1.Effect of curcumin on spinal cord injury repair via inhibiting NF-κB signalling pathway:research progress
Mengdan GAO ; Jingquan LIN ; Liang TONG ; Jinyi ZHANG ; Na HAN ; Xuehong LIU
Chinese Journal of Pharmacology and Toxicology 2016;30(3):272-277
Inflammation response is the most crucial link in the pathogeneses of spinal cord injury (SCI),and is the basis of secondary damage. NF-κB Signalling pathway is activated excessively after SCI,so that numerous NF-κB possessing biological activities is quickly translocated into the nuclear and regulates the target genes,resulting in heightened inflammation and further tissue damage. Suppressing NF-κB signalling pathway and controlling inflammation response effectively are effective approaches to promoting SCI repair. It is found that curcumin has multiple target molecules to suppress NF-κB signalling pathway,block the excessive activation of NF-κB and reduce the expression of proinflammation cytokines,which plays an important role in SCI repair. This article discusses NF-κB signalling pathway,the contribution of NF-κB signalling pathway to SCI and the role of curcumins inhibition of NF-κB signalling pathway in SCI.
2.Liguzinediol exerts positive inotropic effect by enhancing Ca 2+release from sarcoplasmic reticulum mediated by sarcoplasmic reticulum Ca2+ATPase
Wei WANG ; Sha LI ; Mengdan ZHANG ; Ying GAO ; Shuyin XUE ; Kesu CHEN ; Zhongyue WANG ; Long CHEN
Chinese Journal of Pharmacology and Toxicology 2016;30(3):197-202
OBJECTIVE To explore kinetic features and its underlying mechanism of the positive inotropic effect of liguzinediol(LZDO)in rats. METHODS ①An In vivo study was made to record the effect of LZDO 20 mg · kg-1 injected for 30 consecutive min from the left external jugular vein on pressure-volume relationships. ②Ex vivo study was used to record the antagonistic effect of LZDO on reduced contractility induced by caffeine. Caffeine and LZDO were perfused as follows:normal perfusion solution, caffeine 0.5 mmol · L-1,and then caffeine 0.5 mmol · L-1+LZDO 100 μmol · L-1. ③ Ca2+ transient from cardiomyocyte sarcoplasmic reticulum (SR) was measured to analyze the effect of LZDO on Ca2 +release blocked by thapsigargin. Thapsigargin and LZDO were perfused as follows:normal perfusion solution,thapsigargin 2 μmol · L-1,and then thapsigargin 2 μmol · L-1+LZDO 100 μmol · L-1.④The SR vesicles were prepared and the effect of LZDO(1,10 and 100μmol·L-1)on sarcoplasmic reticulum Ca2+ATPase(SERCA2a)activity was determined according to the ultramicro-Ca2+-ATP enzyme kit. RESULTS ① LZDO 20 mg · kg- 1 significantly reduced the end-systolic volume (Ves) and enhanced the end-systolic pressure (Pes),stroke volume (SV),ejection fraction (EF),cardiac output(CO),peak rate of rise of left ventricular pressure(+dp/dtmax)and stroke work(SW)(P<0.05). However,LZDO 20 mg · kg-1 did not significantly change the heart rate(HR )or the end-diastolic volume (Ved). ② Caffeine 0.5 mmol · L- 1 significantly enhanced HR,left ventricular developed pressure (LVDP ),and+dp∶dtmax at 5 min after caffeine and decreased at 30 min. However,LZDO 100μmol·L-1 restored the reduced HR,LVDP,and+dp/dtmax induced by caffeine at 30 min(P<0.05).③Thapsigargin 2μmol·L-1 significantly reduced the SR Ca2+transient from perfusion solution group(100±5)%to(51± 5)%(P<0.05) and LZDO 100 μmol · L-1 failed to restore the decreased Ca2+ transient〔(49 ± 4)%〕. Normalized Ca2+transients were reduced by thapsigargin 2μmol·L-1 and thapsigargin 2μmol·L-1+LZDO 100 μmol · L-1. ④ LZDO(10 and 100 μmol · L-1)significantly increased the activities of SERCA2a in perfusion solution group 0.98±0.10 to 1.17±0.20 and (1.43±0.09)μmol Pi·g-1·h-1,respectively(P<0.05). CONCLUSION LZDO can enhance SR Ca2+ gradient by activating the SERCA2a and might be developed to serve as a potential positive inotropic agent in clinical settings.
3.Proarrhythmic effect and underlying mechanism of combined use of azithromycin and Shengmai injection in guinea pigs
Ying GAO ; Mengdan ZHANG ; Sha LI ; Shuyin XUE ; Huili HUANG ; Ming XIE ; Kesu CHEN ; Fuming LIU ; Long CHEN
Chinese Journal of Pharmacology and Toxicology 2017;31(6):527-533
OBJECTIVE To explore potential proarrhythmic effect and underlying mechanism of azithromycin (AZM) and Shengmai injection (SM) used clinically.METHODS ① In vivo guinea pig ECG recordings were made to analyze effects of jugular intravenous(iv) injection of AZM [38.2 mg· kg-1,one time (clinically relevant dose,CRD)],or SM (4.6 mL· kg-1,one time CRD) or their combination.②In vitro ECG recordings were made to analyze effects of AZM,SM or AZM + SM on ECG in isolated hearts of guinea pigs.AZM [one,five and ten times (clinically relevant concentrations,CRC)] was perfused in this order:41.5 →207.5 → 415 mg· L-1 and SM (one,five and ten times CRC) in this order:5 →25 →50 mL· L-1.Also,AZM (41.5 mg· L-1,one time CRC) +SM (5 mL· L-1,one time CRC) was perfused to isolated hearts of guinea pigs.③ Enzymatically isolated cardiomyocytes from guinea pig left ventricles were perfused in this order:AZM 41.5 mg· L-1 →AZM 41.5 mg· L-1+SM 5 mL· L-1 for action potential,L-type Ca2+ and Na+ current recordings,respectively.RESULTS ① Neither AZM 38.2 mg· kg-1,nor SM 4.6 mL· kg-1 significantly changed the in vivo ECG.However,AZM 38.2 mg· kg-1 +SM 4.6 mL · kg-1 significantly reduced heart rate (P<0.05) and prolonged the P-R (P<0.05) and QRS (P<0.05) intervals.②AZM 41.5,207.5 and 415 mg· L-1 reduced heart rate (P<0.05) and prolonged the P-R (P<0.05) and QRS (P<0.05) intervals in a concentration-dependent manner.AZM 415 mg·L-1 also prolonged QTc (P<0.05) interval.SM 5,25 and 50 mL· L-1 reduced heart rate (P<0.05) and prolonged the P-R interval (P<0.05) in a concentration-dependent manner.SM had no effect on QRS or QTc intervals.Washout partially recovered the above changes.Moreover,AZM 41.5 mg· L-1 + SM 5 mg·L-1 significantly reduced heart rate (P<0.05) and prolonged the P-R (P<0.05) and QRS intervals.③ AZM 41.5 mg·L-1 did not significantly change the action potential amplitude (APA),action potential durations at 50% (APD50) and 90% (APD90) repolarization levels,or L-type Ca2+ and Na+ currents.However,AZM+SM 5 mg· L-1 significantly reduced APA (P<0.05),shortened APD50 (P<0.05) and APD90 (P<0.05) and inhibited the L-type Ca2+ (P<0.05) and Na+ (P<0.05) currents.CONCLUSION AZM and SM has potential prorrhythmic risks.The combined use might cause higher risk of arrhythmia.The underlying mechanism for proarrhythmia is mediated by inhibition of the L-type Ca2+ and Na+ currents.
4.Role of signal transduction and transcription factors STAT1 and STAT3 in the pathogenesis of hepatocellular carcinoma and liver failure
Mengdan GAO ; Yonghong ZHANG ; Yan ZHAO
Journal of Clinical Hepatology 2018;34(9):2017-2020
Hepatocellular carcinoma (HCC) and liver failure are common liver diseases in China and have extremely high incidence and mortality rates. Although there are many related studies, the detailed pathogenesis of these two diseases is still unknown. This article reviews the role of STAT1 and STAT3 phosphorylation proteins in the pathogenesis of HCC and liver failure, such as antiviral defense, acute phase response, liver injury, repair, inflammation, and transformation. A deep understanding of their role in the pathogenesis of HCC and liver failure and the development of related drugs with them as molecular targets play an important role in reducing mortality rate in clinical practice.
5.Hsa-circ-000094 in Peripheral blood can be used as a biomarker for the diagnosis of type 2 diabetes
Yang YE ; Chaoyu CHU ; Yuanyuan XIAO ; Qingge GAO ; Mengdan LIU ; Linlin JI ; Li XU ; Li WEI
Chinese Journal of Endocrinology and Metabolism 2019;35(2):114-120
Objective The purpose of this study was to investigate the differential expression of circRNAs in human blood, as a diagnostic marker for pre-diabetes and type 2 diabetes mellitus( T2DM). Methods Microarray analysis was used to select several differentially expressed circRNAs from three normal patients and three T2DM patients. Enlarge the sample size(normal controls,n=20;subjects with impaired glucose regulation,n=20;and type 2 diabetes mellitus,n=20) to determine a circRNA which the most evident differentially expressed by fluorescence quantitative PCR( Q-PCR). Then they were verified with expanded samples ( normal controls, n= 50; impaired glucose regulations,n=50;type 2 diabetes mellitus, n=50) by Q-PCR. Results A total of 2 953 differentially expressed circRNAs were found in microarray analysis, of which 1 439 were up-regulated and 1 514 were down-regulated. Nine differentially expressed circRNAs were selected from the 1 439 circRNAs that were up-regulated(hsa-circ-103838, hsa-circ-103965, hsa-circ-104227, hsa-circ-002117, hsa-circ-000094, hsa-circ-101226, hsa-circ-101720, hsa-circ-400029, and hsa-circ-100633). The Q-PCR results of the expanded sample( n=60) showed that the difference expression of hsa-circ-000094(Alias:has-circ-0000247) in the nine circRNAs was the most obvious one among the 3 groups, the area under the maximum curve was found by ROC curve analysis, SIGR=0. 802 5[ 95% confidence interval (0.665 5-0.939 5), P=0.001]; ST2DM=0.77[95% confidence interval (0.624-0.916), P=0.003]. In order to verify the clinical diagnostic ability of hsa-circ-000094, the experiment was conducted to further expand the sample ( n=150). The results showed that the expression of hsa-circ-000094 in the three groups was different, the difference and ROC curve analysis were statistically significant, SIGR=0. 673 3 [ 95% confidence interval (0.575 7-0. 771 0), P<0. 01]; ST2DM=0. 723 1 [ 95% confidence interval ( 0. 632 7-0. 813 4), P< 0.01]. Conclusion The higher expression of hsa-circ-000094 in peripheral blood provides a certain diagnostic basis for pre-diabetes as well as type 2 diabetes mellitus.
6.Research progress on the relationship between bilirubin and polycystic ovary syndrome
Mengdan SHEN ; Junping HU ; Mingxia GAO
Clinical Medicine of China 2023;39(2):157-160
Polycystic ovary syndrome (PCOS) is a common reproductive endocrine and metabolic disease, and its pathogenesis is closely related to inflammation, insulin resistance, and metabolic disorders. Bilirubin is the final product of the destruction and degradation of senescent red blood cells in the body. In addition, bilirubin can be not only used to evaluate liver function damage and cytotoxicity, but also can anti-inflammatory, antioxidant, alleviate metabolic disorders, etc. Recently, studies have found a certain correlation between low levels of bilirubin and PCOS: the level of bilirubin in patients with PCOS is low, and the anti-inflammatory and antioxidant properties of bilirubin may play a protective role in the pathogenesis of PCOS.
7.Research advances in immune factors for the prognosis of patients with acute - on - chronic liver failure
Journal of Clinical Hepatology 2017;33(12):2462-2466
Acute - on - chronic liver failure (ACLF)is commonly seen in China,with a complex pathogenesis,difficult clinical treatment, and poor prognosis. Many factors can affect the prognosis of patients with ACLF. This article elaborates on the changes in immune cells and cytokines in ACLF and their influence on the prognosis of ACLF,in order to explore new biomarkers associated with the prognosis of ACLF, provide guidance for clinical treatment,and finally improve the prognosis of patients with ACLF.
8.Research progress of S1PR1 in tumor metastasis-promoting and radiotherapy resistance
Mengdan GAO ; Xuxue YE ; Lihuai LU ; Qiongqiong WANG ; Qingyu ZHOU ; Ya GAO ; Yifei LI ; Congying XIE
Chinese Journal of Radiological Medicine and Protection 2019;39(8):599-602
Distant metastasis is one of the main obstacles to cancer treatment.Overexpression of S1PR1 in malignant tumors enhances cell invasion and migration activity,mediates EMT and induces lymphangiogenesis and angiogenesis via activation of its downstream signaling pathways,eventually results in the occurrence of tumor metastasis.S1PR1 is also closely related to generation of acquired radiotherapy resistance.This article discusses the roles of S1PR1 in tumor metastasis and radiotherapy resistance.
9.Acupuncture point selection for prevention and treatment of generalized anxiety disorder from the perspective of Microbiota-Gut-Brain Axis
Xiaxia JIN ; Leyao QIN ; Mengdan ZHANG ; Tao GAO ; Zhengquan LEI ; Feng ZHOU ; Wendi DONG
International Journal of Traditional Chinese Medicine 2023;45(1):8-12
Disorders of the gut flora (GF) affect the level of 5-hydroxytryptamine (5-HT) in the brain of patients with generalized anxiety disorder (GAD) and influence the development of the disease. Most of the acupuncture points selected for GAD are based on the principles of local acupuncture points and acupuncture points following the distant channels of the meridians, regarding Baihui (DU 20), Fengchi (GB 20), and Yintang (GV 29) as the main acupuncture points, and the acupuncture points selected for the regulation of GF are Zhongwan (CV 12), Tianshu (ST 25), and Guanyuan (RN 4) and Zusanli (ST 36). Recently, many studies have been conducted on the mechanism of action of acupuncture in the treatment of GAD from the perspective of GF, but few have investigated the theoretical of acupuncture points used to prevent and treat GAD. This paper discusses the theoretical basis of acupuncture to regulate the "microbiota-gut-brain axis" (MGBA) for the prevention and treatment of GAD, and proposes the method of "regulating the internal organs and calming the mind and relieving anxiety" through analyzing the researches on the regulation of GF and GAD.
10.A Modern Neuropsychological View of Zhongyi Qingzhi
Simeng GU ; Liyuan JING ; Mengdan GAO ; Fushun WANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2018;20(2):173-182
Depression is one of the prevalent causes of health-related human suffering and is,first and foremost,a disorder of one of the least-studied biological phenomena:emotion.Therefore,it is critically important to understand emotion,in order to understand the etiology of depression.Chinese medicine is the oldest subject about emotion,has developed a theory about basic emotions and their interactions,and also their roles in causes and therapy in most of human diseases,including mental disorders,such as depression.Nowadays,major depressive disorder (MDD) is a prevalent mental disorder with cognitive,affective and behavioral symptoms,and has been identified as a leading cause of disability,and affecting about ~17% of the populations worldwide.Decades of animal and clinical studies have pointed its etiology in dysfunctions in the monoamine transporters.Here we will review some literatures about the relationship between the monoamine neuromodulators and emotional theory in Chinese medicine,which might introduce theoretical perspectives in studies about emotion and depression.