High-Glucose Inhibits Human Fibroblast Cell Migration in Wound Healing via Repression of bFGF-Regulating JNK Phosphorylation

One of the major symptoms of diabetes mellitus (DM) is delayed wound healing, which affects large populations of patients worldwide. However, the underlying mechanism behind this illness remains elusive. Skin wound healing requires a series of coordinated processes, including fibroblast cell proliferation and migration. Here, we simulate DM by application of high glucose (HG) in human foreskin primary fibroblast cells to analyze the molecular mechanism of DM effects on wound healing. The results indicate that HG, at a concentration of 30 mM, delay cell migration, but not cell proliferation. bFGF is known to promote cell migration that partially rescues HG effects on cell migration. Molecular and cell biology studies demonstrated that HG enhanced ROS production and repressed JNK phosphorylation, but did not affect Rac1 activity. JNK and Rac1 activation were known to be important for bFGF regulated cell migration. To further confirm DM effects on skin repair, a type 1 diabetic rat model was established, and we observed the efficacy of bFGF on both normal and diabetic rat skin repair. Furthermore, proteomic studies identified an increase of Annexin A2 protein nitration in HG-stressed fibroblasts and the nitration was protected by activation of bFGF signaling. Treatment with FGFR1 and JNK inhibitors delayed cell migration and increased Annexin A2 nitration levels, indicating that Annexin A2 nitration is modulated by bFGF signaling via activation of JNK. Together with these results, our data suggests that the HG-mediated delay of cell migration is linked to the inhibition of bFGF signaling, specifically through JNK suppression.     

Cholecystokinin from the entorhinal cortex enables neural plasticity in the auditory cortex

Patients with damage to the medial temporal lobe show deficits in forming new declarative memories but can still recall older memories, suggesting that the medial temporal lobe is necessary for encoding memories in the neocortex. Here, we found that cortical projection neurons in the perirhinal and entorhinal cortices were mostly immunopositive for cholecystokinin (CCK). Local infusion of CCK in the auditory cortex of anesthetized rats induced plastic changes that enabled cortical neurons to potentiate their responses or to start responding to an auditory stimulus that was paired with a tone that robustly triggered action potentials. CCK infusion also enabled auditory neurons to start responding to a light stimulus that was paired with a noise burst. In vivo intracellular recordings in the auditory cortex showed that synaptic strength was potentiated after two pairings of presynaptic and postsynaptic activity in the presence of CCK. Infusion of a CCK_B antagonist in the auditory cortex prevented the formation of a visuo-auditory association in awake rats. Finally, activation of the entorhinal cortex potentiated neuronal responses in the auditory cortex, which was suppressed by infusion of a CCK_B antagonist. Together, these findings suggest that the medial temporal lobe influences neocortical plasticity via CCK-positive cortical projection neurons in the entorhinal cortex.     

SPECT-CT全身显像检查对排尿困难患者心理疏导意义

目的：探讨SPECT-CT全身显像检查患者排尿困难的解决方案。方法通过护士与患者的沟通与心理疏导,消除了患者紧张恐惧情绪,并指导病人腹部按摩以及听流水声等多种方法,缓解了排尿困难。结论解决患者排尿困难,减少了膀胱过度充盈显影对骨盆的遮挡,使SPECT-CT全身显像图像质量得到保障。     

Association Between a Single Nucleotide Polymorphism in the TP53 Region and Risk of Ovarian Cancer

TP53 is known as a tumor suppressor gene involved in cell cycle regulation. Many previous epidemiological and clinical studies have evaluated the effects of rs1042522 polymorphism on risk of ovarian cancer. But the results are conflicting and heterogeneous. The primary objective of this study was to examine whether rs1042522 polymorphism is associated with ovarian cancer risk. We performed a comprehensive meta-analysis of 19 case–control studies that analyzed rs1042522 polymorphism in ovarian cancer risk. Odds ratios (ORs) were calculated using distinct genetic models. Heterogeneity between studies was detected by the χ²-based Q test. Additional analyses such as sensitivity analyses and publication bias were also performed. The rs1042522 polymorphism was not overall associated with ovarian cancer risk. But there was a borderline association in the heterozygote model (OR = 1.09, 95 % CI 0.99–1.21). Similar effects were observed in the subgroup of Caucasian population (the heterozygote model: OR = 1.11, 95 % CI 1.00–1.24). No significant heterogeneity and publication bias were revealed in this meta-analysis. This study provides statistical evidence that TP53 rs1042522 polymorphism may play a role in modulating risk of ovarian cancer. This observation requires further analysis of a larger study size.     

Optimal Surgical Options for Descending Necrotizing Mediastinitis of the Anterior Mediastinum

The mortality rates from descending necrotizing mediastinitis (DNM) are between 25 and 40 % mainly because of delayed diagnosis and inappropriate surgical treatment. This study was undertaken to examine two surgical options for DNM and determine the optimal surgical option for DNM of the anterior mediastinum. Fifteen cases of DNM of the anterior mediastinum, January 2001 and October 2010, were retrospectively reviewed. Eleven were anterosuperior mediastinitis, with infection located above the tracheal bifurcation and four had infections involving the entire anterior mediastinum. Depending on the location of mediastinitis, open drainage of the submandibular and neck abscesses, in addition to other surgical treatments, was performed. If the infection was anterosuperior, transcervical mediastinal drainage or thoracotomy was performed. If the entire anterior mediastinum was involved, necrotic tissue was removed with thoracoscopic via subxiphoid incision, the bilateral pleurae were opened for drainage, and a tunnel connecting the neck incision and the subxiphoid incision through the whole anterior mediastinum was made for drainage. The anterosuperior mediastinitis cases were treated with either transcervical mediastinal drainage (n = 8) or thoracotomy (n = 3). Patients healed after an average of 24.5 and 20.0 days in the hospital, respectively. For the four other cases, one patient died of septic shock, while the other three patients were healed after and an average of 43.3 days in the hospital. Mortality rate was 6.7 %. The surgical procedure used to treat DNM should be selected according to the location of the infection. DNM involving the anterosuperior mediastinum can be treated by transcervical mediastinal drainage. If anterosuperior mediastinitis spreads to the side of the trachea, open thoracotomy is a suitable therapy. If the entire anterior mediastinum is involved, debridement and drainage of the anterior mediastinum should be performed with a thoracoscope via the subxiphoid incision.     

SLC17A9 Protein Functions as a Lysosomal ATP Transporter and Regulates Cell Viability

Lysosomes contain abundant ATP, which is released through lysosomal exocytosis following exposure to various stimuli. However, the molecular mechanisms underlying lysosomal ATP accumulation remain unknown. The vesicular nucleotide transporter, also known as solute carrier family 17 member 9 (SLC17A9), has been shown to function in ATP transport across secretory vesicles/granules membrane in adrenal chromaffin cells, T cells, and pancreatic cells. Here, using mammalian cell lines, we report that SLC17A9 is highly enriched in lysosomes and functions as an ATP transporter in those organelles. SLC17A9 deficiency reduced lysosome ATP accumulation and compromised lysosome function, resulting in cell death. Our data suggest that SLC17A9 activity mediates lysosomal ATP accumulation and plays an important role in lysosomal physiology and cell viability.     

Indomethacin Treatment Prevents High Fat Diet-induced Obesity and Insulin Resistance but Not Glucose Intolerance in C57BL/6J Mice

Chronic low grade inflammation is closely linked to obesity-associated insulin resistance. To examine how administration of the anti-inflammatory compound indomethacin, a general cyclooxygenase inhibitor, affected obesity development and insulin sensitivity, we fed obesity-prone male C57BL/6J mice a high fat/high sucrose (HF/HS) diet or a regular diet supplemented or not with indomethacin (±INDO) for 7 weeks. Development of obesity, insulin resistance, and glucose intolerance was monitored, and the effect of indomethacin on glucose-stimulated insulin secretion (GSIS) was measured in vivo and in vitro using MIN6 β-cells. We found that supplementation with indomethacin prevented HF/HS-induced obesity and diet-induced changes in systemic insulin sensitivity. Thus, HF/HS+INDO-fed mice remained insulin-sensitive. However, mice fed HF/HS+INDO exhibited pronounced glucose intolerance. Hepatic glucose output was significantly increased. Indomethacin had no effect on adipose tissue mass, glucose tolerance, or GSIS when included in a regular diet. Indomethacin administration to obese mice did not reduce adipose tissue mass, and the compensatory increase in GSIS observed in obese mice was not affected by treatment with indomethacin. We demonstrate that indomethacin did not inhibit GSIS per se, but activation of GPR40 in the presence of indomethacin inhibited glucose-dependent insulin secretion in MIN6 cells. We conclude that constitutive high hepatic glucose output combined with impaired GSIS in response to activation of GPR40-dependent signaling in the HF/HS+INDO-fed mice contributed to the impaired glucose clearance during a glucose challenge and that the resulting lower levels of plasma insulin prevented the obesogenic action of the HF/HS diet.     

Scorpion Venom Heat-Resistant Peptide (SVHRP) Enhances Neurogenesis and Neurite Outgrowth of Immature Neurons in Adult Mice by Up-Regulating Brain-Derived Neurotrophic Factor (BDNF)

Scorpion venom heat-resistant peptide (SVHRP) is a component purified from Buthus martensii Karsch scorpion venom. Although scorpions and their venom have been used in Traditional Chinese Medicine (TCM) to treat chronic neurological disorders, the underlying mechanisms of these treatments remain unknown. We applied SVHRP in vitro and in vivo to understand its effects on the neurogenesis and maturation of adult immature neurons and explore associated molecular mechanisms. SVHRP administration increased the number of 5-bromo-2’-dexoxyuridine (BrdU)-positive cells, BrdU- positive/neuron-specific nuclear protein (NeuN)-positive neurons, and polysialylated-neural cell adhesion molecule (PSA-NCAM)-positive immature neurons in the subventricular zone (SVZ) and subgranular zone (SGZ) of hippocampus. Furthermore immature neurons incubated with SVHRP-pretreated astrocyte-conditioned medium exhibited significantly increased neurite length compared with those incubated with normal astrocyte-conditioned medium. This neurotrophic effect was further confirmed in vivo by detecting an increased average single area and whole area of immature neurons in the SGZ, SVZ and olfactory bulb (OB) in the adult mouse brain. In contrast to normal astrocyte-conditioned medium, higher concentrations of brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF) or glial cell line-derived neurotrophic factor (GDNF) was detected in the conditioned medium of SVHRP-pretreated astrocytes, and blocking BDNF using anti-BDNF antibodies eliminated these SVHRP-dependent neurotrophic effects. In SVHRP treated mouse brain, more glial fibrillary acidic protein (GFAP)-positive cells were detected. Furthermore, immunohistochemistry revealed increased numbers of GFAP/BDNF double-positive cells, which agrees with the observed changes in the culture system. This paper describes novel effects of scorpion venom-originated peptide on the stem cells and suggests the potential therapeutic values of SVHRP.     

Study of the relationship between compositions of shrub plant of stable-carbon-isotope and environmental factors in Xinjiang representatives of Chenopodiaceae

The paper analyses total of 58 samples representing 32 species of the 14 genera of shrub plant of the carbon isotope composition in Xinjiang representatives of Chenopodiaceae and a detailed discussion on the various factors that can influence them. The value of 38 samples fall between ?14.88‰ and ?11.55‰ with a mean of ?13.34‰, and values of 20 samples between ?27.93‰ and ?22.877‰ with a mean of ?25.38‰. So we obtained a total of 21 of C4 species (59.4%) and 11 of C3 species (40.6%) from 32 species studied Chenopodiaceae of shrubs plant. Then the relationship of plant-carbon-isotope and environmental factors has been analyzed. The results showed that the importance environmental factors for the δ¹³C-value of the Shrubs was annual precipitation (0.78) > temperature (0.66) > elevation (0.55). The three principal components has important factors to influence on C₃/C₄ shrub plant distribution. Environmental conditions play significant roles in the distribution and ecophysiological features of different photosynthetic types and even change the photosynthetic pathways. On the other hand, such as geographic location, Sunshine duration, evaporation capacity are more or less correlation with δ¹³C values, however, they would be interfered by annual precipitation. Desert plants to adapt to drought conditions by increasing water use efficiency (WUE) strategy. In short, plant physiology function is sensitive and timely to adapt environmental change.