Repair mechanism of radiation-induced salivary gland injury by hypoxia-pretreated human urine-derived stem cell exosomes.

OBJECTIVE: To explore the protective effect of human urine-derived stem cell exosomes (hUSC-Exos) on radiation-induced salivary gland (SG) injuries in Sprague Dawley rats. METHODS: Fresh adult urine was collected, and primary hUSCs were isolated and identified. The hUSCs were hypoxia-pretreated with 1% oxygen for 24 h and then transferred to a normoxic culture environment for 24 h. The hUSC-Exos were collected and identified for exosomes. A radiation-induced injury model was established in the rats, and exosomes were introduced by local injection in the SG and tail vein. The submandibular gland was excised for morphological observation 1 week later. Immunohistochemical detection of the glandular tissue was conducted by α-smooth muscle actin (a-SMA), stem cell growth factor receptor (c-Kit) staining, and periodic acid-Schiff staining. Qualitative polymerase chain reaction and western blot analysis were adopted to detect the gene and protein expression of Wnt3a, GSK3ß, and Axin. RESULTS: In both the normoxic and hypoxic hUSC-Exo groups, microvesicular structures with bilayer membranes of approximately 80 nm in diameter were detected, and the expressions of CD9 and CD63 were detected by nanoflow cytometry. Compared with the control group, in the radiation-induced injury model group, the expression of a-SMA was significantly higher, the expression of c-Kit was significantly lower, and the expressions of Wnt3a, GSK3ß, and Axin were significantly upregulated; the differences were statistically significant (p < 0.05). Compared with the model group, in the normoxic and hypoxic hUSC-Exo groups, the expression of a-SMA was significantly decreased, the expression of c-Kit was significantly increased, and the expressions of Wnt3a, GSK3ß, and Axin were significantly upregulated; the differences were statistically significant (p < 0.05). CONCLUSION: Hypoxia-pretreated hUSC-Exos could repair radiation-induced SG injuries by activating the Wnt3a/GSK3ß pathway to suppress the expressions of a-SMA and c-Kit.

Effects on canine intrusion treatment with different Invisalign parameters / 医用生物力学

Objective To study the effects of different parameters (thickness, orthodontic displacement, elastic modulus) of Invisalign on canine displacement and periodontal ligament (PDL) stress during mandibular canine intrusion treatment. Methods Forty-eight different Invisalign models were used to simulate canine intrusion treatment by using the finite element method. Results The initial displacement of the canine and stress on canine PDL were proportional to thickness, intrusion displacement, and elastic modulus of Invisalign. The intrusion displacement had the greatest influence on canine displacement. During canine intrusion treatment, the compressive stress on PDL was the most sensitive parameter and changed easily with the change of parameters. Conclusions The increase of Invisalign thickness, intrusion displacement and elastic modulus can increase canine displacement, however, the stress on PDL also increases, with the largest increasing magnitude in compressive stress on PDL. Therefore, to accelerate tooth movement in Invisalign treatment, it is suggested to use the assisted devices or measurements, such as attachment, supplement of bracket-wires treatment, or implant anchorage.

Effects on canine intrusion treatment with different Invisalign parameters / 医用生物力学

Objective To study the effects of different parameters (thickness,orthodontic displacement,elastic modulus) from Invisalign on canine displacement and periodontal ligament (PDL) stress during mandibular canine intrusion treatment.Methods Forty-eight different Invisalign models were used to simulate canine intrusion treatment by using the finite element method.Results The initial displacement of the canine and stress on canine PDL were proportional to the thickness,intrusion displacement,and elastic modulus of the Invisalign,and the intrusion displacement had the greatest influence on canine displacement.During canine intrusion treatment,the compressive stress on PDL was the most sensitive and changed easily with the change of parameters.Conclusions The canine displacement may increase with the thickness,intrusion displacement and elastic modulus of Invisalign increasing,however,the stress on PDL will also increase,showing the largest increasing magnitude in compressive stress on PDL meanwhile.Therefore,to accelerate tooth movement in Invisalign treatment,it is suggested to use the assisted devices or some other measures such as attachment,supplement of bracket-wires treatment,or implant anchorage.

Effects on canine intrusion treatment with different Invisalign parameters / 医用生物力学

Objective To study the effects of different parameters (thickness,orthodontic displacement,elastic modulus) from Invisalign on canine displacement and periodontal ligament (PDL) stress during mandibular canine intrusion treatment.Methods Forty-eight different Invisalign models were used to simulate canine intrusion treatment by using the finite element method.Results The initial displacement of the canine and stress on canine PDL were proportional to the thickness,intrusion displacement,and elastic modulus of the Invisalign,and the intrusion displacement had the greatest influence on canine displacement.During canine intrusion treatment,the compressive stress on PDL was the most sensitive and changed easily with the change of parameters.Conclusions The canine displacement may increase with the thickness,intrusion displacement and elastic modulus of Invisalign increasing,however,the stress on PDL will also increase,showing the largest increasing magnitude in compressive stress on PDL meanwhile.Therefore,to accelerate tooth movement in Invisalign treatment,it is suggested to use the assisted devices or some other measures such as attachment,supplement of bracket-wires treatment,or implant anchorage.

Bufalin inhibits pancreatic cancer by inducing cell cycle arrest via the c-Myc/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Bufalin, a cardiotonic steroid isolated from toad venom (bufo gargarizans Cantor or B. melanotictus Schneider), has widely demonstrated antitumor effects and exhibits potential antitumor activity in various human cancer cells lines. AIMS OF THE STUDY: The main characteristic of cancers including pancreatic cancer is the ability of uncontrolled proliferation. The aim of this study is to clarify the underlying mechanism by which bufalin inhibits pancreatic cancer cell proliferation. MATERIALS AND METHODS: The effect of bufalin on the suppression of tumor growth in vivo was studied in a bioluminescent mouse model generated using the pancreatic cancer cell line BxPC3-luc2 and the cytotoxicity was evaluated in BcPc3 and Sw1990 cells with MTT. Flow cytometry and western blotting analyses were utilized to detect the effect of bufalin on the cell cycle and to detect the cell cycle-related proteins, respectively. Then, a luciferase reporter assay was applied to screen the activity of potent transcription factors following bufalin exposure and their expression was detected by western blotting. RESULTS: Bufalin suppressed tumor growth in a bioluminescence mouse model generated using BxPC3-luc2 cells and inhibited cell proliferation in vitro through inducing cell cycle arrest at S phase. Bufalin treatment inhibited cyclin D1 and cyclin E1 expression and therefore increased expression of p27, a regulatory molecular that controls cell cycle transition from S to G2 phase. Furthermore, luciferase reporter screening studies revealed that bufalin inhibited the expression and activity of the transcription factors c-Myc and NF-κB, which might cause cell cycle arrest at S phase and the inhibition of cell proliferation. CONCLUSIONS: Taken together, our results indicate that bufalin can inhibit pancreatic cancer by targeting c-Myc, thus suggesting that the mechanism of c-Myc regulation by bufalin might be worthy of further study regarding its potential as a therapeutic target for pancreatic cancer treatment.

Inhibition of P38 MAPK Downregulates the Expression of IL-1ß to Protect Lung from Acute Injury in Intestinal Ischemia Reperfusion Rats.

Acute lung injury (ALI) induced by intestinal ischemia/reperfusion (II/R) has high incidence and mortality, in which IL-1ß was essential for the full development of ALI. However, the detailed regulating mechanism for this phenomenon remains to be unclear. The purpose of this study was to investigate whether inhibition of P38 MAPK could downregulate the expression of IL-1ß to protect lung from acute injury in II/R rats. Here, we found that the level of pulmonary edema at 16 hours after operation (hpo) was obviously enhanced compared to that in 8hpo and sham groups. Immunofluorescent staining demonstrated that IL-1ß and P38 MAPK were detected in lung tissues. And rats with II/R have the highest translation level for IL-1ß and phosphorylation of P38 MAPK in lung tissues at 16hpo compared with 8hpo and sham groups. Moreover, administration of SB239063, an inhibitor of P38 α and ß, could effectively downregulate the expressions of IL-1ß and protects lung tissues from injury in II/R rats. Our findings indicate that the inhibition of P38 α and ß may downregulate the expression of IL-1ß to protect lung from acute injury in II/R, which could be used as a potential target for reducing ALI induced by II/R in the future clinical trial.

Mechanical responses from mandibular canine with different movement types in Invisalign treatment / 医用生物力学

Objective To compare mechanical responses from mandibular canine with different movement types in orthodontic treatment with Invisalign. Methods Based on computed tomography images of the teeth and their supporting tissues, the finite element model of the mandible and periodontal ligaments was established. The translation, inclination and rotation movements of the canine in buccolingual direction were simulated to obtain displacements and stresses of the canine and periodontal ligaments under the three different movements. Results The initial movements of the canine and stress distributions on periodontal ligaments were mainly determined by different movement types of the canine. The stress distributions on periodontal ligaments were similar when the canine was in translation and inclination movements. The bodily movement trend of the canine was much larger in rotation movement than that in translation movement under the same displacement magnitude. Conclusions The mechanical responses and its degrees from canine would be different under different movement types. To get better understanding with such different responses can help design more reasonable orthodontic treatment with Invisalign, avoid the damage to periodontium and achieve the orthodontic treatment with less time.