1.Regulation of Relevant Signaling Pathways by Traditional Chinese Medicine in Intervention of Pancreatic Cancer: A Review
Quanyou ZHAO ; Conghui ZHAO ; Yu ZHANG ; Yiping FU ; Yuting LIU ; Xiaoran WANG ; Zhanzhan LI ; Mingsan MIAO ; Li BAI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):280-289
Pancreatic cancer is a highly malignant solid tumor of the digestive system with extremely poor treatment prognosis. Although its incidence rate is low, its mortality rate is extremely high. In recent years, the number of diagnosed cases worldwide has continued to rise, making pancreatic cancer the sixth leading cause of cancer-related deaths globally. Currently, clinical treatment primarily relies on operation and chemotherapy to suppress tumors. However, these approaches face challenges such as suboptimal efficacy, high postoperative recurrence rates, and severe adverse reactions. Therefore, identifying safe and effective treatment modalities remains a pressing challenge for the medical community. In recent years, research on traditional Chinese medicine (TCM) interventions for pancreatic cancer has increased significantly. Multiple studies have shown that single-herb TCM, TCM formulas, and their derived single compounds can regulate the levels of tumor cell signaling pathways through multiple action targets. They inhibit the development and progression of pancreatic cancer by inhibiting cancer cell proliferation, promoting cell apoptosis, inhibiting tumor angiogenesis, reducing cancer cell invasion and migration capabilities, regulating the cell cycle, and modulating the tumor microenvironment. Additionally, TCM has the advantages of significantly enhancing the anticancer efficacy of chemotherapy drugs and causing fewer adverse reactions. However, the specific action mechanisms by which TCM intervenes in pancreatic cancer remain unclear. Further extensive research is still needed to validate the role of regulating classical signaling pathways such as phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), Wnt/β-catenin, nuclear transcription factor-κB (NF-κB), notch, and hedgehog in the treatment of pancreatic cancer. Therefore, this paper reviewed Chinese and international studies on TCM intervention in pancreatic cancer through relevant signaling pathways in recent years, summarized the potential action mechanisms of TCM in the treatment of pancreatic cancer, and provided references for related research in the future.
2.Regulation of TGF-β1/JNK signaling pathway in patients with different types of mitral valve diseases complicated by atrial fibrillation
Chao CHANG ; Bo FU ; Xiaolong ZHU ; Chongjie ZHANG ; Xia ZHAO ; Hong TANG ; Xijun XIAO ; Yunpeng BAI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(02):291-299
Objective To investigate the regulatory mechanism of transforming growth factor-β1 (TGF-β1) in different types of mitral valvular disease (MVD) with atrial fibrillation (AF). Methods From August 2011 to August 2012, patients with moderate to severe MVD accompanied by AF who required mitral valve replacement at the Department of Cardiovascular Surgery, West China Hospital, Sichuan University, were included. Based on echocardiographic results, patients were divided into two groups: a mitral regurgitation (MR) with AF (MR-AF) group and a mitral stenosis (MS) with AF (MS-AF) group. Left atrial tissue samples were collected during surgery. Techniques such as enzyme-linked immunosorbent assay, real-time fluorescence quantitative polymerase chain reaction, immunohistochemistry, and Western blotting were used to detect key molecules in the TGF-β1/JNK pathway. Results Sixteen patients were enrolled. There were 8 patients in the MR-AF group, including 5 males and 3 females, with an average age of (41.38±11.19) years; and 8 patients in the MS-AF group, including 6 males and 2 females, with an average age of (43.12±5.30) years. The left atrial volume load was higher in MR-AF patients, while the left atrial pressure load was higher in MS-AF patients. In MS-AF patients, the relative expression levels of MAPK9, JUN, CASP3, BAX, and BCL2 mRNA in left atrial tissues were significantly upregulated. The serum TGF-β1 protein level and the relative expression levels of p-JNK, p-c-Jun, and Caspase-3 proteins in the left atrial tissues of the MR-AF group were higher. Myocardial cell damage was more severe in the MS-AF group, and the protein expression level of Bcl-2 was higher. Conclusion Different MVD have distinct hemodynamic characteristics. The myocardium of the left atrium in MR-AF patients is more prone to apoptosis, possibly through the activation of the TGF-β1/JNK signaling pathway.
3.Correlation between Periostin, IL-33, and chronic cough after thoracoscopic lobectomy in patients with coronary artery bypass grafting combined with lung cancer: A prospective cohort study
Yujuan QI ; Yaobang BAI ; Yan JIAO ; Xiaolong ZHU ; Bo FU ; Zhenhua WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(03):363-368
Objective To study the correlation between Periostin, interleukin-33 (IL-33), and chronic cough after thoracoscopic lobectomy in patients with coronary artery bypass grafting (CABG) combined with lung cancer. Methods A total of 102 lung cancer and coronary heart disease patients at Tianjin Chest Hospital from January 2022 to January 2024 were prospectively enrolled, and they were divided into a chronic cough group (n=42) and a non-chronic cough group (n=60) based on whether chronic cough occurred after surgery. Serum levels of Periostin and IL-33 were measured on the 1st, 7th, and 14th days post-lobectomy. The Pearson method was employed to analyze the correlation between Periostin and IL-33 levels and the severity of cough. Univariate and multivariate logistic regression analyses were conducted to identify factors influencing the occurrence of chronic cough. Additionally, receiver operating characteristic (ROC) curve analysis was utilized to assess the potential value of serum Periostin and IL-33 levels in predicting postoperative chronic cough. Results In patients with chronic cough, the peripheral blood Periostin and IL-33 levels measured on days 7 and 14 were significantly higher than those in patients with non-chronic cough, and the interactions between the two groups and at different time points were significant (P<0.001). The degree of cough was positively correlated with the levels of Periostin and IL-33 on days 7 and 14 (P<0.05), but had no significant correlation with the levels on day 1 (P>0.05). In patients with lung cancer, after thoracoscopic lobectomy, Periostin [OR=1.619, 95%CI (1.295, 2.025)] and IL-33 [OR=1.831, 95%CI (1.216, 2.758)] on day 7 and Periostin [OR=1.952, 95%CI (1.306, 2.918)] and IL-33 [OR=1.742, 95%CI (1.166, 2.603)] on day 14 were identified as risk factors for chronic cough. ROC curve analysis showed that the sensitivity of Periostin on day 7 was 69.05%, the specificity was 71.67%, and the area under the curve (AUC) was 0.756 [95%CI (0.616, 0.893)]. The sensitivity of Periostin on day 14 increased to 71.43% and the specificity was 76.67%, AUC was 0.762 [95%CI (0.633, 0.898)]. At the same time, the critical value of IL-33 on day 7 was 45.03 pg/mL, the sensitivity and specificity were both 83.33%, the AUC was 0.884 [95%CI (0.789, 0.980)], and the critical value of IL-33 on day 14 was 56.01 pg/mL, the sensitivity was 85.71%, the specificity was 80.00%, and the AUC was 0.899 [95%CI (0.799, 0.999)]. Joint logistic regression analysis of Periostin and IL-33 levels on days 7 and 14 showed showed that the sensitivity was 95.24%, the specificity was 95.00%, and the AUC reached 0.993 [95%CI (0.979, 1.000)]. Conclusion Periostin and IL-33 levels, measured at various time points, are abnormally elevated following thoracoscopic lobectomy in patients with combined CABG and lung cancer. These levels significantly correlate with cough severity. Given their predictive potential for chronic cough, these markers are deemed valuable biomarkers.
4.Study on leaf epidermal microstructure of medicinal blue herbs
Yunjun BAI ; Yuyang ZHAO ; Yan JIN ; Lu FU ; Yuan YUAN
Journal of Pharmaceutical Practice and Service 2025;43(4):174-179
Objective The complex evolutionary history of the origin of medicinal blue herbs might result in the presence of adulterants, affecting the accuracy and safety of clinical medication. To provide a reference basis for the identification of medicinal blue herbs with leaves as the medicinal part, based on the leaf epidermis microstructure. Methods The species belonging to medicinal blue herbs and their close relatives (10 species from 4 genera) were systematically investigated. The leaf epidermis microstructure of these species was observed and analyzed by optical microscopy and scanning electron microscopy. A species retrieval table was established based on the microstructure characteristics. Results By combining the distribution of stomata, types of subsidiary cells, stomatal index, stomatal density, characteristics of the periclinal walls of epidermal cells, and epidermal appendages, the species Clerodendrum cyrtophyllum, Polygonum tinctorium, Isatis indigotica, I. violascens, I. costata, I. minima, Strobilanthes wallichii, S. dalzielii, S. pentstemonoides, and S. cusia can be accurately distinguished. Conclusion Microscopic characteristics of leaf epidermis can provide reference data for accurately differentiating the botanical origins of medicinal blue herbs.
5.Evaluation of the safety and efficacy of ABO non-identical apheresis platelets with reduced plasma transfusion
Ronghua DIAO ; Qianying RUAN ; Lu BAI ; Hong ZHANG ; Zerong WANG ; Lei FU ; Shichun WANG
Chinese Journal of Blood Transfusion 2025;38(7):909-914
Objective: To evaluate the safety and efficacy of ABO non-identical platelets with reduced plasma (ABO-NPRP) transfusion in patients with hematological diseases. Methods: A retrospective analysis was conducted on 52 therapeutic doses of apheresis platelets with reduced plasma prepared at Chongqing Blood Center of the Chinese People's Liberation Army. The transfusion efficacy (24 h CCI) and the transfusion adverse reactions of these apheresis platelets were also observed in 35 patients with hematological diseases in First Affiliated Hospital of Army Medical University. Comparisons were made with a control group consisting of patients who received only identical apheresis platelets during the same period. Meanwhile, the effect of ABO-NPRP on the subsequent platelet transfusion efficacy was observed. Results: There was no statistically significant difference in PDW, MPV, and PLCR before and after the preparation of apheresis platelets with reduced plasma (P>0.05), while the difference in platelet count was statistically significant [(2.86±0.34)×10
per therapeutic dose vs (2.46±0.28)×10
per therapeutic dose, P<0.001]; there was no statistically significant difference in the 24 h CCI transfusion efficacy between conventional identical apheresis platelets and ABO-NPRP, with transfusion efficacy rates of 76.60% and 78.85%, respectively (P>0.05); there was no statistically significant difference in platelet transfusion efficacy between the group with ABO-NPRP and the group without ABO-NPRP (completely identical transfusion group), with transfusion efficacy rates of 77.78% and 75.25%, respectively (P>0.05). Conclusion: ABO-NPRP transfusion is safe, effective, demonstrating comparable efficacy to conventional identical transfusion. It can serve as an important complementary strategy to optimize the utilization of blood resources.
6.Evaluation of the safety and efficacy of ABO non-identical apheresis platelets with reduced plasma transfusion
Ronghua DIAO ; Qianying RUAN ; Lu BAI ; Hong ZHANG ; Zerong WANG ; Lei FU ; Shichun WANG
Chinese Journal of Blood Transfusion 2025;38(7):909-914
Objective: To evaluate the safety and efficacy of ABO non-identical platelets with reduced plasma (ABO-NPRP) transfusion in patients with hematological diseases. Methods: A retrospective analysis was conducted on 52 therapeutic doses of apheresis platelets with reduced plasma prepared at Chongqing Blood Center of the Chinese People's Liberation Army. The transfusion efficacy (24 h CCI) and the transfusion adverse reactions of these apheresis platelets were also observed in 35 patients with hematological diseases in First Affiliated Hospital of Army Medical University. Comparisons were made with a control group consisting of patients who received only identical apheresis platelets during the same period. Meanwhile, the effect of ABO-NPRP on the subsequent platelet transfusion efficacy was observed. Results: There was no statistically significant difference in PDW, MPV, and PLCR before and after the preparation of apheresis platelets with reduced plasma (P>0.05), while the difference in platelet count was statistically significant [(2.86±0.34)×10
per therapeutic dose vs (2.46±0.28)×10
per therapeutic dose, P<0.001]; there was no statistically significant difference in the 24 h CCI transfusion efficacy between conventional identical apheresis platelets and ABO-NPRP, with transfusion efficacy rates of 76.60% and 78.85%, respectively (P>0.05); there was no statistically significant difference in platelet transfusion efficacy between the group with ABO-NPRP and the group without ABO-NPRP (completely identical transfusion group), with transfusion efficacy rates of 77.78% and 75.25%, respectively (P>0.05). Conclusion: ABO-NPRP transfusion is safe, effective, demonstrating comparable efficacy to conventional identical transfusion. It can serve as an important complementary strategy to optimize the utilization of blood resources.
7.Clinical Efficacy of Xiaoji Hufei Formula in Protecting Children with Close Contact Exposure to Influenza: A Multicenter,Prospective, Non-randomized, Parallel, Controlled Trial
Jing WANG ; Jianping LIU ; Tiegang LIU ; Hong WANG ; Yingxin FU ; Jing LI ; Huaqing TAN ; Yingqi XU ; Yanan MA ; Wei WANG ; Jia WANG ; Haipeng CHEN ; Yuanshuo TIAN ; Yang WANG ; Chen BAI ; Zhendong WANG ; Qianqian LI ; He YU ; Xueyan MA ; Fei DONG ; Liqun WU ; Xiaohong GU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):223-230
ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza, and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter, prospective, non-randomized, parallel, controlled trial was conducted from October 2021 to May 2022 in five hospitals, including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness (ILI) cases were collected, and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention, they were assigned to the observation group (108 cases) or the control group (108 cases). Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine (TCM) symptom score scale for influenza, influenza-related emergency (outpatient) visit rate, influenza hospitalization rate, and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled, with 108 in the observation group and 108 in the control group. Primary outcomes: (1) Incidence of ILI: The incidence was 12.0% (13/108) in the observation group and 23.1% (25/108) in the control group, with the observation group showing a significantly lower incidence (χ2=4.6, P<0.05). (2) Influenza confirmation rate: 3.7% (4/108) in the observation group and 4.6% (5/108) in the control group, with no statistically significant difference. Secondary outcomes: (1) TCM symptom score scale: after onset, nasal congestion and runny nose scores differed significantly between the two groups (P<0.05), while other symptoms such as fever, sore throat, and cough showed no significant differences. (2) Influenza-related emergency (outpatient) visit rate: 84.6% (11 cases) in the observation group and 96.0% (24 cases) in the control group, with no significant difference. (3) Time to onset after exposure: The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group, with a statistically significant difference (P<0.05). ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions, Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.
8.Clinical Efficacy of Xiaoji Hufei Formula in Protecting Children with Close Contact Exposure to Influenza: A Multicenter,Prospective, Non-randomized, Parallel, Controlled Trial
Jing WANG ; Jianping LIU ; Tiegang LIU ; Hong WANG ; Yingxin FU ; Jing LI ; Huaqing TAN ; Yingqi XU ; Yanan MA ; Wei WANG ; Jia WANG ; Haipeng CHEN ; Yuanshuo TIAN ; Yang WANG ; Chen BAI ; Zhendong WANG ; Qianqian LI ; He YU ; Xueyan MA ; Fei DONG ; Liqun WU ; Xiaohong GU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):223-230
ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza, and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter, prospective, non-randomized, parallel, controlled trial was conducted from October 2021 to May 2022 in five hospitals, including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness (ILI) cases were collected, and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention, they were assigned to the observation group (108 cases) or the control group (108 cases). Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine (TCM) symptom score scale for influenza, influenza-related emergency (outpatient) visit rate, influenza hospitalization rate, and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled, with 108 in the observation group and 108 in the control group. Primary outcomes: (1) Incidence of ILI: The incidence was 12.0% (13/108) in the observation group and 23.1% (25/108) in the control group, with the observation group showing a significantly lower incidence (χ2=4.6, P<0.05). (2) Influenza confirmation rate: 3.7% (4/108) in the observation group and 4.6% (5/108) in the control group, with no statistically significant difference. Secondary outcomes: (1) TCM symptom score scale: after onset, nasal congestion and runny nose scores differed significantly between the two groups (P<0.05), while other symptoms such as fever, sore throat, and cough showed no significant differences. (2) Influenza-related emergency (outpatient) visit rate: 84.6% (11 cases) in the observation group and 96.0% (24 cases) in the control group, with no significant difference. (3) Time to onset after exposure: The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group, with a statistically significant difference (P<0.05). ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions, Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.
9.Regulation of natural killer cell subtypes and functions by programmed cell death protein 1 and its receptor at the maternal-fetal interface in mice infected with Toxoplasma gondii during the second trimester
Jiayue SUN ; Qiuhua BAI ; Xiaodan CHEN ; Jiayin LÜ ; Shanshan HE ; Lili TANG ; Dejun LIAO ; Dengyu LIU ; Xiaoyin FU
Chinese Journal of Schistosomiasis Control 2025;37(5):465-474
Objective To investigate the regulatory role of the programmed cell death protein 1 (PD-1) and its ligand programmed cell death protein ligand 1 (PD-L1) signaling on the subtypes and functions of natural killer (NK) cells at the maternal-fetal interface during the second trimester in mice following Toxoplasma gondii infection during the first trimester. Methods Twelve 6- to 8-week-old female mice of the C57BL/6J strain were divided into a control group and an infection group, of 6 mice in each group. On the 6.5th day of pregnancy (Gd6.5), each pregnant mouse in the infection group was intraperitoneally injected with 150 tachyzoites of the Toxoplasma gondii PRU strain, while mice in the control group were injected with an equal volume of physiological saline. On the 12.5th day of pregnancy (Gd12.5), uterus and placenta tissues were sampled from pregnant mice for pathological observations, and the mRNA expression levels of PD-1, PD-L1, and tumor necrosis factor-α (TNF-α) were quantified in uterus and placenta tissues. The PD-1 and DX5 expression was measured on NK cells at the maternal-fetal interface using flow cytometry. In addition, the in vitro JEG-3 trophoblast cells and NK-92MI cells co-culture system was established as the control group, and the addition of T. gondii tachyzoites in the co-culture system served as the infection group. The PD-1, PD-L1, and DX5 mRNA expression was quantified in cells using real-time fluorescence quantitative reverse transcription PCR (RT-qPCR) assay, and the TNF-α concentration was measured in the cell culture supernatant using enzyme-linked immunosorbent assay (ELISA). Results On Gd12.5, clear and intact cellular structures of placental decidual tissues were seen in pregnant mice in the control group, with no remarkable abnormal changes found in the uterine columnar epithelial cells, and inflammatory cell infiltration and blood stasis at varying degrees were found in uterine and placental tissues from pregnant mice in the infection group. The relative PD-1, PD-L1, and TNF-α mRNA expression was (1.004 ± 0.004), (1.001 ± 0.001), and (1.001 ± 0.001) in uterine tissues from pregnant mice in the control group and (2.480 ± 0.720), (3.355 ± 0.920), and (2.391 ± 0.073) in the infection group, respectively. The relative PD-1, PD-L1, and TNF-α mRNA expression was (1.007 ± 0.010), (1.006 ± 0.006), and (1.001 ± 0.001) in the uterine tissues in the control group and (6.948 ± 1.918), (3.225 ± 1.034), and (1.536 ± 0.150) in the infection group, respectively. The relative PD-1, PD-L1, and TNF-α mRNA expression was higher in both the uterine (t = 3.55, 4.43 and 33.02, all P values < 0.05) and placental tissues (t = 5.36, 3.72 and 6.18, all P values < 0.05) in the infection group than in the control group. Flow cytometry showed that the proportions of PD-1+ NK cells, PD-1+ DX5+ NK cells, and DX5+ NK cells were (12.200 ± 1.082)%, (9.373 ± 7.728)%, and (44.000 ± 4.095)% in uterine tissues from pregnant mice in the control group, and (21.733 ± 1.630)%, (18.767 ± 1.242)%, and (73.367 ± 0.611)% in the infection group, respectively. The proportions of PD-1+ NK cells, PD-1+ DX5+ NK cells, and DX5+ NK cells were (1.100 ± 0.510)%, (2.277 ± 1.337)%, and (96.167 ± 2.831)% in placental tissues from mice in the control group, and (26.867 ± 9.722)%, (23.433 ± 6.983)%, and (82.467 ± 2.248)% in the infection group, respectively. The proportions of PD-1+ NK cells (t = 8.45, P < 0.05) and DX5+ NK cells (t = 12.29, P < 0.05) were higher in uterine tissues from pregnant mice in the infection group than in the control group, and no significant difference was seen in the proportion of PD-1+ DX5+ NK cells (Z = -1.09, P > 0.05). The proportions of PD-1+ NK cells (t = 4.58, P < 0.05) and PD-1+ DX5+ NK cells (t = 5.15, P < 0.05) were higher in placental tissues from pregnant mice in the infection group than in the control group, while the proportion of DX5+ NK cells was lower in the infection group than in the control group (t = -6.56, P < 0.05). RT-qPCR assay revealed that the relative PD-1, PD-L1, and DX5 mRNA expression was (1.010 ± 0.005), (1.002 ± 0.003), and (1.001 ± 0.001) in the JEG-3 cells and NK92MI cells co-culture system and (3.638 ± 1.258), (0.397 ± 0.158), and (4.267 ± 1.750) in the control group, and ELISA measured that the TNF-α concentration was higher in the cell culture supernatant in the infection group [(22.056 ± 3.205) pg/mL] than in the control group [(12.441 ± 0.001) pg/mL] (t = 5.20, P < 0.05). The PD-1(t = 3.62, P < 0.05) and DX5 mRNA expression (t = 3.23, P < 0.05) was higher in the infection group than in the control group, and the PD-L1 mRNA expression was lower in the infection group than in the control group (t = -6.63, P < 0.05). Conclusions Following T. gondii infection, both PD-L1 expression and PD-1 expression on DX5+ NK cells at the maternal-fetal interface are upregulated in mice during the second trimester; however, the proportion of DX5+ NK cells decreases. These findings suggest that PD-1/PD-L1 signaling may suppress NK cell functions by modulating DX5+ NK cell subsets.
10.Arsenic trioxide preconditioning attenuates hepatic ischemia- reperfusion injury in mice: Role of ERK/AKT and autophagy.
Chaoqun WANG ; Hongjun YU ; Shounan LU ; Shanjia KE ; Yanan XU ; Zhigang FENG ; Baolin QIAN ; Miaoyu BAI ; Bing YIN ; Xinglong LI ; Yongliang HUA ; Zhongyu LI ; Dong CHEN ; Bangliang CHEN ; Yongzhi ZHOU ; Shangha PAN ; Yao FU ; Hongchi JIANG ; Dawei WANG ; Yong MA
Chinese Medical Journal 2025;138(22):2993-3003
BACKGROUND:
Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI.
METHODS:
In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy.
RESULTS:
A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent.
CONCLUSION
Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals
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Arsenic Trioxide
;
Autophagy/physiology*
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Reperfusion Injury/prevention & control*
;
Mice
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Male
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Proto-Oncogene Proteins c-akt/physiology*
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Arsenicals/therapeutic use*
;
Oxides/therapeutic use*
;
Liver/metabolism*
;
Extracellular Signal-Regulated MAP Kinases/metabolism*
;
Mice, Inbred C57BL

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