N-acetylcysteine Protects against Apoptosis through Modulation of Group I Metabotropic Glutamate Receptor Activity

The activation of group I metabotropic glutamate receptor (group I mGlus) has been shown to produce neuroprotective or neurotoxic effects. In this study, we investigated the effects of N-acetylcysteine (NAC), a precursor of the antioxidant glutathione, on group I mGlus activation in apoptosis of glial C6 and MN9D cell lines, and a rat model of Parkinson's disease (PD). We demonstrated that NAC protected against apoptosis through modulation of group I mGlus activity. In glial C6 cells, NAC promoted phosphorylation of ERK induced by (s)-3,5- dihydroxy-phenylglycine (DHPG), an agonist of group I mGlus. NAC enhanced the group I mGlus-mediated protection from staurosporine (STS)-induced apoptosis following DHPG treatment. Moreover, in rotenone-treated MN9D cells and PD rat model, NAC protected against group I mGlus-induced toxicity by compromising the decrease in phosphorylation of ERK, phosphorylation or expression level of TH. Furthermore, the results showed that NAC prohibited the level of ROS and oxidation of cellular GSH/GSSG (Eh) accompanied by activated group I mGlus in the experimental models. Our results suggest that NAC might act as a regulator of group I mGlus-mediated activities in both neuroprotection and neurotoxicity via reducing the oxidative stress, eventually to protect cell survival. The study also suggests that NAC might be a potential therapeutics targeting for group I mGlus activation in the treatment of PD

OCT3/4 is a potential immunohistochemical biomarker for diagnosis and prognosis of primary intracranial germ cell tumors: a systematic review and meta-analysis

IntroductionIntracranial germ cell tumors (iGCTs), comprising of germinoma (GE) and non-germinomatous GCT (NGGCT), are a group of heterogenous brain tumors. Immunohistochemical markers, such as placental-like alkaline phosphatase (PLAP), are commonly used in diagnosis but show moderate sensitivity. Organic cation transporter 3/4 (OCT3/4) has been proposed as a novel biomarker for diagnosis and prognosis of iGCTs. This paper aimed to compare OCT3/4 with PLAP as potential immunohistochemical biomarkers in iGCTs diagnosis and clarify the relationship between OCT3/4 and prognosis of patients with iGCTs.MethodsMeta-analyses were performed to estimate pooled percentage point differences in positive rates between OCT3/4 and PLAP, their sensitivities, and correlation between OCT3/4 and prognosis in iGCTs.ResultsNine articles were included representing of 241 patients. A fixed-effects model meta-analysis revealed that OCT3/4s positive rate was 8.6% higher (95% CI, 0.7% lower to 17.9% higher) than that of PLAP. Using fixed-effects models, sensitivities of OCT3/4 as a potential immunohistochemical biomarker in CNS GE and NGGCT were 85% (95% CI, 79% to 89%) and 56% (95% CI, 39% to 71%), respectively. In comparison, PLAP had lower sensitivities in both GE (73%; 95% CI, 64% to 91%) and NGGCT (43%; 95% CI, 27% to 61%). Moreover, OCT3/4 was significantly negatively correlated with 5-year progression free survival in patients with CNS GE (HR = 2.56, 95 % CI 1.47 to 4.44; p = 0.0008). Sensitivity analyses showed similar results.DiscussionThis study provides the first comprehensive assessment of the efficacies of OCT3/4 and PLAP in iGCTs detection and prognosis prediction, indicating OCT3/4 seems to be a more sensitive and reliable immunohistochemical marker in iGCT diagnosis

Case report: Identification of potential prognosis-related LAG3 overexpression and DICER1 mutation in pituitary carcinoma: two cases

Metastatic PitNETs are a rare life-threatening condition with poor prognosis and documentation. Due to the scarce literature and lack of precise treatment, we hope to better characterise PitNET using the next-generation whole exon sequencing (WES) and RNA sequencing. This case study outlines a 54 years-old man and a 52 years-old woman who were both diagnosed with PitNET and analysis of peripheral blood and tumours were performed by WES and RNA sequencing. Analysis showed that DICER1 mutations in precancerous lesions and LAG3 overexpression were significant in aiding the prognosis and diagnosis of PitNETs. The first case with overexpressed LAG3 and DICER1 mutation died 26 months later, and the second case with LAG3 overexpression achieved partial remission. This study revealed that heightened expression of LAG3 offered promising targets for ICI and mutations in DICER1 could provide markers for effective diagnosis and prognosis

Impacts of agricultural industrial agglomeration on China's agricultural energy efficiency : A spatial econometrics analysis

The rapid development of traditional agriculture in China was achieved at the expense of high energy consumption and investments. However, the global green development trend made it necessary for the country to transform its agricultural energy utilization. Energy efficiency changes are affected by many factors, particularly industrial agglomeration. In recent years, the Chinese government has introduced a series of policies, including setting major producing regions for grains and advantageous regions for characteristic agricultural product. These have caused significant changes to the spatial layout of the agriculture industry. However, there is still a lack of research on the impact of these changes on agricultural energy efficiency (AEE). In this study, panel data of 30 Chinese provinces from 2000 to 2016 were entered into stochastic frontier models to measure the country's AEE at the provincial level. A series of spatial econometric models were also used to analyze the impact of agricultural industrial agglomeration on China's AEE. The results indicated that the country's AEE exhibited obvious spatial gradients and correlations. After controlling the impacts of spatial correlation and other factors in the models, agricultural industrial agglomeration was found to have an overall positive impact on China's AEE. In the future, policies should be formulated to increase AEE by establishing agricultural functional areas, strengthening the innovation and sharing of green development technologies at the farm level, and promoting the optimization of energy structures in agricultural and rural areas.</p