1.Effect of Liangxue Tuizi Formula (凉血退紫方) on RAF/MEK/ERK Pathway in Skin Tissue and Serum NETs Biomarkers in Henoch-Schönlein Purpura Model Rats with Blood Heat Syndrome
Yingying JIANG ; Manxiang YANG ; Zhenhua YUAN ; Leying XI ; Mingyang CAI ; Diya MA ; Yifan LI ; Yuhang NIU ; Runze LIU ; Jiawen CAO ; Xilin CHEN ; Xianqing REN
Journal of Traditional Chinese Medicine 2025;66(23):2475-2483
ObjectiveTo investigate the potential mechanism of Liangxue Tuizi Formula (凉血退紫方, LXTZF) in treating Henoch-Schönlein Purpura (HSP) by examining its regulatory effect on neutrophil extracellular trap (NETs) dysregulation via the rapidly accelerated fibrosarcoma kinase (RAF)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway. MethodsSeventy Wistar rats were randomly allocated into a blank control group (n=14) and a modeling group (n=56). Rats in the modelling group underwent an eight-week modelling period to establish HSP rat models with blood-heat syndrome via modified ovalbumin (OVA) induction method combined with oral administration of heat-property Chinese herbal medicine. Fifty successfully modeled rats were subsequently randomly divided into five groups (n=10 per group), model group, compound glycyrrhizin group, LXTZF group, RAF inhibitor group, and LXTZF + RAF agonist group. Additionally, 10 rats were selected from the original blank control group for the final experiment. From the 11th week of modelling, rats in the blank control group and the model group received 1 ml/(100 g·d) ultrapure water via oral administration, in addition to 0.5 ml/(kg·d) 0.9% sodium chloride solution via intraperitoneal injection. The LXTZF group and the compound glycyrrhizin group received 7.5 g/(kg·d) LXTZF granule suspension via gavage, 13.5 mg/(kg·d) compound glycyrrhizin suspension via gavage, respectively. The RAF inhibitor group received 1 mg/(kg·d) GW5074 suspension via intraperitoneal injection and ultrapure water via oral administration; the LXTZF + RAF agonist group received 7.5 g/(kg·d) LXTZF granule suspension via gavage and 1 mg/(kg·d) paclitaxel suspension via intraperitoneal injection. All administrations were performed once daily for 4 weeks. After intervention, skin tissue histopathology was examined by hematoxylin and eosin (H&E) staining, immunoglobulin A (IgA) deposition was assessed via immunofluorescence, serum levels of neutrophil elastase (NE), tumor necrosis factor-α (TNF-α), and vascular cell adhesion molecule-1 (VCAM-1) were measured using enzyme-linked immunosorbent assay (ELISA), serum myeloperoxidase (MPO) level was determined by a colorimetric assay; the mRNA expression levels of RAF, MEK, and ERK in skin tissue were detected by real-time quantitative polymerase chain reaction (RT-qPCR); and the protein expression of RAF, MEK, ERK, as well as phosphorylated MEK (p-MEK) and phosphorylated ERK (p-ERK), were analyzed by Western Blot. ResultsSkin tissue in the blank control group rats remained normal, whereas the model group exhibited neutrophil infiltration and haemorrhage with red blood cell rupture. In all drug intervention groups, neutrophil infiltration and haemorrhagic exudation reduced markedly, with LXTZF group demonstrating the most pronounced improvement. Compared with the blank control group, rats in the model group exhibited enhanced IgA fluorescence intensity in skin tissue, elevated serum levels of NE, MPO, TNF-α and VCAM-1, increased mRNA expression of RAF, MEK, ERK1 and ERK2, as well as heightened RAF protein levels and p-MEK/MEK and p-ERK/ERK ratios (P<0.05). Compared with the model group, the drug intervention groups exhibited reduced IgA fluorescence intensity in skin tissue, along with decreased serum levels of NE, MPO, TNF-α, and VCAM-1 (P<0.05). In LXTZF group and RAF inhibition groups, reduced mRNA expression of RAF, MEK, ERK1, and ERK2 was observed in rat skin tissue, alongside decreased RAF protein levels and reduced p-MEK/MEK and p-ERK/ERK ratios (P<0.05). Compared with LXTZF + RAF agonist group, the compound glycyrrhizin group, LXTZF group, and RAF inhibitior group exhibited reduced IgA fluorescence intensity in skin tissue, decreased serum NE, MPO, TNF-α, and VCAM-1 levels, and decreased MEK mRNA expression and p-MEK/MEK ratio (P<0.05). ConclusionThe potential mechanism by which LXTZF treats Henoch-Schönlein purpura with blood heat syndrome may involve blocking the RAF/MEK/ERK signaling pathway in skin tissue, and suppressing excessive formation of NETs, thereby reducing IgA deposition in dermal microvessels and attenuating systemic inflammatory responses.
2.Research progress of anti-radiation natural products
Yiqing YAO ; Jiahao FANG ; Huilin MA ; Xuan WANG ; Diya LYU
Journal of Pharmaceutical Practice and Service 2022;40(5):427-432
With the rapid developments of science and technology, the diagnosis technology based on nuclear physics and radiotherapy technology are widely used in medicine, but radiation at the same time could have different levels of damage to human body. Therefore, it is of great significance to research and develop drugs that can prevent and treat radiation damage. The research progresses and prospects of radiation-resistant natural products, such as polysaccharides, flavonoids, phenolic acids, saponins and so on, were reviewed in this paper in order to provide a reference for further developments.
3.Change and significance of optic nerve sheath pulsatile dynamics in normal-tension glaucoma
Ruiqi PANG ; Hanruo LIU ; Teng MA ; Wenyuan SHI ; Kai CAO ; Diya YANG ; Qiang ZHU ; Ningli WANG
Chinese Journal of Experimental Ophthalmology 2020;38(5):427-432
Objective:To analyze the value and difference of the optic nerve sheath pulse dynamic deformation index (DI) in normal-tension glaucoma (NTG) and high-pressure primary open angle glaucoma (POAG).Methods:A cross-sectional study was conducted to collect clinical data at the Eye Center of Beijing Tongren Hospital from June 2016 to March 2017, 32 patients with NTG and 35 patients with high-pressure POAG were sampled.For all subjects, their basic information, body mass index (BMI), mean arterial blood pressure (MAP), 24 hours intraocular pressure, and ophthalmologic examinations required for diagnosis were recorded.All subjects underwent transorbital ultrasonography and for each 15 seconds of consecutive ultrasound images were taken.The dynamic post-processing technique was used to calculate the DI.The difference in DI between the two groups and the correlation of DI with other variables were analyzed.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital.Written informed consent was obtained from all subjects prior to their entering the study cohort and receiving the transorbital ultrasound examination.Results:The median level of DI in the NTG group was 0.51 (0.48, 0.54), which was higher than that in the high-pressure POAG group (0.23[0.20, 0.25]), exhibiting a significant difference ( Z=-7.01, P<0.01). The mean BMI in the NTG group was lower than that in the high-pressure POAG group([21.29±4.64]kg/m 2vs. [23.53±3.40]kg/m 2), the mean MAP in the NTG group was lower than that in the high-pressure POAG group([91.44±14.30]mmHg vs. [104.05±13.96] mmHg), the differences between the two groups were statistically significant ( t=-2.30, P<0.05; t=-3.65, P<0.01). There was no statistical association between the two groups of DI and age, MAP, BMI, mean intraocular pressure and maximum intraocular pressure (all at P>0.05). Conclusions:The DI of the NTG patient is higher than that of the POAG patient, which indicates that the optic nerve sheath subarachnoid pressure and optic nerve sheath stiffness in NTG patients are lower than those in POAG patients.Therefore, the DI is a potential indicator of non-invasive intracranial pressure and translaminar cribrosa pressure difference detection in ophthalmology.

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