Toxic element characterization against a typical high geology background: Pollution enrichment, source tracking, spatial distribution, and ecological risk assessment.

The geological environment determines the initial content of various elements in soil, while the late input of toxic elements produced through weathering and leaching is a persistent threat to food security and human health. In this study, we selected the Lou Shao Basin, a black rock system background, and combined geostatistical analysis and multivariate statistics to quantify the specific contribution of weathering of the black rock system, and to analyze the source traces, spatial distributions, and ecological risks of the soil toxicity of elements. The results show that the soils in the study area are acidic, which is related to the weathering of sulfides in the black rock system. The concentrations of most elements in the soil were determined to exceed the soil background values, and the Cd, Se and N contents, exceeded more than five times, especially Se, Mo nearly as high as 13 times. Strong positive correlation between Se, Cu, V and P, low correlation between N and Se, Cu, V, P, Ni and Cd.72.52%, 43%, 77.79%, 82%, 77%, and 44.1% of Cd, Se, Ni, Cu, B, and Mo came from the black rock system, respectively, which were greatly affected by geogenic weathering; V, Zn, Pb, and As are mainly from biomass burning sources; N and P are mainly from agricultural surface sources. Comparison found that the Cd and Se elements in the rocks in the study area were 16.78 times and 1.36 times higher than the world shale average, respectively, and need to pay attention to the weathering process of the two, and the spatial distribution of the 12 elements in soils showed a striped and centralized block distribution pattern, specifically around the distribution of carbonate and metamorphic rocks and other high-geology blocks. The ecological risk results showed that Cd was the main element causing high ecological risk, followed by Se and N, which were at moderate to high ecological risk levels, and Se and N showed similar ecological risk patterns, which may be related to the fact that selenium can promote the uptake and transformation of nitrogen. The present results add to the endogenous sources of toxic elements, quantify the source contributions of toxic elements in soils with high geologic backgrounds, fill this knowledge gap, and provide new insights for pollution control and ecological protection in areas with high geochemical backgrounds.

Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis.

With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal bone tissue structure and reduced bone strength in patients with diabetes. Studies have revealed a close association among diabetes, increased fracture risk, and disturbances in iron metabolism. This review explores the concept of ferroptosis, a non-apoptotic cell death process dependent on intracellular iron, focusing on its role in DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic ß-cells, osteoblasts (OBs) and osteoclasts (OCs), contributes to DOP. The intricate interplay between iron dysregulation, which comprises deficiency and overload, and DOP has been discussed, emphasizing how excessive iron accumulation triggers ferroptosis in DOP. This concise overview highlights the need to understand the complex relationship between T2DM and OP, particularly ferroptosis. This review aimed to elucidate the pathogenesis of ferroptosis in DOP and provide a prospective for future research targeting interventions in the field of ferroptosis.

Potential toxic heavy metals in village rainwater runoff of antimony mining area, China: Distribution, pollution sources, and risk assessment.

The potential toxic heavy metal runoff from antimony mining areas poses a serious threat to the water environment and the health of residents in the village. The study found that the average concentrations of As, Sb, Cr, Pb, and Cd in the runoff were 0.1237, 0.1148, 0.0332, 0.0140, and 0.0013 mg/L, which were higher than the normal average concentrations in the water environment of 0.018, 0.0009, 0.05, 0.012, and 0.000013 mg/L, respectively.Sb and As are severely polluted, while Cd, Pb, and Cr have lower pollution levels. The coefficients of variation for As, Sb, Cr, Pb, and Cd range from 0.079 to 1.051, with Sb showing exceptionally high variability. Heavy metal elements Pb, Cd, and Sb accumulate in the southeastern area of the village, with Sb concentrations decreasing from the southeast to the northwest. As is mainly distributed in the northeastern part of the village, while Cr is primarily found in the central-western region. Source analysis indicates that As and Sb originate from mining and industrial activities, dust deposition, and domestic sewage. Cr comes from the natural geological background and metal product industry, Pb from lead-acid batteries, industrial activities, and gasoline additives, and Cd from fertilization in residential green areas and pesticide use. Health risk analysis reveals that the hazard index (HI) values for As and As in the water environment are 1.49 and 2.31, respectively, both exceeding 1, posing a serious threat to the health of village residents. The HI values for Pb, Cr, and Cd elements are all below 1, indicating lower risks. This study identified that Sb in the antimony ore area and its associated metal element As are the main elements leading to potential heavy metal pollution in the runoff of village residential areas, providing direction for subsequent water environment restoration work.

Effect of injectable calcium alginate-amelogenin hydrogel on macrophage polarization and promotion of jawbone osteogenesis.

Due to persistent inflammation and limited osteogenesis, jawbone defects present a considerable challenge in regenerative medicine. Amelogenin, a major protein constituent of the developing enamel matrix, demonstrates promising capabilities in inducing regeneration of periodontal supporting tissues and exerting immunomodulatory effects. These properties render it a potential therapeutic agent for enhancing jawbone osteogenesis. Nevertheless, its clinical application is hindered by the limitations of monotherapy and its rapid release characteristics, which compromise its efficacy and delivery efficiency. In this context, calcium alginate hydrogel, recognized for its superior physicochemical properties and biocompatibility, emerges as a candidate for developing a synergistic bioengineered drug delivery system. This study describes the synthesis of an injectable calcium amelogenin/calcium alginate hydrogel using calcium alginate loaded with amelogenin. We comprehensively investigated its physical properties, its role in modulating the immunological environment conducive to bone healing, and its osteogenic efficacy in areas of jawbone defects. Our experimental findings indicate that this synthesized composite hydrogel possesses desirable mechanical properties such as injectability, biocompatibility, and biodegradability. Furthermore, it facilitates jawbone formation by regulating the bone-healing microenvironment and directly inducing osteogenesis. This research provides novel insights into the development of bone-tissue regeneration materials, potentially advancing their clinical application.

Downregulated microRNA-149-3p triggers malignant development and predicts worse prognosis in oral squamous cell carcinoma.

OBJECTIVE: Accumulating evidence reveals that aberrant expression of microRNAs contributes to the tumorigenesis and development of diverse human cancers. In the current study, we aimed to evaluate the functional role and prognostic value of miR-149-3p in oral squamous cell carcinoma (OSCC). METHODS: Real-time polymerase chain reaction (PCR) analysis was performed to detect the expression of miR-149-3p in 70 OSCC patients (64.10 ± 11.97 years; 31 males and 39 females). The prognostic ability of miR-149-3p in OSCC patients was assessed by Kaplan-Meier survival analysis. Transwell assays and cell adhesion assays were used to investigate the impact of miR-149-3p on cell migration and invasion. The regulation of MMP2 expression by miR-149-3p was determined by real-time PCR, western blotting and dual luciferase reporter assay. RESULTS: Our results revealed a lower level of miR-149-3p in OSCC tissues than in adjacent normal tissues. Downregulation of miR-149-3p was correlated with malignant development and poor outcomes in patients with OSCC. MiR-149-3p repressed the migratory and invasive abilities of OSCC cells. We confirmed that miR-149-3p targeted the 3'-untranslated region of MMP2 mRNA to suppress MMP2 expression. Moreover, the miR-149-3p-mediated decrease in metastasis was reversed by overexpression of MMP2 in OSCC cells. CONCLUSION: Our findings provide an important molecular mechanism by which miR-149-3p inhibits OSCC cell migration and invasion via negative regulation of MMP2 and implicate miR-149-3p as a prospective biomarker and therapeutic target for OSCC.

Survey on uric acid in Chinese subjects with essential hypertension (SUCCESS): a nationwide cross-sectional study.

BACKGROUND: Hyperuricemia (HUA) is associated with hypertension and increased cardiovascular risk. Current data regarding the prevalence of HUA in Chinese hypertensive patients are lacking. Our study aims to explore the prevalence and determinants of HUA in Chinese hypertensive adults. METHODS: Treatment-naive hypertensive adults or those taking single antihypertensive agent were included in a nationwide cross-sectional study. Basic demographics, antihypertensive medications, serum uric acid (UA), and other parameters were documented. RESULTS: The overall prevalence rate of HUA was 38.7% among 33,785 valid cases, 35.1% for males (UA >420 µmol/L), and 45.2% for females (UA >360 µmol/L). A multiple logistic regression analysis, adjusted for demographic and clinical factors (model 1), revealed that female sex [odds ratio (OR), 95% CI, 1.43, 1.36-1.51], age of ≥65 years (1.12, 1.05-1.19), low evaluated glomerular filtration rate [eGFR; 2.06, 1.91-2.23, the lowest [Q1] vs. the highest quartile (Q4)], unmarried (1.58, 1.10-2.27), Western China residency (3.21, 3.33-3.91), longer hypertension duration (1.97, 1.78-2.12, Q4 vs. Q1) and aspirin use (1.21, 1.14-1.29) were associated with HUA. In a multiple logistic regression analysis adjusted for clinical and metabolic parameters (model 2), female sex (OR, 95% CI, 1.34, 1.27-1.41), age of ≥65 years (1.09, 1.03-1.16), low eGFR (2.35, 2.19-2.52, Q1 vs. Q4), new-onset hypertension (2.01, 1.73-2.33), higher quartile of fasting blood glucose (FBG), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) levels, and body mass index (BMI) were associated with higher risk of HUA (1.89, 1.76-2.03; 2.15, 1.99-2.31; 2.86, 2.67-3.06; 1.27, 1.27-1.36, respectively, Q4 vs. Q1). Losartan, valsartan, and nifedipine were associated with lower risk of HUA (OR, 95% CI, 0.77, 0.67-0.88, 0.68, 0.60-0.77; 0.87, 0.77-0.99, 0.79, 0.70-0.89 and 0.80, 0.70-0.91, 0.82, 0.72-0.92), respectively, in models 1 and 2. CONCLUSIONS: The prevalence rate of HUA in Chinese hypertensive patients was 38.7%. Female sex, aging (≥65 years), and low eGFR were independent predictors of HUA. HUA was lower among the patients who were taking losartan, valsartan, and nifedipine. Western region residents, new-onset hypertension, longer hypertension duration, aspirin use, higher FBG, TG, LDL-C levels and BMI were potential risk factors for HUA.

MicroRNA­149­3p inhibits cell proliferation by targeting AKT2 in oral squamous cell carcinoma.

MicroRNAs (miRs) exhibit oncogenic or tumor suppressive functions that contribute to the initiation and development of various types of human cancer. miR­149­3p has been reported to serve multiple roles in the regulation of proliferation, apoptosis and metastasis. However, the effects and detailed mechanism of miR­149­3p in oral squamous cell carcinoma (OSCC) remain unclear. In the present study, miR­149­3p mimic, mimic control, miR­149­3p inhibitor and inhibitor control were transiently transfected into Cal27 and SCC­9 cells. The viability, proliferation and apoptosis of OSCC cells were determined using Cell Counting Kit­8, colony formation and Annexin V assays, respectively. The mRNA expression levels of miR­149­3p and AKT2 were determined by reverse transcription­quantitative PCR. The protein expression levels of AKT2, cleaved caspase­3 and cleaved PARP were examined by western blot analysis. The binding of miR­149­3p to the AKT2 3'­untranslated region was evaluated by a dual luciferase reporter assay. In the present study, overexpression of miR­149­3p reduced the viability and proliferation of OSCC cells. By contrast, increased cell viability and proliferation was observed in miR­149­3p­deficient OSCC cells. Dual luciferase reporter assay indicated that miR­149­3p significantly decreased the luciferase activity of the wild­type AKT2 3'­untranslated region. Moreover, overexpression of miR­149­3p downregulated the mRNA and protein expression levels of AKT2, suggesting that miR­149­3p was a negative modulator of AKT2. Restoration of AKT2 efficiently reversed the miR­149­3p­mediated reduction in the proliferative capacity of OSCC cells. In addition, miR­149­3p enhanced the sensitivity of OSCC cells to the chemotherapeutic drug 5­fluorouracil. Taken together, the current findings revealed an inhibitory effect of miR­149­3p on the proliferation of OSCC cells through the post­transcriptional suppression of AKT2, and indicated a potential chemosensitizing function of miR­149­3p for the treatment of patients with OSCC.

2019 Chinese Hypertension League guidelines on home blood pressure monitoring.

In China, automated blood pressure monitors have been readily available for home use. Home blood pressure monitoring has been indispensable in the management of hypertension. There is therefore a need to establish guidelines for home blood pressure monitoring on the basis of the 2012 consensus document. In this guidelines document, the committee put forward recommendations on the selection and calibration of blood pressure measuring devices, the frequency (times) and duration (days) of blood pressure measurement, and the diagnostic threshold of home blood pressure.

Expert consensus on the management of hypertension in the young and middle-aged Chinese population.

Hypertension, defined as blood pressure (BP) ≥140/90 mmHg, is one of the most common, yet reversible, risk factors for cardiovascular disease (CVD). Globally, 9.40 million people died from hypertension in 2010, accounting for 17.8% of total deaths; disability-adjusted life years (DALYs) caused by hypertension were 170 million person-years, or 7.0% of the total global DALYs.1 Data from China showed that hypertension accounted for 24.6% of all deaths, and 12.0% of total DALYs,2 and the direct medical cost of hypertension in China has reached 36.6 billion yuan per year.3.

Optimized Surface Characteristics and Enhanced in Vivo Osseointegration of Alkali-Treated Titanium with Nanonetwork Structures.

Alkali-treated titanium (Ti) with a porous, homogeneous, and uniform nanonetwork structure (TNS) that enables establishment of a more rapid and firmer osteointegration than titanium has recently been reported. However, the mechanisms underlying the enhanced osteogenic activity on TNS remains to be elucidated. This study aimed to evaluate the surface physicochemical properties of Ti and TNS, and investigate osteoinduction and osteointegration in vivo. Surface characteristics were evaluated using scanning electron microscopy (SEM), scanning probe microscopy (SPM), and X-ray photoelectron spectrometry (XPS), and the surface electrostatic force of TNS was determined using solid zeta potential. This study also evaluated the adsorption of bovine serum albumin (BSA) and human plasma fibronectin (HFN) on Ti and TNS surfaces using quartz crystal microbalance (QCM) sensors, and apatite formation on Ti and TNS surfaces was examined using a simulated body fluid (SBF) test. Compared with Ti, the newly developed TNS enhanced BSA and HFN absorbance capacity and promoted apatite formation. Furthermore, TNS held less negative charge than Ti. Notably, sequential fluorescence labeling and microcomputed tomography assessment indicated that TNS screws implanted into rat femurs exhibited remarkably enhanced osteointegration compared with Ti screws. These results indicate that alkali-treated titanium implant with a nanonetwork structure has considerable potential for future clinical applications in dentistry and orthopedics.

Osseointegration of Alkali-Modified NANOZR Implants: An In Vivo Study.

Ingredients and surface modification methods are being continually developed to improve osseointegration of dental implants and reduce healing times. In this study, we demonstrate in vitro that, by applying concentrated alkali treatment to NANOZR with strong bending strength and fracture toughness, a significant improvement in the bone differentiation of rat bone marrow cells can be achieved. We investigated the influence of materials modified with this treatment in vivo, on implanted surrounding tissues using polychrome sequential fluorescent labeling and micro-computer tomography scanning. NANOZR implant screws in the alkali-treated group and the untreated group were evaluated after implantation in the femur of Sprague⁻Dawley male rats, indicating that the amount of new bone in the alkali-modified NANOZR was higher than that of unmodified NANOZR. Alkali-modified NANOZR implants proved to be useful for the creation of new implant materials.

Shear Bond Strength of Different CAD/CAM Ceramics: Acid vs Er:YAG Laser Etching.

OBJECTIVE: To evaluate whether Er:YAG laser etching could be an alternative surface treatment to hydrofluoric (HF) acid etching. BACKGROUND: Surface treatment is important to bonding properties and utility times of computer aided design/computer aided manufacture (CAD/CAM) dental ceramics. The traditional method of HF acid etching is harmful to humans if not handled properly. MATERIALS AND METHODS: Four different CAD/CAM ceramics (Vita Mark II, IPS Empress CAD, IPS e.max CAD, and Vita Enamic) were cut into 72 blocks and divided into 6 groups according to different surface treatments (n = 12): Group A: no treatment; Group B: HF acid; and Group C to F: different Er:YAG laser power settings (300, 400, 500, and 600 mJ). Ten blocks of each group were measured for shear bond strength (SBS) and the failure modes were evaluated; the rest blocks were observed by scanning electronic microscopy (SEM). RESULTS: HF acid etching resulted in the highest SBS for Vita Mark II, IPS Empress CAD, and Vita Enamic; however, the difference was not statistically significant (p > 0.05) compared to the second highest group of laser with 600 mJ in IPS Empress CAD. For IPS e.max CAD, the highest SBS was obtained from laser group with 400 mJ. The SBS results were consistent with failure modes and surface characterizations in SEM images. CONCLUSIONS: Our results showed that Er:YAG laser had little impact on Vita Mark II and Vita Enamic; but proper power settings could be an alternative surface treatment to HF acid etching (600 mJ for IPS Empress CAD and 400 mJ for IPS e.max CAD).

In Vitro and In Vivo Osteogenic Activity of Titanium Implants Coated by Pulsed Laser Deposition with a Thin Film of Fluoridated Hydroxyapatite.

To enhance biocompatibility, osteogenesis, and osseointegration, we coated titanium implants, by krypton fluoride (KrF) pulsed laser deposition, with a thin film of fluoridated hydroxyapatite (FHA). Coating was confirmed by scanning electron microscopy (SEM) and scanning probe microscopy (SPM), while physicochemical properties were evaluated by attenuated reflectance Fourier transform infrared spectroscopy (ATR-FTIR). Calcium deposition, osteocalcin production, and expression of osteoblast genes were significantly higher in rat bone marrow mesenchymal stem cells seeded on FHA-coated titanium than in cells seeded on uncoated titanium. Implantation into rat femurs also showed that the FHA-coated material had superior osteoinductive and osseointegration activity in comparison with that of traditional implants, as assessed by microcomputed tomography and histology. Thus, titanium coated with FHA holds promise as a dental implant material.

The use of chitosan/PLA nano-fibers by emulsion eletrospinning for periodontal tissue engineering.

OBJECTIVE: In this study, nanofibrous scaffolds base on pure polylactic acid (PLA) and chitosan/PLA blends were fabricated by emulsion eletrospinning. By modulating their mechanical and biological properties, cell-compatible and biodegradable scaffolds were developed for periodontal bone regeneration. METHODS: Pure PLA and different weight ratios of chitosan nano-particle/PLA nano-fibers were fabricated by emulsion eletrospinning. Scanning electron microscope (SEM) was performed to observe the morphology of nano-fibers. Mechanical properties of nano-fibers were tested by single fiber strength tester. Hydrophilic/hydrophobic nature of the nano-fibers was observed by stereomicroscope. In vitro degradation was also tested. Cells were seeded on nano-fibers scaffolds. Changes in cell adhesion, proliferation and osteogenic differentiation were tested by MTT assay and Alizarin Red S staining. Reverse transcription-polymerase chain reaction (RT-PCR) assay was used to evaluate the expression of (Toll-like receptor 4) TLR4, IL-6, IL-8, IL-1ß, OPG, RUNX2 mRNA. RESULTS: It is shown that the mean diameter of nano-fibers is about 200 nm. The mean diameter of chitosan nano-particles is about 50 nm. The combination of chitosan nano-particles enhanced the mechanical properties of pure PLA nano-fibers. By adding a certain amount of chitosan nano-particles, it promoted cell adhesion. It also promoted the osteogenic differentiation of bone marrow stem cells (BMSCs) by elevating the expression of osteogenic marker genes such as BSP, Ocn, collagen I, and OPN and enhanced ECM mineralization. Nonetheless, it caused higher expression of inflammatory mediators and TLR4 of human periodontal ligament cells (hPDLCs). CONCLUSION: The combination of chitosan nano-particles enhanced the mechanical properties of pure PLA nano-fibers and increased its hydrophilicity. Pure PLA nano-fibers scaffold facilitated BMSCs proliferation. Adding an appropriate amount of chitosan nano-particles may promote its properties of cell proliferation and osteogenic differentiation. The higher expression of inflammatory mediators caused by nano-fibers may be regulated via TLR4 pathway.

The effect of Er: YAG laser irradiation on bonding properties of IPS e.max CAD ceramics / 口腔疾病防治

Objective @#To investigate different Er:YAG laser power settings on the bonding properties of IPS e.max CAD ceramics. @*Methods@# 96 IPS e.max CAD ceramics blocks (5 mm × 5 mm × 5 mm) were prepared and randomly divided into 8 groups (n = 12), the untreated blocks served as the control, while one of the experimental groups was treated with 4.5% HF for 20 seconds, six remaining test group (C、D、E、F、G、H) were treated with different Er: YAG laser power settings: 100 mJ、200 mJ、300 mJ、400 mJ、500 mJ and 600 mJ. Morphology of the ceramic surface was observed by atomic force microscopy and its shear bond strength (SBS) was tested. @*Results @#Higher shear bond strength values were found in group C-H compared to group B, the highest is group F (24.12 ± 1.91) MPa. The difference was statistically significant. The atomic force microscope observation of the surface structure showed that the control group was smooth and flat, and the HF-like etching group formed a uniform needle-like convex structure. The laser group gradually formed a regularly arranged cylindrical convex structure, in which the surface of the G and H groups was damaged. @*Conclusion @#The Er: YAG laser power settings of 400 mJ can be used as an effective pretreatment method before bonding of IPS e.max CAD ceramic.

The effect of Er: YAG laser irradiation on bonding properties of IPS e.max CAD ceramics / 口腔疾病防治

Objective@#To investigate different Er:YAG laser power settings on the bonding properties of IPS e.max CAD ceramics. @*Methods @# 96 IPS e.max CAD ceramics blocks (5 mm × 5 mm × 5 mm) were prepared and randomly divided into 8 groups (n = 12), the untreated blocks served as the control, while one of the experimental groups was treated with 4.5% HF for 20 seconds, six remaining test group (C、D、E、F、G、H) were treated with different Er: YAG laser power settings: 100 mJ、200 mJ、300 mJ、400 mJ、500 mJ and 600 mJ. Morphology of the ceramic surface was observed by atomic force microscopy and its shear bond strength (SBS) was tested. @*Results @#Higher shear bond strength values were found in group C-H compared to group B, the highest is group F (24.12 ± 1.91) MPa. The difference was statistically significant. The atomic force microscope observation of the surface structure showed that the control group was smooth and flat, and the HF-like etching group formed a uniform needle-like convex structure. The laser group gradually formed a regularly arranged cylindrical convex structure, in which the surface of the G and H groups was damaged. @*Conclusion@# The Er: YAG laser power settings of 400 mJ can be used as an effective pretreatment method before bonding of IPS e.max CAD ceramic.

Drug-Loadable Calcium Alginate Hydrogel System for Use in Oral Bone Tissue Repair.

This study developed a drug-loadable hydrogel system with high plasticity and favorable biological properties to enhance oral bone tissue regeneration. Hydrogels of different calcium alginate concentrations were prepared. Their swelling ratio, degradation time, and bovine serum albumin (BSA) release rate were measured. Human periodontal ligament cells (hPDLCs) and bone marrow stromal cells (BMSCs) were cultured with both calcium alginate hydrogels and polylactic acid (PLA), and then we examined the proliferation of cells. Inflammatory-related factor gene expressions of hPDLCs and osteogenesis-related gene expressions of BMSCs were observed. Materials were implanted into the subcutaneous tissue of rabbits to determine the biosecurity properties of the materials. The materials were also implanted in mandibular bone defects and then scanned using micro-CT. The calcium alginate hydrogels caused less inflammation than the PLA. The number of mineralized nodules and the expression of osteoblast-related genes were significantly higher in the hydrogel group compared with the control group. When the materials were implanted in subcutaneous tissue, materials showed favorable biocompatibility. The calcium alginate hydrogels had superior osteoinductive bone ability to the PLA. The drug-loadable calcium alginate hydrogel system is a potential bone defect reparation material for clinical dental application.

Synergistic effect of nanotopography and bioactive ions on peri-implant bone response.

Both bioactive ion chemistry and nanoscale surface modifications are beneficial for enhanced osseointegration of endosseous implants. In this study, a facile synthesis approach to the incorporation of bioactive Ca2+ ions into the interlayers of nanoporous structures (Ca-nano) formed on a Ti6Al4V alloy surface was developed by sequential chemical and heat treatments. Samples with a machined surface and an Na+ ion-incorporated nanoporous surface (Na-nano) fabricated by concentrated alkali and heat treatment were used in parallel for comparison. The bone response was investigated by microcomputed tomography assessment, sequential fluorescent labeling analysis, and histological and histomorphometric evaluation after 8 weeks of implantation in rat femurs. No significant differences were found in the nanotopography, surface roughness, or crystalline properties of the Ca-nano and Na-nano surfaces. Bone-implant contact was better in the Ca-nano and Na-nano implants than in the machined implant. The Ca-nano implant was superior to the Na-nano implant in terms of enhancing the volume of new bone formation. The bone formation activity consistently increased for the Ca-nano implant but ceased for the Na-nano implant in the late healing stage. These results suggest that Ca-nano implants have promising potential for application in dentistry and orthopedics.

GTP cyclohydrolase I prevents diabetic-impaired endothelial progenitor cells and wound healing by suppressing oxidative stress/thrombospondin-1.

Endothelial progenitor cell (EPC) dysfunction is a key contributor to diabetic refractory wounds. Endothelial nitric oxide synthase (eNOS), which critically regulates the mobilization and function of EPCs, is uncoupled in diabetes due to decreased cofactor tetrahydrobiopterin (BH4). We tested whether GTP cyclohydrolase I (GTPCH I), the rate-limiting enzyme of BH4 synthesis, preserves EPC function in type 1 diabetic mice. Type 1 diabetes was induced in wild-type (WT) and GTPCH I transgenic (Tg-GCH) mice by intraperitoneal injection of streptozotocin (STZ). EPCs were isolated from the peripheral blood and bone marrow of WT, Tg-GCH, and GTPCH I-deficient hph-1 mice. The number of EPCs was significantly lower in STZ-WT mice and hph-1 mice and was rescued in STZ Tg-GCH mice. Furthermore, GTPCH I overexpression improved impaired diabetic EPC migration and tube formation. EPCs from WT, Tg-GCH, and STZ-Tg-GCH mice were administered to diabetic excisional wounds and accelerated wound healing significantly, with a concomitant augmentation of angiogenesis. Flow cytometry measurements showed that intracellular nitric oxide (NO) levels were reduced significantly in STZ-WT and hph-1 mice, paralleled by increased superoxide anion levels; both were rescued in STZ-Tg-GCH mice. Western blot analysis revealed that thrombospondin-1 (TSP-1) was significantly upregulated in the EPCs of STZ-WT mice and hph-1 mice and suppressed in STZ-treated Tg-GCH mice. Our results demonstrate that the GTPCH I/BH4 pathway is critical to preserve EPC quantity, function, and regenerative capacity during wound healing in type 1 diabetic mice at least partly through the attenuation of superoxide and TSP-1 levels and augmentation of NO level.