Ketamine Administration Leads to Learning-Memory Dysfunction and Decreases Serum Brain-Derived Neurotrophic Factor in Rats.

OBJECTIVE: This study investigated the effects of acute or chronic ketamine administration on learning and memory function as well as levels of brain-derived neurotrophic factor (BDNF) in the hippocampus and blood in order to explore the potential correlation between learning-memory dysfunction and ketamine. METHODS: Rats were treated with 25 mg/kg ketamine for 3 d (n = 20) or 14 d (n = 20). Saline-treated rats were used as controls. The Morris water maze test was used to evaluate spatial learning and memory after 10 d of withdrawal. The level of BDNF in serum and the hippocampus were measured by ELISA. RESULTS: The number of platform crossings and residence time in the target platform quadrant were significantly reduced in ketamine 3 d and 14 d groups than in the saline controls (both p < 0.05). In addition, the average escape latency of ketamine 3 d and 14 d groups were significantly longer than that of the saline 3 d and 14 d groups (p < 0.0001), respectively. Further examination found that only serum samples from ketamine 14 d group showed significantly decreased BDNF level compared to that from saline 14 d groups (p < 0.05). However, no differences were detected in hippocampus samples. CONCLUSION: Chronic ketamine exposure (25 mg/kg) causes spatial learning and memory deficits in SD rats, which may be associated with decreased serum BDNF levels.

Meta-Analysis of Diagnostic Performance of Instantaneous Wave-Free Ratio versus Quantitative Flow Ratio for Detecting the Functional Significance of Coronary Stenosis.

BACKGROUND: Fractional flow reserve (FFR), as a functional measurement of coronary stenosis, is recommended for guiding revascularization in intermediate coronary lesions. However, it still remains underutilized for potential reasons including time consumption, costs, or contraindications associated with adenosine administration. Here we performed this meta-analysis to assess the diagnostic performance of two adenosine-free indices, instantaneous wave free-ratio (iFR), and quantitative flow ratio (QFR) in evaluating coronary stenosis severity with FFR as the reference standard. METHODS: PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched to include relevant studies with the diagnostic accuracy of iFR or QFR referenced to FFR. A bivariate model was applied to pool diagnostic parameters. We used Cochran's Q test and I2 index to assess heterogeneity and identify the potential source of heterogeneity by meta-regression. RESULTS: A total of 8213 lesions from 28 studies (19 for iFR and 9 for QFR) were included in this meta-analysis. The pooled sensitivity and specificity were 0.79 (95% CI, 0.75 to 0.83) and 0.85 (95% CI, 0.82 to 0.87) for iFR and 0.90 (95% CI, 0.84 to 0.93) and 0.88 (95% CI, 0.86 to 0.90) for QFR, respectively. Significantly higher sensitivity and specificity were observed in the bivariate analysis for QFR than for iFR (P < 0.001 for both). The area under summary receiver-operating curve of iFR and QFR was 0.89 (95% CI, 0.86 to 0.92) and 0.92 (95% CI, 0.89 to 0.94). CONCLUSION: Evidence suggests that both of the two indices have good performance in detecting functional ischemia of coronary arteries and QFR might be a promising method without requiring the pressure wire. Further application of QFR may potentially provide important information to clinicians in the assessment of coronary lesions.

Prevention of neointimal formation after angioplasty using tetramethylpyrazine-coated balloon catheters in a rabbit iliac artery model.

BACKGROUND: Restenosis remains a clinical problem; drug-coated balloons (DCBs) have demonstrated high efficiency in this situation. DCBs prevent neointimal hyperplasia by inhibiting cell proliferation and migration. Tetramethylpyrazine (TMP) is a traditional Chinese medicine originally isolated from the rhizome of Ligusticum Walliichii, which can inhibit platelet aggregation and smooth muscle cell proliferation. We hypothesized that TMP-coated balloons (TCB) could reduce neointimal hyperplasia through the NF-κB signalling pathway. METHODS: Twenty-one New-Zealand White rabbits (2.5-3.0 kg, male) were fed high-fat diets; 36 bilateral iliac artery stenosis models were successfully established by balloon straining. Rabbits were randomly treated with TCB (n=20) or plain balloons (PBA, n=16) (3 died during model construction). Angiographies were recorded at baseline, the immediate period, and 4 weeks later. Animals were euthanized and arteries collected for histological analysis and immunohistochemical staining. Protein expression of proliferating cell nuclear antigen (PCNA) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 of the vessel samples were analyzed using Western blotting. RESULTS: No difference existed in the baseline lesion characteristics or procedural results. Angiographic follow-up was successfully performed on 18 rabbits (TCB: n=20, PBA: n=16), except for 3 deaths related to the operation. Treatment with TCB was superior to that with PBA, with lower late lumen loss (0.45±0.23 vs. 0.84±0.17 mm, P<0.01). Pathological analysis confirmed the efficiency of TCB through decreasing the area stenosis rate compared with PBA (46.48%±8.22% vs. 75.24%±6.10%, P<0.01). As determined by Western blotting, significant reductions occurred in PCNA and NF-κB p65 protein intensity in the TCB group versus the PBA group (all P<0.01). TCB efficiently mitigated restenosis in the rabbit iliac artery model. CONCLUSIONS: This study elucidated that TCB could restrain intimal hyperplasia of vessels by inhibiting the activation of the NF-κB pathway to reduce inflammatory response and decrease the rate of cell proliferation through suppressing PCNA expression.

Capturing functional long non-coding RNAs through integrating large-scale causal relations from gene perturbation experiments.

Characterizing functions of long noncoding RNAs (lncRNAs) remains a major challenge, mostly due to the lack of lncRNA-involved regulatory relationships. A wide array of genome-wide expression profiles generated by gene perturbation have been widely used to capture causal links between perturbed genes and response genes. Through annotating >600 gene perturbation profiles, over 354,000 causal relationships between perturbed genes and lncRNAs were identified. This large-scale resource of causal relations inspired us to develop a novel computational approach LnCAR for inferring lncRNAs' functions, which showed a higher accuracy than the co-expression based approach. By application of LnCAR to the cancer hallmark processes, we identified 38 lncRNAs involved in distinct carcinogenic processes. The "activating invasion & metastasis" related lncRNAs were strongly associated with metastatic progression in various cancer types and could act as a predictor of cancer metastasis. Meanwhile, the "evading immune destruction" related lncRNAs showed significant associations with immune infiltration of various immune cells and, importantly, can predict response to anti-PD-1 immunotherapy, suggesting their potential roles as biomarkers for immune therapy. Taken together, our approach provides a novel way to systematically reveal functions of lncRNAs, which will be helpful for further experimental exploration and clinical translational research of lncRNAs.