Prior nasal delivery of antagomiR-122 prevents radiation-induced brain injury.

Radiation-induced brain injury is a major adverse event in head and neck tumor treatment, influencing the quality of life for the more than 50% of patients who undergo radiation therapy and experience long-term survival. However, no effective treatments are available for these patients, and preventative drugs and effective drug-delivery methods must be developed. Based on our results, miR-122-5p was upregulated in the mouse radiation-induced brain injury (RBI) model and patients with nasopharyngeal carcinoma (NPC) who received radiation therapy. Intranasal administration of a single antagomiR-122-5p dose before irradiation effectively alleviated radiation-induced cognitive impairment, neuronal injury, and neuroinflammation in the mouse RBI model. Results further indicated that miR-122-5p inhibition in microglia reduced the levels of proinflammatory cytokines and enhanced the phagocytic function to protect against radiation-induced neuronal injury in cell models. Further, we profiled transcriptome data and verified that Tensin 1 (TNS1) may be the target of miR-122-5p in RBI. In summary, our results reveal a distinct role for miR-122-5p in regulating neuroinflammation in RBI, indicating that a non-invasive strategy for intranasal miR-122-5p administration may be an attractive therapeutic target in RBI, providing new insights for clinical trials. Further systematic safety assessment, optimization of drug administration, and clarity of mechanism will accelerate the process into clinical practice.

Nasal Delivery of AntagomiR-741 Protects Against the Radiation-Induced Brain Injury in Mice.

Radiation-induced brain injury (RBI) is a serious complication in patients who have received radiotherapy for head and neck tumors. Currently, there is a scarcity of information on early diagnostic and preventive methods of RBI. Accumulating evidence suggests that microRNAs are involved in the regulation of radiation injury, but the molecular biological mechanism of miRNAs in RBI is largely unknown. Therefore, in our study, microRNA sequencing was used to discover differential miRNAs in the hippocampus of RBI-modeled mice, which suggested that miR-741-3p was most significantly upregulated. To clarify the underlying mechanism of miR-741-3p in RBI-modeled mice, an inhibitor of miR-741-3p (antagomiR-741) was delivered into the brain via the nasal passage before irradiation. The delivery of antagomiR-741 significantly reduced miR-741-3p levels in the hippocampus of RBI-modeled mice, and the cognitive dysfunction and neuronal apoptosis induced by radiation were also alleviated at 6 weeks postirradiation. Downregulation of miR-741-3p was found to improve the protrusion and branching status of microglia after irradiation and reduced the number of GFAP-positive astrocytes. Additionally, antagomiR-741 suppressed the radiation-induced production of pro-inflammatory cytokines IL-6 and TNF-α in the hippocampus and S100B in the serum. Furthermore, Ddr2, PKCα and St8sia1 were revealed as target genes of miR-741-3p and as potential regulatory targets for RBI. Overall, our study provides identification and functional evaluation of miRNA in RBI and lays the foundation for improving the prevention strategy for RBI based on the delivery of miRNA via the nose-brain pathway.

A Systematic Review and Meta-analysis of the Therapeutic Effect of Acupuncture on Migraine.

Background: Migraine is an intractable headache disorder, manifesting as periodic attacks. It is highly burdensome for patients and society. Acupuncture treatment can be beneficial as a supplementary and preventive therapy for migraine. Objectives: This systematic review and meta-analysis aimed to investigate the efficacy and safety of acupuncture for migraine, and to examine transcranial doppler changes after acupuncture. Methods: Reports, conference, and academic papers published before March 15, 2019 in databases including PubMed, Cochrane library, Embase, China National Knowledge Infrastructure, WANFANG Database, Chinese journal of Science and Technology, and China Biomedical were searched. Randomized controlled trials (RCTs) involving acupuncture, sham acupuncture, and medication in migraine were included. The Cochrane Collaboration software, RevMan 5.3, was used for data processing and migration risk analysis. Results: Twenty-eight RCTs were included. 15 RCTs included medication only, 10 RCTs included sham acupuncture only, and 3 RCTs included both. The study included 2874 patients, split into 3 groups: acupuncture treatment group (n = 1396), medication control group (n = 865), and sham acupuncture control group (n = 613). The results showed that treatment was more effective in the acupuncture group than in the sham acupuncture group (MD = 1.88, 95% CI [1.61, 2.20], P < 0.00001) and medication group (MD = 1.16, 95% CI [1.12, 1.21], P < 0.00001). Improvement in visual analog scale (VAS) score was greater in the acupuncture group than in the sham acupuncture group (MD = -1.00, 95% CI [-1.27,-0.46], P < 0.00001; MD = -0.59, 95% CI [-0.81,-0.38], P < 0.00001), and their adverse reaction rate was lower than that of the medication group (RR = 0.16, 95% CI [0.05, 0.52], P = 0.002). The improvement of intracranial blood flow velocity by acupuncture is better than that by medication, but the heterogeneity makes the result unreliable. Conclusions: Acupuncture reduced the frequency of migraine attacks, lowered VAS scores, and increased therapeutic efficiency compared with sham acupuncture. Compared with medication, acupuncture showed higher effectiveness with less adverse reactions and improved intracranial blood circulation. However, owing to inter-study heterogeneity, a prospective, multicenter RCT with a large sample is required to verify these results.

The Relationship Between Enlarged Perivascular Spaces and Cognitive Function: A Meta-Analysis of Observational Studies.

Enlarged perivascular spaces (ePVS), visible on magnetic resonance imaging (MRI), are associated with aortic pulse wave changes produced by arterial stiffening. However, the relationship between ePVS and cognition is still unclear. We aimed to benchmark current knowledge of associations between ePVS and cognitive function using a meta-analysis of all available published data. We searched three databases for studies examining ePVS and cognition, identified seven studies involving 7,816 participants, plotted multivariate-adjusted odds ratio (OR) and 95% CI and generated summary OR with a fixed effects model. EPVS were related to the risk of impaired cognition (OR = 1.387, 95% CI = 1.198-1.606, z=4.38, P<0.001) with low heterogeneity. There was publication bias, which could be corrected by trimming and supplementation (OR=1.297, 95% CI= 1.130-1.490). EPVS were associated with impaired cognition and may be a sign of cognitive impairment rather than particular diseases. More studies are required to validate ePVS as a measurable risk marker for cognition using consistent methods to determinea characteristic appearance of ePVS.

Rapid access to cyclopentadiene derivatives through gold-catalyzed cycloisomerization of ynamides with cyclopropenes by preferential activation of alkenes over alkynes.

In this communication, gold-catalyzed intermolecular cycloisomerization of cyclopropenes and ynamides is investigated. The current transformation displayed an activation priority of double bonds over triple bonds by the cationic gold catalyst, giving the corresponding cyclopentadienes in good to excellent yields. Additionally, this protocol can be expanded to a one-pot two-step procedure for the synthesis of substituted cyclopentanones.