RESUMEN
Chronic itch often clinically coexists with anxiety symptoms, creating a vicious cycle of itch-anxiety comorbidities that are difficult to treat. However, the neuronal circuit mechanisms underlying the comorbidity of anxiety in chronic itch remain elusive. Here, we report anxiety-like behaviors in mouse models of chronic itch and identify γ-aminobutyric acid-releasing (GABAergic) neurons in the lateral septum (LS) as the key player in chronic itch-induced anxiety. In addition, chronic itch is accompanied with enhanced activity and synaptic plasticity of excitatory projections from the thalamic nucleus reuniens (Re) onto LS GABAergic neurons. Selective chemogenetic inhibition of the Re â LS circuit notably alleviated chronic itch-induced anxiety, with no impact on anxiety induced by restraint stress. Last, GABAergic neurons in lateral hypothalamus (LH) receive monosynaptic inhibition from LS GABAergic neurons to mediate chronic itch-induced anxiety. These findings underscore the potential significance of the Re â LS â LH pathway in regulating anxiety-like comorbid symptoms associated with chronic itch.
Asunto(s)
Ansiedad , Neuronas GABAérgicas , Área Hipotalámica Lateral , Prurito , Animales , Ratones , Neuronas GABAérgicas/metabolismo , Enfermedad Crónica , Modelos Animales de Enfermedad , Núcleos Talámicos de la Línea Media/metabolismo , Masculino , Conducta Animal , Vías Nerviosas , Plasticidad Neuronal , Núcleos SeptalesRESUMEN
<p><b>OBJECTIVE</b>To investigate the expression of phosphoglycerate kinase 1 (PGK1) and its prognostic value in endometrial carcinoma (EC).</p><p><b>METHODS</b>The expression of PGK1 was detected immunohistochemically in 30 normal endometrium and 130 EC specimens. The relationship between PGK1 protein expression and the clinicopathological features of the patients was evaluated.</p><p><b>RESULTS</b>Immunohistochemical analysis revealed low PGK1 expression in 55.4% (72/130) and high PGK1 expression in 44.6% (58/130) of the EC specimens, as compared with the rates of 90% (27/30) and 10% (3/30) in normal endometrium, respectively (P<0.001). PGK1 expression was significantly correlated with FIGO stage (P<0.001), histological grade (P=0.002) and lymph node metastasis (P<0.001). Kaplan-Meier survival analysis indicated that patients with a high PGK1 expression had a shorter overall survival rate than those with a low PGK1 expression (P<0.001). Multivariate analysis showed that a high PGK1 expression was not the independent predictor of the prognosis of EC (P=0.077).</p><p><b>CONCLUSION</b>A high expression of PGK1 is associated with aggressive and metastatic behaviors of EC, and detection of PGK1 provides assistance in evaluating the prognosis of patients with EC.</p>
RESUMEN
<p><b>OBJECTIVE</b>To analyze the expression of MAP2K4 and vimentin in human endometrial carcinoma (EC) and their association with the clinicopathological features and prognosis of the patients.</p><p><b>METHODS</b>MAP2K4 and vimentin expressions were detected immunohistochemically in paraffin-embedded tissue sections from 128 patients with EC, and the correlation of MAP2K4 and vimentin expressions with the clinicopathological factors of the patients was analyzed.</p><p><b>RESULTS</b>MAP2K4 and vimentin proteins were positively expressed in 49 (38.3%) and 83 (64.8%) of the patients, respectively. A positive expression of MAP2K4 was negatively correlated with FIGO stage of the tumor (P=0.010) and lymph node status (P=0.016); a positive expression of vimentin was positively correlated with FIGO stage of the tumor (P=0.025), histological grades (P=0.017), depth of myometrial invasion (P=0.044) and lymph node status (P=0.032). MAP2K4 was inversely associated with vimentin expression in EC(r=-0.598, P<0.001). Patients positive for MAP2K4 tended to have a higher overall survival rate (P=0.002), and those positive for vimentin tended to have a lower overall survival rate (P=0.007); patients positive for MAP2K4 but negative for vimentin had the longest survival time, while those negative for MAP2K4 and positive for vimentin had lowest survival rate (P=0.004).</p><p><b>CONCLUSION</b>Detection of MAP2K4 and vimentin might help in early diagnosis and prognostic evaluation of patients with EC.</p>