Associations between handgrip strength and skeletal muscle mass with all-cause mortality and cardiovascular mortality in people with type 2 diabetes: A prospective cohort study of the UK Biobank.

AIMS: To explore the associations between handgrip strength (HGS) and skeletal muscle mass (SMM) with all-cause and cardiovascular disease (CVD) mortality risk in type 2 diabetes (T2DM) patients. MATERIALS AND METHODS: Data were obtained from the UK Biobank. Baseline survey was conducted between 2006 and 2010, and followed up for a median of 12.52 years. HGS was measured using dynamometer, and SMM was measured using bioelectrical impedance method. Mortality was available via links to the National Health Service Information Centre. Sex-specific analyses were conducted. RESULTS: A total of 13 392 T2DM participants were included, with a mean age of 60.39 years and 52.35% men. During the follow-up, there were 3006 (22.45%) deaths, including 746 (5.57%) CVD deaths. The risk for all-cause mortality and CVD mortality among both men and women increased progressively with decreasing HGS quartiles (p trend <.05). A 1 SD decrease in HGS was found to both increase the all-cause risk (HR: 1.31 [95% CI: 1.24-1.38]) and CVD mortality risk (HR: 1.35 [95% CI: 1.22-1.50]) for men, and all-cause risk (HR: 1.26 [95% CI: 1.11-1.42]) and CVD mortality risk (HR: 1.43 [95% CI: 1.09-1.89]) for women. There was no statistically significant trend association between SMM/height2 and mortality risk, and the restricted cubic regression splines indicated that SMM/height2 showed a U-shaped nonlinear relationship (pnonlinear <.05). CONCLUSIONS: Grip strength displayed a linear downward trend with mortality risk among T2DM patients, whereas muscle mass showed a U-shaped relationship. Low grip strength seemed to be a better predictor for mortality compared to low muscle mass.

Effects of the Timing of Intense Physical Activity on Hypertension Risk in a General Population: A UK-Biobank Study.

PURPOSE OF REVIEW: It has recently been suggested that the timing of exercise is important in the subsequent development of hypertension. We used the UK Biobank database which prospectively collates data in over 500,000 people aged between 40 and 69 years to determine the relationship between the chronoactivity pattern of exercise and the risk of incident hypertension. RECENT FINDINGS: We analyzed data from 70,617 participants with 7-day Axivity AX3 triaxial accelerometry information available. Comparisons were made by a K-means clustering analysis separating groups according to the daily timing of physical activity and intensity. Subgroup, sensitivity analyses, and Cox proportional hazard model were performed. The mean age of the cohort was 61.17 (± 7.89) years with 40.05% men, and there was a mean follow-up of 7.54 (± 1.65) years. Participants were separated into 4 clusters with 6341 developing hypertension. Cluster 1 (early morning physical activity) and Cluster 2 (early morning and later physical activity) had a significantly reduced risk of incident hypertension (adjusted HR 0.870 [95%CI 0.812-0.932) vs. 0.895 [95%CI 0.825-0.972], respectively) when compared with Cluster 3 (physical activity intensity spread evenly throughout the day). Cluster 1 and Cluster 2 cases with High Intensity physical activity had a lower risk of hypertension; however, Low Intensity physical activity in Cluster 1 still reduced the risk of incident hypertension. There was a lower risk of hypertension in Cluster 1 and Cluster 2 in both morning and evening sleep chronotypes. The development of incident hypertension is significantly reduced in those who engage in some level of physical activity earlier in the day. Hypertension (high blood pressure) is a global problem with a high economic health burden that has been shown to be a major risk factor for diabetes, cardiovascular, and kidney disease. Our study has used a large maintained UK biological database to determine the impact of physical exercise on reducing the subsequent development of hypertension during follow-up from data provided by more than 70,000 participants. When we segregated patients into clusters of exercise timing, we found that the risk of developing hypertension over time was reduced for patients who performed exercise earlier in the morning than at other times of the day. This benefit was still evident even when the intensity of regular physical activity was low.

Reinforced dentin remineralization via a novel dual-affinity peptide.

OBJECTIVES: In light of the constantly flowing saliva, anti-caries remineralization agents are inclined to be taken away. Owing to their limited residence time, the remineralization effect is not as desirable as expected. Hence, our study aimed to synthesize a novel peptide (DGP) with high affinity to both collagen fibrils and hydroxyapatite, and investigated its dentin remineralization efficacy in vitro and anti-caries capability in vivo. METHODS: DGP was synthesized through Fmoc solid-phase reaction. The binding ability and interaction mechanism of DGP to demineralized dentin were investigated. Dentin specimens were demineralized, then treated with DGP and deionized water respectively. The specimens were incubated in artificial saliva and in-vitro remineralization effectiveness was analyzed after 14 days. The rat caries model was established to further scrutinize the in-vivo efficacy of caries prevention. RESULTS: DGP possesses an enhanced adhesion force of 12.29 ± 1.12 nN to demineralized dentin. The favorable adsorption capacity is ascribed to the stable hydrogen bonds between S2P-101 and ASP-100 of DGP and GLY33 and PRO-16 of collagen fibers. Abundant mineral deposits and remarkable tubule occlusion were observed in the DGP group. DGP-treated dentin obtained notable microhardness recovery and higher mineral content after a 14-day remineralization regimen. DGP also demonstrated potent caries prevention in vivo, with substantially fewer carious lesions and significantly lower Keyes scoring. SIGNIFICANCE: DGP proves to possess a high affinity to demineralized dentin regardless of saliva flowing, thus enhancing remineralization potency significantly in vitro and in vivo, potential for dental caries prevention and combatting initial dentin caries clinically.

Metronidazole and Ketoprofen-Loaded Mesoporous Magnesium Carbonate for Rapid Treatment of Acute Periodontitis In Vitro.

In the clinical pharmacological treatment of acute periodontitis, local periodontal administration is expected to be preferable to systemic administration. However, the action of the active medicine component is hindered and diminished by the limitation of drug solubility, which does not provide timely relief of the enormous pain being suffered by patients. This study aimed to develop a mesoporous magnesium carbonate (MMC) medicine loading system consisting of MMC, metronidazole (MET), and ketoprofen (KET), which was noted as MET-KET@MMC. A solvent evaporation process was utilized to load MET and KET in MMC. Scanning electron microscopy, nitrogen sorption, thermogravimetric analysis, and X-ray diffraction were performed on the MET-KET@MMC. The rapid drug release properties were also investigated through the drug release curve. The rapid antiseptic property against Porphyromonas gingivalis (P. gingivalis) and the rapid anti-inflammatory property (within 1 min) were analyzed in vitro. The cytotoxicity of MET-KET@MMC was tested in direct contact with human gingival cells and human oral keratinocytes. Crystallizations of MET and KET were completely suppressed in MMC. As compared to crystalline MET and KET, MMC induced higher apparent solubility and rapid drug release, resulting in 8.76 times and 3.43 times higher release percentages of the drugs, respectively. Over 70.11% of MET and 85.97% of KET were released from MMC within 1 min, resisting bacteria and reducing inflammation. MET-KET@MMC nanoparticles enhanced the solubility of drugs and possess rapid antimicrobial and anti-inflammatory properties. The MET-KET@MMC is a promising candidate for the pharmacotherapy of acute periodontitis with drugs, highlighting a significant clinical potential of MMC-based immediate drug release systems.

An engineered dual-functional peptide with high affinity to demineralized dentin enhanced remineralization efficacy in vitro and in vivo.

Dental caries continues to be a major global public health problem. Remineralization of demineralized dentin is regarded as one of the hotspots in the current study in the treatment of dental caries. However, traditional remineralization agents, which usually lack the ability to bind to demineralized dentin collagen, are easily removed by the fluids in the oral cavity, thus decreasing the remineralization efficacy. Non-collagenous proteins (NCPs) have significant effects on the biomineralization of dentin due to their dual high binding capacity to the collagen fibers and minerals. But NCPs are hard to extract, store and use directly. Inspired by the biological behavior of NCPs, in this study, we selected two functional sequences of NCPs to develop a novel and engineered dual-functional peptide (which is referred to as CYP) with collagen-binding and mineral-absorbing capability. The binding ability of CYP to collagen fibers and demineralized dentin was investigated, and the results suggested that CYP was endowed with good binding capacity to demineralized dentin, which could resist the washing of the fluid. In addition, we confirmed that CYP exerted formidable remineralization effects in collagen fibers and demineralized dentin following an in vitro remineralization regimen. Furthermore, the dual functions of CYP with good biocompatibility can simultaneously bind collagen and induce nanocrystal precipitation, thereby significantly absorbing calcium and phosphorus ions to form regenerated minerals for reversing the tooth decay process in the rat caries model. Overall, the dual functional peptide CYP fabricated in this study provides an ideal and smart strategy for dentin remineralization and the treatment of caries.

Associations between Consumption of Dietary Fibers and the Risk of Type 2 Diabetes, Hypertension, Obesity, Cardiovascular Diseases, and Mortality in Chinese Adults: Longitudinal Analyses from the China Health and Nutrition Survey.

Although many studies have explored the relationship between total dietary fiber intake and the risk of chronic non-communicable diseases, the results are mixed. There is also a lack of research on the association between dietary fiber intake from different food sources and disease. Using data from the China Nutrition and Health Database from 2004 to 2015, Cox proportional risk models were used to explore the associations between total dietary fiber and fiber intake from different food sources and the occurrence of type 2 diabetes, hypertension, obesity, cardiovascular disease, and all-cause mortality. After multi-factorial adjustment, the hazard ratios (95% confidence interval) of total dietary fiber intake (quartile 4 vs. quartile 1) in type 2 diabetes, hypertension, obesity, cardiovascular disease, and all-cause mortality cohorts were 1.20 (0.93, 1.55), 0.91 (0.75, 1.12), 0.93 (0.64, 1.35), 1.13 (0.60, 2.12), 1.13 (0.60, 2.12), and 1.13 (0.84, 1.52). Whole-grain fiber intake was positively associated with hypertension but not with the occurrence of other diseases. No association was observed between legume fibers, fruit fibers, and vegetable fibers in the cohorts of type 2 diabetes, hypertension, obesity, cardiovascular diseases and all-cause mortality. Our study did not find any association between total dietary fiber and dietary fiber intake from different food sources and type 2 diabetes, obesity, cardiovascular disease, and all-cause mortality in the Chinese population. The role of dietary fiber in the Chinese population may be overestimated. More extraordinary efforts are needed to further confirm the association between dietary fiber and these diseases in the Chinese population.

Dual-functional adhesive containing amorphous calcium phosphate nanoparticles and dimethylaminohexadecyl methacrylate promoted enamel remineralization in a biofilm-challenged environment.

OBJECTIVE: The cariogenic biofilm on enamel, restoration, and bonding interface is closely related to dental caries and composite restoration failure. Enamel remineralization at adhesive interface is conducive to protecting bonding interface and inhibiting secondary caries. This study intended to assess the remineralization efficiency of adhesive with dimethylaminohexadecyl methacrylate (DMAHDM) and nanoparticles of amorphous calcium phosphate (NACP) on initial caries lesion of biofilm-coated enamel. METHODS: Artificial initial carious lesion was created via 72-hour immersion in demineralization solution and cariogenic biofilm was formed after 24-hour culture of Streptococcus mutans (S. mutans). Specimens were then divided into 4 groups: enamel control, enamel treated with NACP, DMAHDM and NACP+DMAHDM respectively. Samples next underwent 7-day cycling, 4 h in BHIS (brain heart infusion broth containing 1 % sucrose) and 20 h in AS (artificial saliva) per day. The pH of BHIS was tested daily. So did the concentration of calcium and phosphate in BHIS and AS. Live/dead staining, colony-forming unit (CFU) count, and lactic acid production of biofilms were measured 7 days later. The enamel remineralization efficiency was evaluated by microhardness testing and transverse microradiography (TMR) quantitatively. RESULTS: Enamel of NACP+DMAHDM group demonstrated excellent remineralization effectiveness. And the NACP+DMAHDM adhesive released a great number of Ca2+ and PO43- ions, increased pH to 5.81 via acid neutralization, decreased production of lactic acid, and reduced CFU count of S. mutans (P < 0.05). SIGNIFICANCE: The NACP+DMAHDM adhesive would be applicable to preventing secondary caries, strengthening enamel-adhesive interface, and extending the lifespan of composite restoration.

Haploidentical transplantation has a superior graft-versus-leukemia effect than HLA-matched sibling transplantation for Ph- high-risk B-cell acute lymphoblastic leukemia.

BACKGROUND: Compared with human leukocyte antigen (HLA)-matched sibling donor (MSD) transplantation, it remains unclear whether haploidentical donor (HID) transplantation has a superior graft-versus-leukemia (GVL) effect for Philadelphia-negative (Ph-) high-risk B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to compare the GVL effect between HID and MSD transplantation for Ph- high-risk B-ALL. METHODS: This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Immunosuppressant withdrawal and prophylactic or pre-emptive donor lymphocyte infusion (DLI) were administered in patients without active graft-versus-host disease (GVHD) to prevent relapse. All patients with measurable residual disease (MRD) positivity posttransplantation (post-MRD+) or non-remission (NR) pre-transplantation received prophylactic/pre-emptive interventions. The primary endpoint was the incidence of post-MRD+. RESULTS: A total of 335 patients with Ph- high-risk B-ALL were enrolled, including 145 and 190, respectively, in the HID and MSD groups. The 3-year cumulative incidence of post-MRD+ was 27.2% (95% confidence interval [CI]: 20.2%-34.7%) and 42.6% (35.5%-49.6%) in the HID and MSD groups (P = 0.003), respectively. A total of 156 patients received DLI, including 60 (41.4%) and 96 (50.5%), respectively, in the HID and MSD groups (P = 0.096). The 3-year cumulative incidence of relapse was 18.6% (95% CI: 12.7%-25.4%) and 25.9% (19.9%-32.3%; P = 0.116) in the two groups, respectively. The 3-year overall survival (OS) was 67.4% (95% CI: 59.1%-74.4%) and 61.6% (54.2%-68.1%; P = 0.382), leukemia-free survival (LFS) was 63.4% (95% CI: 55.0%-70.7%) and 58.2% (50.8%-64.9%; P = 0.429), and GVHD-free/relapse-free survival (GRFS) was 51.7% (95% CI: 43.3%-59.5%) and 37.8% (30.9%-44.6%; P = 0.041), respectively, in the HID and MSD groups. CONCLUSION: HID transplantation has a lower incidence of post-MRD+ than MSD transplantation, suggesting that HID transplantation might have a superior GVL effect than MSD transplantation for Ph- high-risk B-ALL patients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01883180, NCT02673008.

Remineralization effectiveness of adhesive containing amorphous calcium phosphate nanoparticles on artificial initial enamel caries in a biofilm-challenged environment.

OBJECTIVES: Dental caries is closely associated with acid-producing bacteria, and Streptococcus mutans is one of the primary etiological agents. Bacterial accumulation and dental demineralization lead to destruction of bonding interface, thus limiting the longevity of composite. The present study investigated remineralization effectiveness of adhesive containing nanoparticles of amorphous calcium phosphate (NACP) in a stimulated oral biofilm environment. METHODS: The enamel blocks were immersed in demineralization solution for 72 h to imitate artificial initial carious lesion and then subjected to a Streptococcus mutans biofilm for 24 h. All the samples then underwent 4-h demineralization in brain heart infusion broth with sucrose (BHIS) and 20-h remineralization in artificial saliva (AS) for 7 days. The daily pH of BHIS after 4-h incubation, lactic acid production, colony-forming unit (CFU) count, and content of calcium (Ca) and phosphate (P) in biofilm were evaluated. Meanwhile, the remineralization effectiveness of enamel was analyzed by X-ray diffraction (XRD), surface microhardness testing, transverse microradiography (TMR) and scanning electron microscopy (SEM). RESULTS: The NACP adhesive released abundant Ca and P, achieved acid neutralization, reduced lactic acid production, and lowered CFU count (P < 0.05). Enamel treated with NACP adhesive demonstrated the best remineralization effectiveness with remineralization value of 52.29 ± 4.79% according to TMR. Better microhardness recovery of cross sections and ample mineral deposits were also observed in NACP group. CONCLUSIONS: The NACP adhesive exhibited good performance in remineralizing initial enamel lesion with cariogenic biofilm. SIGNIFICANCE: The NACP adhesive is promising to be applied for the protection of bonding interface, prevention of secondary caries, and longevity prolonging of the restoration.

Adhesion of Streptococcus mutans on remineralized enamel surface induced by poly(amido amine) dendrimers.

The aim of this study was to investigate the surface topography of remineralized enamel induced by poly(amido amine) (PAMAM) dendrimers and evaluate Streptococcus mutans (S. mutans) adhesion on regenerated enamel for the first time. PAMAM-COOH and PAMAM-NH2 were used as organic templates to induce enamel surface remineralization. The mineral deposits after remineralization were characterized by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), and X-ray diffraction (XRD). The surface topography of the remineralized enamel was analyzed by atomic force microscopy (AFM). An AFM tipless cantilever was functionalized with S. mutans and acted as a force probe to measure the adhesion force between bacteria and the remineralized enamel surface. Colony-forming unit (CFU) counts of biofilm on remineralized enamel surface were performed after 24 h incubation in S. mutans suspension. Both PAMAM-COOH and PAMAM-NH2 achieved effective remineralization on demineralized enamel surfaces, which smoothed the enamel surface and reduced S. mutans adhesion. PAMAM dendrimers are promising materials for early caries treatment because of their excellent remineralization ability. The remineralization induced by PAMAM dendrimers smoothed the surface and reduced S. mutans adhesion, which could prevent secondary caries.

Rechargeable adhesive with calcium phosphate nanoparticles inhibited long-term dentin demineralization in a biofilm-challenged environment.

OBJECTIVES: This study aims to investigate the long-term demineralization-inhibition capability of a rechargeable adhesive with nanoparticles of amorphous calcium phosphate (NACP) on dentin in a biofilm-challenged environment. METHODS: The NACP adhesive was immersed in a pH 4 solution to exhaust calcium (Ca) and phosphate (P) ions and then recharged with Ca and P ions. Dentin samples were demineralized underStreptococcus mutans biofilms for 24 h and randomly divided into two groups: (1) dentin control, (2) dentin with recharged NACP adhesives. Each day, all the samples were immersed in brain heart infusion broth with 1% sucrose (BHIS) for 4 h, and then in artificial saliva (AS) for 20 h. This cycle was repeated for 10 days. The pH of BHIS, the Ca and P ions content of the BHIS and AS were measured daily. After 10 days, the lactic acid production and colony-forming units of the biofilms were tested. The changes of remineralization/demineralization were also analyzed. RESULTS: Dentin in the control group showed further demineralization. The recharged NACP adhesive neutralized acids, increasing the pH to above 5, and released large amounts of Ca and P ions each day. The recharged NACP adhesive decreased the production of lactic acid (P < 0.05), inhibited dentin demineralization and sustained the dentin hardness in the biofilm-challenged environment, showing an excellent long-term demineralization-inhibition capability. CONCLUSIONS: The NACP adhesive could continuously inhibit dentin demineralization in a biofilm-challenged environment by recharging with Ca and P ions. SIGNIFICANCE: The rechargeable NACP adhesive could provide long-term dentin bond protection.

HIV prevalence among 338,432 infertile individuals in Hunan, China, 2012-2018: A cross-sectional study.

BACKGROUND: The prevalence of human immunodeficiency virus (HIV) varies markedly among different risk groups in China, spreading fromhigh-risk populations to the general population. Indeed, China is in a critical period of HIV/acquired immunodeficiency syndrome (AIDS) prevention and control; however, data regarding HIV testing, infection and coinfection among infertile couples are lacking. This study aimed to estimate the HIV/AIDS prevalence to identify risk factors among infertile couples in Hunan, China. METHODS: A cross-sectional hospital-based study was conducted to evaluate the prevalence of HIV/other infections (hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, and Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium (MG) infections) among 338,432 infertile individuals in Hunan, China, from 2012 to 2018. We calculated linear trends in prevalence using bivariate linear regression. RESULTS: The overall prevalence rates of HIV, chlamydia, gonorrhea, MG, syphilis, and HBV and HCV antibody positivity in this study were 0.04%, 1.73%, 0.05%, 2.60%, 2.15%, 12.01% and 0.56%, respectively. The predominant infection was HBV, followed by MG, syphilis, and chlamydia. Only 1.13% of the participants (382/338432) reported sexually transmitted disease (STD) signs and symptoms suggesting genital tract infection. However, from 2012-2018, the variation in HIV prevalence was not significant (ß = 0.000, PTREND = 0.907). The characteristics of the HIV-infected infertile population have not shifted dramatically, with women accounting for 32.56% of HIV cases in China. Overall, 87.60% of HIV-infected individuals have a relatively low education. In total, 37.98% of HIV-positive patients engage in high-risk behaviors. CONCLUSIONS: This study expands upon existing knowledge of HIV prevalence in the infertile Chinese population. However, much work is needed to achieve popularization of prevention knowledge and change concept. Routine HIV screening is urgently needed for all adults with high-risk behaviors.

Nano-calcium phosphate and dimethylaminohexadecyl methacrylate adhesive for dentin remineralization in a biofilm-challenged environment.

OBJECTIVE: Dentin remineralization at the bonded interface would protect it from external risk factors, therefore, would enhance the longevity of restoration and combat secondary caries. Dental biofilm, as one of the critical biological factors in caries formation, should not be neglected in the assessment of caries preventive agents. In this work, the remineralization effectiveness of demineralized human dentin in a multi-species dental biofilm environment via an adhesive containing nanoparticles of amorphous calcium phosphate (NACP) and dimethylaminohexadecyl methacrylate (DMAHDM) was investigated. METHODS: Dentin demineralization was promoted by subjecting samples to a three-species acidic biofilm containing Streptococcus mutans, Streptococcus sanguinis, Streptococcus gordonii for 24h. Samples were divided into a control group, a DMAHDM adhesive group, an NACP group, and an NACP+DMAHDM adhesive group. A bonded model containing a control-bonded group, a DMAHDM-bonded group, an NACP-bonded group, and an NACP+DMAHDM-bonded group was also included in this study. All samples were subjected to a remineralization protocol consisting of 4-h exposure per 24-h period in brain heart infusion broth plus 1% sucrose (BHIS) followed by immersion in artificial saliva for the remaining period. The pH of BHIS after 4-h immersion was measured every other day. After 14 days, the biofilm was assessed for colony-forming unit (CFU) count, lactic acid production, live/dead staining, and calcium and phosphate content. The mineral changes in the demineralized dentin samples were analyzed by transverse microradiography. RESULTS: The in vitro experiment results showed that the NACP+DMAHDM adhesive effectively achieved acid neutralization, decreased biofilm colony-forming unit (CFU) count, decreased biofilm lactic acid production, and increased biofilm calcium and phosphate content. The NACP+DMAHDM adhesive group had higher remineralization value than the NACP or DMAHDM alone adhesive group. SIGNIFICANCE: The NACP+DMAHDM adhesive was effective in remineralizing dentin lesion in a biofilm model. It is promising to use NACP+DMAHDM adhesive to protect bonded interface, inhibit secondary caries, and prolong the longevity of restoration.

A rapid strategy for screening high-efficiency PCSK9 inhibitors from Ginkgo biloba leaves by ligand fishing, HPLC-Q-TOF-MS and interdisciplinary assay.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an attractive target for new cholesterol-lowering drug development. Here, we developed a method integrating ligand fishing, HPLC-Q-TOF-MS and interdisciplinary assay, aiming to explore potential PCSK9 inhibitors from mixtures rapidly and accurately. PCSK9 was expressed and purified firstly, and then the recombined PCSK9 was coated on the surface of magnetic beads (MBs). The PCSK9-immobilized MBs (PCSK9-MBs) were used for ligand fishing combined with HPLC and Q-TOF-MS/MS. Ginkgo biloba leaves (GBL), an herbal medicine widely used in Asia and Europe with good efficacy in treatment of hypercholesterolemia, were chosen as an illustration for ligand fishing. Two PCSK9 ligands were discovered from GBL and identified as kaempferol-3-O-rutinoside (1) and kaempferol 3-O-26″-(6‴-p-coumaroyl) glucosylrhamnoside (KCGR) (2). In order to verify fishing results and pick out more powerful PCSK9 inhibitors, molecular docking assay was further performed and KCGR was optimized to be an excellent PCSK9 inhibitor by the confirmation of affinity and activity bioassay. These results suggested that the developed approach could be applied to screen and analysis potential bioactive constituents from mixtures, which may improve the efficiency of drug discovery. Moreover, KCGR separated from GBL was expected to be a potential candidate of PCSK9 inhibitors.

Remineralization effectiveness of the PAMAM dendrimer with different terminal groups on artificial initial enamel caries in vitro.

OBJECTIVE: Disruption of the demineralization-remineralization balance could trigger the development of dental caries, making it challenging for enamel to "self-heal". Thus, extrinsic assistance is needed to restore enamel lesions and stop undermining progression. The aim of this study was to investigate enamel remineralization in a simulated oral environment via poly (amino amine) (PAMAM) dendrimers quantitatively. METHODS: Bovine enamel specimens were shaken in demineralization solution (pH 4.5, 37°C, 50rpm/min) for 72h to create initial enamel carious lesions. The subsurface-demineralized specimens were then divided into four groups: enamel treated with PAMAM-NH2, enamel treated with PAMAM-COOH, enamel treated with PAMAM-OH, and enamel treated with deionized water. The treated specimens underwent subsequent 12-day pH cycling. Enamel blocks were analyzed by transverse microradiography (TMR), surface microhardness testing and scanning electron microscopy (SEM) before and after demineralization and pH cycling. RESULTS: Groups treated with PAMAM dendrimers showed lower lesion depth and less mineral loss, attained more vertical-section surface microhardness recovery, and adsorbed more mineral deposits (p<0.05). The enamel lesion remineralization values of PAMAM-NH2, PAMAM-COOH, and PAMAM-OH groups were 76.42±3.32%, 60.07±5.92% and 54.52±7.81%, respectively. SIGNIFICANCE: In conclusion, PAMAM with different terminal groups could induce enamel remineralization, among which PAMAM-NH2 showed the most prominent competence, followed by PAMAM-COOH and PAMAM-OH, in that order.

Dentin remineralization via adhesive containing amorphous calcium phosphate nanoparticles in a biofilm-challenged environment.

OBJECTIVES: The remineralization of dentin at a bonded interface would help to strengthen the bonded interface and inhibit secondary caries, and would prolong the longevity of restoration. The aim of this study was to investigate the remineralization of demineralized human dentin in a dental biofilm environment via an adhesive containing nanoparticles of amorphous calcium phosphate (NACP). METHODS: Dentin demineralization was promoted by subjecting samples to a Streptococcus mutans acidic biofilm for 24 h. Samples were divided into a control group, a commercial fluoride-releasing adhesive group, and an NACP adhesive group. All samples were subjected to a remineralization protocol consisting of 4-h exposure per 24-h period in brain heart infusion broth plus 1% sucrose (BHIS) followed by immersion in artificial saliva for the remaining period. The pH of BHIS after 4-h immersion was measured every other day. After 10 days, the biofilm was assessed for colony-forming unit (CFU) count, lactic acid production, live/dead staining, and calcium and phosphate content. The mineral changes in the demineralized dentin samples were analyzed by transverse microradiography, hardness measurement, X-ray diffraction characterization, and scanning electron microscopy. RESULTS: The NACP adhesive achieved acid neutralization, decreased biofilm CFU count, decreased biofilm lactic acid production, and increased biofilm calcium and phosphate content (P < 0.05). The NACP adhesive group had higher remineralization value than the commercial fluoride-releasing adhesive group (P < 0.05). CONCLUSIONS: The NACP adhesive was effective in remineralizing dentin lesions in a biofilm model. Its ability to protect bond interface, inhibit secondary caries, and prolong the longevity of restoration is promising. CLINICAL SIGNIFICANCE: Using NACP-containing adhesives could be recommended because of the protective ability of its hybrid layer even under a biofilm-challenged environment.

Dihydroartemisinin derivative DC32 inhibits inflammatory response in osteoarthritic synovium through regulating Nrf2/NF-κB pathway.

Synovitis is an aseptic inflammation that leads to joint effusion, pain and swelling. As one of the main drivers of pathogenesis in osteoarthritis (OA), the presence of synovitis contributes to pain, incidence and progression of OA. In our previous study, DC32 [(9α,12α-dihydroartemisinyl) bis(2'-chlorocinnmate)], a dihydroartemisinin derivative, was found to have an antirheumatic ability via immunosuppression, but the effect of DC32 on synovitis has not been fully illuminated. In this study, we chose to evaluate the effect and mechanism of DC32 on attenuating synovial inflammation. Fibroblast-like synoviocytes (FLSs) of papain-induced OA rats were isolated and cultured. And DC32 significantly inhibited the invasion and migration of cultured OA-FLSs, as well as the transcription of IL-6, IL-1ß, CXCL12 and CX3CL1 in cultured OA-FLSs measured by qPCR. DC32 remarkably inhibited the activation of ERK and NF-κB pathway, increased the expression of Nrf2 and HO-1 in cultured OA-FLSs detected by western blot. DC32 inhibited the degradation and phosphorylation of IκBα which further prevented the phosphorylation of NF-κB p65 and the effect of DC32 could be relieved by siRNA for Nrf2. In papain-induced OA mice, DC32 significantly alleviated papain-induced mechanical allodynia, knee joint swelling and infiltration of inflammatory cell in synovium. DC32 upregulated the mRNA expression of Type II collagen and aggrecan, and downregulated the mRNA expression of MMP2, MMP3, MMP13 and ADAMTS-5 in the knee joints of papain-induced OA mice measured by qPCR. The level of TNF-α in the serum and secretion of TNF-α in the knee joints were also reduced by DC32 in papain-induced OA mice. In conclusion, DC32 inhibited the inflammatory response in osteoarthritic synovium through regulating Nrf2/NF-κB pathway and attenuated OA. In this way, DC32 may be a potential agent in the treatment of OA.

[Recent advances in direct pulp capping materials].

The long-term effect of direct pulp capping and pulpotomy is closely related to the type of pulp capping materials. Various kinds of direct pulp capping materials are available, such as calcium hydroxide and mineral trioxide aggregates. Diverse new pulp capping materials have been reported recently. The excellent performance of calcium silicates has attracted much attention in previous studies. Moreover, enamel matrix derivative (Emdogain), which is capable of regeneration and remineralization, and other materials with similar capabilities have shown potential for use in pulp capping.