HCN channels in the lateral habenula regulate pain and comorbid depressive-like behaviors in mice.

AIMS: Comorbid anxiodepressive-like symptoms (CADS) in chronic pain are closely related to the overactivation of the lateral habenula (LHb). Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have been implicated to play a key role in regulating neuronal excitability. However, the role of HCN channels in the LHb during CADS has not yet been characterized. This study aimed to investigate the effect of HCN channels in the LHb on CADS during chronic pain. METHODS: After chronic neuropathic pain induction by spared nerve injury (SNI), mice underwent a sucrose preference test, forced swimming test, tail suspension test, open-field test, and elevated plus maze test to evaluate their anxiodepressive-like behaviors. Electrophysiological recordings, immunohistochemistry, Western blotting, pharmacological experiments, and virus knockdown strategies were used to investigate the underlying mechanisms. RESULTS: Evident anxiodepressive-like behaviors were observed 6w after the SNI surgery, accompanied by increased neuronal excitability, enhanced HCN channel function, and increased expression of HCN2 isoforms in the LHb. Either pharmacological inhibition or virus knockdown of HCN2 channels significantly reduced LHb neuronal excitability and ameliorated both pain and depressive-like behaviors. CONCLUSION: Our results indicated that the LHb neurons were hyperactive under CADS in chronic pain, and this hyperactivation possibly resulted from the enhanced function of HCN channels and up-regulation of HCN2 isoforms.

Caroguaianolide A-E, five new cytotoxic sesquiterpene lactones from Carpesium abrotanoides L.

Five new guaiane-type sesquiterpene lactones, caroguaianolide A-E (1-5), along with nine known sesquiterpene lactones (6-14) were isolated from the whole plant of Carpesium abrotanoides L. Their structures were elucidated on the basis of spectroscopic date, HRESIMS analysis, and comparison of experimental and calculated ECD data. All isolated compounds (1-14) were tested in vitro for their cytotoxic activities against the MDA-MB-231, HGC-27 cancer cell lines, of which compounds 1-3, 6, 7, 11 and 12 showed significant cytotoxic activities with IC50 values ranging from 2.67 to 12.34 µM.

Efficacy of coenzyme Q10 in mitigating spinal cord injury-induced osteoporosis.

Spinal cord injury (SCI)­induced osteoporosis may cause mild trauma to bone and increase the risk of bone fracture. The present study aimed to investigate the efficacy of coenzyme Q (CoQ10) on SCI­induced osteoporosis in rats. SCI was induced by surgical transection of the cord at the T10­12 level. Animals were treated with CoQ10 (10 mg/kg; intragastrically) daily from 12 h after the surgery and over 10 subsequent days. At the end of the experimental period, blood was collected from the animals and femurs and tibiae were removed for evaluation using biochemical assays. Treatment with CoQ10 prevented SCI­induced bone loss by rescuing the decreased levels of bone mineral density and bone mineral content observed in the SCI rats. Furthermore, CoQ10 administration reduced bone malondialdehyde levels with a concomitant increase in superoxide dismutase levels, thus alleviating SCI­induced oxidative injury. In addition, serum inflammatory cytokine levels were markedly increased in rats post­SCI, which was attenuated by treatment with CoQ10. Finally, the osteoclast­specific genes receptor activator of nuclear factor kappa­B ligand and cathepsin K were significantly upregulated and the osteoblast­specific gene core­binding factor alpha 1 in the femur was downregulated following SCI, which was effectively restored following treatment with CoQ10. The results suggested that CoQ10 treatment may be effective in attenuating SCI­induced osteoporosis.

A photothermal model of selective photothermolysis with dynamically changing vaporization temperature.

The theory of selective photothermolysis (SP) is used in many fields of laser surgery and medicine. As several parameters and a number of complicated photothermal interactions are involved in SP, numerical simulations have been providing an important and effective way in SP studies. However, with different photothermal models of SP, simulated results differ considerably. In addition, insufficient attention has been paid to tissue pressure variation during SP in these models, so that vessel rupture and other clinical phenomena cannot be explained. A novel photothermal model of SP was proposed using a Monte Carlo method to simulate the laser transport in the tissue, a heat transfer equation with dynamically changing vaporization temperature to calculate the temperature distribution, and the Arrhenius equation to predict the thermal damage. A factor of trapped vaporized tissue water k was introduced to describe the effects on tissue pressure, temperature, and other related parameters. It was shown that the simulation results are affected significantly by k. Temperature and thermal damage volume are almost identical, respectively, to those obtained with models with vaporization at 100°C and models without vaporization when k = 0 and 1, while thermal damage volume is close to that obtained with models of vaporization at 110°C and 130°C, respectively, when k = 0.022 and k = 0.18. To some extent, the current models without vaporization and models with vaporization at constant temperature can be regarded as special cases at specific situations of this new photothermal model of SP. In addition, more descriptive simulation results, such as temperature, thermal damage, and pressure, are accessible with this model, although the accuracy depends on the value of k, the estimation of which is planned as future work.