[The Function of Neuroinflammation in Parkinson Disease].

Parkinson disease (PD) is the second most common neurodegenerative disorder, characterized by a progressive loss of dopaminergic neurons in the substantia nigra (SN). The pathology of PD remains unclear. Recent findings suggests neuroinflammation plays a critical role in PD. Occurrence of neuroinflammation, including microglia and astrocyte activation, T lymphocyte infiltration and blood-brain barrier disruption, has been identified in PD. However, the mechanism of neuroinflammation regulation in PD is not fully deciphered. In this review, we focus on the cutting edge in researches of neuroinflammation in PD, which may provide us new ideas in prevention and recovery of PD.

MicroRNA­34a attenuates the proliferation, invasion and metastasis of gastric cancer cells via downregulation of MET.

Proliferation, invasion and metastasis are key features of gastric cancer, contributing to high mortality rates in patients with gastric cancer worldwide. As a direct target of p53, the functions of microRNA (miR)­34a are important, but controversial, in the progression of gastric cancer. In the present study, the clinical importance of miR­34a in GC specimens (n=40) were investigated and were confirmed in an independent cohort from The Cancer Genome Atlas (TCGA; n=352). The prognostic value of miR­34a was analyzed using a Kaplan­Meier survival curve in the TCGA cohort, in combination with complete follow­up data (n=157). The level of miR­34a was detected in the human gastric cancer cell line and normal gastric epithelial cell line. The effect of miR­34a on proliferation and invasion were evaluated using Cell Counting Kit 8, colony formation and cell invasion assays. The molecular basis of miR­34a was determined by bioinformatics prediction. The correlation between miR­34a and MET was assessed using reverse transcription­quantitative polymerase chain reaction and western blot analyses. The results indicated that miR­34a was downregulated in the gastric cancer tissues, compared with the normal gastric tissues (P<0.01). miR­34a was negatively correlated with the depth of invasion and lymph node metastasis of gastric cancer (P<0.01). In the TCGA cohort, the levels of miR­34a were lower in T3 and T4 tumor stages, compared with the level in the T1 stage, and low levels of miR­34a predicted significantly longer survival rates in patients with GC (P<0.05). miR­34a also attenuated the proliferation ability, and inhibited the colony formation and cell invasion abilities of the cells (P<0.01). A negative correlation was observed between miR­34a and MET in gastric cancer (P<0.01; r=­0.9526), and >60% of cases exhibited consistent expression of miR­34a and MET in gastric cancer (P<0.01). In conclusion, miR­34a was associated with the clinicopathological features of gastric cancer and was a valuable predictor of patient prognosis. miR­34a acted as a tumor suppressor to inhibit gastric cancer proliferation and invasion via the downregulation of MET.

Intervention timing and effect of PJ34 on astrocytes during oxygen-glucose deprivation/reperfusion and cell death pathways.

Poly (ADP-ribose) polymerase-1 (PARP-1) plays as a double edged sword in cerebral ischemia-reperfusion, hinging on its effect on the intracellular energy storage and injury severity, and the prognosis has relationship with intervention timing. During ischemia injury, apoptosis and oncosis are the two main cell death pathway sin the ischemic core. The participation of astrocytes in ischemia-reperfusion induced cell death has triggered more and more attention. Here, we examined the protective effects and intervention timing of the PARP-1 inhibitor PJ34, by using a mixed oxygen-glucose deprivation/reperfusion (OGDR) model of primary rat astrocytes in vitro, which could mimic the ischemia-reperfusion damage in the "ischemic core". Meanwhile, cell death pathways of various PJ34 treated astrocytes were also investigated. Our results showed that PJ34 incubation (10 µmol/L) did not affect release of lactate dehydrogenase (LDH) from astrocytes and cell viability or survival 1 h after OGDR. Interestingly, after 3 or 5 h OGDR, PJ34 significantly reduced LDH release and percentage of PI-positive cells and increased cell viability, and simultaneously increased the caspase-dependent apoptotic rate. The intervention timing study demonstrated that an earlier and longer PJ34 intervention during reperfusion was associated with more apparent protective effects. In conclusion, earlier and longer PJ34 intervention provides remarkable protective effects for astrocytes in the "ischaemic core" mainly by reducing oncosis of the astrocytes, especially following serious OGDR damage.