Alveolar Bone Preservation Using a Combination of Nanocrystalline Hydroxyapatite and Injectable Platelet-Rich Fibrin: A Study in Rats.

Alveolar bone resorption is a post-extraction complication wherein there is a reduction in the dimensions and quality of the alveolar bone. This study aimed to examine the effects of implantation of a combination of nanocrystalline hydroxyapatite (nHA) and injectable platelet-rich fibrin (IPRF) on the expression of tartrate-resistant acid phosphatase (TRAP), alkaline phosphatase (ALP), osteocalcin (OCN), and new bone formation. A total of 32 male rats had their upper right incisors extracted under general anesthesia and were then divided into a control group, nHA group, IPRF group, and nHA-IPRF group. Decapitation was carried out on day 14 and day 28 in each group and the jaws of each rat were subjected to immunohistochemical and histological analysis. The results showed a decrease in TRAP expression in the nHA-IPRF group compared with the control group on day 14 (p = 0.074) and day 28 (p = 0.017). The study also showed an increase in ALP and OCN in the HA-IPRF group on day 14 and day 28 compared with the control group. New bone formation suggested a significant increase in the nHA-IPRF group compared with the control group on day 14 (p = 0.001) and day 28 (p = 0.001). nHA-IPRF implantation can suppress alveolar bone resorption, which is indicated by decreased TRAP expression, and it can increase bone growth, as indicated by increased expression of ALP, OCN, and new bone formation.

Myricetin exerts anti-biofilm activity and attenuates osteomyelitis by inhibiting the TLR2/MAPK pathway in experimental mice.

AIMS: To evaluate the potential of Myricetin against S.aureus induced osteomyelitis. BACKGROUND: Osteomyelitis is infected condition of bone by micro-organisms. The mitogen-activated protein kinase (MAPK), inflammatory cytokines and Toll-like receptor-2 (TLR-2) pathway are mainly involved in osteomyelitis. Myricetin is a plant-food derived flavonoid which shows anti-inflammatory activity. OBJECTIVE: In the present study, we evaluated the potential of Myricetin against S.aureus induced osteomyelitis. MC3T3-E1 cells were used for in vitro studies. METHOD: Murine model of osteomyelitis was developed in BALB/c mice by injecting S.aureus in the medullary cavity of the femur. The mice were studied for bone destruction, anti-biofilm activity, osteoblast growth markers alkaline phosphatase (ALP), osteopontin (OCN) and collagen type-I (COLL-1) were studied by RT-PCR, ELISA analysis for levels of proinflammatory factors CRP, IL-6 and IL-1ß. Expression of proteins by Western blot analysis and anti-biofilm effect by Sytox green dye fluorescence assay. Target confirmation was done by performing in silico docking analysis. RESULTS: Myricetin reduced bone destruction in osteomyelitis induced mice. The treatment decreased bone levels of ALP, OCN, COLL-1 and TLR2. Myricetin decreased serum levels of CRP, IL-6 and IL-1ß. The treatment suppressed activation of MAPK pathway and showed anti-biofilm effect. Docking studies suggested high binding affinity of Myricetin with MAPK protein in silico, by showing lower binding energies. CONCLUSION: Myricetin suppresses osteomyelitis by inhibiting ALP, OCN, COLL-1 via the TLR2 and MAPK pathway involving inhibition of biofilm formation. In silico studies suggested MAPK as potential binding protein for myricetin.

Osteoblasts and Fibroblasts Interaction with a Porcine Acellular Dermal Matrix Membrane.

The use of collagen membranes has remained the gold standard in GTR/GBR. In this study, the features and the biological activities of an acellular porcine dermis collagen matrix membrane applicable during dental surgery were investigated, and also by applying hydration with NaCl. Thus, two tested membranes were distinguished, the H-Membrane and Membrane, compared to the control cell culture plastic. The characterization was performed by SEM and histological analyses. In contrast, the biocompatibility was investigated on HGF and HOB cells at 3, 7, and 14 days by MTT for proliferation study; by SEM and histology for cell interaction study; and by RT-PCR for function-related genes study. In HOBs seeded on membranes, mineralization functions by ALP assay and Alizarin Red staining were also investigated. Results indicated that the tested membranes, especially when hydrated, can promote the proliferation and attachment of cells at each time. Furthermore, membranes significantly increased ALP and mineralization activities in HOBs as well as the osteoblastic-related genes ALP and OCN. Similarly, membranes significantly increased ECM-related and MMP8 gene expression in HGFs. In conclusion, the tested acellular porcine dermis collagen matrix membrane, mainly when it is hydrated, behaved as a suitable microenvironment for oral cells.

Enhancing osteogenic potential of hDPSCs by resveratrol through reducing oxidative stress via the Sirt1/Nrf2 pathway.

CONTEXT: The osteogenic potential of the human dental pulp stromal cells (hDPSCs) was reduced in the state of oxidative stress. Resveratrol (RSV) possesses numerous biological properties, including osteogenic potential, growth-promoting and antioxidant activities. OBJECTIVE: This study investigates the osteogenic potential of RSV by activating the Sirt1/Nrf2 pathway on oxidatively stressed hDPSCs and old mice. MATERIALS AND METHODS: The hDPSCs were subjected to reactive oxygen species (ROS) fluorescence staining, cell proliferation assay, ROS activity assay, superoxide dismutase (SOD) enzyme activity, the glutathione (GSH) concentration assay, alkaline phosphatase staining, real-time polymerase chain reaction (RT-PCR) and Sirt1 immunofluorescence labelling to assess the antioxidant stress and osteogenic ability of RSV. Forty female Kunming mice were divided into Old, Old-RSV, Young and Young-RSV groups to assess the repair of calvarial defects of 0.2 mL RSV of 20 mg/kg/d for seven days by injecting intraperitoneally at 4 weeks after surgery using micro-computed tomography, nonlinear optical microscope and immunohistochemical analysis. RESULTS: RSV abates oxidative stress by alleviating the proliferation, mitigating the ROS activity, increasing the SOD enzyme activity and ameliorating the GSH concentration (RSV IC50 in hDPSCs is 67.65 ± 9.86). The antioxidative stress and osteogenic capabilities of RSV were confirmed by the up-regulated gene expression of SOD1, xCT, RUNX2 and OCN, as well as Sirt1/Nrf2. The collagen, bone matrix formation and Sirt1 expression, are significantly increased after RSV treatment in mice. DISCUSSION AND CONCLUSIONS: For elderly or patients with oxidative stress physiological states such as hypertension, heart disease, diabetes, etc., RSV may potentially improve bone augmentation surgery in regenerative medicine.

Effect of cachexia on bone turnover in cancer patients: a case-control study.

BACKGROUND: Increased bone turnover is frequently observed in advanced cancer and predominantly related to bone metastases or therapy. Cachexia represents an important cause of morbidity and mortality in cancer patients. Key features are weight loss, muscle wasting and chronic inflammation, which induce profound metabolic changes in several organs, including the bone. However, whether cachexia contributes to abnormal bone metabolism in cancer patients is unknown. Aim of the present study was to determine the potential correlation of bone turnover markers with body composition and laboratory parameters in treatment-naïve cancer patients. METHODS: In this cross-sectional study we measured the levels of carboxy terminal telopeptide of collagen (CTX), an indicator of bone resorption, as well as osteocalcin (Ocn) and procollagen type I N-terminal propeptide (PINP), indicators of bone formation, in 52 cancer patients and correlated with body composition and laboratory parameters. Univariate and multivariate logistic analysis were performed to identify determinants of negative bone remodeling balance, estimated by CTX/Ocn and CTX/PINP ratio. RESULTS: Based on weight loss, body mass index and muscle mass, patients were divided into a cachectic (59.6%) and a control (40.4%) group. After correcting for the presence of bone metastases, our results showed a significant upregulation of CTX in cachectic patients compared to non-cachectic cancer patients (median 0.38 vs 0.27 ng/mL, p < 0.05), with no difference in Ocn and PINP levels (mean 14 vs. 16 ng/ml, p = 0.2 and median 32 vs. 26 µg/L, p = 0.5, respectively). In addition, the CTX/Ocn and the CTX/PINP ratio were indicative of bone resorption in 68% and 60% of cachexia patients, respectively (vs. 20% and 31% in the control group, p = 0.002 and p = 0.06). The main determinants of the unbalanced bone turnover were hypoalbuminemia for the CTX/Ocn ratio (OR 19.8, p < 0.01) and high CRP for the CTX/PINP ratio (OR 5.3, p < 0.01) in the multivariate regression analysis. CONCLUSIONS: CTX is substantially higher in cachectic patients compared to non-cachectic oncological patients and hypoalbuminemia as well as elevated CRP concentrations are independent predictors of a negative bone remodeling balance in cancer patients. These results strongly indicate that cachexia correlates with exacerbated bone turnover in cancer.

Molecular events in the clinicopathological diagnosis of alveolar osteitis.

Alveolar osteitis (AO) is an extremely distressing outcome following extraction of a tooth. Its pathophysiology is poorly understood due to varied nature of presentation of the condition. However, a delay in the healing process of bone due to fibrinolysis is believed to be the underlying pathophysiology. This review highlights three major risk factors - trauma, bacterial accumulation due to poor oral hygiene, and smoking - in causing alveolar osteitis, and describes underlying related molecular events. Fibrinolysis results due to traumatic tooth extraction as well as due to accumulation of certain microorganisms which leads to the development of alveolar osteitis. Tumour necrosis factor-alpha (TNF-a), Runt-related transcription factor 2 (Runx 2) and osteocalcin (OCN) can be used as molecular markers for evaluating alveolar osteitis. Assessment assays of such biomarkers can lead to a better understanding of the pathological process in providing a clearer picture to researchers and clinicians.

Expression Level and Clinical Significance of Inflammatory Cytokines and Biochemical Markers in Gingival Crevicular Fluid During Different Crown Adhesion Patterns of Dental Implant.

OBJECTIVE: The aim of this study was to investigate the expression level and clinical significance of inflammatory factors and biochemical markers in gingival crevicular fluid during different crown-binding styles in dental implant patients. METHODS: A total of 38 patients with posterior tooth loss and implant repair were recruited and divided into two groups according to the different ways of crown bonding, including 19 prostheses (19 patients) in the adhesive retainer group and 19 prostheses (19 patients) in the modified adhesive retainer group. Moreover, the peri-implant gingival sulcus fluids of each group of patients were collected at 7, 15, 30, 60, and 90 d of post-treatment, and the expression level of each cytokine as well as biochemical marker were analyzed by enzyme-linked adsorption method, respectively. RESULTS: Compared with the control group, the peri-implant plaque index and gingival bleeding index were decreased in the observation group. In addition, the secretion of peri-implant gingival crevicular fluid in the observation group was significantly higher than that of the control group. The level of IL-6, TNF-α expressions in peri-implant gingival crevicular fluid were gradually decreased with follow-up time, and the rate of decline gets slow at 15 h after operation. The TGFα in peri-implant gingival crevicular fluid in the two groups began to increase at 7 d, reached a peak at about 15 d, then slowly decreased and stabilized after 60 d. While the OCN was gradually increased during the whole detection process, slowly released before 30 d, then increasingly released and maintained at a peak state after 60 d. All the above differences were statistically significant (P < 0.05). CONCLUSION: Different crown-binding patterns of implant teeth have a significant effect on the secretion amount of peri-implant gingival crevicular fluid and the expression level of inflammatory cytokines as well as biochemical markers.

A New NLRP3 Inflammasome Inhibitor, Dioscin, Promotes Osteogenesis.

Refractory periapical periodontitis, which is a persistent infection after root canal treatment, still has no effective treatment. Its most common pathogen is Enterococcus faecalis. Here, the precursor of phytosteroids, dioscin, is introduced to fight against the inflammation induced by Enterococcus faecalis. The findings suggest that dioscin inhibits the nuclear transport of NF-κB and the expression of reactive oxygen species (ROS) induced by lipoteichoic acid from the Enterococcus faecalis. The decrease in mRNA and protein levels of NLRP3, Caspase-1, and IL-1ß is observed in dioscin treated mouse macrophages. In the MC3T3-E1 cells, dioscin also promotes the expression of osteogenic-related factors, ALP, Runx2, and OCN. The increased formation of mineralized nodules after the application of dioscin further indicates that dioscin has the potential to promote osteogenesis. The above results suggest dioscin can be a potential root canal irrigation or root canal sealant for the treatment of refractory apical periodontitis.

Overexpression of miR-182 inhibits ossification of ligamentum flavum cells by targeting NAMPT.

Ossification of the ligamentum flavum (OLF) is a debilitating disease resulting from the development of ectopic bone formation, which leads to the compression of the spinal cord. Nicotinamide phosphoribosyltransferase (NAMPT) was found to be upregulated and microRNA-182 (miR-182) was downregulated in OLF tissue. We investigated the effects of NAMPT and miR-182 expression in OLF cells and the influence on proteins associated with osteogenic differentiation. MiR-182 overexpression inhibited NAMPT, RUNX2, OCN and OPN mRNA and protein expression in OLF cells. Alkaline phosphatase (ALP) assay and Alizarin red staining confirmed reduced levels of osteogenic differentiation and mineralized nodule formation. Knockdown of NAMPT and the NAMPT inhibitor FK866 also inhibits RUNX2, OCN and OPN mRNA expression and protein levels, whereas overexpression of NAMPT promotes the expression of RUNX2, OCN and OPN and the generation of bone nodules. Dual-luciferase reporter assays revealed that miR-182 directly targets NAMPT and downregulates its expression. Transfection of OLF cells with miR-182 downregulated NAMPT and suppressed the regulation of RUNX2, OCN, and OPN by NAMPT overexpression. Overall, these data demonstrate that miR-182 suppresses OLF by downregulating NAMPT.

Exosomes secreted from mutant-HIF-1α-modified bone-marrow-derived mesenchymal stem cells attenuate early steroid-induced avascular necrosis of femoral head in rabbit.

Mesenchymal stem cells (MSCs)-derived exosomes exhibit protective effects on damaged or diseased tissues. Hypoxia-inducible factor 1α (HIF-1α) plays a critical role in bone development. However, HIF-1α is easily biodegradable under normoxic conditions. The bone-marrow-derived mesenchymal stem cells (BMSCs) were transfected with adenovirus carrying triple point-mutations (amino acids 402, 564, and 803) in the HIF-1α coding sequence (CDS). The mutant HIF-1α can efficiently express functional proteins under normoxic conditions. To date, no study has reported the role of exosomes secreted by mutant HIF-1α modified BMSCs in the recovery of the early steroid-induced avascular necrosis of femoral head (SANFH). In this study, we firstly analyzed exosomes derived from BMSCs modified by mutant (BMSC-ExosMU ) or wild-type HIF-1α (BMSC-ExosWT ). In vitro, we investigated the osteogenic differentiation capacity of BMSCs modified by BMSC-ExosMU or BMSC-ExosWT , and the angiogenesis effects of BMSC-ExosMU and BMSC-ExosWT on human umbilical vein endothelial cells (HUVECs). Besides, the healing of the femoral head was also assessed in vivo. We found that the potential of osteogenic differentiation of BMSCs treated with BMSC-ExosMU was higher than the wild-type group in vitro. In addition, BMSC-ExosMU stimulated the proliferation, migration, and tube formation of HUVECs in a dose-dependent manner. Compared with the BMSC-ExosWT or PBS control group, the injection of BMSC-ExosMU into the necrosis region markedly accelerated the bone regeneration and angiogenesis, which were indicated by the increased trabecular reconstruction and microvascular density. Taken together, our data suggest that BMSC-ExosMU facilitates the repair of SANFH by enhancing osteogenesis and angiogenesis.

Formononetin, a methoxy isoflavone, enhances bone regeneration in a mouse model of cortical bone defect.

The bone regeneration and healing effect of formononetin was evaluated in a cortical bone defect model that predominantly heals by intramembranous ossification. For this study, female Balb/c mice were ovariectomised (OVx) and a drill-hole injury was generated in the midfemoral bones of all animals. Treatment with formononetin commenced the day after and continued for 21 d. Parathyroid hormone (PTH1-34) was used as a reference standard. Animals were killed at days 10 and 21. Femur bones were collected at the injury site for histomorphometry studies using microcomputed tomography (µCT) and confocal microscopy. RNA and protein were harvested from the region surrounding the drill-hole injury. For immunohistochemistry, 5 µm sections of decalcified femur bone adjoining the drill-hole site were cut. µCT analysis showed that formononetin promoted bone healing at days 10 and 21 and the healing effect observed was significantly better than in Ovx mice and equal to PTH treatment in many aspects. Formononetin also significantly enhanced bone regeneration as assessed by calcein-labelling studies. In addition, formononetin enhanced the expression of osteogenic markers at the injury site in a manner similar to PTH. Formononetin treatment also led to predominant runt-related transcription factor 2 and osteocalcin localisation at the injury site. These results support the potential of formononetin to be a bone-healing agent and are suggestive of its promising role in the fracture-repair process.

Formononetin, an isoflavone, activates AMP-activated protein kinase/ß-catenin signalling to inhibit adipogenesis and rescues C57BL/6 mice from high-fat diet-induced obesity and bone loss.

Balance between adipocyte and osteoblast differentiation is the key link of disease progression in obesity and osteoporosis. We have previously reported that formononetin (FNT), an isoflavone extracted from Butea monosperma, stimulates osteoblast formation and protects against postmenopausal bone loss. The inverse relationship between osteoblasts and adipocytes prompted us to analyse the effect of FNT on adipogenesis and in vivo bone loss, triggered by high-fat diet (HFD)-induced obesity. The anti-obesity effect and mechanism of action of FNT was determined in 3T3-L1 cells and HFD-induced obese male mice. Our findings show that FNT suppresses the adipogenic differentiation of 3T3-L1 fibroblasts, through down-regulation of key adipogenic markers such as PPARγ, CCAAT/enhancer-binding protein alpha (C/EBPα) and sterol regulatory element-binding protein (SREBP) and inhibits intracellular TAG accumulation. Increased intracellular reactive oxygen species levels and AMP-activated protein kinase (AMPK) activation accompanied by stabilisation of ß-catenin were attributed to the anti-adipogenic action of FNT. In vivo, 12 weeks of FNT treatment inhibited the development of obesity in mice by attenuating HFD-induced body weight gain and visceral fat accumulation. The anti-obesity effect of FNT results from increased energy expenditure. FNT also protects against HFD-induced dyslipidaemia and rescues deterioration of trabecular bone volume by increasing bone formation and decreasing bone resorbtion caused by HFD. FNT's rescuing action against obesity-induced osteoporosis commenced at the level of progenitors, as bone marrow progenitor cells, obtained from the HFD mice group supplemented with FNT, showed increased osteogenic and decreased adipogenic potentials. Our findings suggest that FNT inhibits adipogenesis through AMPK/ß-catenin signal transduction pathways and protects against HFD-induced obesity and bone loss.

Serum and tissue 25-OH vitamin D3 concentrations do not predict bone abnormalities and molecular markers of vitamin D metabolism in the hypovitaminosis D kyphotic pig model.

The hypovitaminosis D kyphotic pig provides a model to study maternal vitamin D (D) carryover on gross and molecular characteristics of bone abnormalities in offspring. Excess maternal D is proposed to protect offspring under nutritional challenges from developing bone abnormalities. Relationships between D sufficiency parameters and bone abnormalities were characterised. Sows (n 37) were fed diets with 0 (-D), 8·125 (+D) or 43·750 (++D) µg D3/kg throughout gestation and lactation. At weaning (3 weeks) pigs were fed diets with 0 (-D) or 7·0 (+D) µg D3/kg, each with 75 and 95 % (LCaP) or 150 and 120 % (HCaP) of the Ca and P requirements. Pigs were euthanised before colostrum consumption at birth (n 27), 3 weeks (n 27) or after the nursery period (7 weeks, n 71) for tissue analysis. At 7 weeks, differences due to maternal D were detected (P≤0·05) in pig growth, serum parameters and mRNA expression regardless of nursery diet. Prevalence of kyphosis in pigs at 13 weeks was affected by maternal D, but not prevented by only HCaP or +D nursery diets. Increased (P≤0·05) serum 25-OH-D3 concentrations in sows fed +D or ++D diets were not reflected by similar magnitudes of 25-OH-D3 in colostrum, 18-d milk, or serum and tissue concentrations in pigs. The mode of action by which maternal dietary D influences development of skeletal abnormalities warrants further investigation.

Maternal dietary vitamin D carry-over alters offspring growth, skeletal mineralisation and tissue mRNA expressions of genes related to vitamin D, calcium and phosphorus homoeostasis in swine.

Maternal dietary vitamin D carry-over effects were assessed in young pigs to characterise skeletal abnormalities in a diet-induced model of kyphosis. Bone abnormalities were previously induced and bone mineral density (BMD) reduced in offspring from sows fed diets with inadequate vitamin D3. In a nested design, pigs from sows (n 23) fed diets with 0 (-D), 8·125 (+D) or 43·750 (++D) µg D3/kg from breeding through lactation were weaned and, within litter, fed nursery diets arranged as a 2×2 factorial design with 0 (-D) or 7·0 (+D) µg D3/kg, each with 95 % (95P) or 120 % (120P) of P requirements. Selected pigs were euthanised before colostrum consumption at birth (0 weeks, n 23), weaning (3 weeks, n 22) and after a growth period (8 weeks, n 185) for BMD, bone mechanical tests and tissue mRNA analysis. Pigs produced by +D or ++D sows had increased gain at 3 weeks (P<0·05), and at 8 weeks had increased BMD and improved femur mechanical properties. However, responses to nursery diets depended on maternal diets (P<0·05). Relative mRNA expressions of genes revealed a maternal dietary influence at birth in bone osteocalcin and at weaning in kidney 24-hydroxylase (P<0·05). Nursery treatments affected mRNA expressions at 8 weeks. Detection of a maternal and nursery diet interaction (P<0·05) provided insights into the long-term effects of maternal nutritional inputs. Characterising early stages of bone abnormalities provided inferences for humans and animals about maternal dietary influence on offspring skeletal health.

A Graphene-like Oxygenated Carbon Nitride Material for Improved Cycle-Life Lithium/Sulfur Batteries.

Novel sulfur (S) anchoring materials and the corresponding mechanisms for suppressing capacity fading are urgently needed to advance the performance of Li/S batteries. Here, we designed and synthesized a graphene-like oxygenated carbon nitride (OCN) host material that contains tens of micrometer scaled two-dimensional (2D) rippled sheets, micromesopores, and oxygen heteroatoms. N content can reach as high as 20.49 wt %. A sustainable approach of one-step self-supporting solid-state pyrolysis (OSSP) was developed for the low-cost and large-scale production of OCN. The urea in solid sources not only provides self-supporting atmospheres but also produces graphitic carbon nitride (g-C3N4) working as 2D layered templates. The S/OCN cathode can deliver a high specific capacity of 1407.6 mA h g(-1) at C/20 rate with 84% S utilization and retain improved reversible capacity during long-term cycles at high current density. The increasing micropores, graphitic N, ether, and carboxylic O at the large sized OCN sheet favor S utilization and trapping for polysulfides.

Osteotropic cancer diagnosis by an osteocalcin inspired molecular imaging mimetic.

BACKGROUND: Although microcalcifications of hydroxyapatite can be found in both benign and malignant osteotropic tumors, they are mostly seen in proliferative lesions, including carcinoma. The aim of this present study is to develop a molecular imaging contrast agent for selective identification of hydroxyapatite calcification in human osteotropic tumor tissues ex vivo and in human osteosarcoma cells in vitro. METHODS: A bioinspired biomarker, hydroxyapatite binding peptide (HABP), was designed to mimic natural protein osteocalcin property in vivo. A fluorescein isothiocyanate dye conjugated HABP (HABP-19) was utilized to characterize hydroxyapatite on human osteotropic tumor tissue sections ex vivo and to selectively image hydroxyapatite calcifications in human osteosarcoma cells in vitro. RESULTS: Using a HABP-19 molecular imaging probe, we have shown that it is possible to selectively image hydroxyapatite calcifications in osteotropic cancers ex vivo and in human SaOS-2 osteosarcoma cells in vitro. CONCLUSION: Hydroxyapatite calcifications were selectively detected in osteotropic tissues ex vivo and in the early stage of the calcification process of SaOS-2 human osteosarcoma in vitro using our HABP-19 molecular imaging probe. This new target-selective molecular imaging probe makes it possible to study the earliest events associated with hydroxyapatite deposition in various osteotropic cancers at the cellular and molecular levels. GENERAL SIGNIFICANCE: It potentially could be used to diagnose and treat osteotropic cancer or to anchor therapeutic agents directing the local distribution of desired therapy at calcified sites.

Human Mesenchymal Stem Cells Improve Angiogenesis and Bone Formation in Severed Finger Rats through SIRT1/Nrf2 Signaling.

BACKGROUND: This study employed a severed finger rat model to analyze the effects of human mesenchymal stem cells (MSCs) on angiogenesis, inflammatory response, apoptosis, and oxidative stress, to evaluate the possible mechanism of the repair effect of MSCs on severed finger (SF) rats. METHODS: Sixty Sprague-Dawley (SD) rats were categorized into five groups (n = 12). The pathological changes of severed finger tissues were investigated by Hematoxylin and eosin (H&E) staining on day 14 after the rats were sacrificed. The levels of inflammatory factors and oxidative stress factors were detected by ELISA. Terminal Deoxynucleotidyl Transferase (TdT) dUTP Nick End Labeling (TUNEL) was employed to assess the apoptosis of chondrocytes in severed finger tissues. The expression of osteocalcin (OCN), osteopontin (OPN), Collagen I (Col-1), and CD31 were detected by immunohistochemistry or immunofluorescence assay, respectively. The expression levels of related proteins were determined by western blot. RESULT: Our study presented evidence that MSCs treatment improved pathological changes of skin and bone tissue, diminished the inflammatory response, prevented oxidative stress injury, suppressed chondrocyte apoptosis, and promoted angiogenesis, and bone formation compared to the model group. In addition, EX527 treatment attenuated the effect of MSCs, SRT1720 and ML385 co-treatment also attenuated the effect of MSCs. Importantly, the MSCs treatment increased the expression of Sirtuin 1(SIRT1)/Nuclear factor erythroid2-related factor 2(Nrf2) relate proteins. CONCLUSION: Our study indicated that the mechanism of the effect of MSCs on a severed finger was related to the SIRT1/ Nrf2 signaling pathway.

Facile introduction of coordinative Fe into oxygen-enriched graphite carbon nitride for efficient photo-Fenton degradation of tetracycline.

Tetracycline (TC) antibiotics have been widely used over the past decades, and their massive discharge led to serious water pollution. Photo-Fenton process has gained ever-increasing attention for its excellent oxidizing ability and friendly solar energy utilization ability in TC polluted water treatment. This work introduced coordinative Fe into oxygen-enriched graphite carbon nitride (OCN) to form FeOCN composites for efficient photo-Fenton process. Hemin was chosen as the source to provide the source of coordinative Fe-Nx groups. The degradation efficiency of TC reached 82.1 % within 40 min of irradiation, and remained 76.9 % after five runs of reaction. The degradation intermediates of TC were detected and the possible degradation pathways were gained. It was found that h+, OH, and O2- played major roles in TC degradation. Notably, the photo-Fenton performance of FeOCN was stable in highly saline water or strong acid/base environment (pH 3.0-9.0). Besides, H2O2 can be generated in-situ in this photo-Fenton process, which is favorable for practical application. It can be anticipated that the coordinative FeOCN composites will promote the application of photo-Fenton oxidation process in TC polluted water treatment.

Clinical and pathological features analysis of invasive breast cancer with microcalcification.

PURPOSE: Microcalcification (MC) is a valuable diagnostic indicator to detect invasive breast cancer (IBC). This study aimed to determine the clinicopathological features of IBC with MC and detect biomarkers related to the potential mechanism of the MC formation in IBC. METHODS: Data from 364 patients with IBC were collected for the clinical characteristic analysis. The analysis of clinical data helped us to establish a predictive model of axillary node metastasis (ANM) before surgery. In addition, 49 tissue samples of IBC patients were collected to test the protein levels of osteocalcin (OCN) and hypoxia-inducible factor-1α (HIF-1α) by immunohistochemistry. RESULTS: Significant differences were observed in tumor size, age, ANM, HER2+ , TNM stage, and mutant P53 between samples from IBC patients with MC and samples from IBC patients without MC. Younger age, a larger tumor size, a higher number of childbirths, and MC were independent predictors for ANM in IBC. HIF-1α protein level was higher in tumor tissue than in normal tissue. High protein levels of OCN and HIF-1α are related to the complication of MC in IBC. Of the patients that exhibited high HIF-1α protein levels, the percentage of high OCN protein levels was larger in patients with ANM. CONCLUSION: Based on this study, we concluded that patients with MC had a comparatively poor prognosis. MC was an independent predictive factor associated with the risk of ANM. High protein levels of OCN and HIF-1α were associated with MC and ANM, which were also related to poor prognosis. OCN and HIF-1α had a positive correlation in IBC.

Immobilization of TiO2NP@ oxidized cellulose nanocrystals for paper-based active packaging materials.

In the current work, we present a renewable alternative coating formulation made of durable titania nanoparticles and oxidized nanocellulose (TiO2NPs@OCNs) nanocomposites and sodium alginate (SA), to create an environmentally friendly and secure food packaging paper. OCNs sugarcane fibers are firstly hydrolyzed using ammonium persulphate (APS). Then, TiO2NPs@OCNs nanocomposites are made in situ with OCNs using a green water-based sol-gel synthesis. Gram (+) microorganisms as well as Gram (-) bacteria are used to test the antibacterial properties of the TiO2NPs@OCN dispersions. The results show that the TiO2NP@OCNs significantly decreases the growth for all bacterial species. The TiO2NP@OCNs nanocomposites are mixed with SA, and the resulting formulations are used to coat paper sheets. The corresponding physicochemical properties are evaluated using FTIR, TGA, AFM, SEM, and EDX. Furthermore, the mechanical strength, air permeability, and water vapor characteristics of the paper sheets treated with SA/TiO2NPs@OCN are carried out, resulting in a great improvement of these properties. Finally, the SA/TiO2NPs@OCNs coated papers have been used as packaging for strawberries. The findings demonstrate that coated papers could preserve strawberry quality better than unpacked fruit and extend strawberry shelf life from 6 to 18 days.