Mechanism of action of buckwheat quercetin in regulating lipid metabolism and intestinal flora via Toll-like receptor 4 or nuclear factor κB pathway in rats on a high-fat diet.

OBJECTIVES: Buckwheat quercetin (QUE) was used as a dietary supplement to investigate the mechanism of QUE on the regulation of lipid metabolism and intestinal flora in hyperlipidemic rats. METHODS: Here, using a high-fat diet-induced hyperlipidemia model, the intervention was carried out by gavage of QUE at doses of 50, 100, and 200 mg/kg. Serum lipid levels, liver biochemical parameters, and histopathologic changes in the liver and intestinal microorganisms were measured in rats by enzyme-linked immunosorbent assay, hematoxylin-eosin, and high-throughput sequencing, respectively. RESULTS: Our results found that QUE, at a dose of 200 mg/kg, significantly reduced body weight, liver index, and lipid levels in rats (P < 0.05); improved hepatic oxidative stress; and repaired liver injury. In addition, the upregulation of beneficial bacteria, such as christensenellaceae and Bifidobacterium, in the organism increased the content of short-chain fatty acids, thus interfering with intestinal pH and improving the intestinal environment, while downregulating the relative abundance of Proteobacteria and Eubacterium_coprostanoligenes_group, and regulating the overproduction of butyrate. The real-time fluorescence quantitative polymerase chain reaction results found that QUE inhibited the expression of Toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) mRNA content and blocked the activation of the TLR4/NF-κB signaling pathway, thus affecting the downregulation of lipid levels and restoring intestinal homeostasis. CONCLUSIONS: A QUE dose of 200 mg/kg may improve lipid levels and the composition of intestinal flora through the TLR4/NF-κB pathway, suggesting that proteobacteria and christensenellaceae abundance changes may be biomarkers of potential diseases.

Simultaneous Delivery of Dual Inhibitors of DNA Damage Repair Sensitizes Pancreatic Cancer Response to Irreversible Electroporation.

Pancreatic ductal adenocarcinoma (PDAC) is an abysmal disease refractory to most standard therapies. Irreversible electroporation (IRE) is a local ablative technique for the clinical treatment of solid tumors, including locally advanced and unresectable PDAC, by intratumorally delivering high-intensity electric pulses to permanently disrupt cell membranes and induce cell death. But the distribution of electric field is uneven within the tumor, and in some regions, tumor cells only experience temporary perturbation to their cell membrane, a phenomenon denoted as reversible electroporation (RE). These tumor cells may survive and therefore are the main culprit of tumor relapse after IRE. We herein showed that RE, although not killing tumor cells, induced DNA double-strand breaks and activated DNA damage repair (DDR) responses. Using reactive oxygen species-sensitive polymeric micelles coloaded with Olaparib, an inhibitor of poly(ADP-ribose) polymerase (PARP), and AZD0156, an inhibitor of ataxia telangiectasia mutated (ATM), the resultant nanoformulation (M-TK-OA) disrupted both homologous recombination and nonhomologous end joining signaling of the DDR response and impaired colony formation in pancreatic cancer cells after RE. The combination of IRE and M-TK-OA significantly prolonged animal survival in both subcutaneous and orthotopic murine PDAC models and elicited CD8+ T cell-mediated antitumor immunity with a sustained antitumor memory. The efficacy of combined IRE and M-TK-OA treatments was partially attributed to the activation of cyclic GMP-AMP synthase-stimulator of interferon genes innate immune responses. Our study suggests that dual inhibition of PARP and ATM with nanomedicine is a promising strategy to enhance the pancreatic cancer response to IRE.

Minimizing the Elastic Energy of Growing Leaves by Conformal Mapping.

During morphogenesis, the shape of living species results from growth, stress relaxation, and remodeling. When the growth does not generate any stress, the body shape only reflects the growth density. In two dimensions, we show that stress free configurations are simply determined by the time evolution of a conformal mapping which concerns not only the boundary but also the displacement field during an arbitrary period of time inside the sample. Fresh planar leaves are good examples for our study: they have no elastic stress, almost no weight, and their shape can be easily represented by holomorphic functions. The growth factor, isotropic or anisotropic, is related to the metrics between the initial and current conformal maps. By adjusting the mathematical shape function, main characteristics such as tips (convex or concave or sharp-pointed), undulating borders, and veins can be mathematically recovered, which are in good agreement with observations. It is worth mentioning that this flexible method allows us to study complex morphologies of growing leaves such as the fenestration process in Monstera deliciosa, and can also shed light on many other 2D biological patterns.

Interaction Between Autophagy and Porphyromonas gingivalis-Induced Inflammation.

Autophagy is an immune homeostasis process induced by multiple intracellular and extracellular signals. Inflammation is a protective response to harmful stimuli such as pathogen microbial infection and body tissue damage. Porphyromonas gingivalis infection elicits both autophagy and inflammation, and dysregulation of autophagy and inflammation promotes pathology. This review focuses on the interaction between autophagy and inflammation caused by Porphyromonas gingivalis infection, aiming to elaborate on the possible mechanism involved in the interaction.

Active Vibration Control of Piezoelectric Sandwich Plates.

This paper deals with the active vibration control of piezoelectric sandwich plate. The structure consists of a substrate plate layer sandwiched between two layers of piezoelectric sensor and actuator. Based on laminate theory and constitutive equation of piezoelectric material, the vibration active control dynamic equation of the sandwich structure is established by using hypothetical mode method and Hamilton principle. The Rayleigh-Ritz method is used to solve it. The form of hypothetical solution is used for approximate solution, which is simple and accurate. The method of this paper is verified by several examples. The parametric studies of the sandwich plate structures are carried out. The results show that applying different boundary conditions and piezoelectric patch positions to the structures have a great influence on the natural frequency. When the driving voltage increases, the deflection of the plate structures increase approximately linearly. The active vibration control studies are investigated as well. The results show that within a certain range, the larger the value of the speed feedback coefficient, the better the active control effect. The positions of the piezoelectric patches affect the effectiveness and cost of active control. When the piezoelectric plate is located at the fixed end, the effect and cost of active control are better than that at the midpoint and free end of the plate.

Phenyl-incorporated carbon nitride photocatalyst with extended visible-light-absorption for enhanced hydrogen production from water splitting.

Developing and employing photocatalysts with extended visible-light-absorption has emerged as a fundamental issue for the enhanced capability of photocatalytic H2 evolution from water splitting. Herein, a wide-spectrum light-responsive phenyl-grafted carbon nitride photocatalyst was synthesized. It was found that benzonquanmine-derived g-C3N4 (BCN) exhibits significantly extended light absorption (∼670 nm) compared with conventional melamine-derived g-C3N4 (MCN). Correspondingly, the photocatalytic H2-evolution rate of BCN (2846 µmol h-1 g-1) is five times as that of MCN under visible-light irradiation. Particularly, an impressive H2-evolution rate of 58 µmol h-1 g-1 could be achieved on BCN even under light irradiation beyond 620 nm. The outstanding photocatalytic H2-evolution performance could be not only attributed to the enriched photons generated from the enhanced solar energy harvesting, but also to the distinctly inhibited rapid recombination of photogenerated electron-hole pairs resulting from the incorporation of phenyl groups. This work furnishes a new train of thought for the designing of carbon-nitride-based photocatalysts with enhanced capability of visible-light-utilization.

Endoscopy-Assisted Laparoscopic versus Laparoscopic Surgery for Gastrointestinal Stromal Tumor and the Impact on Patients' Coagulation, Surgical Condition, and Complications.

Objective: To assess the clinical efficiency of endoscopy-assisted laparoscopic versus laparoscopic surgery for gastrointestinal stromal tumors and the impact on patients' coagulation, surgical condition, and complications. Methods: Between November 2016 and May 2020, 126 eligible patients diagnosed with gastrointestinal stromal tumor (GIST) in our institution were recruited. They were concurrently randomly assigned at a ratio of 1 : 1 to receive either laparoscopic gastrectomy (reference group) or endoscopy-assisted laparoscopic gastrectomy (research group). The two groups were compared in terms of patients' coagulation function, surgical conditions, and complications. Results: The two groups had similar preoperative coagulation indices and the postoperative levels of activated partial thromboplastin time (APTT) and thromboplastin time (TT) (P > 0.05). Compared with the reference group, the research group showed lower PT levels (10.48 ± 0.68 vs. 11.97 ± 0.46) and higher FIB levels (0.67 ± 0.11 vs. 0.29 ± 0.07) (P < 0.05). Compared with the reference group, the study group had shorter operative time (81.21 ± 10.24 min versus 98.98 ± 15.31 min), shorter surgical incision (3.63 ± 1.12 cm versus 5.01 ± 1.14 cm), and less intraoperative bleeding (18.74 ± 6.98 ml versus 58.69 ± 15.87 ml) (P < 0.05). A markedly shorter length of hospital stay, time to the first postoperative exhaustion, and duration of drainage tube and gastric tube dwelling were observed in the research group versus the reference group (P < 0.05). The study group presented higher nutritional levels of patients at 3 days after surgery and a lower incidence of complication. Conclusion: Endoscopy-assisted laparoscopic treatment shows significant improvements in the efficiency of minimally invasive surgery and ensures a better prognosis and quality of life of patients with a good safety profile, so it is worthy of clinical application.

Melatonin Receptor 1B Genetic Variants on Susceptibility to Gestational Diabetes Mellitus: A Hospital-Based Case-Control Study in Wuhan, Central China.

Purpose: The aim of the study was to find out the associations of Melatonin receptor 1B (MTNR1B) genetic variants with gestational diabetes mellitus (GDM) in Wuhan of central China. Patients and Methods: A hospital-based case-control study that included 1679 women was carried out to explore the associations of MTNR1B single nucleotide polymorphisms (SNPs) with GDM risk, which were analyzed through logistic regression analysis by adjusting age, pre-pregnancy BMI and family history of diabetes. Multifactor dimensionality reduction was applied to determine gene-gene interactions between SNPs. Results: MTNR1B SNPs rs10830962, rs10830963, rs1387153, rs7936247 and rs4753426 were significantly associated with GDM risk (P<0.05). The rs10830962/G, rs10830963/G, rs1387153/T, and rs7936247/T were risk variants, whereas rs4753426/T was protective variant for GDM development. Fasting plasma glucose (FPG) and 1h-plasma glucose (PG) were significantly different among genotypes at rs10830962 and rs10830963, whereas 2h-PG levels were not. Gene-gene interactions were not found among the five SNPs on GDM risk. Conclusion: MTNR1B genetic variants have significant associations but no gene-gene interactions with GDM risk in central Chinese population. Furthermore, MTNR1B SNPs have significant relationships with glycemic traits.

Association of glucokinase gene and glucokinase regulatory protein gene polymorphisms with gestational diabetes mellitus: A case-control study.

OBJECTIVES: The aim of this study was to investigate the association of glucokinase (GCK) gene, glucokinase regulatory protein (GCKR) gene polymorphisms with the susceptibility to GDM in Chinese population. RESEARCH DESIGN AND METHODS: This case-control study included 835 GDM patients and 870 non-diabetic pregnant women who had their prenatal examinations at 24-28 gestational weeks at the Maternal and Child Health Hospital of Hubei Province from January 15, 2018 to March 31, 2019. The nurses were trained to collect clinical information and blood samples. The candidate single nucleotide polymorphism (SNPs, GCK rs1799884, rs4607517, rs10278336, rs2268574, rs730497 and GCKR rs780094, rs1260326) were genotyped on Sequenom Massarray platform. Statistical analysis including independent sample t test, chi-square test, logistic regression and one-way ANOVA were performed to evaluate the differences in allele and genotype distributions and their correlations with the odds of GDM. RESULTS: There were statistically significant differences in age, pre-gestational BMI, education level and family history of diabetes between case and control group (P < 0.05). After adjusting for these confounders, GCK rs1799884 was still significantly associated with GDM (P < 0.05), but there were no significant associations between rs4607517, rs10278336 and rs2268574, rs780094 and rs1260326 polymorphisms and GDM odds (P > 0.05). In addition, the pregnant women with rs4607517 TT genotype had the significantly higher fasting blood glucose level than CC genotype (P < 0.05). CONCLUSION: GCK rs1799884 mutation is associated with higher GDM odds in Chinese population. Further larger studies are needed to explore the association between GCK and GCKR polymorphisms and GDM susceptibility.

Non-targeted metabolomics and microbial analyses of the impact of oat antimicrobial peptides on rats with dextran sulfate sodium-induced enteritis.

To study the prevention and mechanism of oat antimicrobial peptides (AMPs) on enteritis. Oat protein was hydrolyzed by alkaline protease and isolated to obtain oat antimicrobial peptides. Rat enteritis models were constructed using dextran sodium sulfate (DSS), and a blank group, a negative control group, a positive control group, and an experimental group (low dose, medium dose, and high dose) were established. Through pathological test, antioxidant test, intestinal microbial and metabolite determination, it was found that AMPS can improve the antioxidant capacity of colon, reduce the production of inflammatory cells, and have the effect of preventing enteritis. In addition, the AMPS group is able to change and reduce the abundance of Bacteroides-eggerthii-DSM-20697 and Desulfovibrionaceae, increase the abundance of probiotics such as roboutsia and Ruminococcus and optimize the diversity of intestinal microorganisms. Then, the combined analysis of microorganism and metabolites showed that Romboutsia and Ruminococcus reduced the contents of amino acid and glucose and promoted the production of phospholipid, while Bacteroides promoted the synthesis of amino acid in the body. From the above, it can be seen that DSS causes damage to the mechanical barrier of the gut. Oat antimicrobial peptides provide a microbial barrier for the gut microbes, which produce acetic acid and succinic acid with small amounts of isobutyric acid, isovaleric acid, and lactic acid. The acidic metabolites produced reduce the pH of the gut and produce substances with antibacterial effects (such as lipophilic molecules, antibiotics, and hydroperoxides). Inhibit the growth and reproduction of other harmful bacteria, Vibrio desulphuris, from adhering to and colonizing the intestinal mucosa. Secreted short-chain fatty acids, such as acetate and butyric acid, maintain tight connections between the epithelial cells of the intestinal mucosa, thus protecting the mechanical barrier of the intestinal mucosa. Moreover, amino acids are converted into phospholipid metabolism through protein digestion and absorption to promote the production of phospholipid in the intestine and repair damaged cell membranes.

LncRNA PITPNA-AS1 promotes gastric cancer by increasing SOX4 expression via inhibition of miR-92a-3p.

BACKGROUND: Gastric cancer (GC) is a malignant tumor of digestive tract with high mortality. Elucidating the molecular mechanisms of GC and obtaining new molecular targets are particularly important for the prevention and treatment of GC. The discovery of long non-coding RNAs (lncRNAs) provides the possibility for further elucidating the molecular mechanisms of GC and discovering new molecular markers. AIM: Here, we aimed to explore the function and the mechanism of lncRNA PITPNA-AS1 in GC. METHODS: High-throughput lncRNA microarray was used to compare the differences in expression profiles between tumor tissues and adjacent tissues, and to filtrate the differentially expressed lncRNAs in tumors. To analyze the relationship between lncRNA expression and clinicopathological parameters in GC. The apoptosis was detected by down-regulation of lncRNA. The effect of down-regulated lncRNA PITPNA-AS1 on the migration and invasion of GC cells was determined by wound healing and Transwell assays. The function of lncRNA PITPNA-AS1 on tumor growth was verified by tumor experiment in nude mice. Analysis of target interaction relationship was performed by luciferase assay. RESULTS: The results of high throughput chip analysis identified that PITPNA-AS1 was up-regulated in GC tissues. Our data revealed that knockdown of PITPNA-AS1 was able to inhibit tumor development of GC cells. Meanwhile, PITPNA-AS1 could regulate SOX4 expression via targeting miR-92a-3p. CONCLUSION: Thus, we concluded that PITPNA-AS1 induced the development of GC cells by inhibiting miR-92a-3p and inducing SOX4. Our finding presents novel insights of GC, which may provide an underlying therapeutic target for GC treatment.

Inflamm-Aging-Related Cytokines of IL-17 and IFN-γ Accelerate Osteoclastogenesis and Periodontal Destruction.

Periodontal disease (PD), as an age-related disease, prevalent in middle-aged and elderly population, is characterized as inflammatory periodontal tissue loss, including gingival inflammation and alveolar bone resorption. However, the definite mechanism of aging-related inflammation in PD pathology needs further investigation. Our study is aimed at exploring the effect of inflamm-aging-related cytokines of interleukin-17 (IL-17) and interferon-γ (IFN-γ) on osteoclastogenesis in vitro and periodontal destruction in vivo. For receptor activator of nuclear factor-κB ligand- (RANKL-) primed bone marrow macrophages (BMMs), IL-17 and IFN-γ enhanced osteoclastogenesis, with the expression of osteoclastogenic mRNA (TRAP, c-Fos, MMP-9, Ctsk, and NFATc1) and protein (c-Fos and MMP-9) upregulated. Ligament-induced rat models were established to investigate the role of IL-17 and IFN-γ on experimental periodontitis. Both IL-17 and IFN-γ could enhance the local inflammation in gingival tissues. Although there might be an antagonistic interaction between IL-17 and IFN-γ, IL-17 and IFN-γ could facilitate alveolar bone loss and osteoclast differentiation.

Clinical evaluation of xenogeneic collagen matrix versus free gingival grafts for keratinized mucosa augmentation around dental implants: A randomized controlled clinical trial.

AIM: To evaluate the outcomes of an apically repositioned flap (ARF) plus xenogeneic collagen matrix (XCM) in augmenting keratinized mucosa width (KMW) around dental implants when compared with ARF plus free gingival grafts (FGG). MATERIALS AND METHODS: Twenty-six participants with at least one site with KMW ≤2 mm were randomized into FGG or XCM group. Clinical examinations were performed at baseline and at 2 and 6 months after surgery, including KMW, keratinized mucosa thickness, gingival index (GI), and probing depth (PD). Post-operative pain and patient satisfaction were also evaluated. RESULTS: At 6 months, FGG attained a greater increase of KMW and thicker mucosa than XCM (4.1 ± 1.6 mm vs. 1.8 ± 1.0 mm, p < .001; 1.7 ± 0.6 mm vs. 1.2 ± 0.3 mm, p < .01). Regarding GI, PD, post-operative pain, aesthetic outcomes, and patient satisfaction, no significant difference could be detected. Moreover, the operation time of XCM group was shorter (60 ± 9 min vs. 39 ± 8 min, p < .001). CONCLUSIONS: FGG could result in greater increase of KMW than XCM, though both could increase KMW, maintain peri-implant health, and attain comparable aesthetic outcomes. The use of XCM was associated with reduced operation time.

Association of vitamin D receptor gene polymorphisms with gestational diabetes mellitus-a case control study in Wuhan, China.

BACKGROUND: Gestational diabetes mellitus (GDM) increased risk of perinatal complications for both the women and the fetuses. The association between the vitamin D receptor (VDR) gene polymorphism and GDM has not been thoroughly investigated in Chinese pregnant women. Therefore, we aimed to determine whether VDR gene single nucleotide polymorphisms (SNPs) rs154410, rs7975232, rs731236, rs2228570 and rs739837 contribute to GDM risk in Wuhan, China. Moreover, we aimed to explore their combined effects on the risk of GDM. METHODS: Pregnant women who had prenatal examinations at 24 to 28 weeks' gestation in our hospital from January 15, 2018 to March 31, 2019 were included in this case-control study. After exclusion, a total of 1684 pregnant women (826 GDM patients and 858 non-diabetic controls) were recruited. The clinical information and blood samples were collected by trained interviewers and nurses. Genotyping of candidate SNPs was conducted on the Sequenom MassARRAY platform. Statistical analyses including t-test, ANOVA, chi-square test and logistic regression were performed to the data with SPSS Software to evaluate differences in genotype distribution and associations with GDM risk. Multifactor dimensionality reduction method was used to explore the gene-gene interactions on the risk of GDM. RESULTS: Differences in age, pre-pregnancy BMI, family history of diabetes and previous history of GDM between the case and control groups were statistically significant (P < 0.05), whereas no significant differences were found in height, gravidity, parity, and age of menarche (P > 0.05). There were no significant differences at genotype distributions of the examined VDR gene SNPs (P > 0.05). After adjusting by age, pre-pregnancy BMI, family history of diabetes, the results of logistic regression analysis showed no associations of the five SNPs with GDM in all the four genotype models(P > 0.05). Furthermore, there were no gene-gene interactions on the GDM risk among the five examined VDR gene SNPs. CONCLUSIONS: The VDR gene SNPs rs154410, rs7975232, rs731236, rs2228570 and rs739837 showed neither significant associations nor gene-gene interactions with GDM in Wuhan, China.

Efficacy of nano-carbonate apatite dentifrice in relief from dentine hypersensitivity following non-surgical periodontal therapy: a randomized controlled trial.

BACKGROUND: Dentine hypersensitivity (DH) could occur or intensify after non-surgical periodontal therapy because of the exposure of dentine tubules, but currently no gold standard exists to treat DH. It has been demonstrated that nano-sized particles presented potential for dentine tubules blocking and remineralization. This randomized controlled trial aimed to investigate the efficacy of dentifrice containing nano-carbonate apatite (n-CAP) in reducing dentine hypersensitivity (DH) after non-surgical periodontal therapy. METHODS: 48 periodontitis patients with DH were included in this clinical trial. After non-surgical periodontal therapy, patients included were randomized to test and control group and the respective dentifrices were applied at chairside, after which they were instructed to brush teeth with the allocated dentifrices twice a day at home. Periodontal parameters were recorded at baseline and the last follow-up. DH was measured by air-blast test and recorded by visual analogue scale (VAS) and Schiff sensitivity scale at baseline, after polishing (0 week) and 2/4/6 weeks. RESULTS: 45 participants completed the follow-up. Periodontal parameters were improved and comparable between groups. Significant reduction in DH was observed in both groups at all time-points compared to baseline in terms of VAS and Schiff score. The test group achieved significantly greater relief from hypersensitivity compared with the control group after 4-week at-home use (for change of VAS, test group: 2.27 ± 2.47 versus control group: 1.68 ± 2.24, p = 0.036; for change of Schiff, test group: 0.94 ± 0.92 versus control group: 0.61 ± 0.83, p < 0.001). The 6-week results showed borderline significance between groups in terms of change of Schiff (p = 0.027) and no significance in terms of change of VAS (p = 0.256). CONCLUSIONS: Home-use of n-CAP based dentifrice had some benefit on alleviation of DH following non-surgical periodontal therapy after 4 weeks compared to the control product. TRIAL REGISTRATION: Chinese Clinical Trials Registry (No. ChiCTR-IPR-17011678, http://www.chictr.org.cn/, registered 16 June, 2017).

Autophagy negative-regulating Wnt signaling enhanced inflammatory osteoclastogenesis from Pre-OCs in vitro.

Periodontitis thereby the alveolar bone loss induced by inflammation, is a wide-spread phenomenon around the world. It is an ongoing challenge faced by clinicians worldwide. This study aimed to identify the effects of lipopolysaccharide (LPS) on osteoclasts (OCs) differentiation in vitro and to investigate its molecular mechanism. For bone marrow derived macrophages (considered as Pro-OCs), LPS impaired their differentiation into OCs in a dose-dependent manner. In contrast, it promoted Pre-OCs (referred to receptor activator of nuclear factor-κB ligand (RANKL) pretreated Pro-OCs) and differentiated to OCs with increased maximum diameter, quantity, the covering area and the fusion index in vitro. It also facilitated OCs proliferation, bone resorption and OCs related genes expression. Furthermore, it was revealed that LPS enhanced OCs genesis from Pre-OCs via activating autophagy pathway consequently elevated the accumulation of TRAP, Cts K and NFATC1, specific genes of OCs. The members of Wnt signaling were expressed as at lower states during the LPS induced OCs formation, but they could be rescued in the presence of autophagy inhibitor. The most promising observation was the direct interaction of LC3B and Dvl2, indicating that the crosstalk between above pathways existed in OCs. Taken together, we consider that LPS activates autophagy which negatively regulates Wnt signaling via autophagic degradation of Dvl2 is significant for osteoclastogenesis from Pre-OCs in vitro. Our study sheds light on the fact that autophagy inhibitors will become a new, potentially applicable therapeutic option in the treatment of periodontal bone loss.

Long-term stability of root coverage procedures for single gingival recessions: A systematic review and meta-analysis.

AIM: To evaluate the long-term (≥2 years) stability of root coverage procedures for single gingival recessions. MATERIALS AND METHODS: A complete literature search was performed up to July 2018. Randomized controlled trials (RCTs) following ≥2 years were selected. Primary outcomes were complete root coverage (CRC) and mean root coverage (MRC). Secondary outcomes were width of keratinized tissue (KTW) and patient-centred parameters. Meta-analysis was conducted when possible. RESULTS: A total of fifteen RCTs were included. The results demonstrated significantly higher MRC in short-term than long-term after coronally advanced flap (CAF; 7.29%, p = 0.006). When CAF combined with connective tissue graft (CTG), no significant difference was observed in CRC or MRC for short-term versus long-term (1.00, p = 0.97; 2.35%, p = 0.09), and it resulted in better long-term efficacy than CAF alone in terms of CRC (0.69, p = 0.0006) and KTW (-0.63 mm, p = 0.04). For CAF plus enamel matrix derivative, the meta-analysis showed no significant difference between the short-term and long-term results of CRC (1.26, p = 0.21). CONCLUSIONS: CAF alone could result in decreased postoperative percentage of root coverage with time. CAF + CTG could maintain long-term stability and result in better root coverage outcomes than CAF.

In vivo mechanical characterization of human facial skin combining curved surface imaging and indentation techniques.

BACKGROUND: The mechanical properties of human facial skin are of considerable importance for clinical research and cosmetic industry. As a result of their susceptibility to the individual difference and complex surroundings of human beings, the in vivo mechanical characterization by objective and quantitative devices is challenging. METHODS: In this study, an experimental setup was custom-designed for the mechanical characterization combining curved surface optical imaging and indentation techniques. By means of an independently developed transparent indenter, the contact area and topography of facial skin can be in vivo and in situ captured in real time. Especially, the perpendicularity between indenter and facial skin can be adjusted and guaranteed by imaging analyses. RESULTS: A modified formula for the contact area calculation of silica gel, one of the most common materials used to simulate human facial skin, has been proposed. The highly improved agreement with the indentation tests shows its reliability and better applicability compared to the classical Hertz theory. Furthermore, we perform the in vivo indentation tests on human facial skin to evaluate the Young's modulus, which shows a potential for better understanding of their mechanical properties. CONCLUSION: The device presented could give convincing results. The in vivo mechanical properties of human facial skin obtained by our modified formula agree well with open literature, and a better reliability than classical Hertz theory is evidenced.

Intervention Studies of Inhaled Corticosteroids Combined with Long-acting Theophylline or Long-acting ß2-agonists in Patients with Moderate to Severe Asthma: A Randomized, Controlled Study.

PURPOSE: To evaluate and contrast the therapeutic effect and safety of fluticasone aerosol combined with theophylline tablets in patients with moderate to severe asthma, compared with salmeterol/fluticasone propionate aerosol. METHODS: After a screening period, patients meeting the inclusion criteria were randomly assigned to the experiment group (fluticasone aerosol combined with theophylline tablets) or the control group (salmeterol/fluticasone aerosol combined with placebo tablets) for 12 weeks of treatment. The main outcome measurements were forced expiratory volume in 1 second and fractional concentration of exhaled nitric oxide value, whereas the secondary measures were forced vital capacity, peak expiratory flow value, and Asthma Control Test/Asthma Quality of Life Questionnaire score. FINDINGS: Forty-four cases completed the course, with 23 cases in the experiment group and 21 cases in the control group. The forced expiratory volume in 1 second values of both groups were significantly improved from before (P < 0.05). The fractional concentration of exhaled nitric oxide values of both groups were significantly decreased from before (P < 0.05). The secondary outcome measurements after treatment achieved obvious improvement from baseline (P < 0.05) in both. There was no significant difference between the 2 groups in all measurements. In addition, the blood biochemistry results, ECG results, and vital signs of both groups had no significant abnormality. IMPLICATIONS: There was no significant difference in therapeutic effect and safety between the 2 groups in treating patients with moderate to severe persistent asthma, which suggests that fluticasone aerosol combined with theophylline tablets is worth considering for use in primary hospitals or for low-income populations.

Mutational Analysis of Glycogen Synthase Kinase 3ß Protein Kinase Together with Kinome-Wide Binding and Stability Studies Suggests Context-Dependent Recognition of Kinases by the Chaperone Heat Shock Protein 90.

The heat shock protein 90 (HSP90) and cell division cycle 37 (CDC37) chaperones are key regulators of protein kinase folding and maturation. Recent evidence suggests that thermodynamic properties of kinases, rather than primary sequences, are recognized by the chaperones. In concordance, we observed a striking difference in HSP90 binding between wild-type (WT) and kinase-dead (KD) glycogen synthase kinase 3ß (GSK3ß) forms. Using model cell lines stably expressing these two GSK3ß forms, we observed no interaction between WT GSK3ß and HSP90, in stark contrast to KD GSK3ß forming a stable complex with HSP90 at a 1:1 ratio. In a survey of 91 ectopically expressed kinases in DLD-1 cells, we compared two parameters to measure HSP90 dependency: static binding and kinase stability following HSP90 inhibition. We observed no correlation between HSP90 binding and reduced stability of a kinase after pharmacological inhibition of HSP90. We expanded our stability study to >50 endogenous kinases across four cell lines and demonstrated that HSP90 dependency is context dependent. These observations suggest that HSP90 binds to its kinase client in a particular conformation that we hypothesize to be associated with the nucleotide-processing cycle. Lastly, we performed proteomics profiling of kinases and phosphopeptides in DLD-1 cells to globally define the impact of HSP90 inhibition on the kinome.