Tianxiangdan (TXD), a traditional Chinese herbal remedy, demonstrates efficacy in mitigating myocardial ischemia-reperfusion (I/R)-induced damage. This study employed network pharmacology to evaluate the therapeutic targets and mechanisms of TXD in treating I/R. High-performance liquid chromatography-mass spectrometry (HPLC-MS) identified 86 compounds in TXD. Network pharmacological analysis predicted potential target genes and their modes of action. Cardiac function, ischaemic ST changes, lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) activity, myocardial fiber, and infarct size were assessed using in vivo and in vitro I/R injury models. Estrogen receptor alpha (ERα) protein expression and estradiol (E2) levels were measured to confirm TXD's impact on estrogen levels and ERα expression. To examine if TXD reduces I/R injury through ERα, an AZD group (300 nmol·L^-1 AZD9496 and 15% TXD serum) was compared to a TXD group (15% TXD serum). The study hypothesized that TXD upregulates the ERα-mediated iron metamorphosis pathway. I/R injury-induced ferroptosis was identified using a Fer-1 group (1.0 μmol·L^-1 Fer-1 and 15% TXD serum) to elucidate the potential association between ferroptosis and ERα proteins. A DCFH-DA probe detected reactive oxygen species (ROS) and Fe²⁺, while Western blotting assessed target protein expression. Both in vitro and in vivo experiments demonstrated that TXD attenuated I/R injury by reducing elevated ST-segment levels, improving cardiac injury biomarkers (LDH, MDA, and SOD), alleviating pathological features, and preventing I/R-induced loss of cell viability in vitro. The effects and mechanisms of TXD on I/R injury-associated ferroptosis were investigated using I/R-induced H9c2 cells. The TXD group showed significantly decreased ROS and Fe²⁺ levels, while the AZ group (treated with AZD9496) exhibited increased levels. The TXD group demonstrated enhanced expression of ERα and glutathione peroxidase 4 (GPX4), with reduced levels of P53 protein and ferritin-heavy polypeptide 1 (FTH1). The AZ group exhibited contrasting effects on these expression levels. The literature indicated a novel connection between ERα and ferroptosis. TXD activates the ERα signaling pathway, promoting protection against I/R-induced myocardial cell ferroptosis. This study provides evidence supporting TXD use for myocardial ischemia treatment, particularly in older female patients who may benefit from its therapeutic outcomes.
Animals ; Ferroptosis/drug effects* ; Estrogen Receptor alpha/genetics* ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Mice ; Humans ; Mice, Inbred C57BL ; Estradiol/metabolism*

Objective : To explore the mechanism of proliferation of gastric cancer cells induced byHelicobacter pylori(Hp) from the perspective of the mitochondrial unfolded protein response(UPRMT). Methods : C57BL6/J mice, human gastric cancer cells AGS and SGC-7901 cells were infected with Hp, mitochondrial proteins were extracted, and the expressions of UPRMT, including activation of transcription factor 5(ATF5), heat shock protein 60(mtHSP60), heat shock protein 70(mtHSP70) and mitochondrial protease(ClpP), were detected by Western blot. Immunohistochemistry was used to locate the expression sites of 4 proteins in mouse gastric tissue. AGS and SGC-7901 cells were infected with Hp, and cell proliferation was detected by RTCA and CCK-8. Finally, the expression of four indexes in gastric cancer tissues was analyzed by TCGA samples in the UALCAN database. Results : Hp infection could significantly promote the expression of ATF5, mtHSP60, mtHSP70 and ClpP in the mitochondria of gastric epithelial cells of C57BL6/J mice, AGS and SGC-7901 cells, and promote the proliferation of gastric cancer cells. When compared to normal gastric tissues in TCGA samples, ATF5, mtHSP60, mtHSP70, and ClpP were highly expressed in gastric cancer tissues, with statistically significant difference(allP<0.01). Conclusion Hp infection can induce UPRMTin gastric epithelial cells and gastric cancer cells, which in turn promotes cell proliferation.

Background and Objectives: Cancer stem cells (CSCs) with tumorigenic potential are reported as the crucial factors of hepatocellular carcinoma (HCC) recurrence and therapy resistance. Bone mesenchymal stem cells (BMSCs) are documented to play an important role in the protection of hepatocytes. Bie Jia Jian pill (BJJP), a Traditional Chinese Medicine, has been used to treat liver fibrosis and liver cancer. This study aimed to explore the potential role of combined use of BJJP with BMSCs in HCC cell lines. Methods: and Results: Flow cytometry was used to identify BMSCs isolated from BALB/c mice and CSCs enriched from Huh7 cells by measuring CD24, CD133, CD44, CD73, CD105, CD166, CD29, CD14 and CD34. Differentiation potential of BMSCs was also determined. Cell viability and proliferation ability of CSCs were determined by CCK-8 assay and clone formation assay. The expressions of CSCs biomarkers and Wnt/β-catenin signal pathway related proteins were determined by PCR and western blot. TOP-Flash/FOP-Flash luciferase assay was applied to measure the activity of β-catenin/TCF. Compared with untreated CSCs, BJJP or BMSCs treatment alone on CSCs lead to increased miR-140 expression and cell apoptosis, as well as decreased expressions of CD24, CD133, EpCAM and cell viability.Downregualted expressions of Wnt/β-catenin signal pathway related proteins, Wnt3a and β-catenin were found in response to BJJP or BMSCs treatment alone. The combination of BJJP＋BMSCs treatment on CSCs could further enhance the suppressive effect on CSCs. Down-regulation of miR-140 in CSCs partially blocked the effects of BMSCs or BMSCs＋BJJP on the expressions of Wnt3a and β-catenin as well as the cell viability and apoptosis of CSCs.Reversed expression pattern was found in CSCs transfected with miR-140 overexpression. Conclusions Taken together, we demonstrate that BJJP＋BMSCs together could further enhance the suppressive effect on CSCs through regulating miR-140 and suppressing Wnt/β-catenin signal pathway. This study demonstrated the potential of BJJP＋BMSCs in therapeutic treatment of HCC.

Background and Objectives: Cancer stem cells (CSCs) with tumorigenic potential are reported as the crucial factors of hepatocellular carcinoma (HCC) recurrence and therapy resistance. Bone mesenchymal stem cells (BMSCs) are documented to play an important role in the protection of hepatocytes. Bie Jia Jian pill (BJJP), a Traditional Chinese Medicine, has been used to treat liver fibrosis and liver cancer. This study aimed to explore the potential role of combined use of BJJP with BMSCs in HCC cell lines. Methods: and Results: Flow cytometry was used to identify BMSCs isolated from BALB/c mice and CSCs enriched from Huh7 cells by measuring CD24, CD133, CD44, CD73, CD105, CD166, CD29, CD14 and CD34. Differentiation potential of BMSCs was also determined. Cell viability and proliferation ability of CSCs were determined by CCK-8 assay and clone formation assay. The expressions of CSCs biomarkers and Wnt/β-catenin signal pathway related proteins were determined by PCR and western blot. TOP-Flash/FOP-Flash luciferase assay was applied to measure the activity of β-catenin/TCF. Compared with untreated CSCs, BJJP or BMSCs treatment alone on CSCs lead to increased miR-140 expression and cell apoptosis, as well as decreased expressions of CD24, CD133, EpCAM and cell viability.Downregualted expressions of Wnt/β-catenin signal pathway related proteins, Wnt3a and β-catenin were found in response to BJJP or BMSCs treatment alone. The combination of BJJP＋BMSCs treatment on CSCs could further enhance the suppressive effect on CSCs. Down-regulation of miR-140 in CSCs partially blocked the effects of BMSCs or BMSCs＋BJJP on the expressions of Wnt3a and β-catenin as well as the cell viability and apoptosis of CSCs.Reversed expression pattern was found in CSCs transfected with miR-140 overexpression. Conclusions Taken together, we demonstrate that BJJP＋BMSCs together could further enhance the suppressive effect on CSCs through regulating miR-140 and suppressing Wnt/β-catenin signal pathway. This study demonstrated the potential of BJJP＋BMSCs in therapeutic treatment of HCC.

Objective To analyze the relationship between the changes of fasting plasma level of leptin and obesity in patients with insulinoma before operation.Methods From January 2003 to May 2008,40 patients with insulinoma diagnosed at Peking Union Medical College Hospital were selected.Preoperative fasting plasma samples of them were collected.From January 2003 to May 2008,the plasma samples of 28 volunteers matched with age,gender and body weight matched with the patients were collected as the controls.All the subjects were divided into overweight-obesity group and normal weight group according to their body mass index (BMI).Plasma levels of leptin of all the subjects were measured by enzyme linked immunosorbent assay (ELISA).The Mann-Whitney U test and the correlation coefficient test were used for statistical analysis.Results The plasma leptin level of patients with insulinoma was 0.35 ng/mL (0.25 ng/mL to 1.13 ng/mL),which was higher than that of the control group (0.29 ng/mL,0.25 ng/mL to 1.15 ng/mL),and the difference was statistically significant (U =324.50,P =0.003).In the normal-weight group,the plasma leptin level of the patients with insulinoma was 0.35 ng/mL (0.27 ng/mL to 0.62 ng/mL),which was higher than that of the control group (0.28 ng/mL,0.25 ng/mL to 0.37 ng/mL),and the difference was statistically significant (U =28.000,P =0.001).While in the overweight-obesity group,the plasma leptin levels of the patients with insulinoma and the controls were 0.35 ng/mL (0.25 ng/mL to 1.13 ng/mL) and 0.34 ng/mL (0.26 ng/mL to 1.15 ng/mL),respectively,and the difference was not statistically significant (U =153.500,P =0.525).Plasma leptin levels in both the patients with insulinoma and the controls,were correlated with BMI (r =0.355,P =0.025;r =0.571,P =0.001,respectively).Conclusion Preoperative fasting plasma level of leptin increase in patients with insulinoma which is correlated with BMI.

Schizophrenia is a serious neurological disorder characterized by incoordination among thinking, cognition, emotion and behavior, and its pathogenesis remains unclear now. In recent years, an increasing number of reports have found that the occurrence of schizophrenia shares a close relationship with prefrontal cortex (PFC), while the later plays an important role in numerous advanced cognitive functions, including working memory, learning and decision making. This review focuses on the recent development of neural circuits, including neurodevelopment, neurotransmitters, synaptic transmission, functional connectivity of brain regions and neural synchrony oscillation in PFC. Hopefully, this review will help to elucidate the pathogenesis of schizophrenia, and provide approaches and ideas for the treatment of relevant psychiatric disorders.

Objective:To compare and analyze the chemical constituents of volatile oils extracted from the different parts ( flow-ers,leaves and roots) of Stelleropsis tianschanica by chromatography-mass spectrometry (GC-MS). Methods:The volatile oil was ex-tracted by diethyl ether-Soxhlet extraction method and analyzed by GC-MS with a capillary gas chromatographic column. The relative contents of the volatile compounds were calculated by chromatographic peak area normalization method.Results: Totally 179 volatile constituents in the different parts of Stelleropsis tianschanica were identified. Among them,81 compounds were identified in leaves,and the relative content accounted for 82.77% of the total volatile compounds;108 compounds were identified in flowers,and the relative content accounted for 82.85% of the total volatile compounds;112 compounds were identified in roots, and the relative content ac-counted for 85.98% of the total volatile compounds. Totally 33 compounds existed in all the three parts,and the content accounted for 39.24% of the total volatile components in leaves,35.86% in flowers and 48.89% in roots. The relative content of(Z,Z)-9,12-oc-tadecadienoic acid in leaves,flowers and roots of S. tianschanica was the highest,which accounted for 11.12%,9.8% and 22.49%, respectively. Conclusion:The different parts of S. tianschanica have similar volatile components, while the specific substances and the contents are different.

In the long course of traditional Chinese medicine (TCM) development history,generations of physicians in their long-term medical practice,have paid attention to assimilate and apply new technology and new theory,constantly enrich and perfect the medical technologies,methods and theory systems.It is particularly important to promote the innovation of TCM theory and guide the clinical application of TCM through the learning and absorption of advantages from modern technologies and biomedicine to transform as part of TCM,and then,to expatiate with TCM language.It is especially important in the promotion of TCM theory innovation and clinical guidance of TCM practice.This paper overviewed the common points between TCM and modern medicine from the aspects of balance and steady state of organism,zangfu-organ relationship,etiology and pathogenesis,syndrome differentiation methods,compatibility of Chinese herbal medicine and formula,medicinal properties and pharmacology,etc.The feasibility of applying modern medicine in the interpretation of TCM and its development prospects was expatiated.It provided new ideas and new methods in TCM development.

Objective: To determine whether microtubule-associated protein 2 (MAP2) and microtubule-associated protein 1B (MAP1B) could be prognostic biomarkers for patients with pancreatic neuroendocrine tumors (PNETs). Methods:With immunohisto-chemical staining, the expressions of MAP2 and MAP1B were examined in 193 and 120 primary tumors and peritumoral tissues, re-spectively. Then, the relationship between the expression of each protein and clinicopathological characteristics, including prognosis was analyzed. Results:MAP2 and MAP1B were expressed in 88 of 193 (45.6%) and 77 of 120 (64.2%) tumors, respectively. The expres-sion of MAP2 was significantly associated with the favorable overall survival of patients with PNETs (P=0.012). Moreover, MAP2 expres-sion was associated with the improved overall survival in a subset of patients with stageⅡand stageⅢtumors (P=0.017). The MAP1B expression did not correlate with other clinicopathological features and prognosis. Conclusion:MAP2 could be a novel, independent prognostcbiomarker for PNETs.

This study was aimed to predict active compounds,drug targets and potential diseases of Yi-Guan decoction (YGD) by network pharmacological technology,and to clarify molecular mechanisms of YGD efficiency on different diseases with liver and kidney yin deficiency syndrome (LKYDS).Chemistry compounds,targets and related diseases from YGD were collected from TCMSP,TCM Database@Taiwan,TCMID,HIT,Drugbank,PubChem and TTD databases.The YGD compounds-targets-diseases network was constructed.The network topology was analyzed by Cytoscape software.The analysis of GO biological processes and KEGG pathways enrichment were performed by DAVID website.The results showed that 849 chemical compounds were identified from Beishashen,Maidong,Danggui,Shengdihuang,Chuanlianzi and Gouqizi.There were 49 active CHM compounds that were both oral bioavailability (OB) ≥ 30％ and drug-likeness (DL) ≥ 0.18,corresponding to 200 target proteins and 264 diseases.The top three GO biological processes were response to organic substance,regulation of cell proliferation,and response to endogenous stimulus,respectively.The top three KEGG pathways were pathways in cancer,hepatitis B,and prostate cancer,respectively.It was concluded that the analysis on YGD was conducted based on network pharmacology,and the compound-target-disease network was built,which may help to clarify the mechanisms of YGD efficiency on different diseases with LKYDS.It can provide clues to find new potential clinical adaptation of disease and new drugs.