrosion resistance. The aim of on the present study was to investigate the fabrication and biological performance of Ta-incorporated HA coatings. METHODS: Ta-incorporated HA coatings were fabricated using the plasma spray technique on a titanium substrate, and the surface characteristics and mechanical properties were examined. In addition, the effects of Ta-incorporated HA coatings on the biological behavior of mesenchymal stem cells (BMSCs) were investigated. RESULTS: Ta-incorporated HA coatings with microporous structure had higher roughness and wettability. In addition, the bonding strength of Ta/HA coatings with the substrate was substantially superior to HA coatings. Furthermore, Ta-incorporated HA coatings not only facilitated initial cell adhesion and faster proliferation, but also promoted the osteogenic differentiation of BMSCs. CONCLUSION: These results indicate that the incorporation of Ta could improve mechanical performance and increase the osteogenic activity of HA coatings. The Ta-incorporated HA coating fabricated by plasma spraying is expected to be a promising bio-coating material for metallic implants.

[Effect of diode laser in the treatment of 78 patients with sinus chronic apical abscess].

PURPOSE: To explore the effect of diode laser in the treatment of sinus chronic apical abscess. METHODS: A total of 78 patients with sinus chronic apical abscess were randomly divided into experimental group and control group, 39 cases in each group. Patients in the control group were treated with conventional root canal preparation and calcium hydroxide sealant. After conventional root canal preparation, the canals in the experimental group were disinfected with diode laser and then calcium hydroxide sealant. SPSS 19.0 software package was used for data analysis. RESULTS: Of 39 patients in the experimental group, only 1 sinus was not healed,the total effective rate was 97.44%;Of 39 patients in the control group,9 sinuses were not healed, the total effective rate was 76.92%. The difference between the two groups was statistically significant. CONCLUSIONS: The results show that the effect of diode laser in the treatment of sinus chronic apical abscess is better, which is worthy of wide application.

Convergent synthesis of a helical, prehairpin HR1 trimer from HIV gp41.

A helical, prehairpin trimer covering the majority of the HR1 region of human immunodeficiency virus gp41 was achieved by chemically coupling three identical 51 amino acid peptides. A 1,3,5-tris(aminomethyl)-2,4,6-triethylbenzene pinwheel 'cap' was used to trimerize the peptides by taking advantage of the unique property of triacyl fluoride and orthogonal protection and deprotection. The resulting protein is fully helical, highly thermostable and soluble.

Heterobiaryl human immunodeficiency virus entry inhibitors.

Previously disclosed HIV (human immunodeficiency virus) attachment inhibitors, exemplified by BMS 806 (formally BMS378806, 1), are characterized by a substituted indole or azaindole ring linked to a benzoylpiperazine via a ketoamide or sulfonamide group. In the present report, we describe the discovery of a novel series of potent HIV entry inhibitors in which the indole or azaindole ring of previous inhibitors is replaced by a heterobiaryl group. Several of these analogues exhibited IC(50) values of less than 5 nM in a pseudotyped antiviral assay, and compound 13k was demonstrated to exhibit potency and selectivity similar to those of 1 against a panel of clinical viral isolates. Moreover, current structure-activity relationship studies of these novel biaryl gp120 inhibitors revealed that around the biaryl, a fine crevice might exist in the gp120 binding site. Taken in sum, these data reveal a hitherto unsuspected flexibility in the structure-activity relationships for these inhibitors and suggest new avenues for exploration and gp120 inhibitor design.

Design and synthesis of human immunodeficiency virus entry inhibitors: sulfonamide as an isostere for the alpha-ketoamide group.

The crystal structures of many tertiary alpha-ketoamides reveal an orthogonal arrangement of the two carbonyl groups. Based on the hypothesis that the alpha-ketoamide HIV attachment inhibitor BMS 806 (formally BMS378806, 26) might bind to its gp120 target via a similar conformation, we designed and synthesized a series of analogs in which the ketoamide group is replaced by an isosteric sulfonamide group. The most potent of these analogs, 14i, demonstrated antiviral potency comparable to 26 in the M33 pseudotyped antiviral assay. Flexible overlay calculations of a ketoamide inhibitor with a sulfonamide inhibitor revealed a single conformation of each that gave significantly better overlap of key pharmacophore features than other conformations and thus suggest a possible binding conformation for each class.