Connexin 36 Mediates Orofacial Pain Hypersensitivity Through GluK2 and TRPA1

Trigeminal neuralgia is a debilitating condition, and the pain easily spreads to other parts of the face. Here, we established a mouse model of partial transection of the infraorbital nerve (pT-ION) and found that the Connexin 36 (Cx36) inhibitor mefloquine caused greater alleviation of pT-ION-induced cold allodynia compared to the reduction of mechanical allodynia. Mefloquine reversed the pT-ION-induced upregulation of Cx36, glutamate receptor ionotropic kainate 2 (GluK2), transient receptor potential ankyrin 1 (TRPA1), and phosphorylated extracellular signal regulated kinase (p-ERK) in the trigeminal ganglion. Cold allodynia but not mechanical allodynia induced by pT-ION or by virus-mediated overexpression of Cx36 in the trigeminal ganglion was reversed by the GluK2 antagonist NS102, and knocking down Cx36 expression in Nav1.8-expressing nociceptors by injecting virus into the orofacial skin area of Nav1.8-Cre mice attenuated cold allodynia but not mechanical allodynia. In conclusion, we show that Cx36 contributes greatly to the development of orofacial pain hypersensitivity through GluK2, TRPA1, and p-ERK signaling.Electronic supplementary materialThe online version of this article (10.1007/s12264-020-00594-4) contains supplementary material, which is available to authorized users.     

喉癌患者PAC-1、CD62P表达与临床病理特征和复发的关系

目的探讨喉癌患者血小板表面血小板膜糖蛋白Ⅱb/Ⅲa纤维蛋白原受体(PAC-1)、血小板P-选择素(CD62P)阳性表达率以及与患者临床病理特征和复发的关系。方法选取2014年1月~2015年12月间在我院耳鼻喉科手术治疗的116例喉癌患者,随访≥2年,并选取同期在我院体检的健康人群60例为对照组,采用流式细胞仪检测法检测外周血PAC-1和CD62P阳性率,并分析与临床病理特征、复发的关系。结果喉癌患者PAC-1和CD62P阳性表达率分别为(17.82±1.76)%和(22.87±3.13)%,明显高于健康人群(P<0.05);而且在喉癌患者PAC-1表达和CD62P表达呈正相关性(r=0.238,P<0.05)。T3-T4分期或N2-N3分期患者PAC-1和CD62P阳性表达率高于T1-T2分期或N0-N1分期患者(P<0.05)。另外远处转移组PAC-1和CD62P阳性表达率高于未发生转移组(P<0.05);随访期间有24例患者复发,复发率为20.69%。复发喉癌患者PAC-1、CD62P阳性表达率分别为(17.02±0.85)%和(21.84±1.17)%,明显高于未复发的喉癌患者(P<0.05)。经Logistics回归分析,PAC-1和CD62P是喉癌患者复发的独立危险因素(P<0.05)。结论PAC-1和CD62P阳性表达率与喉癌患者T分期、淋巴结转移和远处转移密切相关,同时可作为喉癌局部复发、区域淋巴结转移、远处转移的预测指标。     

Ipsilesional motor-evoked potential absence in pediatric hemiparesis impacts tracking accuracy of the less affected hand

This study analyzed the relationship between electrophysiological responses to transcranial magnetic stimulation (TMS), finger tracking accuracy, and volume of neural substrate in children with congenital hemiparesis. Nineteen participants demonstrating an ipsilesional motor-evoked potential (MEP) were compared with eleven participants showing an absent ipsilesional MEP response. Comparisons of finger tracking accuracy from the affected and less affected hands and ipsilesional/contralesional (I/C) volume ratio for the primary motor cortex (M1) and posterior limb of internal capsule (PLIC) were done using two-sample t-tests. Participants showing an ipsilesional MEP response demonstrated superior tracking performance from the less affected hand (p = 0.016) and significantly higher I/C volume ratios for M1 (p = 0.028) and PLIC (p = 0.005) compared to participants without an ipsilesional MEP response. Group differences in finger tracking accuracy from the affected hand were not significant. These results highlight differentiating factors amongst children with congenital hemiparesis showing contrasting MEP responses: less affected hand performance and preserved M1 and PLIC volume. Along with MEP status, these factors pose important clinical implications in pediatric stroke rehabilitation. These findings may also reflect competitive developmental processes associated with the preservation of affected hand function at the expense of some function in the less affected hand.     

TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations

There is a compelling need to understand and assess the toxicity of industrially produced nanoparticles (NPs). In order to appreciate the long-term effects of NPs, sensitive human-based screening tests that comprehensively map the NP properties are needed to detect possible toxic mechanisms. Animal models can only be used in a limited number of test applications and are subject to ethical concerns, and the interpretation of experiments in animals is also distorted by the species differences.Here, we present a novel easy-to-perform highly sensitive whole-blood model using fresh non-anticoagulated human blood, which most justly reflects complex biological cross talks in a human system. As a demonstrator of the tests versatility, we evaluated the toxicity of TiO₂ NPs that are widely used in various applications and otherwise considered to have relatively low toxic properties. We show that TiO₂ NPs at very low concentrations (50 ng/mL) induce strong activation of the contact system, which in this model elicits thromboinflammation. These data are in line with the finding of components of the contact system in the protein corona of the TiO₂ NPs after exposure to blood.The contact system activation may lead to both thrombotic reactions and generation of bradykinin, thereby representing fuel for chronic inflammation in vivo and potentially long-term risk of autoimmunity, arteriosclerosis and cancer. These results support the notion that this novel whole-blood model represents an important contribution to testing of NP toxicity.     

P63阳性基底细胞在前列腺切除术后尿道再上皮化中的作用

目的:探讨前列腺切除术后P63阳性基底细胞在前列腺部尿道上皮修复过程中的作用。方法:15只老年家犬行前列腺增生切除术,术后第3、7、14天取材行HE染色和免疫组织化学染色分别观察前列腺部尿道上皮修复过程和P63蛋白表达水平。结果:术后3 d手术创面偶见P63阳性细胞;术后7 d可见片状P63阳性细胞,且这些细胞与残余前列腺组织相连续;术后14 d可见新生尿道上皮基底层细胞阳性表达P63。结论:残余前列腺组织是BPH术后尿道再上皮化的重要组织,而位于基底层的P63阳性细胞可能是这一修复过程的源细胞之一。