1.Application of Neural Tract Tracing Techniques in Study of Spinal Cord Injury and Regeneration (review)
Wanyue LI ; Yumeng DING ; Xi WANG
Chinese Journal of Rehabilitation Theory and Practice 2017;23(6):657-661
Spinal cord injury is one of the important field of neuroscience, and neural tract tracing techniques are important research tools. The neural fiber types in the spinal cord are complex, and there are some difference in structures between human beings and animals. This article reviewed different types of neural fibers closely related with spinal cord injury and regeneration, the difference between human beings and animals, and the application of neural tract tracing techniques in the study of spinal cord injury and regeneration.
2.Application of PAP PCR to monitor plasma cfDNA in advanced non-small cell lung can-cer
Xiaoyan XU ; Zhao YAN ; Yumeng WANG ; Zhaoting MENG ; Jinliang CHEN ; Qingshan WANG ; Li LIN ; Yudong SU ; Shaofeng DING ; Lin ZHU ; Peng CHEN
Chinese Journal of Clinical Oncology 2018;45(2):83-87
Objective:To explore the application of pyrophosphorolysis-activated polymerization(PAP)to monitor plasma cfDNA in ad-vanced non-small cell lung cancer(NSCLC).Methods:A total of 85 patients diagnosed with advanced NSCLC between March 2016 and June 2017 were enrolled in the present study. EGFR mutations in cfDNA extracted from the plasma were detected using PAP and ARMS-PCR technology.The concordance analysis of EGFR mutations involved plasma vs.tumor tissue and PAP vs.ARMS-PCR.Further-more,38 EGFR-positive patients were selected to monitor EGFR mutations with PAP.Results:No statistical differences in EGFR muta-tions were observed between plasma and tumor tissue(P=0.092),as well as PAP and ARMS-PCR(P=0.210).The detection rate of EGFR mutations in cfDNA was higher in the progressor than in the non-progressor(62.5% vs.21.3%,P<0.001).Conclusions:PAP can be used for detecting and monitoring EGFR mutations in cfDNA to predict disease progression.
3.Mechanism of Cinnamaldehyde in Promoting Wound Healing in Diabetes Rats via PINK1/Parkin-mediated Mitochondrial Autophagy
Kaiqi HONG ; Li CHEN ; Zhenhua ZHU ; Yumeng WANG ; Zhonghang YUAN ; Wei WANG ; Yarong DING ; Chenlei XIE ; Zhongzhi ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(16):134-143
ObjectiveTo establish a rat model of diabetic wound by feeding on a high-fat and high-sugar diet combined with intraperitoneal injection of streptozotocin (STZ) and surgical preparation of full-thickness skin defects, observe the effect of cinnamaldehyde on the wound healing of diabetes rats, and explore the therapeutic mechanism of cinnamaldehyde in improving wound healing of diabetes rats based on the PTEN-induced putative kinase (PINK1)/Parkin pathway-mediated mitochondrial autophagy. MethodForty-eight male SD rats were randomly divided into blank group (n=12) and diabetes group (n=36). The diabetes group was further randomly divided into model group, cinnamaldehyde group, and Beifuxin group, with 12 rats in each group. The blank group and the model group received routine disinfection with physiological saline after creating the wounds, while the cinnamaldehyde group received topical application of polyethylene glycol 400 (PEG 400) gel containing 4 μmol·L-1 cinnamaldehyde, and the Beifuxin group received topical application of Beifuxin gel. Dressings were changed once daily. The wound healing rate of each group was observed. On the 7th and 14th days after intervention, the wound tissues of the rats were collected. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the local tissues. Immunohistochemistry (IHC) was used to detect the expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and collagen fibers. Immunofluorescence (IF) and Real-time polymerase chain reaction (Real-time PCR) were used to detect the protein, and mRNA expression of PINK1, Parkin, microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ). ResultAfter intraperitoneal injection of STZ, compared with the blank group, the random blood glucose values of rats in the diabetic group increased significantly (P<0.01), all higher than 16.7 mmol·L-1, and persistently hyperglycemic for some time after modeling. Compared with the blank group, the model group showed poor growth and healing of granulation tissue in the wounds, and the wound healing rate decreased (P<0.01). On the 7th day after intervention, the blank group had squamous epithelial coverage on the wounds. Compared with the blank group, the model group only had a small amount of scab at the wound edges, with a large number of infiltrating inflammatory cells in the wounds. The protein expression levels of IL-6 and TNF-α in the tissues increased (P<0.01), and the protein and mRNA levels of PINK1, Parkin, and LC3Ⅱ decreased (P<0.01). On the 14th day after the intervention, the granulation tissue in the wounds of the blank group was mature and well-healed. Compared with the blank group, the model group still had infiltrating inflammatory cells and red blood cell exudation. The protein expression levels of VEGF and collagen fibers in the tissues decreased (P<0.01), and the protein and mRNA expression levels of PINK1, Parkin, and LC3Ⅱ increased (P<0.01). Compared with the model group, the cinnamaldehyde group and the Beifuxin group showed better wound healing, with increased wound healing rates (P<0.01). On the 7th day after intervention, the protein expression levels of IL-6 and TNF-α in the tissues decreased (P<0.01), and the protein and mRNA expression levels of PINK1, Parkin, and LC3Ⅱ increased (P<0.01). On the 14th day after intervention, the protein expression levels of VEGF and collagen fibers in the tissues increased (P<0.01), and the protein and mRNA expression levels of PINK1, Parkin, and LC3Ⅱ decreased (P<0.01). ConclusionCinnamaldehyde can promote the wound healing of diabetes rats by increasing the wound healing rate, reducing the levels of inflammatory factors IL-6 and TNF-α, and increasing the levels of VEGF and collagen fibers. Its mechanism may be related to the regulation of the PINK1/Parkin signaling pathway, activation of mitochondrial autophagy, inhibition of inflammatory responses, and promotion of angiogenesis and collagen synthesis, thereby promoting the wound healing of diabetes rats.
4.Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3)-ones as potential HIV-1 inhibitors.
Yumeng WU ; Chengrun TANG ; Ruomei RUI ; Liumeng YANG ; Wei DING ; Jiangyuan WANG ; Yiming LI ; Christopher C LAI ; Yueping WANG ; Ronghua LUO ; Weilie XIAO ; Hongbing ZHANG ; Yongtang ZHENG ; Yanping HE
Acta Pharmaceutica Sinica B 2020;10(3):512-528
A series of 2-(((5-akly/aryl-1-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3)-ones were synthesized and their anti-HIV-1 activities were evaluated. Most of these compounds were highly active against wild-type (WT) HIV-1 strain (IIIB) with EC values in the range of 0.0038-0.4759 μmol/L. Among those compounds, had an EC value of 3.8 nmol/L and SI (selectivity index) of up to 25,468 indicating excellent activity against WT HIV-1. anti-HIV-1 activity and resistance profile studies suggested that compounds and displayed potential anti-HIV-1 activity against laboratory adapted strains and primary isolated strains including different subtypes and tropism strains (ECs range from 4.3 to 63.6 nmol/L and 18.9-219.3 nmol/L, respectively). On the other hand, it was observed that those two compounds were less effective with EC values of 2.77 and 4.87 μmol/L for HIV-1A (K103N + Y181C). The activity against reverse transcriptase (RT) was also evaluated for those compounds. Both and obtained sub-micromolar IC values showing their potential in RT inhibition. The pharmacokinetics examination in rats indicated that compound has acceptable pharmacokinetic properties and bioavailability. Preliminary structure-activity relationships and molecular modeling studies were also discussed.