1.Identification of Cuproptosis-related Biomarkers in Alzheimer's Disease Based on Bioinformatics and Machine Learning and Clinical Validation and Prediction of Potential Traditional Chinese Medicine
Guofang YU ; Chenling ZHAO ; Liwei TIAN ; Wenming YANG ; Ting DONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):160-167
ObjectiveThis study aims to identify cuproptosis-related gene biomarkers in Alzheimer's disease(AD) using bioinformatics and machine learning methods, validate them at the clinical specimen level, and predict potential traditional Chinese medicine(TCM). MethodsDifferentially expressed genes in the AD group and normal group were obtained using the Gene Expression Omnibus (GEO) database, and intersections were taken with reported cuproptosis-related genes to obtain differentially expressed cuproptosis-related genes. Machine learning methods were applied to identify core differential genes of cuproptosis in AD. Peripheral blood's single nucleated cells from clinical AD patients were collected, and the relative gene expression was clinically verified by real-time polymerase chain reaction(Real-time PCR). Potential TCM regulating cuproptosis for AD were predicted by COREMINE database. ResultsA total of 12 cuproptosis-related genes were obtained, mainly involved in pathways of tricarboxylic acid cycle, 2-oxocarboxylic acid metabolism, and carbon metabolism. Five core cuproptosis-related genes, dihydrolipoamide dehydrogenase (DLD), glutaminase (GLS), pyruvate dehydrogenase E1 subunit beta (PDHB), full name nuclear factor (erythroid-derived 2)-related factor 2 (NFE2L2), and dihydrolipoamide branched-chain transacylase E2 (DBT) were finally screened using four machine methods. Thirty cases each of normal and AD patients were collected clinically. Compared with those in the normal group, minimum mental state examination (MMSE) and Montreal cognitive assessment (MoCA) were significantly decreased in the AD group (P<0.01), Homocysteine(Hcy), interleukin(IL)-6, C-reactive protein(CRP) , and β amyloid protein(Aβ) indexes were significantly increased (P<0.01), and malondialdehyde(MDA) indexes were decreased (P<0.05). Superoxide dismutase(SOD) levels were significantly decreased (P<0.01). The mRNA relative expressions of NFE2L2 and DBT were up-regulated (P<0.05), and those of DLD, GLS, and PDHB were significantly down-regulated (P<0.01). The TCM regulating cuproptosis-related genes for the treatment of AD were mainly based on the four Qi such as warmth, calmness, and cold, and the five flavors including bitterness, sweetness, and pungency, and it was attributed to the meridians of the liver, spleen, stomach, and kidney, with the efficacy of tonifying Qi, activating blood, eliminating phlegm, and resoling dampness. ConclusionDLD, GLS, NFE2L2, PDHB, and DBT can be used as novel diagnostic molecular markers for AD cuproptosis-related genes, and the corresponding potential therapeutic TCM can provide new ideas for the treatment of AD by TCM.
2.Gandou Fumu Decoction improves liver steatosis by inhibiting hepatocyte ferroptosis in mice with Wilson's disease through the GPX4/ACSL4/ALOX15 signaling pathway.
Mengying ZHANG ; Chenling ZHAO ; Liwei TIAN ; Guofang YU ; Wenming YANG ; Ting DONG
Journal of Southern Medical University 2025;45(7):1471-1478
OBJECTIVES:
To explore the mechanism of Gandou Fumu Decoction (GDFMD) for improving Wilson's disease (WD) in tx-J mice.
METHODS:
With 6 syngeneic wild-type mice as the control group, 30 tx-J mice were randomized into WD model group, low-, medium- and high-dose GDFMD treatment groups, and Fer-1 treatment group. Saline (in control and model groups) and GDFMD (3.48, 6.96 or 13.92 g/kg) were administered by gavage, and Fer-1 was injected intraperitoneally once daily for 14 days. Oil red and HE staining were used to observe lipid deposition and pathological conditions in the liver tissue; ALT, AST, albumin, AKP levels were determined to assess liver function of the mice. Western blotting and RT-qPCR were used to detect hepatic protein and mRNA expressions of GPX4, ACSL4, ALOX15, FTH1, FLT, TFR1, FAS, SCD1, and ACOX1, and Fe2+, MDA, ROS, SOD, GSH and 4-HNE levels were analyzed to assess oxidative stress.
RESULTS:
The mouse models of WD showed obvious fatty degeneration in the liver tissue significantly increased serum levels of ALT, AST and AKP, decreased albumin level, increased Fe2+, MDA, ROS, 4-HNE levels, decreased SOD and GSH levels (P<0.05), lowered protein expressions of ACOX1, GPX4, FTH1, FLT, FAS, and SCD1, and increased protein contents of TFR1, ACSL4 and ALOX15 in the liver. Treatment with GDFMD and Fer-1 improved liver histopathology and liver function of the mouse models, decreased the levels of Fe2+, MDA and ROS, increased SOD and GSH levels, and reversed the changes in hepatic protein expressions.
CONCLUSIONS
GDFMD improves liver steatosis in mouse models of WD possibly by inhibiting hepatocyte ferroptosis through the GPX4/ACSL4/ALOX15 signaling pathway.
Animals
;
Ferroptosis/drug effects*
;
Mice
;
Signal Transduction/drug effects*
;
Drugs, Chinese Herbal/therapeutic use*
;
Hepatolenticular Degeneration/drug therapy*
;
Hepatocytes/metabolism*
;
Phospholipid Hydroperoxide Glutathione Peroxidase
;
Fatty Liver/metabolism*
;
Arachidonate 15-Lipoxygenase/metabolism*
;
Coenzyme A Ligases/metabolism*
;
Liver/metabolism*
;
Male
3.Expert consensus on the treatment of oral and maxillofacial space infections
Yunpeng LI ; Bing SHI ; Junrui ZHANG ; Yanpu LIU ; Guofang SHEN ; Chuanbin GUO ; Chi YANG ; Zubing LI ; Zhiguang ZHANG ; Huiming WANG ; Li LU ; Kaijin HU ; Ping JI ; Biao XU ; Wei ZHANG ; Jingming LIU ; Zhongcheng GONG ; Zhanping REN ; Lei TIAN ; Hua YUAN ; Hui ZHANG ; Jie MA ; Liang KONG
Chinese Journal of Stomatology 2021;56(2):136-144
Oral and maxillofacial space infections (OMSI) are common diseases of the facial region involving fascial spaces. Recently, OMSI shows trends of multi drug-resistance, severe symptoms, and increased mortality. OMSI treatment principles need to be updated to improve the cure rate. Based on the clinical experiences of Chinese experts and with the incorporation of international counterparts′ expertise, the principles of preoperative checklist, interpretation of examination results, empirical medication principles, surgical treatment principles, postoperative drainage principles, prevention strategies of wisdom teeth pericoronitis-related OMSI, blood glucose management, physiotherapy principles, Ludwig′s angina treatment and perioperative care were systematically summarized and an expert consensus on the diagnosis and treatment of OMSI was reached. The consensus aims to provide criteria for the diagnosis and treatment of OMSI in China so as to improve the level of OMSI treatment.
4.Correlation between hyperglycemia at admission and outcome after intravenous thrombolysis in patients with acute ischemic stroke
Lei WANG ; Guofang CHEN ; Shengkui ZHOU ; Lei PING ; Weiwei LIU ; Yongfang TIAN ; Leijing LIU ; Hui XU ; Zaili LI ; Chen WANG
International Journal of Cerebrovascular Diseases 2018;26(10):726-730
Objective To investigate the effect of blood glucose levels at admission on the outcomes and hemorrhagic transformation in patients with acute ischemic stroke (AIS) after intravenous thrombolysis. Methods From December 2013 to January 2017, patients with AIS treated with intravenous thrombolysis at the Department of Neurology, Xuzhou Central Hospital were enrolled retrospectively. According to the blood glucose levels on admission, they were divided into non-hyperglycemic group ( ≤8 mmol/L ) and hyperglycemic group ( > 8 mmol/L). The functional outcome was assessed with the modified Rankin Scale score at 90 d after onset, and 0-2 was defined as good outcome and > 2 was defined as poor outcome. From 24 h to 7 d after treatment, CT scan was performed again to determine whether there was intracranial hemorrhage or not. Multivariate logistic regression analysis was used to identify the independent influencing factors of outcomes after intravenous thrombolysis. Results A total of 323 patients with AIS were enrolled, including 237 (73. 4%) in the non-hyperglycemic group and 86 (26. 6%) in the hyperglycemic group; 238 (73. 7%) in the good outcome group, and 85 (26. 3%) in the poor outcome group; 25 (7. 7%) in the hemorrhagic transformation group, and 298 (92. 3%) in the non-hemorrhagic transformation group. Univariate analysis showed that there were significant differences in the proportions of patients with ischemic heart disease, atrial fibrillation, past history of stroke or TIA, as well as age, baseline National Institutes of Health Stroke Scale (NIHSS) score, and baseline blood glucose between the poor outcome group and the good outcome group (all P < 0. 05). There were significant differences in the proportion of hypertensive patients and baseline NIHSS score between the hemorrhagic transformation group and the non- hemorrhagic transformation group ( all P < 0. 05 ). Multivariate logistic regression analysis showed that hyperglycemia at admission (odds ratio [OR] 2. 239, 95% confidence interval [CI] 1. 210-4. 143; P = 0. 010)and baseline NIHSS score (OR 3. 528, 95% CI 2. 451-5. 078; P < 0. 001) were the independent influencing factors of poor outcome; hypertension (OR 0. 410, 95% CI 0. 173-0. 972; P = 0. 043 ) and baseline NIHSS score (OR 2. 283, 95% CI 1. 382-3. 772, P = 0. 001 ) were the independent influencing factors of hemorrhagic transformation. Conclusion Hyperglycemia at admission was an independent risk factor for poor outcome in patients with AIS after intravenous thrombolytic therapy, but it was not associated with the risk of hemorrhagic transformation.
5.The clinical research about early diagnosis of small cell lung cancer through mad2 de-tection
Wu YANG ; Liming TAN ; Juanjuan CHEN ; Hua LI ; Houqun YIN ; Yongqin JIANG ; Qiong WU ; Guofang YU ; Yongjian TIAN ; Jianlin YU ; Tingting ZENG ; Lingxian YAN ; Chuan LIU
Chinese Journal of Clinical Oncology 2018;45(2):67-71
Objective:To explore combined detection of mad2 with anti-nuclear mitotic spindle apparatus antibody(MSA)and anti-centromere antibody(ACA)and their clinical value for the diagnosis of small cell lung cancer(SCLC).Methods:One hundred and twen-ty SCLC patients,110 non-small cell lung cancer(NSCLC)patients,and 115 pulmonary nodule(PN)patients were enrolled in this study. The expression of mad2 was analyzed by qt-PCR.MSA and ACA were detected by indirect immunofluorescence(IIF)staining.Results:mad2 was overexpressed in SCLC and NSCLC samples(P<0.05).There were significant differences between the results obtained for SCLC and NSCLC samples by qt-PCR(P<0.05).AUC in ROC curve for mad2 expression was 0.799 with an intermediate diagnostic value. In the correlative analysis,the odds ratio of MSA and ACA was 6.94 and 5.60,respectively.In the correlation analysis,Kappa value of mad2 with MSA was 0.49,and Kappa value of mad2 with ACA was 0.42.In the parallel analysis,the sensitivity and specificity was 83.31% and 79.34%,respectively,while the Youden Index was 0.62.Moreover,in the serial analysis,the sensitivity and specificity was 65.32% and 93.35%,respectively,and the Youden Index was 0.59.Conclusions:In comparison with the NSCLC and PN samples,mad2 was overexpressed in SCLC samples.Therefore,mad2 ought to play a critical role in the pathology of SCLC.The combined expression of mad2 with MSA and ACA may contribute to enhancing the sensitivity and specificity of detection;this expression may allow early diag-nosis and clinical diagnosis of SLCC and may be a promising treatment for SCLC.
6. Expression of Fermintin family homologous protein 2 in non-small cell lung cancer and its clinical significance
Weihua GUO ; Junjie BIAN ; Guofang TIAN ; Zhenxuan LYU ; Yongxian GUI ; Li YE
Chinese Journal of Pathology 2018;47(10):780-783
Objective:
To investigate the expression of Fermintin family homologous protein 2 (FERMT2) in non-small cell lung cancer and its clinical significance.
Methods:
Seventy-two patients with non-small cell lung cancer were collected at Xinxiang Central Hospital, Henan Province, from January 2015 to January 2017.There were 48 male and 24 female patients, the age ranged from 37 to 78 years (mean 58 years). The expression of FERMT2 in tumor samples and para-cancerous tissues were detected by immunohistochemistry. Protein and mRNA expression of FERMT2 were detected by Western blot and real-time fluorescence quantitative PCR, respectively. Western blot method was also used to detect integrin-related protein expression, including integrin beta 1 (CD29), vascular cell adhesion molecule (VCAM1), and mobile related protein-1 (MRP1).
Results:
Immunohistochemistry showed that the positive rates of FERMT2 expression were 81.9%(59/72)in carcinoma tissue and 15.4%(11/72) in para-cancerous tissues, and the difference was statistically significant (
7.Determination of three organic acids in Schisandrae Chinensis Fructus by HPLC.
Li LI ; Yongqing XIAO ; Dingrong YU ; Yinlian MA ; Wenqian HUANG ; Guofang TIAN ; Liang CHEN
China Journal of Chinese Materia Medica 2011;36(23):3286-3289
OBJECTIVETo establish an HPLC method for determination of three organic acids in Schisandrae Chinensis Fructus.
METHODThe separation was performed on a C18 column with acetonitrile-15 mmol x L(-1) KH2 PO4 (1:99) and methanol-0.5% acetic glacial as the mobile phrase to determine the content of kinic acid, citric acid, and protocatechuic acid.
RESULTThree kinds of organic acid can be detective in different samples, and the average content of the three organic acids were about 18%, among which the citric acid was the highest (18%).
CONCLUSIONSince organic acids is an important parts of the material basis in Schisandrae Chinensis Fructus, it is necessary to carry out the pharmacological research associated with the function of Schisandrae Chinensis Fructus. Further, it will provide scientific basis for the drug relevance research between material basis and efficiency, as well as the foundation for the relevance research on the properties and Five Tastes of traditional Chinese medicine.
Biological Products ; analysis ; Chromatography, High Pressure Liquid ; Citric Acid ; analysis ; Drugs, Chinese Herbal ; analysis ; chemistry ; Fruit ; chemistry ; Hydroxybenzoates ; analysis ; Schisandra ; chemistry
8.Determination of two stilbene glycoside in five processed products of Rheum palamatum.
Li LI ; Cun ZHANG ; Yongqing XIAO ; Dongdong CHEN ; Guofang TIAN ; Yun WANG
China Journal of Chinese Materia Medica 2010;35(11):1415-1417
OBJECTIVETo compare of the contents of two stilbene glycoside in five processed products of Rheum palamatum.
METHODThe contents of trans-3, 5, 4'-trihydroxystilbene-4'-O-beta-D-glucopyranoside (a) and trans-3, 5, 4'-trihydroxystilbene-4'-Obeta-D-(6"-O-galloyl)-glucopyranoside (b) were determined by HPLC analysis at 35 degrees C with methanol-1% acetic acid as mobile phase, the wavelengths were set at 280, 300 nm, the flow rate was 1.0 mL x min(-1).
RESULTThe two components could be detected in five processed products, and their contents were more close in the no-parched pieces, the vinegar roasts pieces and the wine roast pieces. However, the contents reduced significantly in other two kinds of pieces which were lower than 80 percent of no-parched pieces.
CONCLUSIONHigh temperature may result in a significant reduction on glycoside in the pieces of rhubarb, and we have received similar results from determination of other glycoside compounds. Further analysis and comparison with the content of their corresponding aglycones, can provide a scientific basis to explain the variation of the material basis in the processed products of rhubarb.
Glycosides ; analysis ; Plant Extracts ; analysis ; Rheum ; chemistry ; Stilbenes ; analysis
9.Glycosides of roasted seeds of Cassia obtusifolia.
Li LI ; Cun ZHANG ; Yongqing XIAO ; Wen LI ; Xiaojie YIN ; Dongdong CHEN ; Guofang TIAN ; Yun WANG
China Journal of Chinese Materia Medica 2010;35(12):1566-1568
OBJECTIVETo study the chemical constituents of the roasted seeds of Cassia obtusifolia, and to illuminate the change of its effective components before and after being roasted.
METHODThe compounds were isolated and repeatedly purified by macroporous resin, silica gel column chromatography. Their structures were elucidated by physical and chemical properties and NMR data.
RESULTThree components were obtained from ethanol extract, and the structures were identified as nor-rubrofusarin-6-O-beta-D-(6'-O-acetyl) -glucopyranoside (1), 1-desmethyl- aurantio-obtusin-2-O-beta-D-glucopyranoside (2), obtusin (3).
CONCLUSIONCompounds 1 and 2 were isolated from the roasted seeds of C. obtusifolia for the first time, and compound 1 was a new compound.
Cassia ; chemistry ; Glycosides ; analysis ; isolation & purification ; Hot Temperature ; Plant Extracts ; analysis ; isolation & purification ; Seeds ; chemistry
10.Variety regulation of aloe-emodin-3-CH2-O-beta-D-glucopyranoside and emodin-8-O-beta-D-glucopyranoside in five processed pieces from Rheum palmatum.
Guofang TIAN ; Cun ZHANG ; Li LI ; Yongqing XIAO ; Dongdong CHEN ; Yun WANG
China Journal of Chinese Materia Medica 2010;35(18):2437-2439
OBJECTIVETo compare the contents of two another anthraquinone-O-glucosides in five different processed products from Rheum palmatum.
METHODAloe-emodin-3-CH2-O-beta-D-glucopyranoside and emodin-8-O-beta-D-glucopyranoside were determined simultaneously by HPLC on an Agilent TC-C18 (2) column at 35 degrees C with the tetrahydrofuran-1% glacial acetic acid (25:75). The detection wavelength was set at 410 nm and the flow rate was 0.9 mL x min(-1).
RESULTThe calibration curves for two components were linear within the range of 0.0090-0.2704 microg (r = 0.9996), 0.0396-1.188 microg (r = 0.9996), and the average recoveries were 97.85%, 97.19% respectively.
CONCLUSIONThe results showed the remarkable variation regulations among the five different processed pieces. The contents of the crude pieces and the pieces roasted vinegar were almost the same, while the pieces roasted with millet wine were a little higher than that of the crude pieces, and the contents at the two components in prepared pieces and charring pieces evidently reduced.
Chemistry, Pharmaceutical ; methods ; Drugs, Chinese Herbal ; analysis ; Glucosides ; analysis ; Rheum ; chemistry

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