1.Correlation between 1H-MRS metabolites in hippocampal and T lymphocyte subsets and cytokines in peripheral blood of patients with temporal lobe epilepsy
Bingbing WANG ; Xin DU ; Qingwei LAI ; Qingyun LI ; Xinyu LI ; Heng WANG ; Peng HU ; Hongbin FAN
Chinese Journal of Behavioral Medicine and Brain Science 2021;30(12):1095-1101
Objective:To analyze the correlation between 1H-MRS in hippocampus and peripheral blood cytokines and T lymphocyte subsets in patients with temporal lobe epilepsy, and to explore the relationship between immune dysfunction and the degree of neuronal injury. Methods:Fifty patients with temporal lobe epilepsy were selected from Affiliated Hospital of Xuzhou Medical University from October 2020 to July 2021.Clinical data of all patients were collected and they were divided into two groups according to MRI results of epileptic sequence: abnormal hippocampal MRI group ( n=20) and normal hippocampal MRI group ( n=30). Bilateral 1H-MRS scanning of hippocampal and detection of T lymphocyte subsets and cytokines in peripheral blood during interictal period were performed in both groups. The levels of hippocampal metabolites NAA, NAA/(Cr+ Cho), T lymphocyte subsets and cytokines in peripheral blood of the two groups were compared.At the same time, the levels of NAA and NAA/ (Cr+ Cho) in the hippocampus on the abnormal side and the normal side in the abnormal hippocampal MRI group were compared within the group. Finally, the correlation between the levels of metabolites NAA, NAA/ (Cr+ Cho) in the hippocampus on the abnormal side obtained by 1H-MRS scanning and T lymphocyte subsets and cytokines in the abnormal group of MRI was analyzed. The data were statistically analyzed by SPSS 26.0 software. Independent sample t-test or Mann-Whitney U test was used for comparison between the two groups. Paired sample t-test was used for intra group comparison of different sides. Spearman correlation analysis was used to analyze the correlation between each index. Results:The NAA and NAA/(Cr+ Cho) values of the abnormal MRI group(normal side NAA: (1.22±0.37), NAA/(Cr+ Cho): (0.56±0.15). abnormal side NAA: (1.02±0.34), NAA/(Cr+ Cho): (0.48±0.13)) were significantly lower than those of the normal MRI group (NAA: (1.51±0.36), NAA/(Cr+ Cho): (0.73±0.19))(NAA: t=2.705, 4.800, both P<0 05; NAA/(Cr+ Cho): t=3.394, 4.914, both P<0 05). The values of NAA and NAA/(Cr+ Cho) in the abnormal side in the MRI abnormal group were significantly lower than those in the normal side( t=6.467, P<0 05). The levels of IL-1β(11.19(3.56, 20.98)pg/ml), IL-5 (3.12(1.86, 6.41)pg/ml), TNF-α(2.55(1.19, 8.28)pg/ml), CD4+ T lymphocytes((43.13±6.82)%) and Th/Ts((1.96±0.66)) in the hippocampal MRI abnormal group were significantly higher than those in normal MRI group (IL-1β: 3.27(1.63, 6.17)pg/ml, IL-5: 1.15(0.96, 2.96)pg/ml, TNF-α: 1.34(1.02, 2.36)pg/ml, CD4+ T: (38.01±7.21)%, Th/Ts: (1.48±0.53))( Z=-3.041, -2.516, -2.496, all P<0.05; t=2.511, 2.810, both P<0 05). The level of CD8+ T ((23.48±5.33)%) in peripheral blood of abnormal MRI group was significantly lower than that of normal group CD8+ T((27.18±6.08)%)( t=2.210, P<0.05). In the abnormal MRI group, the levels of NAA and NAA/ (Cr+ Cho) in the abnormal hippocampus were negatively correlated with the levels of IL-1β, IL-5 and TNF- α ( r=-0.612--0.463, all P<0.05), and positively correlated with CD8+ T lymphocytes ( r=0.537, 0.478, P<0.05). Conclusion:There is neuronal damage and dysfunction in the abnormal hippocampal region of patients with temporal lobe epilepsy with abnormal hippocampal formation, and the degree of neuronal damage is highly correlated with CD8+ T lymphocytes, IL-5, IL-1β and TNF-α in peripheral blood. The imbalance of interictal lymphocyte subsets and chronic inflammatory response may play an important role in the pathogenesis of epilepsy and neuronal injury .
2.A proteomic landscape of pharmacologic perturbations for functional relevance
Zhiwei LIU ; Shangwen JIANG ; Bingbing HAO ; Shuyu XIE ; Yingluo LIU ; Yuqi HUANG ; Heng XU ; Cheng LUO ; Min HUANG ; Minjia TAN ; Jun-Yu XU
Journal of Pharmaceutical Analysis 2024;14(1):128-139
Pharmacological perturbation studies based on protein-level signatures are fundamental for drug dis-covery.In the present study,we used a mass spectrometry(MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds.The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells.Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol,as well as the noncanonical targets of clinically approved tamoxifen,lovastatin,and their derivatives.Furthermore,the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints.This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.
3. Propofol relieves the subcutaneous chloroquine-induced pruritus in rats via TRPV1 and CB1 receptors of spinal cord
Bingbing HENG ; Danfeng YANG ; Shuyang DAI ; Wangning SHANGGUAN ; Danfeng YANG ; Shuyang DAI
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(10):1101-1108
AIM: To explore the possible mechanism of propofol in alleviating pruritus induced by subcutaneous injection of chloroquine in rats. METHODS: The pruritus model of chloroquine in SD rats was established and the administration time was determined. 18 rats with successful pruritus model induced by subcutaneous injection of chloroquine were randomly divided into NS group, I group and P group. Normal saline 80 μL/kg, fat emulsion 80 μL/kg and propofol 0.8 mg/kg were injected through internal jugular vein catheter 5 minutes after subcutaneous injection of chloroquine. Another 6 rats were randomly selected as group C, and the same volume of normal saline as the other 3 groups was injected subcutaneously in the back of the neck and through the internal jugular vein catheter. The rats were killed 16 minutes after the corresponding drugs were injected into the internal jugular vein. The expressions of TRPV1 and CB1 receptors in the spinal cord were detected by Western blot. RESULTS: Compared with NS group and I group, the expression level of TRPV1 receptor in the spinal cord of P group rats was significantly increased (P<0.01), while there was no statistically significant difference between C group, NS group, and I group; The expression level of CB1 receptor was significantly higher than that of group C, NS, and I (P<0.05), while there was no statistically significant difference between group C, NS, and I. CONCLUSION: Propofol can significantly alleviate pruritus caused by subcutaneous injection of chloroquine in rats, which may exert an antipruritic effect by increasing the expression of TRPV1 and CB1 receptors in the spinal cord of rats.