What happens to the osteoporotic bone mesenchymal stem cells? Evidence from RNA sequencing.

Evidence presented that osteoporosis is closely related to the dysfunction of bone mesenchymal stem cells (BMSCs). But most studies are insufficient to reveal what actually happens to the osteoporotic BMSCs. In this study, BMSCs were harvested from ovariectomized and sham-operated rats. After checking the characteristics of rat models and stem cells, the BMSCs were carried out for RNA sequencing. Part of the findings were verified that seven mRNAs (Abi3bp, Aifm3, Ccl11, Cdkn1c, Chst10, Id2, Vcam1) were significantly up-regulated in osteoporotic BMSCs while seven mRNAs (Cep63, Fgfr3, Myc, Omd, Pou2f1, Smarcal1, Timm10b) were down-regulated. In addition, potential miRNA-mRNA and lncRNA-mRNA regulatory networks were illustrated. The changes in osteoporotic BMSCs covered a large set of biological processes, including cell viability, differentiation, immunoreaction, bone repairment and estrogen defect. This study enriched the pathophysiological mechanisms of BMSCs and osteporosis, as well as provided dozens of attractive RNA targets for further treatment.

Acid sphingomyelinase mediates ferroptosis induced by high glucose via autophagic degradation of GPX4 in type 2 diabetic osteoporosis.

BACKGROUND: Ferroptosis has been implicated in the pathological process of type 2 diabetic osteoporosis (T2DOP), although the specific underlying mechanisms remain largely unknown. This study aimed to clarify the role and possible mechanism of acid sphingomyelinase (ASM)-mediated osteoblast ferroptosis in T2DOP. METHODS: We treated hFob1.19 cells with normal glucose (NG) and different concentrations of high glucose (HG, 26.25 mM, 35 mM, or 43.75 mM) for 48 h. We then measured cell viability and osteogenic function, quantified ferroptosis and autophagy levels, and measured the levels of ASM and ceramide in the cells. To further investigate the specific mechanism, we examined these indicators by knocking down ASM expression, hydroxychloroquine (HCQ) treatment, or N-acetylcysteine (NAC) treatment. Moreover, a T2DOP rat model was induced and microcomputed tomography was used to observe the bone microstructure. We also evaluated the serum levels of iron metabolism-associated factors, ceramide and lipid peroxidation (LPO) and measured the expression of ASM, LC3 and GPX4 in bone tissues. RESULTS: HG inhibited the viability and osteogenic function of osteoblasts by inducing ferroptosis in a concentration-dependent manner. Furthermore, the expression of ASM and ceramide and autophagy levels were increased by HG treatment, and these factors were required for the HG-induced reactive oxygen species (ROS) generation and LPO. Similarly, inhibiting intracellular ROS also reduced HG-induced ASM activation and autophagy. ASM-mediated activation of autophagy was crucial for HG-induced degradation of GPX4, and inhibiting ASM improved osteogenic function by decreasing HG-induced autophagy, GPX4 degradation, LPO and subsequent ferroptosis. We also found that inhibiting ASM could alleviated ferroptosis and autophagy and improved osteogenic function in a T2DOP rat model. CONCLUSION: ASM-mediated autophagy activation induces osteoblast ferroptosis under HG conditions through the degradation of GPX4, providing a novel mechanistic insight into the treatment and prevention of T2DOP.

Nanoscale Borate Coating Network Stabilized Iron Oxide Anode for High-Energy-Density Bipolar Lithium-Ion Batteries.

High-capacity metal oxides based on non-toxic earth-abundant elements offer unique opportunities as advanced anodes for lithium-ion batteries (LIBs). But they often suffer from large volumetric expansion, particle pulverization, extensive side reactions, and fast degradations during cycling. Here, an easy synthesis method is reported to construct amorphous borate coating network, which stabilizes conversion-type iron oxide anode for the high-energy-density semi-solid-state bipolar LIBs. The nano-borate coated iron oxide anode has high tap density (1.6 g cm-3 ), high capacity (710 mAh g-1 between 0.5 - 3.0 V, vs Li/Li+ ), good rate performance (200 mAh g-1 at 50 C), and excellent cycling stability (≈100% capacity resention over 1,000 cycles at 5 A g-1 ). When paired with high-voltage cathode LiCoO2 , it enables Cu current collector-free pouch-type classic and bipolar full cells with high voltage (7.6 V with two stack layers), achieving high energy density (≈350 Wh kg-1 ), outstanding power density (≈6,700 W kg-1 ), and extended cycle life (75% capacity retention after 2,000 cycles at 2 C), superior to the state-of-the-art high-power LIBs using Li4 Ti5 O12 anode. The design and methodology of the nanoscale polyanion-like coating can be applied to other metal oxides electrode materials, as well as other electrochemical materials and devices.

Biomineralized Piezoelectrically Active Scaffolds for Inducing Osteogenic Differentiation.

There is an endogenous electric field in living organisms, which plays a vital role in the development and regeneration of bone tissue. Therefore, self-powered piezoelectric material for bone repair has become hot research in recent years. However, the current piezoelectric materials for tissue regeneration still have the shortcomings of lack of biological activity and three-dimensional structure. Here, we proposed a three-dimensional polyurethane foam (PUF) scaffold coated with piezoelectric poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) and modified by a calcium phosphate (CaP) mineralized coating. The preferred scaffold has an open circuit voltage and short circuit current output of 5 V and 200 nA. Combining the physical and chemical properties of the CaP coating, the piezoelectric signal of PVDF-HFP and the three-dimensional structure of PUF, the scaffold exhibits superior promotion of cell osteogenic differentiation and ectopic bone formation in vivo. The mechanism is attributed to an increase in intracellular Ca2+ levels in response to chemical and piezoelectric stimulation with the material. This research not only paves the way for the application of piezoelectric scaffolds to stimulate osteoblasts differentiation in situ, but also lays the foundation for the clinical treatment of long-term osteoporosis.

Comparison of osteogenesis of bovine bone xenografts between true bone ceramics and decalcified bone matrix.

Xenograft bone scaffolds have certain advantages such as mechanical strength, osteoinductive properties, sufficient source and safety. This study aimed to compare osteogenesis of the two main bovine bone xenografts namely true bone ceramics (TBC) and decalcified bone matrix (DBM), and TBC or DBM combined with bone morphogenetic protein (BMP)-2 (TBC&BMP-2 and DBM&BMP-2). The characteristics of TBC and DBM were investigated by observing the appearance and scanning electron microscopic images, examining mechanical strength, evaluating cytotoxicity and detecting BMP-2 release after being combined with BMP-2 in vitro. The femoral condyle defect and radial defect models were successively established to evaluate the performance of the proposed scaffolds in repairing cortical and cancellous bone defects. General observation, hematoxylin and eosin (HE) staining, mirco-CT scanning, calcein double labeling, X-ray film observation, three-point bending test in vivo were then performed. It indicated that the repair with xenograft bone scaffolds of 8 weeks were needed and the repair results were better than those of 4 weeks whatever the type of defects. To femoral condyle defect, TBC and TBC&BMP-2 were better than DBM and DBM&BMP-2, and TBC&BMP-2 was better than TBC alone; to radial defect, DBM and DBM&BMP-2 were better than TBC and TBC&BMP-2, and DBM&BMP-2 was better than DBM alone. This study has shown that TBC and DBM xenograft scaffolds can be more suitable for the repair of cancellous bone and cortical bone defects for 8 weeks in rats, respectively. We also have exhibited the use of BMP-2 in combination with DBM or TBC provides the possibility to treat bone defects more effectively. We thus believe that we probably need to select the more suitable scaffold according to bone defect types, and both TBC and DBM are promising xenograft materials for bone tissue engineering and regenerative medicine. Graphical abstract.

Biological evaluation of acellular bovine bone matrix treated with NaOH.

We mainly proceed from the view of biological effect to study the acellular bovine bone matrix (ABBM) by the low concentration of hydrogen oxidation. After cleaning the bovine bone routinely, it was cleaned with different concentrations of NaOH and stained with hematoxylin-eosin (HE) to observe the effect of decellulization. The effect of bovine bone matrix treated with NaOH were observed by optical microscopy and scanning electron microscopy (SEM), and compared by DNA residue detection. Cell toxicity was also evaluated in MC3T3-E1 cells by CCK-8. For the in vitro osteogenesis detection, alkaline phosphatase (ALP) staining and alizarin red (AR) staining were performed in MC3T3-E1 cells. And the in vivo experiment, Micro CT, HE and Masson staining were used to observe whether the osteogenic effect of the materials treated with 1% NaOH solution was affected at 6 and 12 weeks. After the bovine bone was decellularized with different concentrations of NaOH solution, HE staining showed that ultrasonic cleaning with 1% NaOH solution for 30 min had the best effect of decellularization. The SEM showed that ABBM treated with 1% NaOH solution had few residual cells on the surface of the three-dimensional porous compared to ABBM treated with conventional chemical reagents. DNA residues and cytotoxicity of ABBM treated with 1% NaOH were both reduced. The results of ALP staining and AR staining showed that ABBM treated with 1% NaOH solution had no effect on the osteogenesis effect. The results of micro-CT, HE staining and Masson staining in animal experiments also showed that ABBM treated with 1% NaOH solution had no effect on the osteogenesis ability. The decellularization treatment of ABBM with the low concentration of NaOH can be more cost-effective, effectively remove the residual cellular components, without affecting the osteogenic ability. Our work may provide a novelty thought and a modified method to applicate the acellular bovine bone matrix clinically better. Graphical abstract.

Dietary Quercetin Reduces Plasma and Tissue Methylglyoxal and Advanced Glycation End Products in Healthy Mice Treated with Methylglyoxal.

BACKGROUND: Methylglyoxal (MGO), a precursor of advanced glycation end products (AGEs), has been linked to AGEs-associated diseases. OBJECTIVES: This study investigated the efficacy and mechanisms of dietary quercetin in decreasing plasma and tissue concentrations of MGO and AGEs in MGO-administered mice. METHODS: Male, 6-wk-old CD-1 mice were administered AIN-93G diet and water (Con) or 0.12% MGO in water (MGO) or MGO plus 0.2% (0.2Q) dietary quercetin for 1 wk (n = 5) (experiment 1), and water (Con), 0.12% MGO (MGO), or MGO plus 0.1% (0.1Q), 0.2% (0.2Q), or 0.4% (0.4Q) dietary quercetin for 6 wk (n = 10) (experiment 2). The plasma, kidney, and liver concentrations of MGO, quercetin, and isorhamnetin and their trapping adducts with MGO were determined by LC-MS, and AGE concentrations were measured by the fluorescent method. Furthermore, the expressions of glyoxalase I/II (GLO I/II) and aldose reductase (AR), MGO detoxification enzymes, were determined by Western blot. One-factor ANOVA and post hoc Dunnett's or Tukey's test were used to analyze the data. RESULTS: After 1 wk of treatment, the MGO concentrations in plasma (20.2%) and kidney (29.9%) in 0.2Q mice were significantly lower than those in MGO mice. After 6 wk of treatment, the concentrations of MGO in the plasma (14.7-18.6%), kidney (20-20.8%), liver (15.4-18.6%), and tissue AGEs (28-36.8%) in 0.1Q, 0.2Q, and 0.4Q mice were significantly lower than those in MGO mice. The plasma concentrations of quercetin, isorhamnetin, and their MGO adducts were dose-dependently increased after quercetin administration. In addition, after 6 wk of quercetin administration, the expressions of GLO I/II and AR in the liver and kidney were significantly upregulated to promote MGO detoxification compared with MGO-treated mice. CONCLUSIONS: Quercetin reduced plasma and tissue MGO concentrations and inhibited AGE formation by trapping MGO and regulating the MGO detoxification systems in MGO-administered healthy mice.

Activation of Insulin-Like Growth Factor-2 Ameliorates Retinal Cell Damage and Exerts Protection in in vitro Model of Diabetic Retinopathy.

BACKGROUND: The major event in the development of diabetes-related blindness and vision impairment is the onset of retinal cell damage. Overall awareness of insulin-like growth factor-2 (IGF2) mechanisms emphasizes its protective behavior in retinal cells that help to provide new information about the development of treatment for retinal complications. OBJECTIVES: This study analyzes the effect of in vitro changes associated with the cell survival and rescue mechanism in IGF2 inhibition and activation using chromeceptin and IGF2 peptides in ARPE-19 cells cultured in high glucose conditions. METHOD: Cell death was induced using high glucose (15 mmol/L), IGF2 inhibition was done using chromeceptin (1 µM) (Sigma Aldrich, Saint Louis, MO, USA), and IGF2 activation was done using IGF2 peptide (10 ng/mL). The cells were analyzed for changes in cell proliferation, apoptosis markers, antioxidant molecules, and alteration of cytokines. RESULTS: The study demonstrated that cells lacking IGF2 exhibited a significant increase in reactive oxygen levels with apoptosis patterns. Also, gene expression analysis by qRT-PCR demonstrated a significant increase in Yes-associated protein 1, CDK2, TNF-α, and BIRC5 genes in cells under high glucose stress and IGF inhibition compared to control. Further, the cytokine analysis also revealed that cells devoid of IGF2 activated an increase in cytokines such as IL-8, CX43, ICAM-1, IL-17, CCL3, and MCP-1 and decreased paraoxonase compared to normal control cells. On the other hand, ARPE-19 cells grown in high glucose shows that IGF2 increases the survival genes with reduced levels of inflammatory cytokines. CONCLUSION: The finding of the investigation, therefore, shows that the use of IGF2 activators may prevent the progression of ocular dysfunction in the control of diabetes-related complications.

Bone induction and defect repair by true bone ceramics incorporated with rhBMP-2 and Sr.

OBJECTIVE: To study the bone induction and defect repair of true bone ceramics (TBC) combined with rhBMP-2 and Sr. METHODS: MC3T3-E1 cells were used to evaluate the bioactivity of the composite. Cell proliferation activity was detected by CCK-8, ALP activity was detected by p-nitrophenyl phosphate (PNPP), and the differences of material surface topography were observed by scanning electron microscopy (SEM). Bone induction was verified by the implantation in nude mice. The rabbit femoral condyle defect model was achieved to verify the bone defect repair ability of the material. RESULTS: SEM results showed nearly the same surface morphology and cell proliferation quantified by CCK-8 showed that compared with TBC, both TBC&Sr and TBC&BMP-2&Sr had a significant promoting effect (P < 0.05). ALP activity result showed that the ALP activity of TBC&BMP-2&Sr was significantly higher than that of TBC alone (P < 0.05). The bone induction result showed that TBC&Sr had a small amount of new bone formation, and the new bone area was only 2.5 ± 0.11%. The bone induction activity of TBC&BMP-2&Sr was the highest, the new bone area was up to 75.36 ± 4.21%. Histological result of bone defect repair showed that TBC&BMP-2&Sr was also the highest, the new bone area was up to 72.42 ± 3.14%. The repair effect of TBC& BMP-2 was second, and better than that of TBC&Sr. CONCLUSION: TBC combined with rhBMP-2 and Sr had the good bioactivity, obvious bone conduction and bone defect repair performance, laying the foundation of clinical application potentially.

Open Reduction and Internal Fixation Strategy For Treatment of Comminuted Mandibular Fracture.

PURPOSE: The aim of this study was to evaluate the treatment strategy of open reduction and internal fixation (ORIF) for comminuted mandibular fracture (CMF). METHODS: Clinical studies about CMF were collected. Detailed information was extracted, and data were analyzed and merged from included articles. RESULTS: Twelve studies, including 338 patients with CMF, were reported. A total of 256 patients receive ORIF among these 338 patients, and exhibited followed characteristics: ORIF usually were performed several days after injury; the extraoral approach for ORIF was used for 103 patients among 205 patients who received ORIF with definite information about surgical approach; titanium mesh, or reconstruction plate, combined with mini-plates was used in 17 and 194 patients, respectively; intermaxillary fixation (IMF) usually persisted about 1 to 3 weeks after ORIF; most patients exhibited satisfactory effect without serious complications, and the complication rate varied from 0 to 42%. CONCLUSIONS: ORIF strategy for treatment of CMF including: ORIF was a priority choice for CMF. ORIF usually was performed at several days after injury. Reconstruction plate, or titanium mesh, combined with mini-plates was recommended for ORIF surgery. After ORIF, IMF usually was recommended for about 1 to 3 weeks.

ZnO-Templated Selenized and Phosphorized Cobalt-Nickel Oxide Microcubes as Rapid Alkaline Water Oxidation Electrocatalysts.

Oxygen electrocatalysis is of remarkable significance for electrochemical energy storage and conversion technologies, together with fuel cells, metal-air batteries, and water splitting devices. Substituting noble metal-based electrocatalysts by decidedly effective and low-cost metal-based oxygen electrocatalysts is imperative for the commercial application of these technologies. Herein, a novel strategy is presented to fabricate selenized and phosphorized porous cobalt-nickel oxide microcubes by using a sacrificial ZnO spherical template and the resulting microcubes are employed as an oxygen evolution reaction (OER) electrocatalyst. The selenized samples manifest desirable and robust OER performance, with comparable overpotential at 10 mA cm-2 (312 mV) as RuO2 (308 mV) and better activity when the current reaches 13.7 mA cm-2 . The phosphorized samples exhibit core-shell structure with low-crystalline oxides inside amorphous phosphides, which ensures superior activity than RuO2 with the same overpotential (at 10 mA cm-2 ) yet lower Tafel slope. Such a surface doping method possibly will provide inspiration for engineering electrocatalysts applied in water oxidation.

Metabolic Interaction between Ammonia and Baicalein.

Ammonia is treated as a primary waste product of cellular metabolism in vivo and can contribute to the alteration of neurotransmission, oxidative stress, and cerebral edema and astrocyte swelling when its concentration in the brain is high. The objective of this study was to determine whether bioactive polyphenol baicalein had the capacity to trap ammonia in vitro and in vivo. Under in vitro conditions, baicalein rapidly reacted with ammonia to generate two monoaminated products and one diaminated product under different reaction times. These three major aminated products were purified from the reaction mixture, and their structures were characterized as 5-NH2-baicalein, 6-NH2-baicalein, and 5,6-di-NH2-baicalein based on the analysis of their HR-MS and 1D- and 2D-NMR data. In mice, both 5-NH2-baicalein and 6-NH2-baicalein were detected in 24 h fecal and urine samples collected from mice treated with baicalein (200 mg/kg) through oral gavage, and 6-NH2-baicalein was also detected in mouse plasma and brain samples collected at 0.5 h after baicalein treatment. Significant amounts of 6-NH2-baicalein were detected in all mouse samples including feces, urine, plasma, and brain. The levels of 6-NH2-baicalein in feces and urine were significantly higher than those of 5-NH2-baicalein. Furthermore, the average level of 6-NH2-baicalein was very close to that of baicalein (3.62 vs 3.77 ng/g) in mouse brain, suggesting it is possible that baicalein has the capacity to be absorbed rapidly into the circulation system and then cross the blood-brain barrier into the brain to detoxify ammonia in the blood and brain. In conclusion, this study confirmed that baicalein, a flavonoid with a vic-trihydroxyl structure on the A-ring, has the potential to detoxify ammonia and treat ammonia-associated chronic diseases.

Comparison of SB-SDS and other decellularization methods for the acellular nerve graft: Biological evaluation and nerve repair in vitro and in vivo.

We aimed to compare the performance of acellular nerves prepared by different decellularization methods, screening out the optimal decellularization protocol, repairing the sciatic nerve defects in rats by the allogeneic transplantation, and evaluating the effect of regenerative nerve on the function reconstruction. The Sondell, SB-SDS, TnBP, and the high/low permeation methods were used to decellularize donor nerves. Nerves without any treatment were as the control group. The histological results were evaluated by HE staining and toluidine blue (TB) staining. The proliferation activity of L929 cells was detected by CCK-8 assay. The adhesion of Schwann cells was observed and quantified by SEM. Balb/c mice were used to evaluate the cellular and humoral immunogenicity of the nerve scaffolds. The rat sciatic nerve defect model was applied to observe the repair effect of acellular nerve scaffold in vivo. To SB-SDS group, it remained the original state of the nerves, with no observed nucleus and axons, the neurotoxicity grade detected by CCK-8 being almost 0, and it kept the largest number of Schwann cells adhered to the acellular nerve and the better morphology. Further, it showed that the selected SB-SDS rats acellular nerve scaffold could promote the nerve repair of the rats by HE staining and TB staining. We could conclude that the acellular nerve matrix prepared by the SB-SDS method effectively removes the cellular components in the nerve tissue and retains the main components of the extracellular matrix of the nerve tissue, whose rats decellularized nerve scaffold could promote the sciatic nerve repair better.

GRM4 inhibits the proliferation, migration, and invasion of human osteosarcoma cells through interaction with CBX4.

In recent years, the survey of metabolic glutamate receptor 4 (GRM4) in tumor biology has been gradually concerned. There are currently few studies on GRM4 in osteosarcoma, and the biological function is not clear. Analysis of TCGA database showed that there was no substantial deviation in the expression of GRM4 between osteosarcoma and normal tissues. In the subsequent experiments, there is no significant difference in either mRNA or protein levels among immortalized human osteoblasts and various osteosarcoma cells. With the overexpression of GRM4, cell proliferation, migration and invasion were inhibited obviously. It was further revealed that GRM4 can interact with CBX4 to restrict the nuclear localization of CBX4 and affect the transcriptional activity of HIF-1α. This is the evidence supporting the interaction between GRM4 and CBX4, which could inhibit the malignant behavior of osteosarcoma cells through the GRM4/CBX4/HIF-1α signaling pathway.

An effective frequency-domain feature of atrial fibrillation based on time-frequency analysis.

BACKGROUND: Atrial fibrillation is a type of persistent arrhythmia that can lead to serious complications. Therefore, accurate and quick detection of atrial fibrillation by surface electrocardiogram has great importance on further treatment. The practical electrocardiogram signals contain various interferences in different frequencies, such as myoelectricity interference, power interference and so on. Detection speed and accuracy largely depend on the atrial fibrillation signal features extracted by the algorithm. But some of the discovered atrial fibrillation features are not well distinguishable, resulting in poor classification effect. METHODS: This paper proposed a high distinguishable frequency feature-the frequency corresponding to the maximum amplitude in the frequency spectrum. We used the R-R interval detection method optimized with the mathematical morphology method and combined with the wavelet transform method for analysis. According to the two features-the maximum amplitude in the frequency spectrum and R-R interval irregular, we could recognize atrial fibrillation signals in electrocardiogram signals by decision tree classification algorithm. RESULTS: The data used in the experiment come from the MIT-BIH database, which is publicly accessible via the web and with ethical approval and consent. Based on the input of time-domain and frequency-domain features, we classified sinus rhythm signals and AF signals using the decision tree generated by classification and regression tree (CART) algorithm. From the confusion matrix, we got the accuracy was 98.9%, sensitivity was 97.93% and specificity was 99.63%. CONCLUSIONS: The experimental results can prove the validity of the maximum amplitude in the frequency spectrum and the practicability and accuracy of the detection method, which applied this frequency-domain feature. Through the detection method, we obtained good accuracy of classifying sinus rhythm signals and atrial fibrillation signals. And the sensitivity and specificity of our method were pretty good by comparison with other studies.

Dietary Genistein Inhibits Methylglyoxal-Induced Advanced Glycation End Product Formation in Mice Fed a High-Fat Diet.

BACKGROUND: Methylglyoxal (MGO), an important precursor of advanced glycation end products (AGEs), circulates at high concentrations in diabetic patients' blood and plays an important role in the pathogenesis of diabetes and other chronic diseases. OBJECTIVES: The aim of this study was to determine whether dietary genistein can prevent indicators of metabolic syndrome (MetS) induced by a very-high-fat (VHF) diet or a high-fat (HF) diet plus exogenous MGO, and the accumulation of MGO and AGEs in mice. METHODS: Male, 6-wk-old C57BL/6J mice (n = 15) were fed a low-fat (LF) diet (10% fat energy) or a VHF diet (60% fat energy) alone or including 0.25% genistein (VHF-G) for 16 wk in study 1. In study 2, 75 similar mice were fed the LF diet (LF) or the HF diet alone (HF) or in combination with up to 0.2% MGO in water (HFM) and 0.067% (HFM-GL) or 0.2% (HFM-GH) dietary genistein for 18 wk. Anthropometric and metabolic data were obtained in both studies to determine the effects of MGO and genistein on variables indicative of MetS. RESULTS: Body weight gain, fat deposits, dyslipidemia, hyperglycemia, and fatty liver were ameliorated by dietary genistein in both studies. The plasma MGO concentration in VHF-G mice was 52% lower than that in VHF mice. Moreover, the AGE concentrations in plasma, liver, and kidney of VHF-G mice were 73%, 52%, and 49%, respectively, lower than in the VHF group (study 1). Similarly, the concentrations of plasma MGO and AGE in plasma, liver, and kidney of HFM-GH mice were 33.5%, 49%, 69%, and 54% lower than in HFM mice (study 2). Genistein inhibited AGE formation by trapping MGO to form adducts and upregulating the expressions of glyoxalase I and II and aldose reductase in liver and kidney to detoxify MGO in both studies. CONCLUSIONS: Our data demonstrate for the first time that genistein significantly lowers MGO and AGE concentrations in 2 mouse MetS models via multiple pathways.

Iron oxide nanoparticles in liquid or powder form enhanced osteogenesis via stem cells on injectable calcium phosphate scaffold.

The objectives of this study were to incorporate iron oxide nanoparticles (IONPs) into calcium phosphate cement (CPC) to enhance bone engineering, and to investigate the effects of IONPs as a liquid or powder on stem cells using IONP-CPC scaffold for the first time. IONP-CPCs were prepared by adding 1% IONPs as liquid or powder. Human dental pulp stem cells (hDPSCs) were seeded. Subcutaneous implantation in mice was investigated. IONP-CPCs had better cell spreading, and greater ALP activity and bone mineral synthesis, than CPC control. Subcutaneous implantation for 6 weeks showed good biocompatibility for all groups. In conclusion, incorporating IONPs in liquid or powder form both substantially enhanced hDPSCs on IONP-CPC scaffold and exhibited excellent biocompatibility. IONP incorporation as a liquid was better than IONP powder in promoting osteogenic differentiation of hDPSCs. Incorporating IONPs and chitosan lactate together in CPC enhanced osteogenesis of hDPSCs more than using either alone.

A comparison of a new zero-profile, stand-alone Fidji cervical cage and anterior cervical plate for single and multilevel ACDF: a minimum 2-year follow-up study.

PURPOSE: To compare perioperative parameters, clinical outcomes, radiographic parameters, and complication rates of the new zero-profile, stand-alone Fidji cervical cage with those of the stand-alone cages with a titanium plate for anterior cervical discectomy and fusion (ACDF) for the surgical treatment of single- and multilevel cervical degenerative disc disease (DDD). METHODS: Between October 2009 and December 2013, 152 consecutive patients [86 males and 52 females; mean age 51.0 years (range 30-69 years)] with cervical DDD, who underwent surgery and were followed for more than 2 years, were enrolled in this study and divided into the cage group and plate group. The study compared perioperative parameters, surgery-related and implant-related complication rates, clinical outcomes, and radiologic parameters. RESULTS: The clinical and radiologic results in both groups were satisfactory after a minimum 2-year follow-up. No significant differences between the cage group and plate group in terms of improvement in the 36-Item Short Form Health Survey, visual analogue scale, Neck Disability Index, Japanese Orthopedic Association scores, disc height, mean fusion time, fusion rate, adjacent segment degeneration, and restoration of cervical lordosis, but the cage group was associated with a lower risk of postoperative dysphagia, shorter operation time, less blood loss, less cost of index surgery, and relatively greater simplicity than the plate group. CONCLUSIONS: The zero-profile, stand-alone Fidji cervical cage for ACDF is an effective, reliable, and safe alternate to the conventional method for the treatment of cervical DDD. However, there is no definitive evidence that Fidji cervical cage has better intermediate-term outcomes than the stand-alone cages with a titanium plate for ACDF.

Properties and Osteogenicity of Two Calcium Sulfate Materials with Micro or Nano Morphology.

Calcium sulfate dihydrate (CaSO4 x 2H2O, CSD) was widely used as the artificial bone graft. In this study, two kinds of CSD materials were characterized with XRD, TG/DTA, FT-IR, and SEM. They were both composed of CSD. Spherical shape particles were observed for nano-CSD with diameters of 52-300 nm. The micro-CSD were thin sheet particles with dimensions of 5-10 µm. At 56 days post-implantation in vivo, nano-CSD had good tissue compatibility. A frequently used bioactive material DBM, which was the combination of nano-CSD (nano-CSD-DBM) and micro-CSD (micro-CSD-DBM) in a 1:1 weight ratio separately. Composite materials were implanted in intramuscular pockets in nude mouse model. New bone mineralization could be both observed in the surgery site. Collagen I was also widely distributed by immunohistochemistry assay. And new bone area of nano-CSD-DBM was 28 ± 4.6% at 4 weeks post-operation. But new bone area of micro-CSD-DBM was 16 ± 3.7% (less than nano-CSD-DBM). Nano-CSD showed increased degradation rate with obvious anginogenicity. And nano-CSD-DBM showed more excellent bone induction property as bone substitute implant.

Preparation and Evaluation of Two Apatites with Spherical Nanocrystal Morphology.

Spherical nanocrystal of apatite has been proved to be beneficial for osteoblast growth. Two apatites with spherical nanocrystal morphology were prepared in this study by chemical wet method and further sintering process. SEM exhibited that both apatites had spherical nanocrystal morphology. The crystal morphology and size was approaching to each other. XRD showed the apatites separately were hydroxyapatite and tricalcium phosphate phases. The cellular biocompatibility was evaluated by osteoblasts for these two spherical nanocrstal apatites. The MTT result indicated a higher cell proliferation rate for spherical tricalcium phosphate group. The ALP activity assay also strongly favored the tricalcium phosphate group. RT-PCR results indicated that Collagen I had a higher transcription level on the spherical tricalcium phosphate group. SEM results showed robust cell growth on the materials. It was concluded that the spherical nanophase tricalcium phosphate was superior to the cellular biocompatibility of spherical nanophase hydroxyapatite and the results were helpful in the manufacture of more suitable tissue engineering scaffolds.