1.Effect and Mechanism of Angelicae Sinensis Radix-Polygonati Rhizoma Herb Pair in Treatment of Simple Obesity
Wenjing LI ; Zhongyu WANG ; Yongxin HUANG ; Jingjing XU ; Ying DING ; You WU ; Zhiwei QI ; Ruifeng YANG ; Xiaotong YANG ; Lili WU ; Lingling QIN ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):70-79
ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma (ASR-PR) herb pair in the treatment of simple obesity through network pharmacology and molecular docking, and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets related to simple obesity were identified by retrieving the GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGKB), and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction (PPI) network, and topological analysis was conducted to identify core genes. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR (2.06 g·kg-1), PR (2.06 g·kg-1), or ASR-PR (4.11 g·kg-1) for 10 weeks, while the model group received an equal volume of purified water by gavage. After the administration period, the mice were sacrificed to measure body fat weight and serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Hematoxylin-eosin (HE) staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression levels of epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3) in liver tissue were detected by real-time quantitative polymerase chain reaction (Real-time PCR). ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 (Siberian glycoside A_qt), MOL003889 (methyl protodioscin_qt), MOL009766 (resveratrol), MOL006331 (4′,5-dihydroxyflavone), and MOL004941 (baicalin), thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group, the model group had significantly increased body weight, body fat weight, and serum levels of TG, TC, TNF-α, IL-6, and leptin (P<0.01). EGFR mRNA expression was significantly elevated (P<0.05), while STAT3 mRNA expression was significantly decreased (P<0.01). Histological analysis revealed disordered hepatic architecture in the model group, with pronounced lipid vacuoles, cytoplasmic loosening, lipid accumulation, and steatosis. Adipocytes in white adipose tissue (WAT) and brown adipose tissue (BAT) of the model group exhibited markedly increased diameters, reduced cell counts per unit area, and irregular morphology. Compared with the model group, the ASR-PR group significantly reduced body weight, body fat weight, serum TC, IL-6, TNF-α, leptin levels, and EGFR mRNA expression (P<0.01). TG levels were also significantly decreased (P<0.05), while STAT3 mRNA expression was significantly increased (P<0.01). Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased, and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components, modulate the PI3K/Akt and JAK/STAT signaling pathways, repair damaged liver and adipose tissues, and thereby alleviate the progression of obesity in mice.
2.Effect and Mechanism of Angelicae Sinensis Radix-Polygonati Rhizoma Herb Pair in Treatment of Simple Obesity
Wenjing LI ; Zhongyu WANG ; Yongxin HUANG ; Jingjing XU ; Ying DING ; You WU ; Zhiwei QI ; Ruifeng YANG ; Xiaotong YANG ; Lili WU ; Lingling QIN ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):70-79
ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma (ASR-PR) herb pair in the treatment of simple obesity through network pharmacology and molecular docking, and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets related to simple obesity were identified by retrieving the GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGKB), and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction (PPI) network, and topological analysis was conducted to identify core genes. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR (2.06 g·kg-1), PR (2.06 g·kg-1), or ASR-PR (4.11 g·kg-1) for 10 weeks, while the model group received an equal volume of purified water by gavage. After the administration period, the mice were sacrificed to measure body fat weight and serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Hematoxylin-eosin (HE) staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA), and the mRNA expression levels of epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3) in liver tissue were detected by real-time quantitative polymerase chain reaction (Real-time PCR). ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 (Siberian glycoside A_qt), MOL003889 (methyl protodioscin_qt), MOL009766 (resveratrol), MOL006331 (4′,5-dihydroxyflavone), and MOL004941 (baicalin), thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group, the model group had significantly increased body weight, body fat weight, and serum levels of TG, TC, TNF-α, IL-6, and leptin (P<0.01). EGFR mRNA expression was significantly elevated (P<0.05), while STAT3 mRNA expression was significantly decreased (P<0.01). Histological analysis revealed disordered hepatic architecture in the model group, with pronounced lipid vacuoles, cytoplasmic loosening, lipid accumulation, and steatosis. Adipocytes in white adipose tissue (WAT) and brown adipose tissue (BAT) of the model group exhibited markedly increased diameters, reduced cell counts per unit area, and irregular morphology. Compared with the model group, the ASR-PR group significantly reduced body weight, body fat weight, serum TC, IL-6, TNF-α, leptin levels, and EGFR mRNA expression (P<0.01). TG levels were also significantly decreased (P<0.05), while STAT3 mRNA expression was significantly increased (P<0.01). Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased, and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components, modulate the PI3K/Akt and JAK/STAT signaling pathways, repair damaged liver and adipose tissues, and thereby alleviate the progression of obesity in mice.
3.Protective effect of Shenfu injection against neonatal hypoxic-ischemic brain injury by inhibiting the ferroptosis
Xiaotong Zhang ; Meng Zhang ; Gang Li ; Yang Hu ; Yajing Xun ; Hui Ding ; Donglin Shen ; Ming Wu
Acta Universitatis Medicinalis Anhui 2025;60(1):31-40
Objective :
To observe the brain tissue injury during hypoxia-ischemia, as well as the pathological changes and the expression of ferroptosis-related factors after the use of Shenfu injection(SFI), and to explore the protective effect of SFI on hypoxic-ischemic brain injury(HIBD) by inhibiting ferroptosis.
Methods :
An animal model of HIBD in SD rats was constructed and intervened with SFI. Pathologic changes in brain tissue were observed by HE staining methods. Nissen staining was used to observe neuron survival. Glutathione Peroxidase 4(GPX4) and Divalent Metal Transporter 1(DMT1) expression were detected in brain tissue by Western blot, immunohistochemistry and immunofluorescence. Reduced Glutathione(GSH), Lactate Dehydrogenase(LDH), Malondialdehyde(MDA), Superoxide Dismutase(SOD) and tissue iron content were determined with the kits. BV-2 microglial cell line(BV2) cells were culturedin vitroand divided into control group(Ctrl group), oxygen-glucose deprivation group(OGD group), iron ferroptosis-inducing group(Erastin group), iron ferroptosis-inhibiting group(Fer-1 group), Shenfu injection group(SFI group), and Erastin+Shenfu injection group(Erastin+SFI group). 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA) reactive oxygen species(ROS) fluorescent probe was used to detect the ROS release level; Immunofluorescence was used to observe intracellular GPX4, DMT1 expression.
Results :
Compared with the Sham group, rats in the HIBD group showed significant neuronal cell damage in brain tissue, decreased GPX4 expression(P<0.01), increased DMT1 expression(P<0.01), decreased GSH and SOD levels(P<0.01), and increased LDH, MDA and tissue iron levels(P<0.05,P<0.05,P<0.01). In contrast, after the intervention of SFI, GPX4 expression was elevated(P<0.01), DMT1 expression decreased(P<0.01), GSH and SOD levels were elevated(P<0.01), and LDH, MDA, and tissue iron levels decreased(P<0.05,P<0.05,P<0.01). The cells experiments showed that compared with the Ctrl group, the OGD group had a significantly higher ROS content and a decrease in the expression of GPX4 fluorescence intensity, and an increase in the fluorescence intensity of DMT1(P<0.01), compared with the OGD group, the ROS content was reduced in the SFI group, while the expression of GPX4 was elevated and the expression of DMT1 was reduced(P<0.01).
Conclusion
Hippocampal and cortical regions are severely damaged after HIBD in neonatal rats, and their brain tissues show decreased expression of GPX4 and increased expression of DMT1. The above suggests that ferroptosis is involved in HIBD brain injury in neonatal rats. In contrast, Shenfu injection has a protective effect on HIBD experimental animal model and BV2 cell injury model by reducing iron aggregation and ROS production.
4.Effects of quality of life in patients with intermediate and advanced lung cancer undergoing different treatment regimens
WANG Yue ; HUANG Xiaotong ; ZHAO Fei ; Ding Lili ; WU Bingyi
Journal of Preventive Medicine 2025;37(3):272-275
Objective:
To examine the impacts of chemotherapy/radiotherapy, targeted therapy, and combined treatment on the quality of life in patients with intermediate and advanced lung cancer.
Methods:
The patients with intermediate and advanced lung cancer undergoing chemotherapy/radiotherapy, targeted therapy, and combined treatment for the first time were recruited from a tertiary hospital in Weifang City, Shandong Province, using a quota sampling method in September 2023. Basic information was collected using a general information questionnaire, and the quality of life was assessed using the Chinese version of Functional Assessment of Cancer Therapy-General. The investigation started on the 7th day of treatment, and the follow-ups were conducted at 3 and 6 months. The quality of life in patients with different treatment regimens and at different treatment time were compared using repeated measure analysis of variance.
Results:
There were 26 chemotherapy/radiotherapy patients, 32 targeted therapy patients, and 95 combination therapy patients. There were no significant differences in age, gender, place of residence, education level, self-rated economic status, medical insurance, pathological type and disease stage among the three treatment regimens (all P>0.05). The repeated measure analysis of variance showed an interaction effect between time and group among patients receiving the three treatment regimens (P<0.05). The quality of life scores of patients receiving combination therapy decreased with extended treatment time (all P<0.05). The quality of life scores of patients receiving targeted therapy at 3 and 6 months were lower than those treated for 7 days (both P<0.05). No significant differences were observed in quality of life scores among chemotherapy/radiotherapy patients with different treatment durations (all P>0.05). At 3 and 6 months, patients receiving combination therapy had lower quality of life scores compared to those receiving chemotherapy/radiotherapy or targeted therapy (all P<0.05).
Conclusion
The decline in quality of life for patients with intermediate and advanced lung cancer undergoing chemotherapy/radiotherapy and targeted therapy is less than that for patients receiving combined therapy.
5.Syndrome-Based Treatment Strategy for Hypertension Using the Method of Raising Yang and Promoting Descent
Xiaotong LYU ; Linping ZHU ; Jingshun YAN ; Zejun DU ; Xueying WU ; Zongpei XU
Journal of Traditional Chinese Medicine 2025;66(13):1345-1349
Guided by the theories of yin-yang and collateral disease, this paper identifies the dysregulation of yang qi ascent and descent as the core pathomechanism of hypertension. Based on clinical experience, a treatment approach centered on the method of raising yang and promoting descent was proposed. Clinically, three major syndrome types were identified. Firstly, deficiency of zong qi (ancestral qi) with blood stasis, obstruction of phlegm-turbidity and blood stasis, and hyperactivity of liver yang. Corresponding empirical formulation, Yizong Huoxue Decoction (益宗活血汤) was applied to tonify zong qi, invigorate blood, and raise yang. Secondly, Lizong Huoxue Decoction (理宗活血汤) was used to resolve phlegm, promote yang qi circulation, and regulate qi and blood. Thirdly, Qinggan Tongluo Decoction (清肝通络饮) was used to clear the liver, dredge collaterals, and subdue hyperactive yang. For special types such as non-dipper hypertension, time-specific syndrome differentiation and treatment can be applied based on a thorough understanding of the underlying pathomechanism, aiming to provide new insights into clinical diagnosis and treatment of hypertension.
6.Clinical Application and Mechanism of Buyang Huanwutang in Treatment of Chronic Heart Failure: A Review
Zejun DU ; Linping ZHU ; Xueying WU ; Xiaotong LYU ; Mei ZHAO ; Yuhong LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):286-294
Chronic heart failure (CHF) is a complex clinical syndrome that the cardiac output is not enough to meet the metabolic needs of the body, or depends on the increase of filling pressure to compensate. Its high morbidity and mortality pose a serious threat to human health, necessitating attention and active intervention. At present, western medicine treatment of CHF is mainly based on diuretics, intravenous vasodilators, intravenous positive inotropic drugs, etc., which, however, have problems such as long medication cycles, serious side effects, and limited applicable population. Recent studies have shown that traditional Chinese medicine can act in a multi-pathway, multi-component, and multi-target manner, showing unique advantages in the prevention and treatment of CHF. Buyang Huanwutang has the effects of tonifying Qi, activating blood, and dredging collaterals. Clinical and mechanism studies have confirmed that this prescription is effective in treating CHF and its syndromes. The clinical studies can be classified into two categories. Studies of the first category use simple modern medical diagnostic criteria as the inclusion criteria for CHF patients, which can improve the scientificity and objectivity. Studies of the second category uses modern medicine combined with traditional Chinese medicine disease diagnostic criteria for the screening of CHF patients, which helps to improve the accuracy of efficacy evaluation. However, there are problems such as the lack of unified research standards and the insufficiency of mechanism research. In addition, the available studies remain to be classified or summarized. This study systematically sorted out the clinical and mechanism studies of Buyang Huanwutang in the treatment of CHF in recent years to review the research status. In clinical treatment, Buyang Huanwutang can be used alone, or modified, or combined with other prescriptions or Western medicine. The mechanism studies predict that Buyang Huanwutang can ameliorate CHF by regulating the calcium balance, protecting the mitochondrial structure and function, and regulating intestinal flora. This review aims to provide a theoretical basis and practical guidance for the clinical application and optimization and subsequent in-depth study of Buyang Huanwutang in the treatment of CHF.
7.Diagnostic value of quantitative ultrashort echo time adiabatic T 1ρ imaging in articular cartilage degeneration of the knee joint
Kai CHEN ; Xiaotong LIU ; Yi WANG ; Wenfeng LIU ; Sipei LIANG ; Mei WU
Chinese Journal of Radiology 2024;58(12):1424-1430
Objective:To investigate the value of quantitative ultrashort-echo-time (UTE) adiabatic T 1ρ (AdiabT 1ρ) in the diagnosis of articular cartilage degeneration of knee. Methods:A prospective case-control study was used. From March 2023 to September 2024, 30 healthy volunteers and 50 patients with osteoarthritis (OA) were recruited in the Second Affiliated Hospital, South China University of Technology and the Fifth Affiliated Hospital of Sun Yat-sen University. The unilateral knee joints were scanned by using three-dimensional (3D) UTE-Cones-AdiabT 1ρ sequence. The articular cartilages of knee were divided into 13 subregions slice by slice, with a total of 3 837 subregions. The whole-organ magnetic resonance-imaging score (WORMS) was evaluated in each subregion. According to the extent of lesions, the subregions cartilages were divided into normal group (WORMS 0, 2 589 subregions), localized lesion group (WORMS 1, 2, 2.5, 911 subregions) and diffuse lesion group (WORMS 3, 4, 5, 337 subregions). According to the depth of lesions, they were divided into normal group (WORMS 0, 2 589 subregions), partial cartilage layer lesions group (WORMS 1, 2, 3, 4, 1 108 subregions) and full-thickness lesion group (WORMS 2.5, 5, 140 subregions). WORMS 1 was early cartilage degeneration. The Kellgren-Lawrence (KL) grade of the knee joints was assessed and divided into normal group (KL grade 0, 1 323 subregions), suspicious or mild OA group (KL grades 1 and 2, 1 738 subregions), and moderate or severe OA group (KL grades 3 and 4, 776 subregions). The UTE-Cones-AdiabT 1ρ values and curves for each subregion were obtained by Matlab 2017b software. The ANOVA was used to compare the differences in UTE-Cones-AdiabT 1ρ between different WORMS groups and KL groups. Spearman correlation analysis was used to evaluate the correlation between UTE-Cones-AdiabT 1ρ and WORMS and KL groups. The receiver operating characteristic curve and area under the curve (AUC) were used to determine the efficacy of UTE-Cones-AdiabT 1ρ in diagnosing early cartilage degeneration and suspicious or mild OA. Results:Both normal volunteers and OA patients were able to obtain good cartilage images and well-fitting UTE-Cones-AdiabT 1ρ curves. There were 2 589, 569, 277, 65, 199, 63 and 75 cartilage subregions with WORMS scores of 0, 1, 2, 2.5, 3, 4 and 5, respectively, and the UTE-Cones-AdiabT 1ρ values were (36.1±5.1), (41.5±5.2), (42.3±5.3), (45.2±6.3), (43.0±5.2), (44.1±5.4) and (47.5±5.7) ms, respectively. The difference was statistically significant ( F=161.63, P<0.001). There was a statistically significant difference in UTE-Cones-AdiabT 1ρ among normal group, localized lesion group and diffuse lesion group ( F=450.92, P<0.001), and there was a significant difference in UTE-Cones-AdiabT 1ρ value among normal group, partial cartilage lesion group and full-thickness lesion group ( F=479.13, P<0.001). There was a statistically significant difference in UTE-Cones-AdiabT 1ρ among the normal group, the suspected or mild OA group, and the moderate or severe OA group ( F=36.91, P<0.001). The UTE-Cones-AdiabT 1ρ values in all subregions were positively correlated with WORMS and KL grades ( r=0.55, P<0.001; r=0.26, P<0.001). The AUC of UTE-Cones-AdiabT 1ρ in the diagnosis of early cartilage degeneration was 0.773 (95% CI 0.750-0.796), and the AUC in the diagnosis of suspicious or mild OA was 0.580 (95% CI 0.560-0.601). Conclusion:3D UTE-Cones-AdiabT 1ρ is positively correlated with the degree of cartilage degeneration, which can quantitatively evaluate cartilage degeneration and has the value of early diagnosis of articular cartilage degeneration.
8.Feasibility study of precise dose measurement of ultra-thin solution under 200 kV X-rays using EBT3 films
Xiaotong WANG ; Zhenzhen ZHANG ; Yanchen YING ; Peng ZHANG ; Wenjie WU ; Huiyin LAN ; Shunfei YU ; Binbing WANG
Chinese Journal of Radiation Oncology 2024;33(6):540-547
Objective:To improve the dosimetric accuracy of cell irradiation experiments by developing a method of accurately measuring the absorbed dose of ultra-thin solution in culture dishes under 200 kV medium-energy X-rays using EBT3 films.Methods:EBT3 film dose calibration was performed under Cyberknife 6 MV beam, and the beam quality (half-value layer) and effective energy of the 200 kV beam used in this study generated from Small Animal Radiation Research Platform through measurements and calculations were obtained to determine the EBT3 energy response correction factor. The 200 kV beam was utilized to irradiate three commonly used culture dishes filled with ultra-thin liquid placed on EBT3 films and the corrected EBT3 doses were taken as the liquid absorbed doses. The dose linearity of immersed films was also measured and analyzed. In addition, after modeling the irradiation environment, the independent Monte Carlo calculations of the liquid absorbed dose were performed by MCNP5 program. The calculation results were compared with the film measurement results to verify the accuracy of the measured doses.Results:The 200 kV beam had a half-value layer of 8.77 mm aluminum and effective energy of 57.4 keV, corresponding to an energy response correction factor of 0.889. The average liquid absorbed doses of large, medium and small culture dishes measured by EBT3 films under the specified parameters of 200 kV beam were (1.434±0.004) Gy, (1.467±0.011) Gy and (1.469±0.027) Gy after correction, respectively. The percentage errors from the corresponding Monte Carlo calculation doses were 0.07%, -0.70%, and 0.47%, respectively, where the relatively consistent results could be found. In addition, the dose linearity of immersed EBT3 films was also good, with coefficient of determination R2=0.9972. Conclusion:The method of measuring the dose of ultra-thin cell solution using EBT3 films proposed in this study is feasible, and the dose results obtained yield high accuracy under 200 kV beam.
9.Role of Ferroptosis in Osteoarthritis and Traditional Chinese Medicine Intervention: A Review
Xiaojing GUO ; Huan QIN ; Dongliang XIANG ; Yan WANG ; Li ZHANG ; Bo ZHANG ; Shujin WANG ; Xiaotong LI ; Mingyue ZHAO ; Shanhong WU ; Fei PEI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):263-272
Osteoarthritis (OA) is characterized by articular cartilage degeneration, synovial hyperplasia, hyperosteogeny, and narrowing of joint space, which can be caused by trauma, inflammation, and other factors. With the increasing global population aging, the incidence of OA is rising year by year, making it a major public health problem that urgently needs to be addressed. Exploring effective treatment schemes is particularly important. The pathogenesis of OA is complex, including oxidative stress, autophagy, and apoptosis. Recent studies have found that ferroptosis, a new type of cell death, is also an important pathogenic factor in OA, characterized by a series of complex changes such as iron ion accumulation, glutathione (GSH) depletion, and mitochondrial dysfunction. Research shows that inhibiting ferroptosis in chondrocytes can promote chondrocyte proliferation, delay extracellular matrix (ECM) degradation, and reduce synovial hyperplasia and inflammation. Targeting ferroptosis is a new direction in the treatment of OA. OA treatment includes intra-articular injections of steroids or hyaluronic acid and artificial joint replacement, but there are limitations. Traditional Chinese medicine (TCM) has been widely used in the treatment of various diseases because of its low cost, low drug resistance, and few side effects. Cell and animal experiments have further confirmed that TCM can intervene in the treatment of OA with ferroptosis from multiple targets, multiple levels, and aspects, but the mechanism of its treatment of OA based on ferroptosis has not been clarified. This paper discussed iron metabolism, lipid peroxidation, cysteine/glutamate transporter system Xc- (system Xc-)/GSH/glutathione peroxidase 4 (GPX4) pathway, nicotinamide adenine dinucleotide phosphate(NADPH)/ferroptosis suppressor protein 1 (FSP1)/coenzyme Q10 (CoQ10) pathway, tumor protein p53 in OA, and related molecular targets of Chinese medicine monomers and compounds on ferroptosis inhibition. Their potential therapeutic mechanisms were further analyzed to provide theoretical guidance for the treatment of OA by TCM and useful reference for the research and development of related drugs.
10.Morphological study of GABAergic neurons in the ventral zona incerta of mice involved in chronic itch
Shihao PENG ; Ze FAN ; Ziyi DAI ; Yiwen ZHANG ; Xiaotong SHI ; Yuanyuan ZHU ; Shengxi WU ; Jing HUANG
Chinese Journal of Neuroanatomy 2024;40(1):1-8
Objective:To detect itching,anxiety,depression behaviors in chronic itch models of mice and observe the activation of γ-aminobutiric acid(GABA)neurons in the ventral sector of the zona incerta(ZIv),and provide mor-phological evidence for their involvement in the modulation of itch information.Methods:Diphenylcyclopropenone(DCP)was used in glutamic acid decarboxylase 67-green fluorescent protein(GAD67-GFP)knock-in mice to establish chronic itch model.Itch behaviors were detected by video tracking system to verify whether the models were successfully established.The anxiety,depression behaviors of chronic itch model mice were detected by using elevated plus maze test(EPM)and tail suspention test(TST).By using GAD67-GFP mice,the distribution of GABAergic neurons in va-rious sectors of the zona incerta(ZI)was observed.And combined with immunofluorescence staining method,double labeling of GABAergic neurons with FOS in ZIv were observed respectively in control and DCP group mice.Results:In brain slices of GAD67-GFP mice,GABAergic neurons can be observed within all sectors of ZI and are more concentrat-ed in ZIv.Compared with control group mice,DCP group mice showed a significant increase in the bouts of scratching(P<0.001).The time of immobility in TST was significantly higher in DCP group mice than in control group mice,which displayed depression-like behavior.The EPM test showed that the numbers of entries and proportion of time in the cross region in DCP group mice were less than in control group mice.EPM test revealed that DCP group mice exhibited anxiety-like behavior.The results of immunofluorescence staining showed that the number of FOS-positive cells in ZIv was significantly higher in DCP group mice than in control group mice,and abundant co-labeled neurons of FOS and GABAergic neurons were observed in ZIv.Conclusion:GABAergic neurons were predominantly distributed in ZI,and were more concentrated in ZIv.The activation of GABAergic neurons in ZIv of DCP group mice provides morphological evidence on the involvement of GABAergic neurons in chronic itch and associated negative emotions.


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