Table of Content

Volume 27 Issue 10
27 October 2022

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The mechanism of Shugan Jianpi Formula regulating TLR4/MyD88/NLRP3 signaling axis to inhibit pyroptosis in mice with liver fibrosis

CHEN Sen, FAN Chang, ZHANG Jiafu, MA Yanzhen, JIANG Hui

2022, 27(10):  1081-1089.  doi:10.12092/j.issn.1009-2501.2022.10.001

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AIM: To explore the therapeutic effect and mechanism of Shugan Jianpi Formula on liver fibrosis mice based on TLR4/MyD88/NLRP3 signaling axis.  METHODS: The chemical liver fibrosis mouse model was established by carbon tetrachloride (CCl4) mixed with olive oil. On the first day of modeling, the mice were gavage-administrated with Shugan Jianpi Formula once a day, for 12 weeks. The liver histopathology was observed by HE staining, Masson staining and Sirius red staining. The degree of injury, the ultrastructural changes of mouse liver tissue and the situation of pyroptosis were observed by transmission electron microscope. The expression changes of α-SMA, Collagen Ⅰ, Caspase-1, IL-1β, IL-18 and TLR4/MyD88/NLRP3 signaling axis were detected by RT-qPCR, Western blot and immunohistochemical staining. RESULTS: Pathological analysis showed that the structure of liver lobules in the model group was blurred, the arrangement of hepatocyte cords was disordered, the collagen deposition increased, and the number of pyroptotic bodies in liver cells increased significantly. The RNA and protein expression levels of α-SMA, Collagen Ⅰ, Caspase-1, IL-1β, IL-18, TLR4, MyD88 and NLRP3 were significantly higher than those in the normal group. Compared with the model group, the administration of Shugan Jianpi Formula could improve the degree of liver histopathological damage, inhibit cell pyroptosis, and significantly down-regulate the RNA and protein expression levels of α-SMA, Collagen Ⅰ, Caspase-1, IL-1β, IL-18, as well as TLR4, MyD88 and NLRP3 in liver tissue. CONCLUSION: The anti-fibrosis effect of Shugan Jianpi Formula may be related to the regulation of TLR4/MyD88/NLRP3 signaling axis, reduction of cell death and inhibition of hepatic stellate cell activation. 

Network pharmacology and molecular docking to discuss the mechanism of Jinhutongdan prescription in the treatment of cholelithiasis and experimental verification

CHEN Yugang, TU Yanqiong, WANG Congqing, CHEN Juan, ZHANG Bohong

2022, 27(10):  1090-1098.  doi:10.12092/j.issn.1009-2501.2022.10.002

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AIM: To analyze the mechanism of Jinhutongdan prescription in treating cholelithiasis based on network pharmacology and verify the pharmacological on the active target through animal experiments.  METHODS: (1) The active ingredients of Jinhutongdan recipe were obtained by TCMSP and UniPort. The targets of cholelithiasis treated with Jinhutongdan recipe were obtained by the targets of cholelithiasis related diseases through Genecards database and OMIM database and mapping them with the targets of active ingredients of drugs. Target protein interaction (PPI) network and active ingredients-target network were constructed by Cytoscape3.9.0 software and String database. Using Metascape database to complete GO function and KEGG pathway enrichment analysis, using Cytoscape3.9.0 software to build common target-signal pathway network. We carried out molecular docking by UCSF Chimera1.15 and Autodock-vina software. Top 6 targets ranked by degree value of PPI were selected for molecular docking to verify the binding activity. (2) Forty-eight guinea pigs were randomly divided into 4 groups (n=12), and the other 3 groups were made cholelithiasis model except blank group. Aspirin group and Jinhutongdan recipe group were calculate the stone-formation rate. Serum TNF-α level was detected by ELISA. RESULTS:  (1) 23 active ingredients acted on cholelithiasis through 23 common targets, including EGFR, CCND1, TP53, EGF, IL-6, etc. The KEGG pathway enrichment analysis showed that  13 pathways were related to cholelithiasis. TNF and Isorhamnetin, EGFR and Kaempferol, EGFR and Isorhamnetin, TP53 and beta-sitosterol showed strong binding activity. (2) Animal experiment results: The lithogenesis rate of the model group significantly higher than blank group (P<0.05); The lithogenesis rate of Jinhutongdan recipe was lower than other groups.The serum TNF-α was significantly increased in each group (P<0.01); Compared with  serum TNF-α content in Jinhutongdan group was significantly decreased. CONCLUSION: (1) Jinhutongdan recipe may play a role in the treatment of cholelithiasis by inhibiting inflammation, enhancing immunity,anti tumor, regulating cell proliferation and antioxidation. (2) Jinhutongdan recipe has therapeutic effect on model guinea pigs, the mechanism may be in inhibits inflammatory factors and alleviates inflammatory response by regulating TNF-α expression. 

Dioscin attenuates inflammatory injury in uric acid-induced renal tubular epithelial cells by suppression of NF-κB signaling pathway

LIU Peng, WANG Chen, WANG Yun, QIU Xinping

2022, 27(10):  1099-1105.  doi:10.12092/j.issn.1009-2501.2022.10.003

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AIM: To observe the effect of Dioscin treatment on NF-κB signaling pathway and cellular inflammatory injury and explore its potential mechanism in uric acid-induced mouse tubular epithelial cells (mTECs).  METHODS: After 1.2 mol/L uric acid induced mTECs, Dioscin and NF-κB P65 inhibitor BAY11-7082 were given to intervene respectively. IκB-α, NF-κB P65, PP65, NLRP3, IL-1β and β-actin were detected by Western Blot, immunofluorescence staining and real-time PCR. RESULTS: Western Blot, immunofluorescence staining and real-time PCR analysis showed that expression levels of PP65, NLRP3 and IL-1β were significantly downregulated in the uric acid-induced mTECs with Dioscin and BAY11-7082 treatment. CONCLUSION: Dioscin attenuates uric acid-induced cellular inflammatory damage by suppression NF-κB signaling pathway. 

Experimental study of irisin alleviates house dust mite-induced airway epithelial cells inflammation and apoptosis via the NF-κB and JNK signaling pathways

LI Ying, YAO Wei, WANG Meng, YU Zhihong, GONG Yuanqi, LAN Haibing, QI Xiefei

2022, 27(10):  1106-1112.  doi:10.12092/j.issn.1009-2501.2022.10.004

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AIM: To explore the effects of irisin on house dust mite (HDM)-induced inflammation and apoptosis in human airway epithelial cells. METHODS: The human bronchial epithelial cell (16HBE) were cultured with in RPMI1640 culture medium with 10%of fetal bovine serum. After cells reached 85%confluence, the medium was replaced with serum-free culture medium for 12 h. Then the 16HBE cells were treated with various concentrations of HDM (0, 400, 800, 12 00 U/mL) for 24 h. Reactive oxygen species assay kit was used to detected the intracellular ROS generation. And qPCR was used to  measure the interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α) mRNA expression of the HDM-induced 16HBE cell. The cells were pre-treated with or without irisin for 2 h before  exposure to various concentration of HDM for 24 h. Then reactive oxygen species assay kit was used to detected the intracellular ROS generation. The IL-6, TNF-α mRNA expression of 16HBE cell were measured by qPCR. Meanwhile, the phosphorylated and total P65 NF-κB and JNK proteins were detected by western blot. The pro-apoptosis protein cleaved-caspase3、BAX and the anti-apoptosis protein were also detected by western blot. RESULTS: The quantitative assay showed that intracellular ROS in different concentrations of HDM stimulus group were obviously higher than NC group (P<0.05). And RT-PCR analysis showed a higher expression level of pro-inflammatory cytokine TNF-α and IL-6 mRNA in different concentrations of HDM than in NC group (P<0.05). Compared  with the HDM group, Irisin significantly decreased the level of intracellular ROS of the 16HBE cells (P<0.05). The released of the pro-inflammatory cytokine TNF-α and IL-6 mRNA was also decreased in irisin treated 16HBE cells (P<0.05). And compared with control group, BCL-XL anti-apoptosis protein level was decreased and BAX and c-caspase3 pro-apoptosis protein levels were increased in HDM group (P<0.05), irisin intervention significantly increased the level of BCL-XL and decreased the levels of BAX and cleaved-caspase 3 (P<0.05). Compared the control group, phosphorylated P65 NF-κB and JNK protein levels were significantly increased after HDM stimulated (P<0.05), and irisin intervention decreased the protein levels of phosphorylated P65 NF-κB and JNK (P<0.05). CONCLUSION: Irisin can effectively improve the inflammation and apoptosis of HDM-induced 16HBE cells, and this protective effect may be related to its inhibition of NF-κB and JNK MAPK signaling pathways. Irisin may be a potential drug for treating lung inflammation.

Effect of dexmedetomidine on muscle relaxant effect of cisatracurium in patients with epilepsy

WANG Ting, HAN Mingming, LI Juan

2022, 27(10):  1113-1118.  doi:10.12092/j.issn.1009-2501.2022.10.005

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AIM: To determine the effect of dexmedetomidine on muscle relaxant effect of cisatracurium in patients with epilepsy. METHODS: Sixty patients undergoing elective neurosurgery, aged from 18 to 59 years old, were divided into three groups (n=20) according to the maximum onset time of dexmedetomidine: immediate induction group after dexmedetomidine infusion (Group A), induction group 15 minutes after dexmedetomidine infusion (Group B) and normal saline infusion (Group C). The neuromuscular conduction function was monitored by muscle relaxation monitor, and the ulnar nerve was stimulated in TOF mode (frequency 2 Hz, wave width 0.2 ms, stimulation current 70 mA, string interval 12 s). Patients in group A were given dexmedetomidine 1 μg/kg after entering the room, and anesthesia induction was started immediately after 10 min pumping; Group B patients were given dexmedetomidine 1 μg/kg after entering the room, and anesthesia induction was started 15 minutes after 10 minutes of pump injection; Patients in group C began induction immediately after pumping the same milliliter of normal saline within 10 min. During anesthesia induction, 0.15 mg/kg cisatracurium was injected intravenously, and endotracheal intubation was performed when T1 reached the maximum inhibition. The modified method was used to evaluate the conditions of endotracheal intubation. When T1 recovered to 25%during the operation, cisatracurium 0.05 mg/kg was injected intravenously. The onset time (Tonset), peak time (Tpeak), 25%recovery time (T25%), 25%-50%recovery time (T25-50%), 50%-75% recovery time (T50-75%) and 75%-100%recovery time (T75-100%) of cisatracurium were recorded. Record the operation time, anesthesia time and fluid replacement volume, record the total dosage of propofol, remifentanil and cisatracurium, and calculate the dosage per unit body weight. RESULTS: There was no significant difference in Tonset, Tpeak, T25%, T25-50%, T50-75% and T75-100% among the three groups (P>0.05), but Tpeak, T25-50% and T50-75% in group C were greater than those in group A and B; There was no significant difference in tracheal intubation conditions, body weight per unit time and dosage of cisatracurium among the three groups (P>0.05); The dosage of propofol in group C was significantly higher than that in group A and B (P<0.05). CONCLUSION: Dexmedetomidine has no effect on the muscle relaxation effect of cisatracurium in patients with epilepsy. 

Application of remifentanil in postoperative ICU sedation and analgesia in patients with severe craniocerebral trauma

WU Xiaoxia, ZHOU Hu

2022, 27(10):  1119-1124.  doi:10.12092/j.issn.1009-2501.2022.10.006

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AIM: To investigate the effect of remifentanil in the management of sedation and analgesia after severe traumatic brain injury and its influence on the incidence of inflammatory stress.  METHODS: From January 2017 to April 2020, 92 patients with severe head trauma surgery in our hospital were selected as the research objects, randomly divided into groups, each with 46 cases. Both groups received postoperative sedation and analgesia management, the control group received dexmedetomidine + 0.9%sodium chloride injection, and the observation group received dexmedetomidine combined with remifentanil. The effects of sedation and analgesia, vital signs, and inflammatory stimuli ［C reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10)］ related indicators, serum cortisol, β-endorphin, and the incidence of adverse reactions in the two groups were observed and counted. RESULTS: The scores of sedation and analgesia in the observation group were lower than control group at 2 h, 4 h, and 12 h after administration (P<0.05). The heart rate, average arterial pressure, and respiratory rate of the observation group were lower than control group at 6 h after administration, and the average arterial pressure and respiratory rate at 12 h after administration were lower than those of the control group (P<0.05). At 6 h and 12 h after administration, the levels of CRP, TNF-α, IL-6, IL-10, and cortisol in the observation group were lower than control group, while the levels of β-endorphin were higher than those in the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). CONCLUSION: Remifentanil is used in the management of sedation and analgesia after severe traumatic brain injury, which can effectively improve the effect of sedation and analgesia, reduce inflammatory stimulation, regulate the levels of cortisol, and β-endorphin  It is worthy of clinical application. 

Ketamine for depression treatment: past, present, and future

HE Teng, XU Xiangyang, XU Xiangqing, LIU Cunming, YANG Chun

2022, 27(10):  1125-1132.  doi:10.12092/j.issn.1009-2501.2022.10.007

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Depression has become a serious global public health problem due to its high incidence and great harm, and has aroused the attention of the society. Ketamine, a commonly used intravenous anesthetic and analgesic in clinical practice, has been found to have unique advantages in antidepressant therapy in recent years. With the development of research, the enantiomeric isomers of ketamine, (S)-ketamine and (R)-ketamine have entered the research field of antidepressant therapy. In this paper, we reviewed the progress of research on the antidepressant effects and mechanisms of ketamine, (S)-ketamine and (R)-ketamine, and provide a brief overview of the antidepressant effects of metabolites of ketamine, thereby deepening the understanding of the readers in the field of antidepressant effects of ketamine.

Molecular mechanism and treatment of pulmonary fibrosis

ZHOU Shiqin, LUO Yali, ZHOU Wen, Qi Xiaofeng, XIAO Mengyong

2022, 27(10):  1133-1147.  doi:10.12092/j.issn.1009-2501.2022.10.008

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Pulmonary fibrosis (PF) is a chronic progressive interstitial lung disease. The pathogenesis of PF is not yet clear. The two anti fibrosis drugs approved for IPF treatment, nidanib and pirfenidone, have been proved to reduce the decline of pulmonary function of PF, but both have side effects. So far, there is no obvious and effective treatment to prevent the progress of PF. Therefore, this review focuses on the different cells, molecular mechanisms involved in PF and the current treatment progress of PF, so as to provide theoretical support for a better understanding of these cells, molecular mechanisms and drug development and application in PF.

Ciltacabtagene autoleucel—a novel BCMA-directed CAR T-cell therapy in patients with relapsed or refractory multiple myeloma

DUAN Yuanyuan, LI Zijian

2022, 27(10):  1145-1154.  doi:10.12092/j.issn.1009-2501.2022.10.009

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On February 28, 2022，the U.S. Food and Drug Administration (FDA) approved Ciltacabtagene autoleucel (Cilta-cel) for the treatment of relapsed or refractory multiple myeloma (RRMM) in adults. Cilta-cel is the first FDA-approved cell therapy product in China and the second chimeric antigen receptor (CAR)-T cell immunotherapy to target the B cell maturation antigen (BCMA) approved by FDA around the world. Recent studies have found that patients with RRMM treated with Cilta-cel have an overall remission rate (ORR) of 97%and a 12-month progression-free rate of 77%; common adverse effects include neutropenia, thrombocytopenia, anemia, cytokine release syndrome (CRS), neurotoxicity and so on. In this article, we summarize the mechanism of drug action, indications, pharmacokinetics, clinical studies and adverse effects of Cilta-cel briefly.

Research advance of chrysoeriol on its pharmacological action and underlying mechnism

DENG Ying, BAI Shutong

2022, 27(10):  1155-1162.  doi:10.12092/j.issn.1009-2501.2022.10.010

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Chrysoeriol is a natural flavonoid compound, which is widely present in many kinds of traditional Chinese medicine and medicinal herbs. In recent years, studies of Chrysoeriol on the pharmacological effects and its glycosides have gradually increased, especially in anti-tumor, anti-oxidative damage and anti-inflammatory immune regulation, etc., showing good pharmacological effects, and it has prospective potency as a candidate to develop new drug in those domain. This article briefly reviews the pharmacological effects and underlying mechanisms of chrysoeriol, so that researchers can understand the pharmacological characteristics of this compound, and also provide references for the development of new drugs based on this ingredient.

Research progress on Nrf2 in diabetic cardiomyopathy and intervention of traditional Chinese medicine

WANG Wenjuan, QI Mingrui, TIAN Limin

2022, 27(10):  1163-1170.  doi:10.12092/j.issn.1009-2501.2022.10.011

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As a cardiovascular complication of diabetes, diabetic cardiomyopathy seriously affects the prognosis of patients with diabetes. The incidence and mortality of diabetic cardiomyopathy increase, and has emerged as a research hotspot in current years. The pathogenesis of diabetic cardiomyopathy is complex, involving a range of signaling pathways in its incidence and development. Nuclear factor NF-E2-related factor 2 (Nrf2), as a powerful antioxidant gene, enhances the capacity of the myocardium to withstand oxidative stress via interplay with different signaling elements and exerts anti-inflammatory response, anti-myocardial fibrosis, and anti-apoptosis effects. Researches have shown that certain ingredients of traditional Chinese medicine can alleviate the myocardial injury by affecting the relationship of Nrf2 with other signaling factors via enhancing the expression of Nrf2. Here we review the role of Nrf2 and therapy of traditional Chinese medicine in diabetic cardiomyopathy in hope of providing referential idea for the treatment of diabetic cardiomyopathy.A reference for the prevention and therapy of diabetic cardiomyopathy.

Mechanism of action of bile acid metabolism in regulating inflammatory bowel disease and the research and development of drugs

DUAN Ruixiao, ZHAO Yifan, YE Yongjuan, LIU Min, LI Qiang, ZHOU Yongning

2022, 27(10):  1171-1181.  doi:10.12092/j.issn.1009-2501.2022.10.012

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Inflammatory bowel disease (IBD) is a chronic and relapsing intestinal inflammatory disease with an increasing incidence and non-fatal disease burden worldwide. The etiology of IBD is complex, and the pathogenesis has not been completely clarified. Bile acids (BAs) are the main components of bile, which can participate in the occurrence and development of IBD by binding to bile acid receptors and regulating intestinal flora. This article focuses on the mechanism of BAs metabolism in the pathogenesis of IBD, and the research and development progress of drugs based on BAs and their related targets, so as to lay a foundation for the prevention, treatment and prognosis of IBD in the future.

Reseach progress on the role of ErbB2 in cardiac disease

CHEN Yunjie, ZHOU Xuan, ZHANG Yuanbin, WANG Xu, LIN Zhu, ZHU Suyan

2022, 27(10):  1182-1189.  doi:10.12092/j.issn.1009-2501.2022.10.013

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Cardiac disease is the general term of diseases, caused by damage to the structure or abnormal function of the heart. Its morbidity and mortality have remained high, seriously threatening the lives and health of people. The tyrosine kinase receptor ErbB2 (also known as EGFR2 or HER2) was originally discovered for its oncogenic activity, however, recent studies have found that ErbB2 have protective effects in various heart diseases. Therefore, this article reviews the role and underlying mechanism of ErbB2 in myocardial infarction, myocardial ischemia/reperfusion injury, cardiac hypertrophy, heart failure, doxorubicin-induced cardiotoxic injury and diabetic cardiomyopathy. Furthermore, this article also preliminarily discusses the application prospects, limitations and development directions of ErbB2 as a clinical diagnostic marker and therapeutic target for heart disease. 

Advances in the treatment of potassium-competitive acid blockers in reflux esophagitis

YANG Mengjiao, YUAN Hao, ZHENG Ya, WANG Yuping, GUO Qinghong

2022, 27(10):  1190-1196.  doi:10.12092/j.issn.1009-2501.2022.10.014

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Reflux Esophagitis (RE) is a gastroesophageal motility disorder mainly caused by lower esophageal sphincter disorder caused by a variety of injury factors, acid-suppressing drugs such as Proton Pump Inhibitors (PPIs) are often used clinically. With the increase of PPIs-resistant reflux esophagitis cases, the demand for the pharmacokinetics and pharmacodynamics of acid-suppressing drugs is higher. In recent years, the emergence of a new class of acid-suppressing drugs, potassium-competitive acid blockers (P-CABs), has solved some clinical deficiencies of traditional proton pump inhibitors. It has the characteristics of effective, longer-lasting acid suppression, the inhibitory effect on gastric acid secretion is not affected by the state of gastric acid secretion, the individual differences in drug metabolism and efficacy are smaller, and the drug efficacy is not affected by food intake or not. It has obvious advantages in the efficacy of severe erosive esophagitis and PPIs-resistant severe erosive esophagitis, and is more cost-effective, and is expected to replace PPI as the first-line treatment for reflux esophagitis.    

Progress in the treatment of mucosal pemphigoid

LU Xiaohong, HE Caifeng, Ci Chao, YUAN Tao

2022, 27(10):  1197-1200.  doi:10.12092/j.issn.1009-2501.2022.10.015

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Mucosal pemphigoid is a rare subepidermal immune bullous disease, mainly involving the oral cavity, eyes and other mucous membranes, with the risk of scarring, which can be life-threatening in severe cases. For patients with mucosal pemphigoid, early diagnosis and early treatment can avoid serious complications. For mild patients, dapsone or topical glucocorticoids can be used; for severe patients, combination of immunosup-pressants helps to improve clinical efficacy and reduce the dosage of glucocorticoid, including cyclophosphamide, azathioprine, methotrexate, and mycophenolic acid esters. For some refractory cases without any response to the treatments of dapsone, glucocorticoids and immunosuppressants, biological agents (including rituximab, etanercept, infliximab, and braziltinib), intravenous immune globulin and other therapies can be selected. For some patients with mucosal scarring, surgery or laser therapy can be considered to improve symptoms. However, it is necessary to further demonstrate the clinical efficacy of some immunosuppressants and biologic agents on mucosal pemphigoid in a lot of larger clinical trials.