1.Mechanism of Qingrun Prescription-containing Serum Improving Insulin Resistance in HepG2 Cells via Branched-chain α-keto Acid Dehydrogenase Regulation of Branched-chain Amino Acids (BCAAs)/mTOR Pathway
Xiangwei BU ; Xiaohui HAO ; Runyun ZHANG ; Meizhen ZHANG ; Ze WANG ; Haoshuo WANG ; Jie WANG ; Qing NI ; Lan LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):90-98
ObjectiveTo investigate the effect of Qingrun prescription(QRP)-containing serum on improving insulin resistance in HepG2 cells and its potential mechanisms. MethodsAn insulin resistance model was established in HepG2 cells with 1×10-6 mol·L-1 insulin. Branched-chain α-keto acid dehydrogenase (BCKDH) gene silencing was achieved using siRNA, and the cells were divided into 8 groups: normal group, model group (1×10-6 mol·L-1 insulin), metformin group (1 mmol·L-1 metformin), high-, medium-, and low-dose QRP groups (20%, 10%, and 5% QRP-containing serum, respectively), QRP + siRNA-silenced BCKDH (si-BCKDH) group (10% QRP-containing serum + si-BCKDH), and QRP + si-NC group (10% QRP-containing serum + si-NC). Glucose levels in the supernatant were measured with a glucose assay kit, while glycogen content was assessed using a glycogen assay kit. Levels of branched-chain amino acids (BCAAs) and branched-chain keto acids (BCKAs) were determined using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). mRNA transcription and protein expression levels of BCKDH, dishevelled, Egl-10, and pleckstrin (DEP) domain-containing mammalian target of rapamycin (mTOR)-interacting protein (DEPTOR), mTOR, and ribosomal protein S6 kinase 1 (S6K1) were detected using real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot. ResultsCompared to the normal group, the model group exhibited significantly decreased glucose consumption and glycogen content, increased levels of BCAAs and BCKAs, downregulated expression of BCKDH and DEPTOR, and upregulated mTOR and S6K1 expression (P<0.01). In comparison to the model group, QRP treatment at all doses significantly enhanced glucose consumption and glycogen content while reducing BCAAs and BCKAs levels (P<0.01). The high- and medium-dose QRP groups demonstrated significant upregulation of BCKDH mRNA transcription and protein expression, as well as DEPTOR mRNA transcription. Moreover, the DEPTOR protein expression level was significantly increased in high-, medium-, and low-dose QRP groups, while mTOR and S6K1 mRNA and protein expression levels were markedly downregulated (P<0.05, P<0.01). Compared to the QRP + si-NC group, the QRP + si-BCKDH group exhibited increased BCAAs and BCKAs levels, significantly decreased BCKDH mRNA transcription and protein expression, downregulated DEPTOR mRNA and protein expression, and upregulated mTOR and S6K1 mRNA and protein expression (P<0.05, P<0.01). ConclusionQRP may improve insulin resistance by reprogramming BCAAs metabolism. This effect involves upregulating BCKDH, reducing BCAAs and BCKAs levels, and suppressing the mTOR pathway activation.
2.Quality evaluation of Huocao based on UPLC fingerprint and multi-component content determination.
Zheng-Ming YANG ; Ci-Ga DIJIU ; Jian-Long LAN ; Jiang LUO ; Yue-Bu HAILAI ; Tao WANG ; Wen-Bing LI ; Ying LI ; Yuan LIU
China Journal of Chinese Materia Medica 2023;48(11):3000-3013
Huocao(a traditional Chinese herbal medicine) moxibustion is a characteristic technology in Yi medicine suitable for cold-dampness diseases. Huocao, as the moxibustion material, is confusedly used in clinical practice and little is known about its quality control. In this study, UPLC method was used to establish the chemical fingerprint of non-volatile components in Huocao, and the contents of eight phenolic acids such as chlorogenic acid were determined. Multivariate statistical analysis was performed to obtain the indicator components of Huocao for quality evaluation, and thus a comprehensive evaluation system for the quality of Huocao was built. The UPLC fingerprints of 49 batches of Huocao were established, and there were 20 common peaks, of which eight phenolic acids including neochlorogenic acid and chlorogenic acid were identified. Except for three batches of Huocao, the similarity of the other 46 batches was higher than 0.89, suggesting that the established fingerprint method could be used for quality control of the medicinal herb. The correlation coefficient between entropy weight score of the eight phenolic acids and comprehensive fingerprint score in Huocao was 0.875(P<0.01), which indicated that the eight phenolic acids could be used as indicator components for the quality evaluation of Huocao. Furthermore, in multivariate statistical analysis on the common peaks of fingerprint and the contents of the eight phenolic acids, chlorogenic acid, isochlorogenic acid A and isochlorogenic acid C were screened to be the indicator components. The results revealed that the proposed method achieved a simple and accurate quality control of Huocao based on UPLC fingerprint and multi-component content determination, which provided useful data for establishing the quality standard of Huocao.
Chlorogenic Acid
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Entropy
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Hydroxybenzoates
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Quality Control
3. Research progress of circular RNA in drug resistance of liver cancer
Guo-Lin HUANG ; Xiao-Bu LAN ; Yan-E QIN ; Li LI ; Jie YANG
Chinese Pharmacological Bulletin 2023;39(1):13-17
Circular RNAs are novel non-coding RNAs with multiple biological functions, which can participate in biological processes such as the occurrence, development, invasion, and metastasis of liver cancer, as well as drug resistance of liver cancer. This article reviews the roles and mechanisms of circR-NAs in chemotherapy resistance, targeted therapy resistance and immunotherapy resistance in liver cancer, in order to provide new ideas for solving liver cancer resistance.
4.Development of small molecule extracellular signal-regulated kinases (ERKs) inhibitors for cancer therapy.
Xiaoli PAN ; Junping PEI ; Aoxue WANG ; Wen SHUAI ; Lu FENG ; Faqian BU ; Yumeng ZHU ; Lan ZHANG ; Guan WANG ; Liang OUYANG
Acta Pharmaceutica Sinica B 2022;12(5):2171-2192
The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway is widely activated by a variety of extracellular stimuli, and its dysregulation is associated with the proliferation, invasion, and migration of cancer cells. ERK1/2 is located at the distal end of this pathway and rarely undergoes mutations, making it an attractive target for anticancer drug development. Currently, an increasing number of ERK1/2 inhibitors have been designed and synthesized for antitumor therapy, among which representative compounds have entered clinical trials. When ERK1/2 signal transduction is eliminated, ERK5 may provide a bypass route to rescue proliferation, and weaken the potency of ERK1/2 inhibitors. Therefore, drug research targeting ERK5 or based on the compensatory mechanism of ERK5 for ERK1/2 opens up a new way for oncotherapy. This review provides an overview of the physiological and biological functions of ERKs, focuses on the structure-activity relationships of small molecule inhibitors targeting ERKs, with a view to providing guidance for future drug design and optimization, and discusses the potential therapeutic strategies to overcome drug resistance.
5.Clinical characteristics and pregnancy outcomes of pregnant women with left ventricular non-compaction
Huanying WANG ; Zhaoliang BAO ; Dong YANG ; Yanna LI ; Lan BU ; Wenhong DING ; Jun ZHANG
Chinese Journal of Obstetrics and Gynecology 2022;57(5):332-338
Objective:To investigate the clinical characteristics and pregnancy outcomes in pregnant women with left ventricular non-compaction (LVNC).Methods:The clinical data of seven pregnant women with LVNC from January 2011 to December 2021 in Beijing Anzhen Hospital,Capital Medical University were retrospectively analyzed, including age, gestational age of symptom first occured, LVNC history, clinical symptoms, New York Heart Association (NYHA) cardiac function class, echocardiography, blood brain natriuretic peptide (BNP), treatment and the maternal and fetal outcomes.Results:Five cases were diagnosed before pregnancy, of which there were three women with medication; one case diagnosed in the month of pregnancy; one case diagnosed at 36 weeks of gestation. NYHA cardiac function was grade Ⅰ in four cases and grade Ⅱ in three cases before or during the first trimester of pregnancy. Of the five pregnant women who underwent echocardiography, there were one case of left ventricular insufficiency, three cases of mild left ventricular dysfunction and one case of normal left ventricular function before or during the first trimester of pregnancy. Of the five pregnant women to the second and third trimester of pregnancy, there were one case of grade Ⅳ, one case of grade Ⅲ, two cases of grade Ⅱ-Ⅲ and one case of grade Ⅱ in NYHA class ; three cases of left ventricular insufficiency, two cases of normal left ventricular function by echocardiography four cases had cardiac symptoms at 15-24 weeks of gestation and were treated with medication. In four cases, blood BNP increased to 214-1 197 ng/L during pregnancy, and were 89-106 ng/L after termination of pregnancy. There were 4 cases with arrhythmia. Indications for termination of pregnancy: LVNC complicated with heart failure in two cases, LVNC complicated with decreased cardiac function and threatened preterm birth in one case, complicated with pregnancy at full term in two cases, LVNC complicated with severe pulmonary hypertension in one case, and left ventricular dysfunction in one case. Cesarean section in four cases in the third-trimester, in one case in the second-trimester, and forceps curettage in two cases were taken. Two full-term infants,two preterm infants were born without LVNC.Conclusions:Women diagnosed with LVNC and low left ventricular ejection fraction before pregnancy are more prone to decreased cardiac function during pregnancy. Carrying out pregnancy risk assessment and strengthening the multi-disciplinary team management of high risk factors in pregnancy are conducive to achieve good pregnancy outcomes.
6.Attainment of Lipid Targets Following Coronary Artery Bypass Graft Surgery:Can We Do Better?
Nick S. R. LAN ; Umar S. ALI ; Bu B. YEAP ; P. Gerry FEGAN ; Robert LARBALESTIER ; Damon A. BELL
Journal of Lipid and Atherosclerosis 2022;11(2):187-196
Objective:
Patients undergoing coronary artery bypass graft (CABG) surgery remain at high cardiovascular risk; however, few studies have evaluated lipid management and attainment of lipid targets in these patients. We investigated the proportion of CABG surgery patients who attained low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (HDL-C) targets.
Methods:
Data were retrospectively obtained from patients undergoing CABG surgery at an Australian tertiary hospital between February 2015 and August 2020. The most recent lipid profile was recorded (at least 3 weeks post-operatively). We studied patients with electronically available data to ensure accuracy. Target LDL-C was defined as <1.4 (54 mg/dL) and <1.8 mmol/L (70 mg/dL), and target non-HDL-C as <2.2 (85 mg/dL) and <2.6 mmol/L (100 mg/dL), as per the 2019 and 2016 European dyslipidaemia guidelines, respectively.
Results:
Follow-up lipid results were available for 484 patients (median post-operative follow-up, 483 days; interquartile range, 177.5–938.75 days). The mean age was 62.7±10.5 years and 387 (80.1%) were male. At discharge, 469 (96.9%) patients were prescribed statins, 425 (90.6%) high-intensity. Ezetimibe was prescribed for 62 (12.8%) patients and a proprotein convertase subtilisin-kexin type 9 inhibitor for 1. LDL-C levels <1.4 and <1.8 mmol/L were attained in 118 (24.4%) and 231 (47.7%) patients, respectively, and non-HDL-C levels <2.2 and <2.6 mmol/L in 140 (28.9%) and 237 (49.0%) patients, respectively.
Conclusion
The use of non-statin lipid-lowering therapies was limited, and many CABG surgery patients did not attain lipid targets despite high-intensity statins. Further studies are required to optimise lipid management in this very high-risk population.
7.Research progress on chemical constituents,pharmacological activities,and quality control of Patrinia villosa.
Yu FAN ; Dong-Mei SHA ; Ma-Li-Niu SHA ; Jian-Long LAN ; Lai-Yue-Bu HAI ; Bie-Jun-Zhang QU ; Xin-Jia YAN ; Yuan LIU
China Journal of Chinese Materia Medica 2022;47(22):6005-6019
Patrinia villosa, regarding its functions in clearing heat and detoxification and eliminating carbuncles and pus, is widely used as a traditional medicinal herb that contains rich nutrition and substances such as various amino acids, vitamins, and soluble su-gar, and it is also an edible wild herb in Chinese folk tradition for 2 000 years. In 1973, Japanese scholars firstly separated three iridoids from Japanese P. villosa, and by 2021, chemical components such as flavonoids, iridoids, organic acids, triterpenoids, phenylpropanoids, and steroids have been found, which have multiple pharmacological effects, including antioxidant, antitumor, anti-diarrhea, antibacterial, sedative, and liver protection capabilities. Studies indicate that flavonoids, saponins, phenylpropanoids, and triterpenoids in P. villosa are vital substances for its pharmacological activities. However, the quality of this medicinal material cannot be controlled due to the unclear records in ancient books in the past dynasties and different drug use habits in different places, and thus its circulation is chaotic. At present, researchers have used flavonoids, organic acids, phenylpropanoids, triterpenoid saponins, and other compounds to conduct studies in this regard. Therefore, on the basis of the existing literature resources, we comprehensively summarize the chemical constituents, pharmacological activities, and quality control of P. villosa to further provide a reference for the safety and effectiveness of clinical drug use and lay a foundation for the follow-up experimental research.
Patrinia/chemistry*
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Flavonoids/pharmacology*
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Saponins
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Triterpenes/pharmacology*
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Iridoids
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Quality Control
8.Textual research on classical prescriptions in Mongolian medicine.
Bi-Lige MENGHE ; Wu-Li-Ji AO ; Xiu-Lan WANG ; Li-Guo YANG ; Na-Bu-Qi SUDU ; Guang GUO ; Zhi-Jie BAO ; Qi-Er MU ; Xiao-Hua BAO
China Journal of Chinese Materia Medica 2021;46(19):5137-5143
Mongolians have a long history of using prescriptions, which can be classified into four stages as follows: the germination and experience accumulation stage before the 13 th century, the theoretical formation stage from the 13 th to 16 th century, the rapid development stage from the 17 th to 20 th century, and the leaping development stage from the mid-20 th century to the present. The prescriptions from the ancient classical or representative medical books have always been used by Mongolian physicians for generations, and they are still in use due to the definite curative effects. In 2008, the Notice on Issuing the Supplementary Provisions to the Registration and Management of Traditional Chinese Medicine(TCM) described that China has attached more importance to the excavation and development of classical prescriptions. As stipulated in the Law of the People's Republic of China on Traditional Chinese Medicine, the classical prescriptions should be those available in ancient TCM classics and still in wide use, with exact curative effects, distinct features, and obvious advantages. This paper expounded the historical formation and development of classical prescriptions in Mongo-lian medicine, introduced the five most influential ancient medical books revealing the formation and development of these classic prescriptions, and traced the origin of such classical prescriptions as Wenguanmu Siwei Decoction, Shouzhangshen Bawei Decoction, Jianghuang Siwei Decoction and summarized the origin, development history and characteristics of classical prescriptions in Mongolian medicine, aiming to provide a reference for their further research and development.
Books
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China
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Drugs, Chinese Herbal
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Humans
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Medicine, Chinese Traditional
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Medicine, Mongolian Traditional
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Prescriptions
9.Mechanisms of Classical Prescriptions and Their Active Components in Immunosenescence Regulation: A Review
Yue TU ; Guang-xia NI ; Yi-gang WAN ; Huang HUANG ; Bu-hui LIU ; Qi-jun FANG ; Mei-zi WANG ; Jia-xin CHEN ; Liang YUE ; Zi-lin LI ; Fee-lan CHONG
Chinese Journal of Experimental Traditional Medical Formulae 2021;27(18):190-197
As the body ages, the immune system will undergo a series of changes, which are termed "immunosenescence" and are embodied in immune cells. Previous studies have shown that the immune cells involved in the regulation of immunosenescence include intrinsic immune cells and adaptive immune cells. Intrinsic immune cells are neutrophils, monocytes/macrophages, myeloid-derived suppressor cells, dendritic cells, natural killer cells, etc., and the underlying mechanisms involve the regulation of cell number, phagocytosis, chemotaxis, adhesion, the function of toll-like receptor (TLR), antigen presentation, macrophage polarization, cytotoxicity, migration, etc. The adaptive immune cells include T-lymphocytes and B-lymphocytes, and the underlying mechanisms involve the regulation of cell development, proliferation, differentiation, cell number, telomerase activity, self-reactive antibodies, etc. Immunosenescence is the manifestation of aging in the human body and is also an important target for delaying aging by Chinese medicine and western medicine. In recent years, scholars have found some classical prescriptions and their active components (such as Dushentang and total saponins in
10.Clinical efficacy of early pancreatic duct stenting in the treatment of acute pancreatitis
Weijie YAO ; Zuozheng WANG ; Yafei YANG ; Zhu LAN ; Jianjun SONG ; Dong JIN ; Minghai SHI ; Ming LI ; Wenping BU ; Genwang WANG
Chinese Journal of Digestive Surgery 2021;20(12):1318-1323
Objective:To investigate the clinical efficacy of early pancreatic duct stenting in the treatment of acute pancreatitis.Methods:The retrospective and descriptive study was conducted. The clinical data of 201 patients with acute pancreatitis who were admitted to General Hospital of Ningxia Medical University from October 2011 to December 2017 were collected. There were 106 males and 95 females, aged from 18 to 90 years, with a median age of 62 years. Of 201 patients, there were 178 cases with moderate severe acute pancreatitis and 23 cases with serious severe acute pancreatitis. Patients were treated with pancreatic duct stenting within 48 hours after admission. Observation indicators: (1) treatment; (2) follow-up. Follow-up was conducted using outpatient examination and telephone interview to detect recurrence of acute pancreatitis after surgery up to June 2019. Measurement data with normal distribution were represented by Mean± SD, and the independent sample t test was used for comparison between groups, and the matched samples t test was used for comparison between before and after. Measurement data with skewed distribution were represented by M( P25 ,P75) or M(range), and the Mann-Whitney U test was used for comparison between groups, and the Wilcoxon signed rank sum test was used for comparison between before and after. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test . Results:(1) Treatment: 201 patients received pancreatic duct stenting successfully, 63 of which were detected pancreatic obstruction with white-floc. The interval time from admission to surgery , operation time, time for initial oral intake, duration of hospital stay and hospital expenses of 201 patients were 10 hours(4 hours,22 hours), (35±15)minutes, 3 days(2 days,5 days), 6 days(5 days,10 days) and 3.8×10 4 yuan (3.0×10 4 yuan,4.9×10 4 yuan). Of 201 patients, 22 patients were transferred to intensive care unit, including 1 case with serious severe underwent inhospital death and 1 case with moderate severe and 7 cases with serious severe underwent auto-discharge from hospital. There were 25 cases with local complications, including 17 cases with pancreatic infectious necrosis, 7 cases with pancreatic walled-off necrosis and 1 case with spleen infarction. All 25 patients were cured after surgical inter-vention or conservative treatment. Further analysis showed that cases being transferred to intensive care unit, cases undergoing surgical treatment, the time for initial oral intake, duration of hospital stay and cases undergoing auto-discharge from hospital were 6, 11, 3 days(2 days,5 days), 6 days(5 days,10 days) and 1 for the 178 moderate severe cases, versus 16, 5, 7 days(4 days,9 days), 9 days (7 days,17 days) and 7 for the 23 serious severe cases, showing significant differences ( χ2=91.561, 6.730, Z=6.485, 5.463, χ2=47.561, P<0.05). The white blood cell count, serum amylase indexes and chronic health evaluation Ⅱ score of 201 patients were (14±6)×10 9/L, 928 U/L(411 U/L,1 588 U/L), 9±5 before admission, versus (10±4)×10 9/L, 132 U/L(72 U/L,275 U/L), 6±4 at 48 hours after admission, respectively, showing significant differences ( t=12.219, Z=11.639, t=16.016, P<0.05). (2) Follow-up: of 201 patients, 153 cases were followed up for 40 months (27 months,55 months). During the follow-up, 32 of the 153 cases had recurrence of acute pancreatitis. Conclusion:Early pancreatic duct stenting is safe and feasible in the treatment of acute pancreatitis.

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