Prediction of Protein Interaction Sites Using Mimotope Analysis

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Brain derived neurotrophic factor (BDNF) contributes to the pain hypersensitivity following surgical incision in the rats

<p>Abstract</p> <p>Background</p> <p>The pathogenic role of brain derived neurotrophic factor (BDNF) in the incisional pain is poorly understood. The present study explores the role of the BDNF in the incision-induced pain hypersensitivity.</p> <p>Methods</p> <p>A longitudinal incision was made in one plantar hind paw of isoflurane-anesthetized rats. Dorsal root ganglias (DRG) and spinal cords were removed at various postoperative times (1–72 h). Expression pattern of BDNF was determined by immunohistochemistry and double-labeling immunofluorescence. Lidocaine-induced blockade of sciatic nerve function was used to determine the importance of afferent nerve activity on BDNF expression in the DRG and spinal cord after incision. BDNF antibody was administered intrathecally (IT) or intraperitoneal (IP) to modulate the spinal BDNF or peripheral BDNF after incision.</p> <p>Results</p> <p>After hind-paw incision, the BDNF was upregulated in the ipsilateral lumbar DRG and spinal cord whereas thoracic BDNF remained unchanged in response to incision. The upregulated BDNF was mainly expressed in the large-sized neurons in DRG and the neurons and the primary nerve terminals in the spinal cord. Sciatic nerve blockade prevented the increase of BDNF in the DRG and spinal cord. IT injection of BDNF antibody greatly inhibited the mechanical allodynia induced by incision whereas IP administration had only marginal effect.</p> <p>Conclusion</p> <p>The present study showed that incision induced the segmental upregulation of BDNF in the DRG and spinal cord through somatic afferent nerve transmission, and the upregulated BDNF contributed to the pain hypersensitivity induced by surgical incision.</p

Differential responses of two rubber tree clones to chilling stress

Chilling stress is one of the most important environmental factors that limit the growth, distribution and yield of rubber tree in China. The effects of chilling stress on the grated plants of two rubber trees clones, GT1 and Wenchang217, were studied by physiological methods in controlled light chamber in order to explore the physiological mechanism of cold tolerance in rubber tree. Our results show a significant change in the tested physiological parameters after chilling treatment between two rubber clones. In comparison with the case of rubber tree clone GT1, the level of malondialdehyde (MDA) increased while superoxide dismutase, especially peroxidase and catalase decreased significantly in the seedlings of rubber tree clone Wenchang217 in response to chilling stress. As the cold tolerance ability of rubber tree clone GT1 is stronger than that of rubber tree clone Wenchang217, activation of oxidative quenching enzyme system should be one of the important factors that determine the cold tolerance of rubber tree.Keywords: Chilling stress, cold tolerance, Hevea brasiliensis Muell. Arg., physiological parameter, seedlin

Surgical Incision Induces Anxiety-Like Behavior and Amygdala Sensitization: Effects of Morphine and Gabapentin

The role of affective dimension in the postoperative pain is still poorly understood. The present study investigated the development of anxiety-like behavior and amygdala sensitization in incisional pain. Using hind-paw incision model in rats, we showed that surgical incision induced the anxiety-like behavior as determined by elevated plus-maze and open-field tests. Intraperitoneal (IP) morphine administration reversed mechanical allodynia and anxiety-like behavior in a dose-dependent manner. Gabapentin also partially reduced incision-evoked mechanical allodynia and anxiety-like behavior in a dose-dependent manner. After incision, the expression of phosphorylated cAMP response elements (CRE-) binding protein (p-CREB) was transiently upregulated in the central and basolateral nuclei in the bilateral amygdala. The upregulation of p-CREB was inhibited by morphine and gabapentin. The present study suggested that surgical incision could induce anxiety and amygdala sensitization that can be inhibited by morphine and gabapentin. Thus treatment of surgery-induced affective disturbances by morphine and gabapentin may be a potential important adjunct therapy in the postoperative pain management

Brain-Derived Neurotrophic Factor Precursor in the Hippocampus Regulates Both Depressive and Anxiety-Like Behaviors in Rats

Depression and anxiety are two affective disorders that greatly threaten the mental health of a large population worldwide. Previous studies have shown that brain-derived neurotrophic factor precursor (proBDNF) is involved in the development of depression. However, it is still elusive whether proBDNF is involved in anxiety, and if so, which brain regions of proBDNF regulate these two affective disorders. The present study aims to investigate the role of proBDNF in the hippocampus in the development of depression and anxiety. Rat models of an anxiety-like phenotype and depression-like phenotype were established by complete Freund's adjuvant intra-plantar injection and chronic restraint stress, respectively. Both rat models developed anxiety-like behaviors as determined by the open field test and elevated plus maze test. However, only rats with depression-like phenotype displayed the lower sucrose consumption in the sucrose preference test and a longer immobility time in the forced swimming test. Sholl analysis showed that the dendritic arborization of granule cells in the hippocampus was decreased in rats with depression-like phenotype but was not changed in rats with anxiety-like phenotype. In addition, synaptophysin was downregulated in the rats with depression-like phenotype but upregulated in the rats with anxiety-like phenotype. In both models, proBDNF was greatly increased in the hippocampus. Intra-hippocampal injection anti-proBDNF antibody greatly ameliorated the anxiety-like and depressive behaviors in the rats. These findings suggest that despite some behavioral and morphological differences between depression and anxiety, hippocampal proBDNF is a common mediator to regulate these two mental disorders

Relationship between Serum Levels of OPG and TGF- β

The objective of this study was to investigate the relationship between serum levels of OPG, TGF-β1, and TGF-β2 and BMD decrease rate (BDR) in native Chinese women. This cross-sectional study was performed on 465 healthy native Chinese women aged 35–80 years. Serum levels of OPG, TGF-β1, and TGF-β2 were determined. BDR was measured by DXA at the posteroanterior spine, hip, and distal forearm. At all skeletal sites tested, there was a negative correlation between BDR and serum levels of both OPG (r=−0.122 to –0.230, all P = 0.007–0.000) and TGF-β2 (r=−0.100 to –0.173, all P = 0.029–0.000) and a positive correlation between BDR and serum TGF-β1 (r=0.245−0.365, all P=0.000). After adjustment for age and BMI, there were no statistically significant correlations between serum levels of OPG or TGF-β2 and BDR. However, statistically significant correlations between serum TGF-β1 and BDR at the lumbar spine and ultradistal forearm remained. Multiple linear regression stepwise analysis showed that serum OPG could explain 1.4–3.7% of BDR variation. Serum TGF-β1 was a positive determinant of BDR and could explain 5.3–13.3% of BDR variation

Cytochrome P450 3A Enzymes Are Key Contributors for Hepatic Metabolism of Bufotalin, a Natural Constitute in Chinese Medicine Chansu

Bufotalin (BFT), one of the naturally occurring bufodienolides, has multiple pharmacological and toxicological effects including antitumor activity and cardiotoxicity. This study aimed to character the metabolic pathway(s) of BFT and to identify the key drug metabolizing enzyme(s) responsible for hepatic metabolism of BFT in human, as well as to explore the related molecular mechanism of enzymatic selectivity. The major metabolite of BFT in human liver microsomes (HLMs) was fully identified as 5β-hydroxylbufotalin by LC-MS/MS and NMR techniques. Reaction phenotyping and chemical inhibition assays showed that CYP3A4 and CYP3A5 were key enzymes responsible for BFT 5β-hydroxylation. Kinetic analyses demonstrated that BFT 5β-hydroxylation in both HLMs and human CYP3A4 followed the biphasic kinetics, while BFT 5β-hydroxylation in CYP3A5 followed substrate inhibition kinetics. Furthermore, molecular docking simulations showed that BFT could bind on two different ligand-binding sites on both CYP3A4 and CYP3A5, which partially explained the different kinetic behaviors of BFT in CYP3A4 and CYP3A5. These findings are very helpful for elucidating the phase I metabolism of BFT in human and for deeper understanding the key interactions between CYP3A enzymes and bufadienolides, as well as for the development of bufadienolide-type drugs with improved pharmacokinetic and safety profiles

The JCMT BISTRO Survey: Studying the Complex Magnetic Field of L43

We present observations of polarized dust emission at 850 μm from the L43 molecular cloud, which sits in the Ophiuchus cloud complex. The data were taken using SCUBA-2/POL-2 on the James Clerk Maxwell Telescope as a part of the BISTRO large program. L43 is a dense (NH 10 22 2 ~ –1023 cm−2) complex molecular cloud with a submillimeter-bright starless core and two protostellar sources. There appears to be an evolutionary gradient along the isolated filament that L43 is embedded within, with the most evolved source closest to the Sco OB2 association. One of the protostars drives a CO outflow that has created a cavity to the southeast. We see a magnetic field that appears to be aligned with the cavity walls of the outflow, suggesting interaction with the outflow. We also find a magnetic field strength of up to ∼160 ± 30 μG in the main starless core and up to ∼90 ± 40 μG in the more diffuse, extended region. These field strengths give magnetically super- and subcritical values, respectively, and both are found to be roughly trans-Alfvénic. We also present a new method of data reduction for these denser but fainter objects like starless cores