Protein phosphatase 2A deficiency in hippocampal CA1 inhibits priming effect of morphine on conditioned place preference in mice.

Studies have shown that protein phosphorylation plays an important role in morphine abuse. However, the neurobiological mechanism of protein phosphatase 2A (PP2A) underlying the morphine-priming process is still unclear. Here we constructed T29-2-Cre; PP2Afl/fl conditional knockout mice (KO) and investigated the role of hippocampal PP2A in morphine priming. We observed that the deficit of PP2A inhibited the priming behavior of morphine and blocked the priming-induced long-term potentiation (LTP) in the hippocampus of KO mice. Moreover, the expression levels of Rack1 and the membrane GluN2B were significantly reduced in the nucleus accumbens of KO mice compared with those in the control mice, which may be attributed to the decreased HDAC4 in the hippocampus of KO mice. Consistent with it, the similar inhibited priming effects were also observed in the wild-type mice treated with sodium butyrate (NaB)-a nonspecific inhibitor of histone deacetylases-3 h after morphine administration. Taken together, our results suggest that hippocampal PP2A may be involved in morphine priming through the PP2A/HDAC4/Rack1 pathway.

Preliminary assessment of a portable Raman spectroscopy system for post-operative urinary stone analysis.

PURPOSE: We aimed to evaluate the reliability of a portable device that applies Raman spectroscopy at an excitation wavelength of 1064 nm for the post-operative analysis of urinary stone composition. MATERIALS AND METHODS: Urinary stone samples were obtained post-operatively from 300 patients. All samples were analyzed by the portable Raman spectroscopy system at an excitation wavelength of 1064 nm as well as by infrared spectroscopy (IR), and the results were compared. RESULTS: Both Raman spectroscopy and IR could detect multiple stone components, including calcium oxalate monohydrate, calcium oxalate dihydrate, calcium phosphate, uric acid, cystine, and magnesium ammonium phosphate hexahydrate. The results from 1064-nm Raman analysis matched those from IR analysis for 96.0% (288/300) of cases. Although IR detected multiple components within samples more often than Raman analysis (239 vs 131), the Raman analysis required less time to complete than IR data acquisition (5 min vs 30 min). CONCLUSIONS: These preliminary results indicate that 1064-nm Raman spectroscopy can be applied in a portable and automated analytical system for rapid detection of urinary stone composition in the post-operative clinical setting. TRIAL REGISTRATION: Chinese Clinical Trail Register ID: ChiCTR2000039810 (approved WHO primary register) http://www.chictr.org.cn/showproj.aspx?proj=63662 .

A novel model based on lipid metabolism-related genes associated with immune microenvironment predicts metastasis of breast cancer.

BACKGROUND: Breast cancer (BC) is the most prevalent malignant tumor among women worldwide and a significant cause of cancer-related deaths in females. Recent studies have shown that lipid metabolism-related genes (LMRGs) exhibit prognostic potential in various types of tumors, including BC. Our study aimed to establish a novel model to predict the metastasis of BC. METHODS: Clinical information and corresponding RNA data of patients with BC were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. Consensus clustering was performed to identify novel molecular subgroups. Estimation of Stromal and Immune Cells in Malignant Tumor Tissues using Expression, microenvironment cell populations counter, microenvironment cell populations counter, and single-sample gene set enrichment analyses were employed to determine the tumor immune microenvironment and immune status of the identified subgroups. Functional analyses, including Gene Ontology and gene set enrichment analyses, were conducted to elucidate the underlying mechanisms. A prognostic risk model was constructed using the Least Absolute Shrinkage and Selection Operator algorithm and multivariate Cox regression analysis. RESULTS: This study identified differential gene expression between patients with BC exhibiting metastasis and those without metastasis using public databases. Using the obtained data, we established predictive models based on six LMRGs. Furthermore, consensus clustering and prognostic score grouping analysis revealed that differentially expressed LMRGs influence tumor prognosis by regulating tumor immunity. To facilitate clinical application, we developed a nomogram integrating the risk model and clinical characteristics to accurately predict the prognosis of patients with BC. CONCLUSION: We developed and validated a novel signature associated with LMRGs for predicting disease-free survival in patients with BC. The expression of LMRGs correlates with the immune microenvironment of patients with BC, providing new insights and improved strategies for the diagnosis and treatment of BC.

The deficiency of Maged1 attenuates Parkinson's disease progression in mice.

Melanoma-associated antigen D1 (Maged1) has critical functions in the central nervous system in both developmental and adult stages. Loss of Maged1 in mice has been linked to depression, cognitive disorder, and drug addiction. However, the role of Maged1 in Parkinson's disease (PD) remains unclear. In this study, we observed that Maged1 was expressed in the dopaminergic (DA) neurons of the substantia nigra in mice and humans, which could be upregulated by the in vivo or in vitro treatment with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-Methyl-4-phenylpyridinium iodide (MPP+). Genetic ablation of Maged1 in mice attenuated motor deficits, the loss of DA neurons, and disease progression induced by MPTP. Moreover, Maged1 deficiency protected DA neurons against MPP+-induced toxicity in primary cultured cells. Mechanistically, loss of Maged1 upregulated the Akt signaling pathway and downregulated the mTOR signaling pathway in SH-SY5Y cells, which may in turn attenuate the cell apoptosis and impairment of autophagy. Consistent with it, the degeneration of midbrain and striatum among elderly Maged1 knockout mice was relatively mild compared to those in wild-type mice under physiological conditions. Taken together, this study suggested that Maged1 deficiency inhibited apoptosis and enhanced autophagy, which may provide a new potential target for the therapy of PD.