Investigation of the efficacy of Dengzhan Shengmai capsule against heart failure with preserved ejection fraction.

ETHNOPHARMACOLOGICAL RELEVANCE: Heart failure with preserved ejection fraction (HFpEF) has emerged as a condition with high incidence and mortality rates in recent years. Dengzhan Shengmai capsule (DZSMC) is a Chinese patent medicine based on the classic recipe "Shengmai powder". The relevant Chinese medicine ratio of Erigeron breviscapus (Vaniot) Hand.-Mazz., Panax ginseng C.A.Mey., Schisandra chinensis (Turcz.) Baill., and Ophiopogon japonicus (Thunb.) Ker Gawl. is 30 : 6 : 6 : 11 . Traditional Chinese medicine (TCM) is being increasingly explored as a safe and effective treatment modality for HFpEF. Clinical studies have shown that DZSMCs can effectively treat heart failure, however, the mechanism of action of DZSMCs in the treatment of HFpEF are still not clear. AIM OF THE STUDY: To investigate the efficacy and underlying mechanisms of Dengzhan Shengmai capsule (DZSMC), in the treatment of HFpEF by focusing on its ability to treat microvascular inflammation. MATERIALS AND METHODS: First, the efficacy of DZSMCs against HFpEF was predicted by network pharmacology. After 3 days of adaptive feeding in SPF-grade polypropylene cages, the mice in the Model group, DZSMC group, and Captopli group underwent single kidney resection, and micropumps were implanted in their backs for continuous infusion of aldosterone at a rate of 0.3 µg/h for 4 weeks. Moreover, the mice were given DZSMCs or Captopli via oral gavage for four weeks. Overall, cardiac function was evaluated in mice, and cardiac ultrasound and blood biochemical indices were evaluated in HFpEF mice. RESULTS: DZSMCs can ameliorate myocardial hypertrophy and cardiomyocyte damage caused by excessive myocardial stress, ultimately mitigating long-term cardiac impairment; it aids in the restoration of myocardial fibre proliferation and enhances mitochondrial morphology and function. In a murine model of ventricular hypertrophy and left ventricular dysfunction, which are indicative of cardiac insufficiency, the administration of DZSMCs resulted in notable improvements. Echocardiographic and overall assessments of cardiac function revealed a reduction in cardiac dysfunction and ventricular hypertrophy post-DZSMC intervention. Moreover, intervention with DZSMCs led to a reduction in the serum levels of several markers associated with chronic systemic inflammation, such as sST2, IL1RL1, CRP, and IL-6. Simultaneously, the levels of indicators of microvascular inflammation, including VCAM and E-SELECTIN, also decreased following DZSMC intervention. These findings suggest the potential multifaceted impact of DZSMCs in alleviating cardiac abnormalities, mitigating systemic inflammation, and reducing microvascular inflammatory markers, highlighting their promising therapeutic role in managing myocardial health. CONCLUSIONS: These results provide novel evidence that DZSMCs improve HFpEF by regulating microvascular inflammation.

Comparison of ultrasound-guided and traditional localisation in intraspinal anesthesia: a systematic review and network meta-analysis.

OBJECTIVES: The optimal puncture technique for neuraxial anaesthesia in different populations is unclear. We sought to obtain data from randomised controlled trials comparing the impact of ultrasound-guided technology and traditional positioning technology on the success rate of neuraxial anaesthesia. DESIGN: Systematic review and network meta-analysis using study populations, interventions, intervention comparisons, outcome measures and study types. DATA SOURCES: PubMed, Embase, Cochrane Library and Web of science were searched until 31 September 2022. ELIGIBILITY CRITERIA: We included randomised controlled trials comparing three types of neuraxial anaesthesia: ultrasound-assisted, ultrasound real-time guidance and conventional positioning to describe which neuraxial anaesthesia modality is best for patients and to recommend the appropriate one for different populations. DATA EXTRACTION AND SYNTHESIS: Five independent reviewers retrieved, screened and edited included studies using standardised methods. Assess risk of bias using the Cochrane Collaboration and Evidence Project tools. Network meta-analysis was performed using STATA V.15 statistical software. RESULTS: Twenty-two studies containing three different interventions were included. The SUCRA values of first-pass success rates for the three neuraxial anaesthesia methods were real-time guidance (82.8%), ultrasound-assisted (67.1%) and traditional positioning (0.1%). Both ultrasound techniques improved first-pass success rates compared with traditional localization, but there was no significant difference between the two. Subgroup analysis showed that the use of real-time ultrasound guidance for neuraxial anaesthesia in pregnant and patients with obesity improved first-pass success rates. Ultrasound-assisted technology can improve first-attempt success rates in older patients with abnormal lumbar spine anatomy. CONCLUSION: Compared with conventional positioning, ultrasound guidance technology can improve the first-pass success rate of neuraxial anaesthesia, but there is no significant difference between ultrasound-assisted and real-time guidance technology. The results of subgroup analysis tell us that the most suitable neuraxial anaesthesia method is different for different groups of people. PROSPERO REGISTRATION NUMBER: PROSPERO number: CRD42022376041.

Effect of perioperative acupoint electrical stimulation on macrophages in mice under operative stress.

The strong perioperative stress response caused by surgical anesthesia can significantly suppress immune function, and the body is in a state of immunosuppression for 3 to 4 days after surgery, which leads to an increase in the probability of postoperative infection. Traditional Chinese medicine believes that acupuncture points can "reconcile yin and yang", promote the recovery of immune function, and help reduce the incidence of postoperative infection. Macrophages are an important type of immune cells that participate in the body's innate immunity. They have powerful phagocytosis and clearance functions. They can be polarized into M1 and M2 types under the regulation of the body, and play different roles in fighting microbial infections. Among them, the M1 type can participate in the elimination of pathogens. In this study, we will investigate the perioperative acupoint electrical stimulation to alleviate the immunosuppressive state of surgical stress mice, clarify the regulation of perioperative acupoint electrical stimulation on glucocorticoids and the relationship between NF-κB molecules and macrophage polarization.The key molecules of related pathways were verified by glucocorticoid receptor inhibitors, and it was found that electrical stimulation of acupoints during the perioperative period can affect the polarization of macrophages in surgically stressed mice to the M1 type by reducing the level of glucocorticoids and promoting the expression of NF κB molecules. Further reveal the partial mechanism of electroacupuncture regulating the anti-inflammatory and pro-inflammatory processes of macrophages in the immune response.

SATB1/SLC7A11/HO-1 Axis Ameliorates Ferroptosis in Neuron Cells After Ischemic Stroke by Danhong Injection.

Neuronal damage after ischemic stroke (IS) is frequently due to ferroptosis, contributing significantly to ischemic injury. However, the mechanism against ferroptosis in IS remained unclear. The aim of this study was to investigate the potential mechanism of Danhong injection (DHI) and the critical transcription factor SATB1 in preventing neuronal ferroptosis after ischemic stroke in vivo and in vitro. The results showed that DHI treatment significantly reduced the infarct area and associated damage in the brains of the pMCAO mice, and enhanced the viability of OGD-injured neurons. And several characteristic indicators of ferroptosis, such as mitochondrial necrosis and iron accumulation, were regulated by DHI after IS. Importantly, we found that the expression and activity of SATB1 were decreased in the pMCAO mice, especially in neuron cells. Meanwhile, the SATB1/SLC7A11/HO-1 signaling pathway was activated after DHI treatment in ischemic stroke and was found to improve neuronal ferroptosis. Inhibition of SATB1 significantly reduced SLC7A11-HO-1 and significantly attenuated the anti-ferroptosis effects of DHI in the OGD model. These findings indicate that neuronal ferroptosis after IS can be alleviated by DHI through SATB1/SLC7A11/HO-1 pathway, and SATB1 may be an attractive therapeutic target for treating ischemic stroke.

[Analysis of absorbed constituents and network pharmacology research of Xiaoer Fupi Granules].

Xiaoer Fupi Granules, a refined version of the classical prescription Shenling Baizhu Powder, has the effect of invigora-ting spleen, replenishing Qi, harmonizing stomach and resolving accumulation and is commonly used to treat Qi deficiency in spleen and stomach, disordered transportation and transformation, and indigestion of children. However, its medicinal constituents and mechanism remain unclear. We studied the main active constituents and action mechanism of Xiaoer Fupi Granules by integrating network pharmacology and prototype constituent analysis in vivo. This study will help to increase the reliability of database analysis results and lay a foundation for precise medication and mining of quality control markers. On the basis of Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine(BATMAN-TCM), the "key chemical constituents-target" network was constructed. Ultra-performance liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry(UPLC-LTQ-Orbitrap-MS) was employed to analyze the absorbed constituents in rat urine and plasma, so as to validate the network. Further, we used BATMAN-TCM to construct the "absorbed constituents-target-pathway" network and explore the functioning mechanism of Xiaoer Fupi Granules. A total of 86 chemical constituents of Xiaoer Fupi Granules were predicted via BATMAN-TCM, among which only 18.6% were detected in rat plasma and urine. Accor-ding to the "absorbed constituents-target-pathway" network, 8 chemical constituents such as stearic acid and caprylic acid capable of regulating gastric acid and insulin secretion may be the critical constituents of Xiaoer Fupi Granules in invigorating spleen and harmonizing stomach. This study identified the critical active constituents and predicted the action mechanism of Xiaoer Fupi Granules, providing the reference for the research on the material basis of Xiaoer Fupi Granules.

In situ lattice tuning of quasi-single-crystal surfaces for continuous electrochemical modulation.

The ability to control the atomic-level structure of a solid represents a straightforward strategy for fabricating high-performance catalysts and semiconductor materials. Herein we explore the capability of the mechanically controllable surface strain method in adjusting the surface structure of a gold film. Underpotential deposition measurements provide a quantitative and ultrasensitive approach for monitoring the evolution of surface structures. The electrochemical activities of the quasi-single-crystalline gold films are enhanced productively by controlling the surface tension, resulting in a more positive potential for copper deposition. Our method provides an effective way to tune the atom arrangement of solid surfaces with sub-angstrom precision and to achieve a reduction in power consumption, which has vast applications in electrocatalysis, molecular electronics, and materials science.

Yi-Xin-Shu capsule ameliorates cardiac hypertrophy by regulating RB/HDAC1/GATA4 signaling pathway based on proteomic and mass spectrometry image analysis.

BACKGROUND: Cardiac hypertrophy (CH) forms the main pathological basis of chronic heart failure (CHF). Mitigating and preventing CH is the key strategy for the treatment of ventricular remodeling in CHF. Yi-Xin-Shu capsule (YXS) has been commonly applied in the clinical treatment of CHF in Asian countries for several decades. However, the underlying mechanism of YXS has not been revealed yet. PURPOSE: To assess the efficiency of YXS in CH and identify its potential therapeutic targets for the managing of CH. METHOD: Ultrasonic cardiogram was used to evaluate the cardiac function of CH rats. Hematein Eosin (HE)-staining, Masson-staining and transmission electron microscope were used to measure the morphological changes, cardiac fibrosis degree and ultrastructure characteristics of cardiomyocytes, respectively. ELISA was used to detect the myocardial injury biomarkers. Then, the potential targets regulated by YXS were screened out via proteomic analysis and mass spectrometry image analysis. Finally, the targets were validated by real-time quantitative (RT-q) PCR, immunofluorescence, immunohistochemistry, and western-blotting methods. RESULTS: YXS improved the cardiac function of CH rats and attenuated the injuries in morphology and subcellular structure of cardiomyocytes. A core protein-protein interaction network was established on differentially expressed proteins (DEP) using proteomics analysis. GATA binding protein 4 (GATA4) was identified as the key target regulated by YXS. The results of mass spectrometry image analysis indicated that the expressions of histone deacetylase 1 (HDAC1) and retinoblastoma (RB) could also be regulated by YXS. Further valuative experiments showed that YXS may attenuate CH by regulating the RB/HDAC1/GATA4 signaling pathway. CONCLUSIONS: For the first time, this study discloses the precise mechanism investigation of the efficacy of YXS against CH. These data demonstrate that YXS may protect against CH by regulating the RB/HDAC1/GATA4 signaling pathway.

Signature network-based survey of the effects of a traditional Chinese medicine on heart failure.

ETHNOPHARMACOLOGICAL RELEVANCE: Heart failure (HF) after myocardial infarction (MI) is one of the most common disabling and painful diseases. A traditional Chinese medicine (TCM) formula, Shengmaisan, is known as a multitarget medicine that is widely used clinically to treat heart failure (HF) in Asian countries. However, its mechanism has not been comprehensively demonstrated. AIM OF THE STUDY: To use a prediction network to figure out which disease link SMZ mainly alleviates in HF and find biomarkers related to myocardial fibrosis in the serum for clinical reference. MATERIALS AND METHODS: In this article, we collected a large amount of actual measurement data and our own proteomics data, along with the biomarkers of heart failure staging under study to establish a precise network. Then, we tested and verified the medicinal effect of SMZ in treatment of HF after MI by Measurement of left ventricular wall thickness and ejection fraction by echocardiography. Then we tested the serum level of the potential targets of SMZ predicting by the network we developed using ELISA. RESULTS: the cardiac ejection fraction and retarding the thinning of the anterior wall of the left ventricle increased after treating with SMZ. The serum level of EGFR and MAPK1 decreased in the groups treated with SMZ. CONCLUSION: SMZ can improve the cardiac function of rats with MI by increasing the cardiac ejection fraction and retarding the thinning of the anterior wall of the left ventricle. In addition, SMZ could delay heart failure mainly by inhibiting the progression of myocardial fibrosis through decreasing the EGFR and MAPK1 levels.

Precise Investigation of the Efficacy of Multicomponent Drugs Against Pneumonia Infected With Influenza Virus.

Background: Viral pneumonia is one of the most serious respiratory diseases, and multicomponent traditional Chinese medicines have been applied in the management of infected patients. As a representative TCM, HouYanQing (HYQ) oral liquid shows antiviral activity. However, the unclear mechanisms, as well as the ambiguous clinical effects, limit widespread application of this treatment. Therefore, in this study, a proteomics-based approach was utilized to precisely investigate its efficacy. Methods: Based on the efficacy evaluation of HYQ in a mouse model of pneumonia caused by influenza A virus (H1N1) and the subsequent proteomics analysis, specific signatures regulated by HYQ treatment of viral pneumonia were identified. Results: Experimental verifications indicate that HYQ may show distinctive effects in viral pneumonia patients, such as elevated galectin-3-binding protein and glutathione peroxidase 3 levels. Conclusion: This study provides a precise investigation of the efficacy of a multicomponent drug against viral pneumonia and offers a promising alternative for personalized management of viral pneumonia.

Systematic Survey of the Alteration of the Faecal Microbiota in Rats With Gastrointestinal Disorder and Modulation by Multicomponent Drugs.

Gastrointestinal disorder (GID) is a global health disease which leads to heavy public medical burden. Disorders in the intestinal flora have been found in gastrointestinal disorder patients. However, the interaction between GID and the intestinal flora in faecal has not been studied comprehensively. In addition, multicomponent drugs represented by traditional Chinese medicine (TCM) are widely used for treating GID, but their modulation of the intestinal flora has not been investigated. Therefore, in this study, a high-throughput sequencing strategy was used to investigate alterations in the intestinal flora in a rat GID model, followed by an investigation of the modulation by a representative TCM, Xiaoerfupi (XEFP) granule. The results showed that in rats with GID, the relative abundances of Erysipelotrichaceae, Lachnospiraceae, Streptococcaceae increased and that of Ruminococcaceae decreased. At the macro level, the levels of LysoPC(16:0), LysoPC(20:2), LysoPC(15:0), LysoPC(20:2 (11Z, 14Z)), LysoPC(20:1), LysoPC(15:0), LysoPC(20:0) and LysoPE (0:0/20:0) in serum increased and levels of PC(36:4), PC(38:4), PC(o-36;4), PE (MonoMe(13,5)/MonoMe(11,5)) decreased. The imbalance of metabolites was restored by XEFP through ether lipid metabolism pathway. Increase in the phyla Firmicutes/Bacteroidetes (F/B) ratio of the GID rats was restored by XEFP as well. Moreover, XEFP can relief the symptoms of GID rats by increasing bacteria Ruminococcaceae and decreasing Streptococcaceae, Erysipelotrichaceae and Lachnospiraceae in faecal microbiota level. This study represents a comprehensive survey of the interaction between GID and the intestinal flora and a systematic evaluation of modulation by a multicomponent drug.

Serum Metabolomic Analysis of Coronary Heart Disease Patients with Stable Angina Pectoris Subtyped by Traditional Chinese Medicine Diagnostics Reveals Biomarkers Relevant to Personalized Treatments.

To improve the treatment of patients with coronary heart disease (CHD), personalized treatments based on potential biomarkers could make a difference. To investigate if such potential biomarkers could be found for CHD inhomogeneous, we combined traditional Chinese medicine based diagnosis with untargeted and targeted metabolomics analyses. Shi and Xu patient subtype groups of CHD with angina pectoris were identified. Different metabolites including lipids, fatty acids and amino acids were further analyzed with targeted metabolomics and mapped to disease-related pathways. The long-chain unsaturated lipids ceramides metabolism, bile acid metabolism were differentially affected in the Xu subtype groups. While, Shi-subtype patients seemed to show inflammation, anomalous levels of bioactive phospholipids and antioxidant molecules. Furthermore, variations in the endothelial damage response and energy metabolism found based on ELISA analysis are the key divergence points between different CHD subtypes. The results showed Xu subtype patients might benefit from long-chain unsaturated lipids ceramides as therapeutic targets. Shi subtype patients might benefit more from levels of polyunsaturated fatty acid consumption and treatments that help in restoring energy balance. Metabolic differences can be essential for treatment protocols. Thus, patient group specific differences can serve as important information to refine current treatment approaches in a personalized manner.

Yixin-Shu Capsules Ameliorated Ischemia-Induced Heart Failure by Restoring Trx2 and Inhibiting JNK/p38 Activation.

Traditional Chinese medicine has shown great safety and efficacy in the treatment of heart failure (HF), whereas the mechanism remains unclear. In this study, the protective effect of Yixin-shu (YXS) capsules, a conventional medicine for various cardiovascular diseases, against myocardial ischemia-induced HF in rats was systematically investigated by RNA-seq technology. HF rats treated with YXS (0.8 or 1.6 g/kg/d, ig) for 6 weeks had significantly decreased brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) and collagen III and attenuated cardiac structure rupture and collagen deposition. Additionally, YXS treatment decreased the levels of interleukin-1ß (IL-1ß), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and lactate dehydrogenase (LDH) and TUNEL-positive rate and the nitrotyrosine staining, but increased levels of glutathione (GSH), total antioxidant capacity (T-AOC) activity, and mitochondrial membrane potential. Further experiments demonstrated that YXS restored Trx2 and inhibited the phosphorylation of JNK and p38, thereby improving cardiac function in the rats with HF. Silencing Trx2 decreased the protection of YXS in the response to H2O2 as evidenced by the increase of caspase-3 activity and decrease of GSH level. Thus, YXS enhanced heart function and decreased myocardial damage through restoring Trx2 and inhibiting JNK and p38 activation in ischemia-induced HF.

Systematic Investigation of the Efficacy of Sinitang Decoction Against Ulcerative Colitis.

The aim of this study was to investigate the precise clinical use of Sinitang decoction (SNT) in ulcerative colitis (UC). Network pharmacology-based analysis of the drug components-targets-diseases-pathways was used to predict the possible clinical applications of SNT. Next, 2,4,6-trinitrobenzenesulfonic acid (TNBS) was used to establish a rat model of UC, and the efficacy of SNT against UC was tested, followed by a proteomic analysis of the specific signatures regulated by SNT against UC. SNT was predicted to be effective in inflammatory bowel disease, UC, and several other diseases. In the rats with UC, SNT decreased the disease activity index and colon mucosal damage index compared to the untreated UC model rats. Additionally, SNT reversed the upregulated levels of serum tumor necrosis factor (TNF)-α, prostaglandin E2 (PGE2), interleukin (IL)-6, and nitric oxide (NO) in UC model rats. The proteomic analysis identified 78 proteins that were differentially regulated by SNT in the rats with UC, which were associated with the Gene Ontology terms sulfur compound binding, calcium ion binding, and Toll-like receptor (TLR)-4 binding. Among these differentially regulated proteins, C-reactive protein (CRP) and collagen alpha-1(XII) chain (COL12A1) were found to be signature proteins associated with the efficacy of SNT against UC. This study represents the first precise investigation of the efficacy and mechanisms of SNT against UC, and shows that SNT is a promising candidate for personalized management of UC.

Exploration of the mechanism of traditional Chinese medicine by AI approach using unsupervised machine learning for cellular functional similarity of compounds in heterogeneous networks, XiaoErFuPi granules as an example.

'Polypharmacology' is usually used to describe the network-wide effect of a single compound, but traditional Chinese medicine (TCM) has a polypharmacological effect naturally based on the 'multi-components, multi-targets and multi-pathways' principle. It is a challenge to investigate the polypharmacology mechanism of TCM with multiple components. In this study, we used XiaoErFuPi (XEFP) granules as an example to describe an unsupervised learning strategy for polypharmacology research of TCM and to explore the mechanism of XEFP polypharmacology against multifactorial disease function dyspepsia (FD). Unsupervised clustering of compounds based on similarity evaluation of cellular function fingerprints showed that compounds of TCM without similar targets and chemical structure could also exert similar therapeutic effects on the same disease, as different targets participate in the same pathway closely associated with the pathological process. In this study, we proposed an unsupervised machine learning strategy for exploring the polypharmacology-based mechanism of TCM, utilizing hierarchical clustering based on cellular functional similarity, to establish a connection from the chemical clustering module to cellular function. Meanwhile, FDA-approved drugs against FD were used as references for the mechanism of action (MoA) of FD. First, according to the compound-compound network built by the similarity of cellular function of XEFP compounds and FDA-approved FD drugs, the possible therapeutic function of TCM may represent a known mechanism of FDA-approved drugs. Then, as unsupervised learning, hierarchical clustering of TCM compounds based on cellular function fingerprint similarity could help to classify the compounds into several modules with similar therapeutic functions to investigate the polypharmacology effect of TCM. Furthermore, the integration of quantitative omics data of TCM and approved drugs (from LINCS datasets) provides more quantitative evidence for TCM therapeutic function consistency with approved drugs. A spasmolytic activity experiment was launched to confirm vanillic acid activity to repress smooth muscle contraction; vanillic acid was also predicted to be active compound of XEFP, supporting the accuracy of our strategy. In summary, the approach proposed in this study provides a new unsupervised learning strategy for polypharmacological research investigating TCM by establishing a connection between the compound functional module and drug-activated cellular processes shared with FDA-approved drugs, which may elucidate the unique mechanism of traditional medicine using FDA-approved drugs as references, facilitate the discovery of potential active compounds of TCM and provide new insights into complex diseases.

[Possible pharmaceutical effect and active components in different parts of Eucommia ulmoides based on network pharmacology].

The difference in pharmacological activities and active components between leaves, barks and flowers of Eucommia ulmoides(EU) are still unclear. However, clarifying the differences in pharmacological effects of different parts of EU is of great significance for the development of EU products, and their corresponding active components provide basis for quality control of different parts of EU. Based on the chemical compositions of different parts of EU, integrated strategy of target prediction and target analysis of the compounds was used to investigate the difference in the pharmacological effects of leaves, barks and followers. The "component-target-function" association network was constructed to mine the specific material basis corresponding to specific efficacy of different parts of EU. In this study, the author found that EU may have the activities of anti-oxidation, neuromodulation, blood pressure regulation, myo-cardial expansion, and anti-apoptosis according to target prediction and function analysis. However, the effects of different parts of EU were different. Leaves were involved in the process of bone development such as osteoblast differentiation and bone mineralization in a specific way. In addition, the leaves may affect the process of bone development by regulating the metabolism of vitamin D and affecting the absorption of calcium. Leaves may also specifically act on estrogen and estradiol response processes where estrogen receptors were involved. Regarding its protective function for the liver, leaves may play a role by regulating vitamin A-related pathways. As compared with leaves, the specific pharmacological effects of barks may be related to the development of the urinary system. Flowers specifically participate in functions related to pain sensation, glutamate signaling pathway, and excitatory postsynaptic potential. Based on the hie-rarchical network of "component-target-pathway", we further found that specific activities of different parts of EU were inseparable from its specific chemical compositions. Phenylpropanoids, terpenoids and rings, iridoids, flavonoids and other components which are specific in leaves can target the specific effects of leaves, while the flavonoids in barks and the quinones in flowers may be the material basis for their respective specific effects. The prediction of the activities of different parts of EU provides a new basis for the focuses and differences in subsequent Eucommia product development. At the same time, the material basis research based on differential efficacy also provides a basis for the quality control of Eucommia differentiated products.

Cross-plane transport in a single-molecule two-dimensional van der Waals heterojunction.

Two-dimensional van der Waals heterojunctions (2D-vdWHs) stacked from atomically thick 2D materials are predicted to be a diverse class of electronic materials with unique electronic properties. These properties can be further tuned by sandwiching monolayers of planar organic molecules between 2D materials to form molecular 2D-vdWHs (M-2D-vdWHs), in which electricity flows in a cross-plane way from one 2D layer to the other via a single molecular layer. Using a newly developed cross-plane break junction technique, combined with density functional theory calculations, we show that M-2D-vdWHs can be created and that cross-plane charge transport can be tuned by incorporating guest molecules. The M-2D-vdWHs exhibit distinct cross-plane charge transport signatures, which differ from those of molecules undergoing in-plane charge transport.

The lipid homeostasis regulation study of arenobufagin in zebrafish HepG2 xenograft model and HepG2 cells using integrated lipidomics-proteomics approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Arenobufagin (ArBu) is an important anti-tumor ingredient of Chan'su which has long been used as traditional Chinese medicine in clinic for tumor therapy in China. AIM OF THE STUDY: The purpose of our study is to investigate the lipid homeostasis regulation effects of ArBu on zebrafish model of liver cancer and hepatoma cells, and to provide a reference for further clarifying its active mechanisms. MATERIALS AND METHODS: The zebrafish xenograft model was established by injecting HepG2 cells stained with CM-Dil red fluorescent dye. Both the xenograft model and HepG2 cells were used to evaluate the anti-hepatoma activity of ArBu. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was the main method to study lipidomics, proteomics and the semiquantification of endogenous metabolites. Bioinformatics was used as an assistant tool to further explore the antitumor mechanism of ArBu. RESULTS: The lipidomics analysis revealed that ArBu caused differential lipids changes in a dose-dependent manner, including PCs, PEs, TGs, SMs, DGs, Cer and PA. PCs, PEs, SMs and TGs were markedly altered in both two models. The influence of glycerophospholipid metabolism was the major and commonly affected pathway. Notably, DGs and Cer were significantly changed only in HepG2 cells. Furthermore, the proteomics research in HepG2 cells fished the target proteins related to lipid homeostasis abnormalities and tumor suppression. ArBu reduced the expression of 65 differential proteins associated with the lipid metabolism, apoptosis and autophagy, such as LCLAT1, STAT3, TSPO and RPS27. Meanwhile, 7 amino acids of 29 determined metabolites were significantly changed, including tyrosine, glutamate, glutamine, leucine, threonine, arginine and isoleucine. CONCLUSION: ArBu has a significant anti-hepatoma effect in vitro and a therapeutic effect on zebrafish xenograft model. It regulated the lipid homeostasis. Activated SM synthase and arginine deiminase, inhibited sphingomyelinase, amino acid supply and JAK-STAT3 signaling pathway, and the affected glycerophospholipid metabolism might explain these results.

[Research advances in chemical constituents and pharmacological activities of different parts of Eucommia ulmoides].

To date, 205 compounds have been identified from different medicinal parts of Eucommia ulmoides, including lignans, iridoid terpenoids, phenols, flavonoids, terpenoids and steroids, polysaccharides and others. Their pharmacological effects include blood pressure-lowering, blood sugar-lowering, blood lipids-regulating, prevention of osteoporosis, anti-inflammation, liver protection, anti-cancer and so on. Their efficacy and mechanism from different parts are slightly different. In this paper, the chemical composition, pharmacological action and mechanism of different parts of E. ulmoides were systematically summarized, as well as its quality control and processing research, to provide theoretical basis for further rational development and utilization of E. ulmoides.

Systematical Identification of the Protective Effect of Danhong Injection and BuChang NaoXinTong Capsules on Transcription Factors in Cerebral Ischemia Mice Brain.

Cerebral ischemia has led to a high rate of both disability and mortality with massive healthcare costs. Although transcriptional regulation is typically mediated by different combinations of TFs, a combined regulatory unit to synergistically activate transcription has remained unclear in cerebral ischemia, especially in different drug treatments. In this study, TFs alterations after 6 h cerebral ischemic injury and repair were performed by a concatenated tandem array of consensus transcription factor response elements (catTFREs), and vital TFs were obtained by TFs-target imbalanced network. Drug intervention used Danhong injection (DHI) and BNC (BuChang NaoXinTong Capsules), which has been widely prescribed in Chinese herb medicine for the treatment of cerebrovascular and cardiovascular diseases. There were 198 TFs identified after 6 h MCAO operation, and six TFs (Sox2, Smad3, FoxO1, Creb1, Egr,1 and Smad4) were considered as critical TFs in response to cerebral ischemia. Moreover, Smad3 was identified as a hub TF among six vital TFs, and the transcription activity of Smad3 was further verified. These 6 TFs were all reversed by DHI or BNC, indicating different medications may regulate different transcription factors through TF synergy. Moreover, validation results indicated that Smad3 was a putative target TF for DHI and BNC-mediated protection against cerebral ischemia. The observations of the present study provide a fresh understanding of biomolecules and possible new avenues for therapeutic interventions, in addition to the new intervention pattern for different treatments for ischemia stroke.

[Marker genes of geniposide-induced hepatotoxicity based on genomic strategy].

The aim of this paper was to screen out relevant genes of geniposide-induced hepatotoxicity based on genomics,in order to provide a scientific basis for the non-clinical evaluation of drugs containing Gardeniae Fructus and geniposide. Fifty-five SD rats were randomly divided into normal control group,24 h group and 72 h group. The changes of appearance,behavior and weight of rats were observed after administration by gavage for 3 days. The activities of ALT and AST were detected. Molecular mechanism of geniposideinduced hepatotoxicity was investigated by Affymetrix miRNA 4. 0 and Affymetrix Rat Gene 2. 0 to examine the gene expression levels in Sprague-Dawley rat livers at 24 h and 72 h after administration of overdose-geniposide( 300 mg·kg-1 daily),and then verified by Realtime quantitative PCR. Compared with the normal control group,the activities of ALT and AST were markedly increased. In addition,experimental results indicated that 324 genes were differentially expressed,among which 259 were up-regulated and 65 down-regulated.Nine candidate genes were verified by qRT-PCR,including Bcl2,Il1 b,Tpm3,MMP2,Col1α1,Ifit1,Aldob,Nr0 b2,Cyp2 c23. And Bcl2,Col1α1,Aldob,Nr0 b2 and Cyp2 c23 were found to be correlated with geniposide-induced hepatotoxicity. This study provides an important clue for mechanism of geniposide-induced hepatotoxicity.