Pt,P-codoped carbon nitride nanoenzymes for fluorescence and colorimetric dual-mode detection of cholesterol.

Cholesterol is an important lipid compound found in a variety of foods, and its level in human blood is closely related to human health. Therefore, development of rapid and accurate POCT (point-of-care testing) methods for cholesterol detection is crucial for assessing food quality and early diagnosis of diseases, in particular, in a resource-limited environment. In this study, a smartphone-assisted colorimetric biosensor is constructed based on platinum,phosphorus-codoped carbon nitride (PtCNP2) for the rapid detection of cholesterol. Phosphorus-doped carbon nitride is prepared by thermal annealing of urea and NH4PF6, into which platinum is atomically dispersed by thermal refluxing. The obtained PtCNP2 exhibits an excellent peroxidase-like activity under physiological pH, whereby colorless o-phenylenediamine (OPD) is oxidized to colored 2,3-diaminophenazine (DAP) in the presence of hydrogen peroxide (H2O2), which can be produced during the oxidation of cholesterol by cholesterol oxidase. A smartphone-assisted visual sensing system is then constructed based on the color recognition software, and rapid on-site detection of cholesterol is achieved by reading the RGB values. Meanwhile, the generated DAP shows an apparent fluorescence signal and can realize highly sensitive detection of cholesterol by the change of the fluorescence signal intensity. Such a cholesterol sensor exhibits a wide linear detection range of 0.5-600 µg mL-1 and a low detection limit of 59 ng mL-1. The practicality of the sensor is successfully demonstrated in the rapid detection of cholesterol in serum and food.

Least Absolute Shrinkage and Selection Operator-Based Prediction of the Binding Constant of p-Sulfonatocalix[6]/[8]arenes with Alkaloids.

p-Sulfonatocalix[n]arenes (SCnA) have demonstrated great potential for drug encapsulation through host-guest complexation to improve solubility, stability, and bioavailability. In this study, the solubilization effect of SCnA (n = 4, 6, 8) on 95 active compounds derived from traditional Chinese medicine (TCM) was investigated. Based on the significant solubilization effect on alkaloids, SC6A/SC8A and 76 alkaloids were selected as the host and guest, respectively, to determine the binding constant by competitive fluorescence titration. LASSO regression was adopted to investigate the mechanism of the complex of SCnA with alkaloids. The binding constant of alkaloids-SC6A and alkaloids-SC8A was related to the alkaloid alkalinity. Also, the electronegativity, polarization, first ionization potential, hydrogen bond potential, the molecular size, and shape of alkaloids are critical properties to determine alkaloids-SC6A binding constant as well as electronegativity, polarization, hydrophobicity, and the molecular size and shape of alkaloids play an important role for the alkaloids-SC8A binding constant.

WGCNA and transcriptome profiling reveal hub genes for key development stage seed size/oil content between wild and cultivated soybean.

BACKGROUND: Soybean is one of the most important oil crops in the world. The domestication of wild soybean has resulted in significant changes in the seed oil content and seed size of cultivated soybeans. To better understand the molecular mechanisms of seed formation and oil content accumulation, WDD01514 (E1), ZYD00463 (E2), and two extreme progenies (E23 and E171) derived from RILs were used for weighted gene coexpression network analysis (WGCNA) combined with transcriptome analysis. RESULTS: In this study, both seed weight and oil content in E1 and E171 were significantly higher than those in E2 and E23, and 20 DAF and 30 DAF may be key stages of soybean seed oil content accumulation and weight increase. Pathways such as "Photosynthesis", "Carbon metabolism", and "Fatty acid metabolism", were involved in oil content accumulation and grain formation between wild and cultivated soybeans at 20 and 30 DAF according to RNA-seq analysis. A total of 121 oil content accumulation and 189 seed formation candidate genes were screened from differentially expressed genes. WGCNA identified six modules related to seed oil content and seed weight, and 76 candidate genes were screened from modules and network. Among them, 16 genes were used for qRT-PCR and tissue specific expression pattern analysis, and their expression-levels in 33-wild and 23-cultivated soybean varieties were subjected to correlation analysis; some key genes were verified as likely to be involved in oil content accumulation and grain formation. CONCLUSIONS: Overall, these results contribute to an understanding of seed lipid metabolism and seed size during seed development, and identify potential functional genes for improving soybean yield and seed oil quantity.

Efficacy of kangaroo mother care combined with neonatal phototherapy in newborns with non-pathological jaundice: A meta-analysis.

Background: The kangaroo-mother care method (KMC) is a skin-to-skin contact-centered care approach with numerous benefits for neonates, but its impact on the treatment of jaundiced neonates is unknown. This study aimed to investigate the efficacy of KMC combined with neonatal phototherapy (NNPT) in treating neonates with non-pathological jaundice. Methods: Relevant articles were searched in PubMed, Embase, Web of Science, and Cochrane Library databases from database establishment to April 2022. The outcomes included, without limitation, serum bilirubin levels, and duration of phototherapy. Results: This meta-analysis included five studies (4 randomized controlled trials and 1 observational study) involving four hundred eighty-two neonates with non-pathological jaundice. The results showed that the group receiving KMC combined with NNPT had lower serum bilirubin at 72 h after intervention [weighted mean difference (WMD) = -1.51, p = 0.03], shorter duration of phototherapy [standard mean difference (SMD) = -1.45, p < 0.001] and shorter duration of hospitalization (SMD = -1.32, p = 0.002) compared to NNPT group. There was no difference in peak bilirubin in both groups of neonates (WMD = -0.12, p = 0.62). Conclusions: KMC combined with NNPT helped to treat non-pathological jaundice in newborns compared to NNPT alone.

Current status and high-risk factors of blood-borne occupational exposure among midwives in China: A cross-sectional survey.

BACKGROUND: To identify the problems and high-risk factors of blood-borne occupational exposure among midwives in China. METHODS: Midwives from the obstetrics department and delivery room of hospitals in institutions. The self-compiled questionnaire on the current status of blood-borne occupational exposure of Chinese midwives was used for data collection. RESULTS: The incidence rate of blood-borne occupational exposure was 46.77%. The independent risk factors were working years ≤5 years (P = .001), unable to take standard prevention at work (P = .000), unaware of human immunodeficiency virus treatment procedures (P = .000), and average daily working hours of 8 hours (P = .002), the high risk of blood-borne occupational exposure at work (P = .000), and contact with patient fluids, blood without gloves (P = .000). DISCUSSION: Midwives are at high risk of blood-borne occupational exposure, and midwives with ≤5 years of service are the focus group. Failure to achieve standard prevention, the length of working hours and the ignorance of the treatment process of acquired immunodeficiency syndrome have a certain impact on the occurrence of blood-borne occupational exposure. CONCLUSION: It is necessary to focus on cultivating high-level midwifery talents to overcome the shortage of midwives and rationally use midwifery resources, as well as to strengthen standard prevention and improve the occupational protection and guarantee system for midwives.

An eco-friendly extraction and purification method of nuciferine from Folium nelumbinis with p-sulfonatocalix[6]arenes.

INTRODUCTION: Folium nelumbinis is used as vegetable, functional food and herbal medicine in Asia. p-Sulfonatocalix[6]arene (SC6A) is a water-soluble supramolecular macrocycle and has never been applied to the extraction of herbal products. OBJECTIVE: In this study, SC6A-assisted extraction of nuciferine from Folium nelumbinis has been carried out to develop an eco-friendly extraction process with high extraction efficacy and easy operation. METHODS: Single-factor experiments were adopted to obtain the optimal conditions for the SC6A-assisted extraction of nuciferine from Folium nelumbinis, and then nuciferine and SC6A were separated easily by one-step alkalization. The host-guest complexes between nuciferine and SC6A were analyzed by competitive fluorescence titration, DSC, FT-IR and 1 H-NMR. RESULTS: The optimal SC6A/Folium nelumbinis/solution ratio for extraction was 0.4:1:20 (g/g/mL), with a granulometric fraction below 180 µm and an extraction time of 1 h with soaking. The purity and recovery of nuciferine extracted with SC6A were increased 29.24 and 35.73 times compared with extraction with aqueous solution, respectively. Moreover, a good reusability of SC6A in the extraction of nuciferine was demonstrated. Competitive fluorescence titration, DSC, FT-IR and 1 H-NMR characterization indicated that SC6A could form host-guest complexes with nuciferine at a ratio of 1:1. CONCLUSION: The study provided an eco-friendly, safe and effective nuciferine extraction method, which can be used for the development of nutrition supplements containing nuciferine.

Comprehensive evaluation integrating omics strategy and machine learning algorithms for consistency of calculus bovis from different sources.

In the clinical application of Traditional Chinese Medicine (TCM) substitutes, the consistency evaluation of TCM substitutes from different sources is recognized as the main bottleneck. As the most widely used analytical method in TCM consistency evaluation, fingerprint similarity evaluation suffers from insufficient method sensitivity and poor conformity with the actual characteristics of TCM, which is difficult to adapt to the analytical needs of complex substance systems of TCM. This work aims to develop an effective and more accurate method for consistency evaluation using omics strategy and machine learning algorithms. The natural calculus bovis (NCB) were graded into three groups according to the similarity to in vitro cultured bovis (IVCB), and chemical markers between samples of each grade were screened out. Support vector machine (SVM) models with different kernels were then constructed by using the chemical markers as feature variables. The results showed that the classification accuracy of the SVM classifier of NCB and the consistency evaluation SVM model classifier was 95.74% and 100.0%, respectively. The approach demonstrated in the study presented a good analytical performance with higher sensitivity, accuracy for consistency evaluation of TCM.

The Effect of Bergamot Essential Oil Aromatherapy on Improving Depressive Mood and Sleep Quality in Postpartum Women: A Randomized Controlled Trial.

BACKGROUND: The postpartum period is a physiologically and psychologically crucial transition phase for every woman who gives birth. Aromatherapy may improve mood and alleviate sleep challenges. However, few randomized controlled clinical trials have focused on the effect of aromatherapy in postpartum women. PURPOSE: This study was designed to explore the effect of a bergamot essential oil aromatherapy intervention on depressive mood and sleep quality in postpartum women. METHODS: This randomized controlled trial used consecutive sampling. The participants were all women in a postpartum care center in eastern Taiwan and were randomly assigned to either the experimental (n = 29) or control (n = 31) group. Bergamot essential oil aroma was used in the experimental group, and pure water aroma was used in the control group. The experimental and control interventions were both performed while the participants were residents at the postpartum care center in the afternoon for 15 minutes each day. Before the aroma intervention, pretests were conducted using the Edinburgh Postnatal Depression Scale and the Postpartum Sleep Quality Scale. The first and second posttests were conducted using the same two scales at 2 and 4 weeks after the intervention, respectively. RESULTS: At both the first and second posttests, depressive mood was significantly lower (p < .001) in the experimental group than in the control group, supporting the positive effect of the bergamot essential oil aroma intervention on depressive mood in postpartum women. No significant intergroup difference in sleep quality (p > .05) was observed at either the first or second posttest, indicating an uncertain effect of the bergamot essential oil aroma intervention on sleep quality. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results of this study support the effectiveness of bergamot essential oil aromatherapy in alleviating depressive mood in postpartum women. In addition, the results provide a practical reference for clinical postpartum nursing care.

Moxibustion Regulates Gastrointestinal Motility via HCN1 in Functional Dyspepsia Rats.

BACKGROUND Moxibustion therapy has been found to ameliorate clinical symptoms of functional dyspepsia (FD). We aimed to examine the regulatory effect of moxibustion on the gastrointestinal (GI) motility in FD and explore the underlying mechanism based on the hyperpolarization-activated cyclic nucleotide-gated cation channel 1 (HCN1). MATERIAL AND METHODS Moxibustion therapy was used in FD rats induced by using classic tail-pinch and irregular feeding. Weight gain and food intake were recorded weekly, followed by detecting gastric residual rate (GRR) and small intestine propulsion rate (IPR). Next, western blotting was performed to determine the expression levels of HCN1 in the gastric antrum. qRT-PCR was used to detect HCN1 in the small intestine and hypothalamic satiety center. Double immunolabeling was used for HCN1 and ICCs in gastric antrum and small intestine. RESULTS The obtained results suggested that moxibustion treatment could increase weight gain and food intake in FD rats. The GRR and IPR were compared among the groups, which showed that moxibustion treatment could decrease GRR and increase IPR. Moxibustion increased the expression of HCN1 in the gastric antrum, small intestine, and hypothalamic satiety center. Histologically, the co-expressions of HCN1 and ICCs tended to increase in gastric antrum and small intestine. Meanwhile, HCN channel inhibitor ZD7288 prevented the above-mentioned therapeutic effects of moxibustion. CONCLUSIONS The results of the present study suggest that moxibustion can effectively improve the GI motility of FD rats, which may be related to the upregulation of HCN1 expression in gastric antrum, small intestine, and satiety center.

Pharmacodynamic substances in Salvia miltiorrhiza for prevention and treatment of hyperlipidemia and coronary heart disease based on lipidomics technology and network pharmacology analysis.

In this study, untargeted lipidomics based on UPLC-Q/TOF-MS, network pharmacology and atomic force microscopy were used to explore the common biomarkers of hyperlipidemia and coronary heart disease, the therapeutic mechanism of the main components of Salvia miltiorrhiza as well as the action mechanism of key lipids. Firstly, the serum samples of 30 healthy people, 30 patients with coronary heart disease and 30 patients with hyperlipidemia were analyzed by using lipidomics technology to obtain biomarkers which can be used to link hyperlipidemia and coronary heart disease and to find potential targets; then, the key components and core targets of Salvia miltiorrhiza intervention in hyperlipidemia and coronary heart disease were analyzed by network pharmacology, the results were verified by atomic force microscopy. It showed that SMS2 might be the key target. And through network pharmacology and atomic force microscope analysis, it can be inferred that salvianolic acid A can combine with SMS2 to play a therapeutic role.

Stepwise rapid tracking strategy to identify active molecules from Ixeris sonchifolia Hance based on "'affinity mass spectrometry-atomic force microscopy imaging'" technology.

In this study, a novel stepwise rapid tracking strategy was reported to identify the active molecules from Ixeris sonchifolia Hance (IsH) in the treatment of coronary heart disease (CHD) based on "affinity mass spectrometry (MS)-atomic force microscopy (AFM) imaging" technology. First, vascular endothelial growth factor receptor 2 (VEGFR2) of the vascular endothelial growth factor (VEGF) signal transduction pathway located on the cell membrane was revealed to be the core target protein in CHD treatment through network pharmacology and bioinformatics. In addition, affinity MS screening based on VEGFR2 identified isochlorogenic acid A and luteolin-7-O-glucuronide as having stronger affinity with VEGFR2. Then, the active molecule was elucidated based on the observation that its actions accompanied the molecular morphological changes by AFM imaging and it could act on the binding pocket of VEGFR2 through molecular docking which further demonstrated the analysis and inference of AFM imaging. The methyl thiazolyl tetrazolium (MTT) assay finally confirmed that the active molecules specifically combined with the potential core target protein to protect the viability of cardiomyocytes, which identified the main potential active molecules in IsH for the treatment of CHD and provided a possible mechanism for the protective role of the drug. The technology established in this study could facilitate the rapid tracing of potential active molecules in traditional Chinese medicine (TCM), which would provide further a reference for research on quality, molecular mechanisms and new drugs.

Quality consistency evaluation of Kudiezi Injection based on multivariate statistical analysis of the multidimensional chromatographic fingerprint.

Traditional Chinese Medicine Injection (TCMI) was restricted due to the batch-to-batch variability caused by the variable compositions of botanical raw materials and complexities of the current manufacturing process. To evaluate and control the quality of Kudiezi Injection (KDZI), a comprehensive and practical method based on multidimensional chromatographic fingerprint associated with multivariate statistical analysis was proposed. The multidimensional chromatographic fingerprint was established by integrating three kinds of chromatographic fingerprints, including High Performance Liquid Chromatography-Ultraviolet spectrum (HPLC-UV), Gas Chromatography-Mass Spectrometer (GC-MS) and High performance ion-exchange chromatography (HPIEC), which were used to detect flavones, nucleosides, organic acids, amino acids and saccharides in KDZI. In addition, four main multivariate statistical analyses were compared to assess the batch-to-batch consistency of samples. Results showed that the cosine method, which has been widely used in the quality evaluation of TCM, failed to distinguish the differences among batches based on neither chromatographic peaks' area nor contents information. t-test and Bayes' theorem could reveal the content difference among batches, while hierarchical clustering analysis could differentiate KDZI batches, and Luteolin-7-O-ß-D-glucuronopyranoside, Tau, Ser, guanine and allose were the main indicators. In conclusion, multidimensional chromatographic fingerprints could reflect the quality information of KDZI comprehensively and hierarchical clustering analysis was suitable to identify the differences among batches. This could provide an integrated method for consistency evaluation of TCMI, process improvement of TCMI and solving similar problems in TCMI.

Case Report: Fainting During Acupuncture Treatment.

CONTEXT: The first issue to be considered in acupuncture is the safety of and adverse effects from treatment. Fainting is an uncommon adverse reaction. Some researchers believe that fainting is related to the mechanism underlying acupuncture treatment, but due to moral and technical issues, studies involving fainting during the acupuncture process haven't been conducted. OBJECTIVE: The study intended to determine if specific risk factors are associated with fainting during acupuncture treatment. DESIGN: The research team performed 2 case studies involving fainting during acupuncture. SETTING: The study took place in the Physiotherapy Departments of the Leribe Motebang Hospital and the Mamohau Hospital in the Kingdom of Lesotho. PARTICIPANTS: Participants were 2 out of 2050 patients who received acupuncture treatment between October 2017 and April 2018 at one of the hospitals. They had fainted, with different clinical manifestations, during acupuncture treatment. Their main symptoms were dizziness, general weakness associated forehead sweating, palpitations, dyspnea, and nausea. RESULTS: In both cases, the patient had complained of hunger before treatment. Both claimed that they had never experienced such a situation previously. CONCLUSIONS: The research team suggests that the fainting occurred for the patients in the two case studies secondary to the hungry state. Hunger may be one of the most important causes of fainting connected to acupuncture. The failure of a practitioner to perform treatment for fainting in a timely and effective manner, or his or her improper handling of it, can lead to serious consequences. Therefore, factors that may cause fainting should be minimized to avoid their occurrence during acupuncture.

Xin-Ji-Er-Kang Alleviates Myocardial Infarction-Induced Cardiovascular Remodeling in Rats by Inhibiting Endothelial Dysfunction.

The present study was designed to elucidate the beneficial effects of XJEK on myocardial infarction (MI) in rats, especially through the amelioration of endothelial dysfunction (ED). 136 Sprague-Dawley rats were randomized into 13 groups: control group for 0wk (n = 8); sham groups for 2, 4, and 6 weeks (wk); MI groups for 2, 4, and 6 wk; MI+XJEK groups for 2, 4, and 6w k; MI+Fosinopril groups for 2, 4, and 6 wk (n = 8~10). In addition, 8 rats were treated for Evans blue staining and Tetrazolium chloride (TTC) staining to determine the infarct size. Cardiac function, ECG, and cardiac morphological changes were examined. Colorimetric analysis was employed to detect nitric oxide (NO), and enzyme-linked immunosorbent assay (ELISA) was applied to determine N-terminal probrain natriuretic peptide (NT-ProBNP), endothelin-1 (ET-1), angiotensin II (Ang II), asymmetric dimethylarginine (ADMA), tetrahydrobiopterin (BH4), and endothelial NO synthase (eNOS) content. The total eNOS and eNOS dimer/(dimer+monomer) ratios in cardiac tissues were detected by Western blot. We found that administration of XJEK markedly ameliorated cardiovascular remodeling (CR), which was manifested by decreased HW/BW ratio, CSA, and less collagen deposition after MI. XJEK administration also improved cardiac function by significant inhibition of the increased hemodynamic parameters in the early stage and by suppression of the decreased hemodynamic parameters later on. XJEK also continuously suppressed the increased NT-ProBNP content in the serum of MI rats. XJEK improved ED with stimulated eNOS activities, as well as upregulated NO levels, BH4 content, and eNOS dimer/(dimer+monomer) ratio in the cardiac tissues. XJEK downregulated ET-1, Ang II, and ADMA content obviously compared to sham group. In conclusion, XJEK may exert the protective effects on MI rats and could continuously ameliorate ED and reverse CR with the progression of MI over time.

Insights on the Multifunctional Activities of Magnolol.

Over years, various biological constituents are isolated from Traditional Chinese Medicine and confirmed to show multifunctional activities. Magnolol, a hydroxylated biphenyl natural compound isolated from Magnolia officinalis, has been extensively documented and shows a range of biological activities. Many signaling pathways include, but are not limited to, NF-κB/MAPK, Nrf2/HO-1, and PI3K/Akt pathways, which are implicated in the biological functions mediated by magnolol. Thus, magnolol is considered as a promising therapeutic agent for clinic research. However, the low water solubility, the low bioavailability, and the rapid metabolism of magnolol dramatically limit its clinical application. In this review, we will comprehensively discuss the last five-year progress of the biological activities of magnolol, including anti-inflammatory, antimicroorganism, antioxidative, anticancer, neuroprotective, cardiovascular protection, metabolism regulation, and ion-mediating activity.

Xin-Ji-Er-Kang ameliorates kidney injury following myocardial infarction by inhibiting oxidative stress via Nrf2/HO-1 pathway in rats.

AIM: Cardiovascular diseases, such as coronary heart disease and myocardial infarction (MI) are currently considered as the leading causes of death and disability. The aim of the present study is to investigate the effects of Xin-Ji-Er-Kang (XJEK) on kidney injury and renal oxidative stress. In addition, the associated mechanism involved in these processes was examined in an MI model, and particularly focused on the nuclear factor erythroid 2-related factor (NRF2)/heme oxygenase-1 (HO-1) pathway. MATERIALS AND METHODS: A total of 138 Sprague-Dawley rats were used in the present study. The control group was designated as 0 wk (n = 8). A total of 3 phases (2, 4, 6 wk) of administration were used in the sham-operated groups (sham, n = 10), MI groups (MI, n = 10), MI + XJEK groups (XJEK, n = 10) and MI + fosinopril groups (fosinopril, n = 10). Additional 10 rats were used to evaluate the infarct area. At 2, 4 or 6 wk post-MI, the hemodynamic parameters were monitored, the rats were sacrificed, then blood, heart and renal tissues were collected for furtherly analysis. RESULTS: The results indicated that XJEK administration continuously ameliorated renal hypertrophy index, blood urea nitrogen and cystatin C concentrations. XJEK further improved post-MI cardiac function by limiting scar formation and caused a downregulation in the hemodynamic parameters at the end of 2 and 4 wk. The hemodynamic parameters were upregulated after 6 wk treatment with XJEKcompared with those noted in the MI groups. Similarly, XJEK treatment for 2 wk potentiated Nrf2 nuclear translocation and HO-1 expression and inhibited the deficiency of nuclear Nrf2 and HO-1 at 6 wk post-MI compared with that of the MI groups, indicating the attenuation of the renal oxidative stress condition. The levels of malondialdehyde and angiotensin II (Ang II) in plasma and renal tissues, as well as the levels of aldosterone, 8-hydroxydeoxyguanosine, angiotensin II type 1 receptor and NADPH Oxidase-4 in the kidney tissue significantly decreased following XJEK treatment for 6 wk. In addition, the XJEK treatment groups revealed a significant upregulation in the activity of superoxide dismutase and in the total antioxidant capacity activity compared with those noted in the corresponding MI groups. CONCLUSION: These results demonstrated that progressive nephropathy in MI rats was associated with intrarenal activation of the renin-angiotensin-aldosterone system. Concomitantly, this process was associated with oxidative stress and impaired Nrf2 activation. The improvement in the severity of nephropathy by XJEK in this model may be associated with the reversal of these abnormalities.

In silico Identification and Mechanism Exploration of Hepatotoxic Ingredients in Traditional Chinese Medicine.

BACKGROUNDS AND AIMS: Recently, a growing number of hepatotoxicity cases aroused by Traditional Chinese Medicine (TCM) have been reported, causing increasing concern. To date, the reported predictive models for drug induced liver injury show low prediction accuracy and there are still no related reports for hepatotoxicity evaluation of TCM systematically. Additionally, the mechanism of herb induced liver injury (HILI) still remains unknown. The aim of the study was to identify potential hepatotoxic ingredients in TCM and explore the molecular mechanism of TCM against HILI. MATERIALS AND METHODS: In this study, we developed consensus models for HILI prediction by integrating the best single classifiers. The consensus model with best performance was applied to identify the potential hepatotoxic ingredients from the Traditional Chinese Medicine Systems Pharmacology database (TCMSP). Systems pharmacology analyses, including multiple network construction and KEGG pathway enrichment, were performed to further explore the hepatotoxicity mechanism of TCM. RESULTS: 16 single classifiers were built by combining four machine learning methods with four different sets of fingerprints. After systematic evaluation, the best four single classifiers were selected, which achieved a Matthews correlation coefficient (MCC) value of 0.702, 0.691, 0.659, and 0.717, respectively. To improve the predictive capacity of single models, consensus prediction method was used to integrate the best four single classifiers. Results showed that the consensus model C-3 (MCC = 0.78) outperformed the four single classifiers and other consensus models. Subsequently, 5,666 potential hepatotoxic compounds were identified by C-3 model. We integrated the top 10 hepatotoxic herbs and discussed the hepatotoxicity mechanism of TCM via systems pharmacology approach. Finally, Chaihu was selected as the case study for exploring the molecular mechanism of hepatotoxicity. CONCLUSION: Overall, this study provides a high accurate approach to predict HILI and an in silico perspective into understanding the hepatotoxicity mechanism of TCM, which might facilitate the discovery and development of new drugs.

Protective effect of Xin-Ji-Er-Kang on cardiovascular remodeling in high-salt induced hypertensive mice: Role ofoxidative stress and endothelial dysfunction.

BACKGROUND: Xin-Ji-Er-Kang (XJEK) is a Chinese herbal formula that has beenreported to exert effective protection against cardiovascular diseases, such as hypertension and myocarditis. OBJECTIVE: The aim of the present study was to investigate the effect of XJEK on high-salt-induced hypertensive mice and its possible mechanism. METHODS: The model of hypertension was established through a high-salt diet. Sixty male Kunming mice were randomized into six groups, namely the Control, Model, Low-dose XJEK, Middle-dose XJEK, High-dose XJEK and Fosinopril groups (n=10 per group). Different steady interventions were given to each group: 0.9% Sodium chloride was added to the diet of the Control group and 8% sodium chloride to the diet of the other five groups from the very beginning. An additional 4, 8 and 12 g/kg/day XJEK were intragastrically administered to the Low-dose, Middle-dose and High-dose XJEK groups, respectively, and 2 mg/kg/day fosinopril to the fosinopril group, from the start of week 5. Systolic blood pressure (SBP) was measured weekly from weeks 1 to 8 using the tail-cuff method. At the end of week 8, left ventricular (LV) systolic pressure, LV end-diastolic pressure and rate of rise of LV pressure were examined using a TransonicScisense catheter (Transonic Systems Inc,Ithaca, NY,USA). Endothelium-dependent relaxations induced by acetylcholine were observed in an isolated thoracic aorta ring. Serum and heartsweresampled for the measurement of the following indexes:Serum nitric oxide (NO), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content (determined by colorimetricanalysis); serum angiotensin II(Ang II), endothelin-1, endothelial NO synthase (eNOS), asymmetric dimethylarginine (ADMA), tetrahydrobiopterin (BH4) concentration and l-arginine (determined by enzyme-linked immunosorbent assay); heart to body weight (HW/BW) ratio; myocardial morphological change (determined by HE and VG staining); myocardial eNOS expression (determined by immunofluorescence), and myocardial endothelin receptor A (ETA) expression (determined by western blotting). RESULTS: Statistical data showed that the HW/BW ratio was significantly decreased in the drug treatment group. XJEK treatment could improve the heart systolic and diastolic function and ameliorate hemodynamic parameters and vascular remodeling indexes. Colorimetric results showed that, compared with the model group, XJEK increased serum SOD, NOlevels, and decreased those of serum MDA and Ang II. XJEK reverted changes in cardiac pathology, decreased the myocardial cross-sectional area, collagen volume fraction and perivascular collagen area and improved endothelial dysfunction (ED) by promoting eNOS activity, enhancing NO bioavailability, increasing the expression of BH4 and decreasing ETA content. In addition, treatment with XJEK decreased ADMA content in the myocardium. CONCLUSION: In conclusion, XJEK mitigates cardiac remodeling in high-salt-induced hypertensive mice. The potential mechanism involves improved oxidative stress and endothelial dysfunction, independently of ameliorating BP.

Characterization of Inulin-Type Fructan from Platycodon grandiflorus and Study on Its Prebiotic and Immunomodulating Activity.

Platycodon grandiflorus is a plant widely used in traditional Chinese medicine, of which polysaccharides are reported to be the main components responsible for its bio-functions. In this work, the inulin-type fructan (PGF) was obtained by DEAE anion exchange chromatography from the water extracted from P. grandifloras. Characterization was performed with methanolysis, methylation, and NMR and the results showed that PGF is a ß-(2-1) linked fructan, with terminal glucose and with a degree of polymerization of 2⁻10. In order to study its biofunctions, the prebiotic and immunomodulation properties were assayed. We found that PGF exhibited good prebiotic activity, as shown by a promotion on six strains of lactobacillus proliferation. Additionally, the PGF also displayed direct immunomodulation on intestinal epithelial cells and stimulated the expressions of anti-inflammatory factors. These results indicated that the inulin from P. grandiflorus is a potential natural source of prebiotics as well as a potential intestinal immunomodulator, which will be valuable for further studies and new applications.

BuShenKangShuai Tablet Alleviates Hepatic Steatosis via Improving Liver Adiponectin Resistance in ApoE-/- Mice.

BuShenKangShuai tablet (BSKS) is a Chinese herbal compound, which has been used to treat nonalcoholic fatty liver disease and cardiovascular diseases in clinic for over four decades. This study intends to explore whether BSKS administration can alleviates hepatic steatosis via improving liver adiponectin resistance in ApoE-/- mice. ApoE-/- mice were fed with western-type diet for 6 weeks and then were administrated with BSKS or atorvastatin for 6 weeks by gavage, and then blood and liver were collected for analysis. The results showed that BSKS attenuated hepatic steatosis, decreased blood lipids, and increased the serum level of adiponectin. We also found that adiponectin resistance in the liver was improved by BSKS, while the expression of TLR4 and NF-κB p65 was inhibited, followed by the suppression of proinflammatory mediators of TNF-α. Our data provided evidence that BSKS was able to alleviate hepatic steatosis in vivo. The underlying mechanism of BSKS was focused on improving liver adiponectin resistance, thereby regulating dyslipidemia and inhibiting inflammatory signaling pathway.