Treatment of radiation-induced brain injury with bisdemethoxycurcumin.

Radiation therapy is considered the most effective non-surgical treatment for brain tumors. However, there are no available treatments for radiation-induced brain injury. Bisdemethoxycurcumin (BDMC) is a demethoxy derivative of curcumin that has anti-proliferative, anti-inflammatory, and anti-oxidant properties. To determine whether BDMC has the potential to treat radiation-induced brain injury, in this study, we established a rat model of radiation-induced brain injury by administering a single 30-Gy vertical dose of irradiation to the whole brain, followed by intraperitoneal injection of 500 µL of a 100 mg/kg BDMC solution every day for 5 successive weeks. Our results showed that BDMC increased the body weight of rats with radiation-induced brain injury, improved learning and memory, attenuated brain edema, inhibited astrocyte activation, and reduced oxidative stress. These findings suggest that BDMC protects against radiation-induced brain injury.

[Evaluation of the effect of invisible correction and SGTB in the treatment of mandibular retrusion].

PURPOSE: To compare the clinical effects of invisible correction and SGTB in two-stage treatment of mandibular retrusion. METHODS: Eighty-five patients with bony mandibular regression who did not pass the peak of growth and development were selected. Among them, 40 cases were guided by invisible correction and 45 cases were guided by SGTB functional correction. Lateral head X-rays before and after treatment were measured, and the effect before and after treatment was compared by SPSS 16.0 software package. RESULTS: After treatment, the SNB angle and NP-FH (face angle) increased and the ANB angle decreased in both groups, all of which had significant changes(P＜0.001). At T1, the changes of SNB angle, ANB angle and NP-FH angle in the invisible group were smaller than those in the SGTB group(P＜0.05). The difference between MP-FH angle and MP-SN angle before and after treatment was greater in the SGTB group than in the invisible group(P＜0.001). CONCLUSIONS: In patients with receding mandible before the peak of growth and development, the mandible was significantly moved forward after orthodontics. Both invisible orthodontics and SGTB promote changes in the position of the mandible, improves coordination between the upper and lower jaws. In the control of the posterior teeth in the vertical direction, the invisible group is stronger than the SGTB group.

Mitochonic acid 5 regulates mitofusin 2 to protect microglia.

Microglial apoptosis is associated with neuroinflammation and no effective strategies are currently available to protect microglia against inflammation-induced apoptosis. Mouse microglial BV-2 cells (5 × 106) were incubated with 10 µg/mL lipopolysaccharides for 12 hours to mimic an inflammatory environment. Then the cells were co-cultured with mitochonic acid 5 (MA-5) for another 12 hours. MA-5 improved the survival of lipopolysaccharide-exposed cells. MA-5 decreased the activity of caspase-3, which is associated with apoptosis. MA-5 reduced the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells, and increased adenosine triphosphate levels in cells. MA-5 decreased the open state of the mitochondrial permeability transition pore and reduced calcium overload and diffusion of second mitochondria-derived activator of caspase (Smac). MA-5 decreased the expression of apoptosis-related proteins (mitochondrial Smac, cytoplasmic Smac, pro-caspase-3, cleaved-caspase-3, and caspase-9), and increased the levels of anti-apoptotic proteins (Bcl2 and X-linked inhibitor of apoptosis protein), mitochondria-related proteins (mitochondrial fusion protein 2, mitochondrial microtubule-associated proteins 1A/1B light chain 3B II), and autophagy-related proteins (Beclin1, p62 and autophagy related 5). However, MA-5 did not promote mitochondrial homeostasis or decrease microglial apoptosis when Mitofusin 2 expression was silenced. This shows that MA-5 increased Mitofusin 2-related mitophagy, reversed cellular energy production and maintained energy metabolism in BV-2 cells in response to lipopolysaccharide-induced inflammation. These findings indicate that MA-5 may promote the survival of microglial cells via Mitofusin 2-related mitophagy in response to lipopolysaccharide-induced inflammation.

A mimetic peptide of α2,6-sialyllactose promotes neuritogenesis.

Oxidative stress contributes to the pathogenesis of neurodegenerative diseases. With the aim to find reagents that reduce oxidative stress, a phage display library was screened for peptides mimicking α2,6-sialyllactose (6'-SL), which is known to beneficially influence neural functions. Using Sambucus nigra lectin, which specifically binds to 6'-SL, we screened a phage display library and found a peptide comprising identical sequences of 12 amino acids. Mimetic peptide, reverse peptide and scrambled peptide were tested for inhibition of 6'-SL binding to the lectin. Indeed, lectin binding to 6'-SL was inhibited by the most frequently identified mimetic peptide, but not by the reverse or scrambled peptides, showing that this peptide mimics 6'-SL. Functionally, mimetic peptide, but not the reverse or scrambled peptides, increased viability and expression of neural cell adhesion molecule L1 in SK-N-SH human neuroblastoma cells, and promoted survival and neurite outgrowth of cultured mouse cerebellar granule neurons challenged by H2O2-induced oxidative stress. The combined results indicate that the 6'-SL mimetic peptide promotes neuronal survival and neuritogenesis, thus raising hopes for the treatment of neurodegenerative diseases. This study was approved by the Medical Ethics Committee of Shantou University Medical College, China (approval No. SUMC 2014-004) on February 20, 2014.

Differential changes in Neuregulin-1 signaling in major brain regions in a lipopolysaccharide-induced neuroinflammation mouse model.

Neuregulin 1 (Nrg1) is involved in multiple biological processes in the nervous system. The present study investigated changes in Nrg1 signaling in the major brain regions of mice subjected to lipopolysaccharide (LPS)-induced neuroinflammation. At 24 h post­intraperitoneal injection of LPS, mouse brain tissues, including tissues from the cortex, striatum, hippocampus and hypothalamus, were collected. Reverse transcription­polymerase chain reaction was used to determine the expression of Nrg1 and its receptors, Neu and ErbB4, at the mRNA level. Western blotting was performed to determine the levels of these proteins and the protein levels of phosphorylated extracellular signal-regulated kinases (Erk)1/2 and Akt1. Immunohistochemical staining was utilized to detect the levels of pNeu and pErbB4 in these regions. LPS successfully induced sites of neuroinflammation in these regions, in which changes in Nrg1, Neu and ErbB4 at the mRNA and protein levels were identified compared with controls. LPS induced a reduction in pNeu and pErbB4 in the striatum and hypothalamus, although marginally increased pErbB4 levels were found in the hippocampus. LPS increased the overall phosphorylation of Src but this effect was reduced in the hypothalamus. Moreover, increased phosphorylation of Akt1 was found in the striatum and hippocampus. These data suggest diverse roles for Nrg1 signaling in these regions during the process of neuroinflammation.

[Clinical effect of premolar extraction with high torque self-locking appliances].

PURPOSE: To analyze the clinical effect of extraction correction of patients with maxillary protrusion by using Damon high torque appliances. METHODS: Forty patients with extraction of four first premolars due to orthodontic treatment were selected. They had protrusion of maxilla and were randomly divided into two groups. Both arches of Damon group were treated with Damon high torque appliances and MBT group were corrected with traditional MBT straight wire appliance; patients in two groups received sliding mechanics for adduction of upper anterior teeth. Cephalometric radiophotographs were analyzed before（T0）and after adduction of upper anterior teeth（T1）. The difference between the two groups was analyzed with SPSS15.0 software package. RESULTS: The upper incisors showed a more retruded position in the two groups at T1,although they showed a similar amount in both groups. The backward movement of upper lip was 2.31mm in Damon group, which was significantly less than that of 2.81mm in MBT group(P<0.05). No significant difference in the first molar mesialization was detected between Damon group(2.33 mm) and MBT group(2.36mm) (P>0.05). For anterior teeth retraction, nasolabial angle (NLA) in MBT and Damon group were 107.44°and 106.33°, increase of NLA in MBT group was 9.17°,which was significantly larger than that of 7.22°in Damon group (P<0.05). U1-MxP in MBT and Damon were 110.61°and 114.11°. U1-MxP decreased 12.06°in MBT group, while significant change was deteced in Damon group of 7.61°(P<0.05). CONCLUSIONS: Application of Damon high torque appliances in extraction treatment of maxillary protrusion patients yielded better control of the labial crown torque of anterior teeth, and avoided excessive lingual inclination of anterior teeth compared with MBT in adduction of upper anterior teeth.

L1 modulates PKD1 phosphorylation in cerebellar granule neurons.

The neural cell adhesion molecule L1 (L1CAM) is crucial for the development of the nervous system, with an essential role in regulating multiple cellular activities. Protein kinase D1 (PKD1) serves as a key kinase given its diverse array of functions within the cell. Here, we investigated various aspects of the functional relationship between L1 and phosphorylated PKD1 (pPKD1) in cerebellar granule neurons. To study the relationship between L1 and PKD1 phosphorylation, human cerebellar tissue microarrays were subject to immunofluorescence staining. We observed a positive correlation between L1 protein levels and PKD1 phosphorylation. In addition, L1 also co-localized with pPKD1. To analyze the regulatory role of L1 on PKD1 phosphorylation, primary mouse cerebellar granule neurons were treated with various concentrations of rL1 for 48 h. Using Western blot, we revealed that L1 significantly increased PKD1 phosphorylation compared with vehicle control, with the maximal effect observed at 5 nM. ERK1/2 phosphorylation was significantly increased by 2.5 nM and 10nM L1, with no apparent change in SRC phosphorylation. However, SRC expression was markedly reduced by 10nM rL1. AKT1 expression and phosphorylation levels were significantly increased by rL1, with the maximal effect observed at 2.5 and 5 nM, respectively. Our combined data revealed a positive relationship between L1 and pPKD1 in both cultured cerebellar neurons and human cerebellar tissue, suggesting that L1 functions in the modulation of PKD1 phosphorylation.

Modified physiological and operative score for the enumeration of mortality and morbidity risk assessment model in general surgery.

AIM: To establish a scoring system for predicting the incidence of postoperative complications and mortality in general surgery based on the physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM), and to evaluate its efficacy. METHODS: Eighty-four patients with postoperative complications or death and 172 patients without postoperative complications, who underwent surgery in our department during the previous 2 years, were retrospectively analyzed by logistic regression. Fifteen indexes were investigated including age, cardiovascular function, respiratory function, blood test results, endocrine function, central nervous system function, hepatic function, renal function, nutritional status, extent of operative trauma, and course of anesthesia. Modified POSSUM (M-POSSUM) was developed using significant risk factors with its efficacy evaluated. RESULTS: The significant risk factors were found to be age, cardiovascular function, respiratory function, hepatic function, renal function, blood test results, endocrine function, nutritional status, duration of operation, intraoperative blood loss, and course of anesthesia. These factors were all included in the scoring system. There were significant differences in the scores between the patients with and without postoperative complications, between the patients died and survived with complications, and between the patients died and survived without complications. The receiver operating characteristic curves showed that the M-POSSUM could accurately predict postoperative complications and mortality. CONCLUSION: M-POSSUM correlates well with postoperative complications and mortality, and is more accurate than POSSUM.

[Quantitation & optimization of guanosine fermentation process: prevention of NH4+ accumulation increases guanosine production by 70%].

Metabolic engineering has become a powerful tool for optimization of industrial fermentation processes. Metabolic engineering usually undergoes three steps: construction of a recombinant strain with improved properties, genetic and biochemical analysis of the strain, and identification of target for further improvement. Metabolic fluxes analysis is an important part of the biochemical analysis. Based on the law of mass conservation and assuming pseudo-steady-state for the intermediates in the metabolic pathways, we have quantitatively analyzed the time course of the flux distribution in Bacillus subtilis and used the data to reveal the nature of the so-called "40 hour" phenomenon in fermentation of guanosine, a key raw material for the synthesis of additives for human consumption and animal feeds. The phenomenon refers to the observation that guanosine production, which proceeds at high rate from 12 hour on, declines around 40 hour while consumption of glucose keeps increasing, leading to the lower yield of the nucleoside. Equations based upon the metabolic network of Bacillus subtilis consisted of EMP pathway, HMP pathway, TCA cycle, oxidative phosphorylation pathway and others reactions of the intermediates, was constructed. The equations were solved by using the quantitative data obtained in this study. The air flow and volume, concentration of oxygen and carbon dioxide in the exit-gas were monitored online; the concentration of biomass, glucose and guanosine was analyzed manually; and the concentration of acetate, citric acid, pyruvate, and 17 amino acids were HPLC quantified. The solutions of the equation were proved to be valid, as the experimental data on oxygen consumption agrees with that of predicted form the equation. The results indicated that at 40h of the fermentation process the flux of HMP pathway, which provides the precursor of the nucleoside, decreased while that of EMP pathway and the pathways that generate amino acids and organic acids increased. The shift correlated with the accumulation of NH4+ in the broth. The assimilation of NH4+ is an energy consuming process and could shift the metabolism to the energy generating EMP pathway. Accordingly, measures were taken to prevent the accumulation of NH4+. The interference indeed stopped the metabolism shift and boosted the guanosine production at 30 g/L, 70% higher than the level reported in literature.

[Analysis on metabolic flux shift during guanosine fermentation].

Taking the typical metabolic control product-guanosine as an example, the method of metabolic flux shift investigation based on process multi-levels parameter correlation analysis was established. The metabolic pathway, multi-parameter correlation, accumulation of amino acid and organic acid during guanosine fermentation process were integratively analyzed. The metabolic flux shift from HMP to EMP was ascertained, which was assumed to be caused by the accumulation of ammonium ion. The subsequent optimization based on controlling flux distribution between EMP and HMP did improve the yield by 35% when the metabolic flux shift was prevented.