Impact of occlusal contact pattern on dental stability and oromandibular system after orthodontic tooth movement in rats.

How to ensure dental stability in new positions and reduce the likelihood of relapse is a major clinical concern in the orthodontic field. Occlusal contacts between arches may affect the transmission of masticatory forces, thereby influencing the biological response of the periodontal and the oromandibular system. Occlusion factors that may influence the stability after orthodontic tooth movement (OTM) remain largely unknown. Hence, this research was conducted in order to investigate the influence of different occlusal contact patterns on tooth stability and oromandibular system including the masseter muscle and the temporomandibular joint following OTM. By modifying the occlusal surfaces, in vivo animal study models with distinct occlusal patterns corresponding to clinical circumstances were established. The relapse distance of teeth and the level of inflammatory factors in the gingival cervical fluid were analyzed. We also closely observed the histological remodeling of periodontal tissue, masseter tissue, and joint tissue after one week of relapse. Moreover, genes expression in the alveolar bone was analyzed to illustrate the potential biological mechanisms of relapse under the influence of different occlusal contact patterns following OTM. Different occlusal contact patterns after OTM in rats were established. The intercuspation contact between cusp and fossa group exhibited the lowest level of relapse movement, inflammatory factors and osteoclast activity (P < 0.05). On the other hand, groups with interferences or inadequate contacts exhibited more relapse movement, and tend to promote inflammation of periodontal tissue and activate bone resorption (P < 0.05). Adequate occlusal contacts without interference may enhance tooth stability and reduce the likelihood of relapse. After active orthodontic treatment, necessary occlusal adjustment should be made to achieve the desired intercuspation contact relationship and ensure adequate contact between the arches. The elimination of occlusal interferences is crucial to achieving optimal stability and promoting overall healthy condition of the oromandibular system.

Semi-autonomous two-stage dental robotic technique for zygomatic implants: An in vitro study.

OBJECTIVE: To assess the feasibility and accuracy of a semi-autonomous two-stage dental robotic technique for zygomatic implants. METHODS: Twenty-six zygomatic implants were designed and randomly divided into two groups using 10 three-dimensionally printed resin models with severe maxillary atrophy. In one group, the conventional drilling technique was used, in the other group, the drilling process for the alveolar ridge section (first stage) was completed, after which drilling for the zygoma section (second stage) was done. Based on preoperative planning combined with postoperative cone-beam computed tomography (CBCT), coronal, apical, depth, and angle deviations were measured. Zygomatic implant placement technique-related deviations (sinus slot, intrasinus, and extrasinus) were also recorded and analyzed. RESULTS: The two-stage technical group's coronal, apical, depth, and angle deviations were 0.57 ± 0.19 mm, 1.07 ± 0.48 mm, 0.30 ± 0.38 mm, and 0.91 ± 0.51°, respectively. The accuracy of the two-stage technique was significantly higher than that of the conventional one-stage technique (p < 0.05). The apical deviation in the intrasinus group was 1.12 ± 0.56 mm, which was significantly better than that in the other two groups (p < 0.05). The angle deviation in the sinus slot group was 1.96 ± 0.83°, which was significantly worse than that in the other two groups (p < 0.05). CONCLUSION: Using the semi-autonomous two-stage dental robotic technique for zygomatic implants is feasible and is more accurate than using the conventional one-stage technique. CLINICAL SIGNIFICANCE: The two-stage technique enabled the semi-autonomous robot to overcome the mouth-opening restriction for zygomatic implants and improved accuracy.

Autonomous dental robotic surgery for zygomatic implants: A two-stage technique.

Zygomatic implants (ZIs) can be a treatment option for patients with severe atrophy in the maxilla, but deviation during ZI placement could lead to serious complications. Surgical guides and dynamic navigation have been used to improve the accuracy of ZI placement, but both techniques are subject to human error. A 2-stage technique is described that enabled an autonomous dental robot to overcome mouth-opening restrictions for ZI placement. The technique enables the complete digitalization of ZI placement, further improving the accuracy of the drilling process.

Comparison of biochemical characteristics and gel properties of chicken myofibrillar protein affected by heme-iron and nonheme-iron oxidizing systems.

In this study, the effect of hemin and non-heme iron on the biochemical and gelling properties of chicken myofibrillar protein (MP) was compared. Results revealed that free radicals from hemin incubated MP were significantly higher than that in FeCl3 incubated samples (P < 0.05), and had higher ability to initiate protein oxidation. The carbonyl content, surface hydrophobicity, random coil increased with oxidant concentration, whereas the total sulfhydryl and α-helix content decreased in both oxidizing systems. The turbidity and particle size were increased after oxidant treatment, indicating oxidation promoted the cross-linking and aggregation of protein, and the degree of aggregation was higher in hemin treated MP compared with that incubated with FeCl3. The biochemical changes of MP resulted in an uneven and loose gel network structure, which significantly reduced the gel strength and water holding capacity (WHC) of the gel.

Inactivation of Clostridium perfringens C1 Spores by the Combination of Mild Heat and Lactic Acid.

Clostridium perfringens is a major pathogen causing foodborne illnesses. In this experiment, the inactivation effects of heat and lactic acid (LA) treatments on C. perfringens spores was investigated. Heat treatment (80 °C, 90 °C and 100 °C), LA (0.5% and 1%), and combined LA and heat treatments for 30 and 60 min were performed. Residual spore counts showed that the count of C. perfringens spores was below the detection limit within 30 min of treatment with 1% LA and heat treatment at 90 °C. Scanning electron microscopy and confocal scanning laser microscopy results showed that the surface morphology of the spores was severely disrupted by the co-treatment. The particle size of the spores was reduced to 202 nm and the zeta potential to −3.66 mv. The inner core of the spores was disrupted and the co-treatment resulted in the release of 77% of the nuclear contents 2,6-pyridinedicarboxylic acid. In addition, the hydrophobicity of spores was as low as 11% after co-treatment with LA relative to the control, indicating that the outer layer of spores was severely disrupted. Thus, synergistic heating and LA treatment were effective in inactivating C. perfringens spores.

Natural killer cell-derived exosomal miR-1249-3p attenuates insulin resistance and inflammation in mouse models of type 2 diabetes.

Natural killer (NK) cells have been suggested to be associated with type 2 diabetes by regulating systemic inflammation. However, the mechanism by which NK cells regulate insulin sensitivity remains unknown. This study shows that NK-derived exosomes from lean mice attenuate obesity-induced insulin resistance and inflammation in mice of type 2 diabetes. Moreover, lean NK-derived exosomes enhance insulin sensitivity and relieve inflammation in adipocytes and hepatocytes. MiR-1249-3p, which is significantly upregulated in lean NK-derived exosomes, can be transferred from NK cells to adipocytes and hepatocytes via exosomes. NK-derived exosomal miR-1249-3p dramatically induces cellular insulin sensitivity and relieves inflammation. Mechanistically, exosomal miR-1249-3p directly targets SKOR1 to regulate the formation of ternary complex SMAD6/MYD88/SMURF1, which mediates glucose homeostasis by suppressing the TLR4/NF-κB signaling pathway. This study reveals an emerging role for NK-derived exosomal miR-1249-3p in remission of insulin resistance, and provides a series of potential therapeutic targets in type 2 diabetes.

Tumor-Derived EV-Encapsulated miR-181b-5p Induces Angiogenesis to Foster Tumorigenesis and Metastasis of ESCC.

Pathological angiogenesis is necessary for tumor development and metastasis. Tumor-derived extracellular vesicles (EVs) play an important role in mediating the crosstalk between cancer cells and vascular endothelial cells. To date, whether and how microRNAs (miRNAs) encapsulated in tumor-derived EVs affect angiogenesis in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we showed that miR-181b-5p, an angiogenesis-promoting miRNA of ESCC, can be transferred from ESCC cells to vascular endothelial cells via EVs. In addition, ESCC-derived EVs-miR-181b-5p dramatically induced angiogenesis by targeting PTEN and PHLPP2, and thereby facilitated tumor growth and metastasis. Moreover, miR-181b-5p was highly expressed in ESCC tissues and serum EVs. High miR-181b-5p expression level in ESCC patients was well predicted for poor overall survival. Our work suggests that intercellular crosstalk between tumor cells and vascular endothelial cells is mediated by tumor-derived EVs. miR-181b-5p-enriched EVs secreted from ESCC cells are involved in angiogenesis that control metastasis of ESCC, providing a potential diagnostic biomarker or drug target for ESCC patients.

Lipid oxidation induced by heating in chicken meat and the relationship with oxidants and antioxidant enzymes activities.

The aim of the current research was to examine lipid oxidation in chicken meat heated to different temperatures followed by refrigerator storage and the factors contributing to lipid oxidation. It showed that lipid oxidation was significantly promoted when meat was heated up to 70°C and stored for 2 and 4 D as measured by thiobarbituric acid reactive substance. The monounsaturated fatty acids and polyunsaturated fatty acids also decreased significantly (P < 0.05) with the increase of heating temperature. The liberation of nonheme iron and increase of hydroxyl radical were observed in heated chicken meat, and the activities of antioxidant enzymes was decreased considerably at higher temperatures. The changes of these prooxidants and antioxidants might constitute a possible mechanism for the stronger lipid oxidation in heated meat.

Antibacterial activity and action mode of chlorogenic acid against Salmonella Enteritidis, a foodborne pathogen in chilled fresh chicken.

The study evaluated the antibacterial activity of chlorogenic acid (CA) against Salmonella Enteritidis S1, a foodborne pathogen in chilled fresh chicken. Its minimum inhibitory concentration for S. Enteritidis S1 was 2 mM. 1 MIC CA treatment reduced the viable count of S. Enteritidis S1 by 3 log cfu/g in chilled fresh chicken. Scanning electron microscopy examination indicated that CA induced the cell envelope damage of S. Enteritidis S1. Following this, 1-N-Phenylnaphthylamine assay and LPS content analysis indicated that CA induced the permeability of outer membrane (OM). Confocal laser scanning microscopy examination further demonstrated that CA acted on the inner membrane (IM). To support this, the release of intracellular protein and ATP after CA treatment was also observed. CA also suppressed the activities of malate dehydrogenase and succinate dehydrogenase, two main metabolic enzymes in TCA cycle and electron transport chain. Thus, damage of intracelluar and outer membranes as well as disruption of cell metabolism resulted in cell death eventually. The finding suggested that CA has the potential to be developed as a preservative to control S. Enteritidis associated foodborne diseases.

Changes of hydroxyl-linoleic acids during Chinese-style sausage processing and their relationships with lipids oxidation.

A Chinese-style sausage was processed using pork as the raw material. During the whole process, 13-hydroxyoctadecadienoic acid (13-HODE), 9-hydroxyoctadecadienoic acid (9-HODE), 9,10-dihydroxyoctadecenoic acid (9,10-DHODE) and 9,10,13-trihydroxyoctadecenoic acid (9,10,13-THODE) kept increasing. All of them were found to be correlated negatively and significantly with lipoxygenases (LOX) activity, and positively and significantly with peroxide value (POV) and thiobarbituric acid reactive substances (TBARS). The ratio of 13-HODE to 9-HODE decreased slowly during drying stage and stayed higher than 2 during the whole process, and it was found to be positively and significantly with LOX activity. The ratio of variation of 13-HODE to variation of 9-HODE in every sampling period (the ratio of Δ13-HODE to Δ9-HODE) decreased sharply from 2.75 in the stage of curing for 12 h to 1.37 in the stage drying from 24 d to 30 d. The changes of ratio of 13HODE to 9-HODE and ratio of Δ13-HODE to Δ9-HODE indicated LOX-catalyzed oxidation predominated in curing and early drying stages, and such predominance was taken over by non-enzymatic oxidation during late drying stage; LOX-catalyzed oxidation was the major contributor to lipids oxidation during the whole process of the Chinese-style sausage preparing.

Peptide PD29 treats bleomycin-induced pulmonary fibrosis by inhibiting the TGF-ß/smad signaling pathway.

Pulmonary fibrosis (PF) is an end-stage change in lung disease characterized by fibroblast proliferation, massive extracellular matrix (ECM) aggregation with inflammatory damage, and severe structural deterioration. PD29 is a 29-amino acid peptide which has the potential to alleviate PF pathogenesis via three mechanisms: anti-angiogenesis, inhibition of matrix metalloproteinase activities, and inhibition of integrins. In this study, fibrotic lung injuries were induced in SD rats by a single intratracheal instillation of 5 mg/kg bleomycin (BLM). Then, these rats were administered 7.5, 5, or 2.5 mg/kg PD29 daily for 30 days. BLM induced-syndromes including structure distortion, excessive deposition of ECM, excessive inflammatory infiltration, and pro-inflammatory cytokine release were used to evaluate the protective effect of PD-29. Oxidative stress damage in lung tissues was attenuated by PD29 in a dose-dependent manner. The expression of TGF-ß1 and the phosphorylation of Smad-2/-3-its downstream targets-were enhanced by BLM and weakened by PD29. In vitro, PD29 inhibited TGF-ß1-induced epithelial-mesenchymal transition (EMT) and transformation in A549 cells and mouse primary fibroblasts into myofibroblasts. In summary, PD29 reversed EMT and transformation of fibroblasts into myofibroblasts in vitro and prevented PF in vivo possibly by suppressing the TGF-ß1/Smad pathway.

The pronounced high expression of discoidin domain receptor 2 in human interstitial lung diseases.

The most typical structural feature of human interstitial lung diseases (ILDs) is the accumulation of vast amounts of collagens within the lung interstitium. The membrane receptors that are responsible for recognising collagens and then transducing signals into the cells include four members of the integrin family (α1ß1, α2ß1, α10ß1 and α11ß1) and two members of the discoidin domain receptor family (DDR1 and DDR2). However, it remains unknown whether these six collagen receptors similarly contribute to the pathogenesis of fibrotic lung diseases. Quantitative real-time PCR (qPCR) was utilised to assess the mRNA expression of the genes studied. Immunoblot experiments were performed to analyse the protein abundance and kinase activity of the gene products. The tissue location was determined by immunohistochemical staining. qPCR data showed that DDR2 mRNA displays the most dramatic difference between idiopathic pulmonary fibrosis (IPF) patients and healthy groups. The outstanding increases in DDR2 proteins were also observed in some other types of ILD besides IPF. DDR2-expressing cells in ILD tissue sections were found to exhibit spindle or fibroblastic shapes. Our investigation suggests that DDR2 might represent a major cell surface protein that mediates collagen-induced cellular effects in human ILD and, hence, is suitable for their diagnosis and therapy.

Optimization and physicochemical properties of nutritional protein isolate from pork liver with ultrasound-assisted alkaline extraction.

The aim of this study was to investigate the optimal conditions of ultrasound-assisted alkaline extraction (UAAE) on pork liver protein isolate (UPLPI) and its physico-chemical properties. Response surface methodology was used to determine the optimal conditions for UAAE, which were at ultrasonic power 265 W, ultrasonic time 42 min, NaOH concentration 0.80%, temperature 50°C, and solvent/raw material ratio 70. The extraction yield and efficiency of UPLPI were significantly improved over the conventional alkaline extraction (PLPI). The results of amino acid composition showed that UAAE could increase serine (36.5 g/kg), arginine (38.1 g/kg), alanine (37.5 g/kg), proline (48.7 g/kg), phenylalanine (55.6 g/kg) and lysine (47.2 g/kg) elution amount. The changes in fourier transform infrared spectra indicated unfolding and destruction of the protein structure in UPLPI. The differential scanning calorimetry analysis presented UPLPI with a slightly lower onset and peak denaturation temperature over PLPI. Surface hydrophobicity increased and the microstructures presented larger and more pores of UPLPI, therefore, it had better in vitro digestibility than PLPI. Therefore, UPLPI might have a potential application prospect in the food field due to its changes on molecular structure as well as on the microstructure of protein by UAAE.

Treatment Effects of the Second-Generation Tyrosine Kinase Inhibitor Dasatinib on Autoimmune Arthritis.

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease that primarily manifests as persistent synovitis and progressive joint destruction. Imatinib exhibited a therapeutic effect in murine collagen-induced arthritis (CIA) via selective inhibition tyrosine kinases. The second-generation tyrosine kinase inhibitor dasatinib exhibits more durable hematological and cytogenetic effects and more potency compared to imatinib. However, the effect of dasatinib on CIA is poorly understood. The present study investigated the treatment effect of dasatinib on autoimmune arthritis. We demonstrated that dasatinib alleviated arthritis symptoms and histopathological destruction in CIA mice. Dasatinib treatment inhibited the production of proinflammatory cytokines including IL-1ß, TNF-α, and IL-6, and promoted the production of the anti-inflammatory cytokine IL-10. Dasatinib treatment also suppressed the expression of anti-mouse CII antibodies including total IgG, IgG1, IgG2, and IgG2b, in CIA mice. We further demonstrated that dasatinib inhibited the migration and proliferation of fibroblast-like synoviocytes (FLS) from RA patients and promoted FLS apoptosis. The mRNA expression of MMP13, VEGF, FGF, and DKK1 was down-regulated in FLS treated with dasatinib. Our findings suggest that dasatinib exhibited treatment effects on CIA mice and that FLS are an important target cell of dasatinib treatment in autoimmune arthritis.

Synergistic antibacterial mechanism of the Lactobacillus crispatus surface layer protein and nisin on Staphylococcus saprophyticus.

SlpB, a surface layer protein isolated from Lactobacillus crispatus, has the potential to enhance the antimicrobial activity of nisin. Previous research indicated that, when combined with nisin, SlpB acted synergistically to inhibit Staphylococcus saprophyticus growth, thus extending the shelf life of chicken meat. In order to understand how SlpB enhances the antibacterial activity of nisin, electron microscopy, confocal laser scanning microscopy, flow cytometry and transmembrane electrical potential analysis were used to study cell wall organization and cell membrane integrity. No remarkable bacteriolytic effects were observed, indicating that cell death could not be attributed to cell lysis, although SlpB caused dramatic modifications of cell wall, thereby altering cell shape. The combination of SlpB and nisin also induced the release of ATP or UV-absorbing materials, as well as sudden dissipation of the transmembrane electrical potential by compromising membrane integrity. Considering that SlpB led to structural disorganization of the cell wall, and nisin access is enhanced to form a stable pore, cell death is a predictable outcome. SlpB significantly enhanced the effect of nisin at half of the minimum inhibitory concentration, which resulted in cell death by destroying the cell wall and cell membrane, therefore providing a new, feasible approach in food preservation.

Anti-fibrotic effects of Salvia miltiorrhiza and Ligustrazine Injection on LX-2 cells involved with increased N-myc downstream-regulated gene 2 expression.

OBJECTIVE: To investigate the effects of Salvia miltiorrhiza and Ligustrazine Injection (SML) on proliferation and apoptosis of human hepatic stellate cell LX-2 and the expression of N-myc downstreamregulated gene 2 (NDRG2, a tumor suppressor gene). METHODS: HSCs from the LX-2 cell line were cultured in vitro. The proliferative state of different initial LX-2 cell numbers was measured using a 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. LX-2 cells were plated in 96-well plates at an approximate density of 2.50×104 cells/mL and cultured for 24 h followed by the application of different concentrations of SML (1, 2, 4 and 8 µL/mL). Cell proliferation was measured using the MTT assay at 24 and 48 h. Apoptosis was detected by flow cytometry at 24 h. LX-2 cells were treated with different concentrations of SML and extracted with protein lysis buffer. The levels of NDRG2 and ß-catenin were measured by Western blot. RESULTS: With the exception of the 1 and 2 µL/mL concentrations, 4 and 8 µL/mL SML inhibited cell proliferation in a concentration-dependent manner at 24 and 48 h (P<0.05). With the exception of the 1 and 2 µL/mL concentrations, the NDRG2 expression level was greatly increased in a concentration-dependent manner. However, the level of ß-catenin was unaffected. CONCLUSION: SML inhibit LX-2 cell proliferation in a concentration-dependent manner, and the mechanism may be associated with NDRG2 over-expression.

Differential expression of heat shock protein 90, 70, 60 in chicken muscles postmortem and its relationship with meat quality.

OBJECTIVE: The aim of this study was to investigate the expression of heat shock protein (HSP) 90, 70, and 60 in chicken muscles and their possible relationship with quality traits of meat. METHODS: The breast muscles from one hundred broiler chickens were analyzed for drip loss and other quality parameters, and the levels of heat shock protein (HSP) 90, 70, and 60 were determined by immunoblots. RESULTS: Based on the data, chicken breast muscles were segregated into low (drip loss≤5%), intermediate (5%0.05). CONCLUSION: Results of this study suggests that higher levels of HSP90 and HSP60 may be advantageous for maintenance of cell function and reduction of water loss, and they could act as potential indicator for better water holding capacity of meat.

Dec1 expression predicts prognosis and the response to temozolomide chemotherapy in patients with glioma.

Differentiated embryo chondrocyte expressed gene 1 (Dec1), a crucial cell differentiation mediator and apoptosis inhibitor, is abundantly expressed in various types of human cancer and is associated with malignant tumor progression. As poor differentiation and low apoptosis are closely associated with poor survival rates and a poor response to radio/chemotherapy in patients with cancer, the prognostic value of Dec1 expression was examined in the present study and its correlation with response to temozolomide (TMZ) chemotherapy was analyzed in patients with glioma. Dec1 expression was analyzed by immunohistochemistry in 157 samples of newly diagnosed glioma and 63 recurrent glioblastoma cases that relapsed during TMZ chemotherapy. Correlations with clinical variables, prognosis and the response to TMZ chemotherapy were analyzed in the newly diagnosed gliomas. Dec1 expression was also compared with the apoptosis index determined by TdT­mediated dUTP nick ending­labeling assay in recurrent glioblastomas. The antiglioma effect of TMZ in nude mice xenografts with Dec1 expression was examined in vivo. High expression of Dec1, which was significantly associated with high pathological tumor grade and poor response to TMZ chemotherapy, was demonstrated to be an unfavorable independent prognostic factor and predicted poor survival in patients with newly diagnosed glioma. In patients with recurrent glioblastoma, there was a negative correlation between Dec1 expression and the apoptotic index. In nude mice treated with TMZ, Dec1 overexpression potentiated proliferation, but attenuated TMZ­induced apoptosis. In conclusion, Dec1 is a prognostic factor for the clinical outcome and a predictive factor for the response to TMZ chemotherapy in patients with glioma.

Targeting of Discoidin Domain Receptor 2 (DDR2) Prevents Myofibroblast Activation and Neovessel Formation During Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a lethal human disease with short survival time and few treatment options. Herein, we demonstrated that discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase that predominantly transduces signals from fibrillar collagens, plays a critical role in the induction of fibrosis and angiogenesis in the lung. In vitro cell studies showed that DDR2 can synergize the actions of both transforming growth factor (TGF)-ß and fibrillar collagen to stimulate lung fibroblasts to undergo myofibroblastic changes and vascular endothelial growth factor (VEGF) expression. In addition, we confirmed that late treatment of the injured mice with specific siRNA against DDR2 or its kinase inhibitor exhibited therapeutic efficacy against lung fibrosis. Thus, this study not only elucidated novel mechanisms by which DDR2 controls the development of pulmonary fibrosis, but also provided candidate target for the intervention of this stubborn disease.

Structure-Based Design of Tetrahydroisoquinoline-7-carboxamides as Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors.

The structure-based design of 1, 2, 3, 4-tetrahydroisoquinoline derivatives as selective DDR1 inhibitors is reported. One of the representative compounds, 6j, binds to DDR1 with a Kd value of 4.7 nM and suppresses its kinase activity with an IC50 value of 9.4 nM, but it is significantly less potent for a panel of 400 nonmutated kinases. 6j also demonstrated reasonable pharmacokinetic properties and a promising oral therapeutic effect in a bleomycin-induced mouse pulmonary fibrosis model.