1.Ferroptosis as a double-edged sword in liver fibrosis
Yiyun AO ; Anqi WU ; Zhenggen WANG
Journal of Clinical Hepatology 2026;42(4):965-971
Ferroptosis exhibits a clear “double-edged sword” effect in liver fibrosis, with its impact strictly dependent on the type of target cells. In hepatocytes, ferroptosis induced by specific signaling pathways (such as glutathione peroxidase 4 inhibition) is a key factor for driving hepatic injury and initiating fibrogenesis, and dying hepatocytes activate hepatic stellate cells by releasing damage-associated molecules; on the contrary, in activated hepatic stellate cells, ferroptosis becomes a therapeutic target for promoting liver fibrosis regression, and selective elimination can be achieved by disrupting their distinctive antioxidant defense mechanisms. Moreover, ferroptosis modulates the dynamic balance of the fibrotic liver microenvironment by regulating macrophage polarization and intercellular communication. Based on the above mechanisms, targeting ferroptosis has emerged as a promising strategy for precise treatment. This article summarizes related research advances and discusses the major challenges and future directions for clinical translation.
2.Detoxification Strategies of Triptolide: A Review
Wenchen WANG ; Ming CHEN ; Shuangjie WU ; Zhenggen LIAO ; Wei DONG ; Xinli LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):278-287
Tripterygium wilfordii is a traditional Chinese medicinal herb belonging to the genus Tripterygium in the Celastraceae family, which has the effects of clearing heat and detoxifying, dispelling wind and dampness, and invigorating blood circulation to relieve pain, and is used to treat diseases such as rheumatoid arthritis, glomerulonephritis, nephrotic syndrome, lupus erythematosus, scabies, and stubborn tinea. Its chemical composition is diverse. Among them, triptolide(TP) is one of the main active and toxic components of T. wilfordii. It has significant biological activities such as anti-inflammation, anti-tumor, and immunosuppression. However, it causes serious adverse reactions such as liver and kidney function damage and reproductive system disorders. At the same time, TP has poor water solubility and low bioavailability, and the enhancement of bioavailability by increasing the dosage undoubtedly improves the exposure of the drug in non-target organs, leading to the occurrence of adverse reactions, and these largely limit the clinical application of TP. Based on this, this article extracted relevant data from the Web of Science, PubMed, and China National Knowledge Infrastructure(CNKI) databases, summarized the research on the adverse reactions of TP in recent years, and reviewed the progress of toxicity reduction research from the perspectives of structural modification, novel drug delivery systems, and compatibility. Structural modification can precisely alter the chemical structure of TP, reduce the activity of its toxic groups, and retain its biological activity while fundamentally reducing the occurrence of adverse reactions. New drug delivery systems can achieve targeted delivery of TP, increase its concentration in target organs, and reduce its exposure in non-target organs, thereby enhancing therapeutic efficacy and reducing adverse effects. In addition, the combination of TP with Chinese medicine compound, single-flavored Chinese medicine or monomer can reduce the adverse effects of TP and enhance the efficacy to different degrees, which is of clinical value. This paper systematically explains attenuation research from the above three perspectives, aiming to provide a theoretical basis for the full utilization of biological activity and drug development of TP.
3.Association of dominant eye and non-dominant eye with severity of chronic primary angle-closure glaucoma
Chukai HUANG ; Qiang WANG ; Mingzhi ZHANG ; Lifang LIU ; Zhenggen WU ; Di MA
Chinese Journal of Experimental Ophthalmology 2020;38(5):410-414
Objective:To investigate the association of ocular dominance with the severity of chronic primary angle-closure glaucoma (PACG).Methods:Ocular dominance was assessed via the " hole in card" method.The anatomical symmetry (including anterior chamber depth, lens thickness and axial length) in both eyes was analyzed via A scan ultrasound.The severely glaucomatous eye was determined by the mean defect of visual field.The association of ocular dominance with the severity of chronic PACG was then analyzed.This study followed the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong.Written informed consent was obtained from all subjects prior to their entering the study cohort.Results:Visual acuity (LogMAR) was 0.39±0.24 in the dominant eye group, and 0.43±0.29 in the non-dominant eye group.Anterior chamber depth was (2.53±0.26)mm in the dominant eye group, and (2.54±0.29)mm in the non-dominant eye group.Lens thickness was (4.96±0.31)mm in the dominant eye group, and (4.92±0.33)mm in the non-dominant eye group.Axial length was (22.58±0.61)mm in the dominant eye group, and (22.73±1.11)mm in the non-dominant eye group.No significant difference was found in visual acuity, anterior chamber depth, lens thickness or axial length between the dominant and non-dominant eye groups ( t=-1.643, -0.797, 1.867, -1.345; all at P>0.05). The vertical cup-disc ratio of the dominant eye group was lower than that of the non-dominant eye group (0.55 [0.40, 0.80] vs. 0.80 [0.63, 0.90]). The mean defect in the visual field of the dominant eye group was lower than that in the non-dominant eye group (-6.54 [-16.70, -3.85]dB vs.-18.77 [-28.19, -8.55]dB), and the intraocular pressure in the dominant eye group was lower than that in the non-dominant eye group (21.00 [17.00, 27.75]mmHg vs. 24.50 [19.00, 36.25]mmHg) (1 mmHg=0.133 kPa). Significant differences were found in mean defect, vertical cup-disc ratio and intraocular pressure between the two groups ( Z=-3.781, -3.528, -2.126; all at P<0.05). The ratio of the severely glaucomatous eye being the non-dominant eye was 84.09%, which was much higher than that of the severely glaucomatous eye being the dominant eye (15.91%). The non-dominant eye was related to the severity of chronic PACG ( χ2=40.909, P<0.001, Pearson contingency coefficient r=0.563). Conclusions:The non-dominant eye is associated with the severity of chronic PACG.
4.Effect of ferulic acid on learning and memory impairments of vascular dementia rats and its mechanism of action.
Yun LUO ; Haiping ZHAO ; Jing ZHANG ; Jie WANG ; Wuliang YANG ; Ming YANG ; Zhenggen LIAO
Acta Pharmaceutica Sinica 2012;47(2):256-60
This study is to investigate the effect of ferulic acid on learning and memory impairments of vascular dementia (VD) rats and its mechanism of action. VD rats model was replicated by permanent bilateral common carotid artery occlusion (2VO). The learning and memory capability of VD rats was evaluated by Morris water maze. The activity of acetylcholinesterase (AChE) and superoxide dismutase (SOD) and the content of glutamic acid (Glu) and malondialdehyde (MDA) in hippocampus of VD rats' brain were determined, separately. The results showed that ferulic acid could alleviate learning and memory deficits of VD rats significantly. Ferulic acid was found to inhibit the activity of AChE and increased the activity of SOD in rat hippocampus. In addition, ferulic acid could also decrease the content of Glu and MDA in rat hippocampus. These results suggested that ferulic acid could alleviate VD rats' learning and memory deficits, which might be due to antioxidation, the improvement of cholinergic system in brain, or the inhibitory of nerve injury by excitatory amino acids.
5.The enhancing effect of Angelica dahurica extracts on absorption of baicalin--the active composition of Scutellaria.
Jingyun ZHU ; Xinli LIANG ; Guangfa WANG ; Guowei ZHAO ; Zhenggen LIAO ; Yunchao CAO ; Xulong CHEN ; Ming YANG
Acta Pharmaceutica Sinica 2011;46(2):232-7
To explore the mechanism of the absorption enhancement of Angelica dahurica extract (Ade), the absorption mechanism of baicalin in the Scutcllaria water extraction as well as the effect of Angelica dahurica extract on absorption of baicalin were investigated. In order to determine the main absorption site, everted intestinal sac model was used to study the effect of Angelica dahurica extract on the absorption of baicalin at duodenum, jejunum, ileum and colon. In situ single pass intestinal perfusion model was performed to study the absorption of various concentrations of baicalin and the effect of Angelica dahurica extract on the absorption of baicalin at the main absorption site. To authenticate the consequence of perfusion by getting the blood from the hepatic portal vein and determine the concentration of the baicalin in the blood. The result showed that baicalin could be absorbed at all of the four intestinal segments with increasing absorption amount per unit as follows: ileum > colon > jejunum > duodenum. The absorption ofbaicalin in the duodenum significantly increased with Angelica dahurica extract, thus, duodenum was chosen to be the studying site. Apparent permeability values (Papp) and absorption rate constant (Ka) of baicalin in the duodenum increased gradually with higher concentrations. When the concentration of baicalin rises to a certain degree, the absorption increase had a saturable process, the absorption of baicalin may be an active transportation. Baicalin may be not a substrate of P-gp as verapamil which had not significantly affected the Papp and Ka of baicalin. The absorption of baicalin in the duodenum significantly increased (P < 0.01) in the two models with Angelica dahurica extract and the concentration of baicalin in the blood from the hepatic portal vein showed that the Angelica dahurica extract can increase the absorption of baicalin.
6.The comparative study of perfusion MR imaging in primary central nervous system lymphomas and high grade astrocytomas
Biao HUANG ; Changhong LIANG ; Hongjun LIU ; Guangyi WANG ; Zhenggen ZHOU
Chinese Journal of Radiology 2008;(3):276-280
Objective To investigate the value of perfusion MR imaging in differential diagnosis between primary central nervous system lymphomas(PCNSL)and high grade astrocytomas.Methods Twelve patients with PCNSL and 23 patients with high grade astrocytomas were preoperatively examined using a 1.5T MR unit.Routine MR sequences were performed followed by dynamic susceptibility contrastenhanced MR perfusion imaging.The perfusion color images and the time-signal intensity curves of the two tumor groups were compared.The relative cerebral blood volume(rCBV)within the tumor parenchyma was measured and the data were analyzed with unpaired Student's t-test.Results The rCBVs within the tumor parenchyma of the PCNSL and high grade astrocytomas were 1.78±0.5 1 and 3.87±0.87 respectively.The rCBV in the PCNSL was significantly lower than that of the high grade astrocytoma(P<0.05).When the time-signal intensity curves were compared,the PCNSL showed a trend towards the baseline after the first pass and the curves even overshot above the baseline in 7 out of 12 cases,whereas the high grade astrocytoma showed a trend to be close to the baseline but couldn't return to the baseline completely.Conclusion The MR perfusion imaging can be very useful in distinguishing the PCNSL from high grade astrocytomas.
7.Proteomics research for early diagnosis of acute renal allograft rejection
Xiongfei JIA ; Weifeng HE ; Gaoxing LUO ; Chengjun GAN ; Zhenggen HUANG ; Shunzong YUAN ; Xiaojuan WANG ; Xu PENG ; Wenguang CHENG ; Jianglin TAN ; Jie HU ; Jun WU
Journal of Third Military Medical University 2003;0(24):-
Objective Non-invasive detection is the focus of intense research in diagnosis of acute renal allograft rejection currently. Urine protein is considered the cue to reflect the pathological changes in kidney disease. In this study, we explored the urine markers for early acute renal allograft rejection. Methods The urine protein of two patients with acute renal allograft rejection were examined by 2D gel electrophoresis and bioinformatics. We adopted pH 4-7 ready strip IPG and stained the gel with Sypro-Ruby. The digitized 2D maps of urine protein were quantitatively analyzed using 2D-analysis software packages. By analyzing the differential expressions of proteome between different time points (1, 2, 3 days before acute rejection and 7, 14, 21 days after acute rejection), 30 protein spots were selected and analyzed by MALDI-TOF-MS/MS. Results We obtained 2D gel electrophoresis maps of urine protein of the patients with acute renal allograft rejection, which are of good reproducibility and resolution. Sixteen protein spots were identified, resulting in thirteen corresponding proteins. Out of these proteins, we screened three proteins (alpha-1-antichymotrypsin, tumor rejection antigen gp96, Zn-Alpha-2-Glycoprotein) closely related to acute rejection. Conclusion The urine protein spots on 2D gel electrophoresis maps for the patients with acute renal allograft rejection were of obvious difference when detected at different time points of acute rejection. Alpha-1-antichymotrypsin, tumor rejection antigen gp96 and Zn-Alpha-2-Glycoprotein might be the candidate protein markers to diagnose acute renal allograft rejection after renal transplantation.

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