Effect of Metabolic Reprogramming on Toxin Eliminating Therapeutics in Targeting Lung Cancer Stem Cells / 中国实验方剂学杂志

Objective::To observe the effect of realgar nanoparticles (a representative drug in toxin eliminating therapeutics) targeting hypoxia-inducible factors (HIF), which act as effector molecules on metabolic reprogramming of lung cancer stem cells, and to explore the effect mechanism of lung cancer stem cells and metabolic reprogramming in the process of lung cancer metastasis, so as to verify the effectiveness of toxin eliminating therapeutics in the prevention and treatment of lung cancer metastasis. Method::Lung cancer A549 cells were cultured in vitro, and lung cancer stem cells were then identified and selected. The stem cells were divided into blank control group, cisplatin group (5 mg·L-1), realgar nanoparticles low, medium and high dose groups (100, 200, 400 mg·L-1). After intervention, glucose oxidase method was used to detect the effect of realgar nanoparticles on the glucose metabolism of lung cancer stem cells, real-time polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression levels of hypoxia-inducible factors-1α (HIF-1α), C-myc and p53, while Western blot was used to detect the expression of related proteins HIF-1α, phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) and mammalian target of rapamycin (mTOR), and enzyme linked immunosorbent assay (ELISA) was used to detect the glucose transporter 1 (GLUT1), pyruvate dehydrogenase kinase 1 (PDK1), pyruvate kinase M (PKM), phosphofructokinase(PFK), pyruvate dehydrogenase (PDH) and lactic dehydrogenase (LDH) expression. Result::As compared with the blank control group, realgar nanoparticles can reduce the glucose consumption of lung cancer stem cells, and the glucose consumption was reduced with the increase of dose in a time-and dose-dependent manner (P<0.01). Realgar nanoparticles can inhibit the mRNA expression of HIF-1α, a key factor in metabolic reprogramming of lung cancer stem cells (P<0.05, P<0.01), down-regulated C-myc mRNA and up-regulated the p53 mRNA expression (P<0.05, P<0.01), down-regulated protein expressions of PI3K, Akt, mTOR(P<0.05, P<0.01), and inhibited the expression of related enzymes GLUT1, PDK1, PFK, PKM, PDH, and LDH levels (P<0.05, P<0.01). With the increase of dose, the regulation and control ability of realgar nanoparticles gradually increased. Conclusion::Toxin eliminating therapeutics can drive the metabolic reprogramming of lung cancer stem cells by targeting HIF effector molecule, and then inhibit the invasion and metastasis of lung cancer.

Gene mutation analysis and prenatal diagnosis of a family with Bartter syndrome / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the mutation of related genes and prenatal diagnosis of a family with Bartter syndrome (BS).</p><p><b>METHODS</b>The high-throughput capture sequencing technique and PCR-Sanger sequencing were used to detect pathogenic genes in the proband of this family and analyze the whole family at the genomic level. After the genetic cause was clarified, the amniotic fluid was collected from the proband's mother who was pregnant for 5 months for prenatal diagnosis.</p><p><b>RESULTS</b>The proband carried compound heterozygous mutations of c.88C>T(p.Arg30*) and c.968+2T>A in the CLCNKB gene; c.88C>T(p.Arg30*) had been reported as a pathogenic mutation, and c.968+2T>A was a new mutation. Pedigree analysis showed that the two mutations were inherited from the mother and father, respectively. Prenatal diagnosis showed that the fetus did not inherit the mutations from parents and had no mutations at the two loci. The follow-up visit confirmed that the infant was in a healthy state, which proved the accuracy of genetic diagnosis and prenatal diagnosis.</p><p><b>CONCLUSIONS</b>The compound heterozygous mutations c.88C>T(p.Arg30*) and c.968+2T>A in the CLCNKB gene are the cause of BS in the proband, and prenatal diagnosis can prevent the risk of recurrence of BS in this family.</p>

Study of the mechanical properties of Co-Cr ceramic alloy after recasts / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To study the mechanical properties of Co-Cr ceramic alloy after recasts.</p><p><b>METHODS</b>Co-Cr ceramic alloy cast samples were prepared and recast for 3 times without adding any new Co-Cr ceramic alloy. The tensile strength, 0.2% yield strength, percentage of elongation, flexural strength, flexural modulus and Vickers hardness of each specimen were measured.</p><p><b>RESULTS</b>Being cast for different times, the Co-Cr ceramic alloy showed no significant differences on their tensile strength, 0.2% yield strength, percentage of elongation, flexural strength, flexural modulus and Vickers hardness.</p><p><b>CONCLUSION</b>Co-Cr ceramic alloy can be recast for 3 times at least, without decrease of the mechanical properties.</p>

Cyclic fatigue test of cobalt-chromium alloy cast clasps / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the change of retentive forces of cast cobalt-chromium (Co-Cr) alloy clasp in cyclic fatigue test.</p><p><b>METHODS</b>Samples of three types of cast Co-Cr alloy (Group A: Hardalloy; B: Regalloy™; C: Vera PDN™) clasps were fabricated and placed at undercut depths of 0.25 mm, 0.50 mm. The clasps were drawn from the model molar cyclicly to simulate 5 years of clinical use in an universal testing machine. Retentive force were record at 21 different time point for each clasp during the whole fatigue testing process. Data were subjected to ANOVA, Chi-square test and linear regression analysis.</p><p><b>RESULTS</b>All clasps showed decreasing retention during the cyclic fatigue test. Clasps engaged in 0.50 mm undercut depth exhibited greater initial retentive force [Group A: (8.714 +/- 1.104) N, B: (9.072 +/- 0.653) N, C: (9.588 +/- 1.980) N] as well as greater loss of retention [Group A: (4.408 +/- 0.662) N, B: (3.484 +/- 0.494) N, C: (3.290 +/- 1.484) N] at the end of the test than clasps engaged in 0.25 mm undercut did [initial forces were (7.940 +/- 0.357), (7.834 +/- 1.308) and (8.156 +/- 1.067) N for Group A, B, C, respectively; loss of retention were (2.444 +/- 0.736) N, (2.954 +/- 1.048) N and (1.832 +/- 1.180) N for group A, B, C, respectively]. Negative correlation was found between the clasp retention and the logarithm of cycling times.</p><p><b>CONCLUSIONS</b>Co-Cr alloy cast clasp could provide adequate retentive force for 5 years of clinical use.</p>

Human thioredoxin exerts cardioprotective effect and attenuates reperfusion injury in rats partially via inhibiting apoptosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Thioredoxin is one of the most important redox regulating proteins. Although thioredoxin has been shown to protect cells against different kinds of oxidative stress, the role of thioredoxin in myocardial ischemia and reperfusion injury has not been fully understood. This study was conducted to explore the protective role of human thioredoxin on myocardial ischemia and reperfusion injury and its potential mechanisms.</p><p><b>METHODS</b>Purified human thioredoxin was injected into adult Wistar rats, which were subjected to 30 minutes of myocardial ischemia followed by 2 or 24 hours of reperfusion. We detected 1) the infarct size; 2) the level of malondisldehyde (MDA) in serum; 3) the expression of caspase-9, and cytochrome c in/out of mitochondria by Western blotting; 4) apoptosis by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay and caspase-3 and its protein by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting; 5) the expression of bcl-2 and bax in cardium by immunohistochemical (IHC) assay.</p><p><b>RESULTS</b>Human thioredoxin reduced myocardial ischemia/reperfusion injury as evidenced by significant decrease of myocardial infarct size (P < 0.01), notable reduction of myocyte apoptosis (P < 0.01), lower systemic oxidative stress level (P < 0.01) after reperfusion for 2 hours, and few inflammatory cell infiltration after reperfusion for 24 hours in rats. Furthermore, treatment with human thioredoxin significantly reduced the release of mitochondrial cytochrome C (P < 0.05), and inhibited the activity of caspase-9 (P < 0.05) and caspase-3 (P < 0.01 in mRNA and P < 0.05 at protein level). Meanwhile, human thioredoxin markedly increased bcl-2 expression (P < 0.05).</p><p><b>CONCLUSIONS</b>These results strongly suggest that human thioredoxin has cardioprotective effects on myocardial ischemia/reperfusion and its anti-apoptotic role may be mediated by modulating bcl-2 and the mitochondria-dependent apoptotic signaling pathway.</p>

Effect of desensitizer on shear bond strength of adhesive system / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of desensitizer on shear bond strength of adhesive system.</p><p><b>METHODS</b>Twenty specimens were made and divided randomly into an experiment group and a control group. In the experiment group, the dentin bonding surface was applied with Green Or and in the control, the dentin bonding surface was untreated. The IPS-Empress specimens were bonded to the dentin bonding specimens using Variolink II adhesive system. The shear bond strength of all testing samples was determined with Instron testing machine. The surfaces of the drawing sections were observed using the scanning electron microscope (SEM).</p><p><b>RESULTS</b>The shear bond strength of the experimental group and the control group was (5.53 +/- 0.96) MPa and (7.32 +/- 1.34) MPa respectively and there was statistically significant difference between two groups (P = 0.003). In the experimental group, adhesive failure was the most prevalent type of failure, while in the control group, cohesive failure was the most prevalent type.</p><p><b>CONCLUSIONS</b>The application of Green Or on the dentin bonding surface decreased the shear bond strength between dentin and IPS-Empress specimens when using Variolink II adhesive system.</p>

Study on elastic limit and relevant enclasp force of non-precious metal casting clasp / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the elastic limit and relevant enclasp force of the non-precious metal casting clasp.</p><p><b>METHODS</b>Casting clasp samples of five cobalt-chromium alloys and one 18 - 8 nickel-chromium alloy were made from prefabricated clasp wax by invesing, casting, sandblasting, and ultrasonic cleaning. The process of casting clasp samples deflected by loading and returned by unloading was tested and electric signals were collected by an omnipotent material machine. The analog electric signal was converted to digital signal by an analog to digital converter and stored in a computer. The elastic limit and the relevant enclasp force were analyzed using a relative software.</p><p><b>RESULTS</b>The elastic limit and the relevant enclasp force of the casting clasp made from the 18 - 8 nickel-chromium alloy were smallest and those of the clasps made from the cobalt-chromium alloys in various brands were different. The range of the elastic limit of the cobalt-chromium alloy casting clasp with the length of 5.0 mm in undercut was 0.28 mm-0.33 mm and the relevant enclasp force was 14.42 g-19.28 g.</p><p><b>CONCLUSIONS</b>In clinic, we should select the suitable undercut deepness wherein the cobalt-chromium alloy casting clasps, according to different brands of the casting alloy, undercut length, undercut slope, and the clasp thickness.</p>