Upregulation of ubiquitin conjugating enzyme E2B (Ube2b) ameliorates neuropathic pain by regulating Kcna2 (potassium voltage-gated channel subfamily A member 2) in primary afferent neurons.

Neuropathic pain is a kind of pain caused by damage to somatosensory nervous system. Currently, neuropathic pain is still a medical problem for clinicians. Ubiquitin conjugating enzyme E2B (Ube2b) is validated to be implicated with nerve function, but whether Ube2b can play a role in neuropathic pain is still elusive. In this work, we constructed chronic constriction injury (CCI) rat model by ligating the left sciatic nerve, Ube2b protein expression was confirmed to be decreased in spinal cord tissues of CCI rats via Western blot analysis and immunofluorescence (IF) staining. Moreover, Ube2b elevation alleviated the thermal hyperalgesia and mechanical hyperalgesia in CCI rats according to paw withdrawal thermal latency (PWTL) and paw withdrawal mechanic threshold (PWMT). In addition, Hematoxylin-eosin staining revealed that Ube2b elevation suppressed chronic sciatic nerve injury. All these data suggested that Ube2b could ameliorate neuropathic pain in CCI rats. Mechanically, Ube2b upregulation elevated the protein level of Kcna2 (potassium voltage-gated channel subfamily A member 2) and decreased the protein level of DNMT3a (DNA methyltransferase 3 alpha). Ube2b elevation could increase Kcna2 expression via suppressing DNMT3a. Rescue assays unveiled that Ube2b overexpression modulated-mechanical hyperalgesia and thermal hyperalgesia were reversed by Kcna2 depletion, indicating that Ube2b alleviated neuropathic pain via mediating Kcna2 via the regulation of DNMT3a. In summary, we found that Ube2b elevation ameliorated neuropathic pain through regulating Kcna2, which might offer a novel biomarker for the therapies of neuropathic pain.

Inhibition of GPR4 attenuates SH-SY5Y cell injury in cerebral ischemia/reperfusion via anti-apoptotic pathways.

Cerebral ischemia/reperfusion injury (CIRI) can lead to increased vascular endothelial permeability and blood-brain barrier damage in patients with stroke. G protein-coupled receptor 4 (GPR4) is a functional pH sensor that plays a key role in renal ischemia-reperfusion-induced apoptosis. However, whether GPR4 has a role in cerebral ischemia remains to be further studied. Our study found that after oxygen-glucose deprivation/reoxygenation (OGD/R) treatment, the levels of GPR4 and CHOP in SH-SY5Y cells were significantly increased, which was accompanied by a decrease in cell viability, and an increase in LDH release and apoptosis. After knockdown of GPR4 using shRNA, CHOP levels in SH-SY5Y cells were also decreased, which unexpectedly increased cell activity and decreased LDH release and apoptosis rate. Interestingly, CHOP overexpression reversed the effect of GPR4 knockdown, suggesting that OGD/R-induced CIRI may involve endoplasmic reticulum stress-related apoptosis. In conclusion, our study provided a basis for further research on the mechanism of CIRI.

Safety Assessment of Electronic Cigarettes and Their Relationship with Cardiovascular Disease.

Smoking leads to the occurrence and development of a variety of diseases. Most importantly, it is an independent risk factor of cardiovascular atherosclerosis. In recent years, electronic cigarettes have become a popular alternative to traditional cigarettes, since modern micro-electronic techniques provide the possibility of simulating the process of traditional smoking. Additionally, it is convenient and fashionable. Nevertheless, comments about the safety of electronic cigarettes remain controversial. Although the research about electronic cigarettes increased exponentially, there has been no systematic study of its safety. The aim of the current study is to review the literature reports about the safety of electronic cigarettes, and to understand their hazards and disadvantages. It was found that most of the current research about electronic cigarettes comprises short-term and in vitro studies. There are few reports of in vivo and long-term studies. Notably, the level of harmful components such as volatile organic compounds, tobacco-specific nitrosamines and heavy metals in electronic cigarettes are even higher than in traditional cigarettes. Therefore, the harm of electronic cigarettes should not be underestimated. In conclusion, the question of whether electronic cigarettes are a safe and sufficient substitute for traditional smoking needs further investigation.