LPA signaling is required for dopaminergic neuron development and is reduced through low expression of the LPA1 receptor in a 6-OHDA lesion model of Parkinson's disease.

Lysophosphatidic acid (LPA) is a bioactive phospholipid that activates at least five known G-protein-coupled receptors (GPCRs): LPA1-LPA5. The nervous system is a major locus for LPA1 expression. LPA has been shown to regulate neuronal proliferation, migration, and differentiation during central nervous system development as well as neuronal survival. Furthermore, deficient LPA signaling has been implicated in several neurological disorders including neuropathic pain and schizophrenia. Parkinson's disease (PD) is a neurodegenerative movement disorder that results from the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). The specific molecular pathways that lead to DA neuron degeneration, however, are poorly understood. The influence of LPA in the differentiation of mesenchymal stem cells (MSCs) into DA neurons in vitro and LPA1 expression in a 6-hydroxydopamine (6-OHDA) lesion model of PD in vivo were examined in the present study. LPA induced neuronal differentiation in 80.2 % of the MSC population. These MSCs developed characteristic neuronal morphology and expressed the neuronal marker, neuron-specific enolase (NSE), while expression of the glial marker, glial fibrillary acidic protein (GFAP), was absent. Moreover, 27.6 % of differentiated MSCs were positive for tyrosine hydroxylase (TH), a marker for DA neurons. In the 6-OHDA PD rat model, LPA1 expression in the substantia nigra was significantly reduced compared to control. These results suggest LPA signaling via activation of LPA1 may be necessary for DA neuron development and survival. Furthermore, reduced LPA/LPA1 signaling may be involved in DA neuron degeneration thus contributing to the pathogenesis of PD.

The value of positron emission tomography computed tomography in predicting invasiveness of ground glass nodules: A protocol for systematic review and meta-analysis.

BACKGROUND: The study was conducted to investigate the value of Positron emission tomography computed tomography (PET/CT) in predicting invasiveness of ground glass nodule (GGN) by the method of meta-analysis. METHODS: Two researchers independently searched for published literature on PET/CT diagnosis of GGN as of November 30, 2020. After extracting the data, RevMan5.3 was used to evaluate the quality of the included literature. The Stata14 software was used to test the heterogeneity of the original study that met the inclusion criteria, to calculate the combined sensitivity, specificity, positive likelihood ratio and negative likelihood ratio, the prior probability and posttest probability. The summary receiver operator characteristic curve was drawn and the area under the curve was calculated. Using Deeks funnel plot to evaluate publication bias. RESULTS: Five studies were finally included, including 298 GGN cases. The included studies had no obvious heterogeneity and publication bias. The combined sensitivity and specificity of PET/CT for predicting invasive adenocarcinoma presenting as GGN were 0.74 (95% confidence interval [CI]: 0.68-0.79), 0.82 (95% CI: 0.71-0.90), positive likelihood ratio and negative likelihood ratio were 4.1 (95% CI: 2.5-6.9), 0.32 (95% CI: 0.25-0.40), and the diagnostic odds ratio was 13 (95% CI: 7-26). The prior probability is 20%, the probability of GGN being invasive adenocarcinoma when PET/CT was negative was reduced to 7%, and the probability of GGN being invasive adenocarcinoma when PET/CT was positive was increased to 51%. The area under the curve of the summary receiver operator characteristic curve was 0.85. CONCLUSION: PET/CT has high diagnostic accuracy for invasive adenocarcinoma presenting as GGN.

High expression of RACK1 is associated with poor prognosis in patients with pancreatic ductal adenocarcinoma.

Receptor for activated C kinase 1 (RACK1) is associated with certain aspects of cancer biology and signaling pathways, but its function in pancreatic ductal adenocarcinoma (PDAC) remains unknown. In the present study, 157 patients with PDAC were enrolled. RACK1 mRNA and protein expression levels were analyzed in PDAC tissues and matched adjacent noncancerous tissues by reverse transcription-quantitative polymerase chain reaction and western blotting. RACK1 expression levels in paraffin-embedded PDAC tissues were determined by immunohistochemistry. The associations between RACK1 expression and clinical data were evaluated using χ2 analysis. The relationship between RACK1 expression and the survival data of patients was analyzed using Kaplan-Meier and log rank tests. RACK1 mRNA and protein were revealed to be overexpressed in PDAC tumor tissues compared with adjacent noncancerous tissues. RACK1 expression was associated with clinical stage (P=0.001), lymph node invasion (P=0.003) and liver metastasis (P=0.001). Furthermore, patients with PDAC and high RACK1 expression demonstrated shorter overall survival times compared with patients with low RACK1 expression (P=0.002). Multivariate analysis indicated that RACK1 overexpression was an independent prognostic factor for patients with PDAC. Overexpression of RACK1 may contribute to tumor progression, and may be a potential prognostic biomarker for patients with PDAC.

IGF1-Dependent Synaptic Plasticity of Mitral Cells in Olfactory Memory during Social Learning.

During social transmission of food preference (STFP), mice form long-term memory of food odors presented by a social partner. How does the brain associate a social context with odor signals to promote memory encoding? Here we show that odor exposure during STFP, but not unconditioned odor exposure, induces glomerulus-specific long-term potentiation (LTP) of synaptic strength selectively at the GABAergic component of dendrodendritic synapses of granule and mitral cells in the olfactory bulb. Conditional deletion of synaptotagmin-10, the Ca2+ sensor for IGF1 secretion from mitral cells, or deletion of IGF1 receptor in the olfactory bulb prevented the socially relevant GABAergic LTP and impaired memory formation after STFP. Conversely, the addition of IGF1 to acute olfactory bulb slices elicited the GABAergic LTP in mitral cells by enhancing postsynaptic GABA receptor responses. Thus, our data reveal a synaptic substrate for a socially conditioned long-term memory that operates at the level of the initial processing of sensory information.

Docosahexaenoic Acid-Phosphatidylcholine Improves Cognitive Deficits in an Aß23-35-Induced Alzheimer's Disease Rat Model.

Both Docosahexaenoic acid (DHA) and Phosphatidylcholine (PC) have been shown to halt the pathogenesis of Alzheimer disease (AD) and vascular dementia. This study aimed to investigate the role of DHA-containing PC (DHA-PC) in the improvement of Aß25-35-induced cognitive deficits in rats. Aß25-35-induced AD rats were treated for 30 days with DHA-PC, which was extracted from Sthenoteuthis oualaniensis spawns. Cognitive improvement of the AD rats was detected using the Morris water maze (MWM). The results demonstrated that DHA-PC could improve the learning and memory abilities of AD rats in a dose-dependent pattern. Further analyses showed that expression of phosphorylated tau decreased, and the neuronal morphology recovered in brains of DHA-PC-treated AD rats, as compared with mock-treated AD rats. In addition, DHAPC treatment increased the activity of GSH-Px and SOD in the cortex and hippocampus of AD rats. Taken together, these data suggest that DHA-PC is able to improve the cognitive deficits in AD rats, probably through decreasing the phosphorylation of tau in the cortex and hippocampus CA1 area, and increasing the GSH-Px and SOD activities in the brain of AD rats.