[Meta-analysis and trial sequential analysis of Chaihuang Granules in treatment of upper respiratory tract infection in children].

This study aimed to evaluate the efficacy and safety of Chaihuang Granules in the treatment of upper respiratory tract infection in children. The databases such as CNKI, Wanfang, VIP, SinoMed, Cochrane Library, PubMed, EMbase, Web of Science, Chinese Clinical Trial Registry, and ClinicalTrials.gov were searched for randomized controlled trial(RCT) of Chaihuang Granules for the treatment of upper respiratory tract infection in children, and supplemented by manual searching of gray literature. Two investigators independently screened the literature, extracted data, and assessed the methodological quality. Meta-analysis was performed using RevMan 5.4 software, trial sequential analysis was conducted using TSA 0.9.5.10 Beta software, and evidence quality evaluation was carried out using GRADE profiler 3.6.1 software. Eighteen RCTs involving 2 459 patients(1 262 in the treatment group and 1 197 in the control group) were included. Meta-analysis showed that compared with conventional therapy alone, Chaihuang Granules significantly improved the total effective rate(RR=1.18, 95%CI[1.15, 1.22], P<0.000 01), reduced the disappearance time of symptoms/signs(MD=-1.39, 95%CI[-1.66,-1.12], P<0.000 01), improved cytokine levels(MD=-2.40, 95%CI[-3.80,-1.00], P=0.000 8), improved humoral immune levels(MD=0.75, 95%CI[0.60, 0.90], P<0.000 01), and reduced the recurrence rate(MD=-2.11, 95%CI[-2.98,-1.25], P<0.000 01). However, the incidence of adverse reactions was not increased(RR=0.94, 95%CI[0.59, 1.49], P=0.78). Subgroup analysis showed that:(1) both Chaihuang Granules used alone(RR=1.19, 95%CI[1.11, 1.27], P<0.000 01) and in combination with other therapies(RR=1.18, 95%CI[1.14, 1.22], P<0.000 01) effectively improved the total effective rate.(2) In terms of symptoms/signs disappearance time, Chaihuang Granules effectively reduced the duration of fever(MD=-1.18, 95%CI[-1.78,-0.58], P=0.000 1), cough with sputum(MD=-1.82, 95%CI[-2.38,-1.25], P<0.000 01), cough(MD=-1.31, 95%CI[-1.89,-0.74], P<0.000 01), sore throat(MD=-1.57, 95%CI[-2.25,-0.89], P<0.000 01), and lung rales(MD=-1.49, 95%CI[-2.06,-0.92], P<0.000 01).(3) Regarding cytokine levels, Chaihuang Gra-nules effectively improved the levels of interleukin(IL)-2(MD=-0.94, 95%CI[-1.16,-0.72], P<0.000 01), IL-6(MD=-4.71, 95%CI[-6.39,-3.03], P<0.000 01), and tumor necrosis factor-α(TNF-α)(MD=-2.07, 95%CI[-2.43,-1.71], P<0.000 01).(4) In terms of cellular immune levels, Chaihuang Granules effectively improved the levels of CD3~+(MD=4.11, 95%CI[1.53, 6.69], P=0.002), CD4~+(MD=4.21, 95%CI[1.69, 6.73], P=0.001), CD8~+(MD=-2.65, 95%CI[-3.93,-1.37], P<0.000 1), and CD4~+/CD8~+(MD=0.25, 95%CI[0.14, 0.37], P<0.000 1).(5) In terms of humoral immune levels, Chaihuang Granules effectively improved the levels of IgA(MD=0.44, 95%CI[0.23, 0.64], P<0.000 1), IgM(MD=0.31, 95%CI[0.15, 0.46], P=0.000 1), and IgG(MD=2.02, 95%CI[1.60, 2.43], P<0.000 01). Trial sequential analysis showed that the cumulative Z-curve of the total effective rate crossed the boundary value, further confirming its clinical efficacy. The GRADE evidence quality evaluation showed that the evidence quality of the above outcome indicators was low or very low, and the recommendation strength was weak. Compared to conventional therapy alone, Chaihuang Granules can effectively improve the total effective rate of treatment, alle-viate symptoms and signs of upper respiratory tract infection in children, improve inflammatory conditions, enhance immune function, and reduce the recurrence rate. Due to the limited quality of the included studies, high-quality RCT is still needed to provide evidence support for the above conclusions.

[Meta-analysis and trial sequential analysis of Compound Qinlan Oral Liquid in treatment of acute upper respiratory tract infection].

This study aims to evaluate the efficacy and safety of Compound Qinlan Oral Liquid in the treatment of acute upper respiratory tract infection. Computer-based online searching of CNKI, VIP, SinoMed, Wanfang, ChiCTR, ClinicalTrials.gov, Cochrane Library, PubMed, EMbase, and Web of Science was performed to retrieve the randomized controlled trial(RCT) regarding Compound Qinlan Oral Liquid in the treatment of acute upper respiratory tract infection. In addition, manual searching of gray literature was conducted. After two evaluators independently selected articles, extracted data, and evaluated the quality of methodology included in the studies, Meta-analysis was carried out in RevMan 5.4 and trial sequential analysis(TSA) in TSA 0.9.5.10 Beta. GRADE profiler 3.6.1 was employed to evaluate the evidence quality. A total of 21 RCTs were included in this study, involving 2 651 patients(1 330 patients in the observation group and 1 321 patients in the control group). Meta-analysis showed that compared with conventional western medicine alone, Compound Qinlan Oral liquid improved the total response rate(RR=1.15, 95%CI[1.12, 1.19], P<0.000 01) without increasing the incidence of adverse reactions(RR=0.77, 95%CI[0.47, 1.25], P=0.16). The results of subgroup analysis are described as follows:(1) Compared with conventional western medicine alone, Compound Qinlan Oral Liquid improved the total response rate(RR=1.10, 95%CI[1.05, 1.14], P<0.000 01) and shortened the time to symptom relief(SMD=-0.76, 95%CI[-1.02,-0.51], P<0.000 01). There was no significant difference in the incidence of adverse reactions between the two groups(RR=1.16, 95%CI[0.54, 2.47], P=0.71).(2) Compared with conventional western medicine alone, Compound Qinlan Oral Liquid + conventional western medicine improved the total response rate(RR=1.20, 95%CI[1.15, 1.25], P<0.000 01), decreased traditional Chinese medicine(TCM) syndrome scores(MD=-0.58, 95%CI[-0.75,-0.41], P<0.000 01), shortened the time to symptom relief(SMD=-2.44, 95%CI[-3.09,-1.80], P<0.000 01) and physical sign improvement(MD=-2.57, 95%CI[-4.11,-1.04], P=0.001), lowered the serum levels of inflammatory cytokines(SMD=-2.16, 95%CI[-2.61,-1.70], P<0.000 01), improved respiratory function indicators(SMD=1.48, 95%CI[1.00, 1.96], P<0.000 01), and enhanced the humoral immunity(MD=0.94, 95%CI[0.69, 1.18], P<0.000 01). There was no significant difference in the incidence of adverse reactions between the two groups(RR=0.57, 95%CI[0.29, 1.09], P=0.09). TSA showed that the cumulative Z curve of total response rate crossed the traditional threshold and TSA threshold, further confirming the clinical efficacy of Compound Qinlan Oral Liquid. The GRADE graded the evidence of the above outcome indicators as low or extremely low, and yielded weak recommendation. Compared with conventional western medicine alone, Compound Qinlan Oral Liquid can improve the total effective rate and reduce the time to symptom relief. The combination of Compound Qinlan Oral Liquid and conventional western medicine can improve the total response rate, mitigate the symptoms and improve the physical signs, reduce inflammation, and improve respiratory function and immunity of the patients with acute upper respiratory tract infection. In view of the limited number and quality of the included studies, the above conclusions still require high-quality RCT to provide evidence support.

Based on 16 S rRNA sequencing and metabonomics to reveal the new mechanism of aluminum potassium sulfate induced inflammation and abnormal lipid metabolism in mice.

More and more discoveries have been made about the chronic toxic effects of aluminum, but the specific mechanism of action remains unclear. In this study, we explored the perturbation of aluminum on intestinal microflora and its effects on host and microbial metabolites through a more realistic nutrient absorption model. The microorganisms Turicibacter, Lactobacillus murinus, Lactobacillus_reuteri and Bifidobacterium pseudolongum may be the main targets of the aluminum affecting microbiota. Lysine, proline, putrescine, serotonin and cholesterol may be important metabolites affected by aluminum ions after the interference of intestinal flora composition, leading to abnormal metabolism pathways of amino acids and lipids in the body, and thus promoting inflammation and lesion. The possible mechanisms of aluminum action on the body: (1) Affecting immune cell response, ROS generation and production of a series of pro-inflammatory factors to promote inflammation; (2) Through the disturbance of intestinal microbiota composition structure, change the abundance of metabolites, and then affect amino acid metabolism, lipid metabolism pathways. The joint analysis of multiple omics showed significant difference in microbiome abundance and metabolomics expression between high dose group and the control group.

[Core prescriptions in treatment of edema by traditional Chinese medicine masters and mechanism prediction].

The core prescriptions and formulation characteristics in the treatment of edema by traditional Chinese medicine(TCM) masters were analyzed through data mining and their mechanisms were explored by network pharmacology. We collected journal reports on the treatment of edema by TCM masters in three sessions from China National Knowledge Infrastructure(CNKI) and constructed a database by Traditional Chinese Medicine Inheritance Support System 3.0. The prescriptions in the case studies were analyzed by association rules and k-means clustering. The chemical components and targets of Chinese medicines in core prescriptions were collected through TCMSP and TCMID. Edema-related targets were collected from DrugBank and GeneCards. The protein-protein interaction(PPI) network was constructed by STRING and the core targets were screened out. FunRich 3.1.3 was used to enrich the expression sites of core prescriptions. Metascape was used to perform Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis of intersection targets. Cytoscape 3.6.0 was used to visualize the "Chinese medicine-active ingredient-core target-pathway" network. The results showed that 315 pieces of medical records in the treatment of edema by TCM masters were obtained and five core prescriptions were analyzed by association rules and k-means clustering. Core prescription 1 contained Poria, Atractylodis Macrocephalae Rhizoma, Astragali Radix, Alismatis Rhizoma, Glycyrrhizae Radix et Rhizoma, and Codonopsis Radix, involving 166 chemical components and 1 125 targets. Core prescription 2 contained Astragali Radix, Salviae Miltiorrhizae Radix et Rhizoma, Poria, Chuanxiong Rhizoma, Paeoniae Radix Rubra, and Angelicae Sinensis Radix, involving 138 chemical components and 1 112 targets. Core prescription 3 contained Poria, Salviae Miltiorrhizae Radix et Rhizoma, Astragali Radix, Atractylodis Macrocephalae Rhizoma, Alismatis Rhizoma, and Coicis Semen, involving 126 chemical components and 1 121 targets. Core prescription 4 contained Poria, Forsythiae Fructus, Atractylodis Macrocephalae Rhizoma, Imperatae Rhizoma, Cicadae Periostracum, and Coicis Semen, involving 58 chemical components and 820 targets. Core prescription 5 contained Poria, Atractylodis Macrocephalae Rhizoma, Astragali Radix, Alismatis Rhizoma, Trionycis Carapax, and Dioscoreae Rhizoma, involving 68 chemical components and 919 targets. The core targets of core prescriptions included AKT1, ALB, CASP3, MAPK3, EGFR, SRC, MAPK1, and TNF. The potential targets of core prescriptions in the treatment were highly expressed in the stomach, bladder, lung, and kidney. KEGG pathways were enriched in inflammation and cell cycle pathways, especially the inflammation-relation pathways. The therapeutic effect of core prescriptions on edema is presumedly achieved by tonifying the spleen, draining water, activating blood, and benefiting Qi to resist inflammation and regulate the immune system. This study is expected to provide references for the summary of TCM masters' experience and new drug development.

Core prescriptions in treatment of edema by traditional Chinese medicine masters and mechanism prediction / 中国中药杂志

The core prescriptions and formulation characteristics in the treatment of edema by traditional Chinese medicine(TCM) masters were analyzed through data mining and their mechanisms were explored by network pharmacology. We collected journal reports on the treatment of edema by TCM masters in three sessions from China National Knowledge Infrastructure(CNKI) and constructed a database by Traditional Chinese Medicine Inheritance Support System 3.0. The prescriptions in the case studies were analyzed by association rules and k-means clustering. The chemical components and targets of Chinese medicines in core prescriptions were collected through TCMSP and TCMID. Edema-related targets were collected from DrugBank and GeneCards. The protein-protein interaction(PPI) network was constructed by STRING and the core targets were screened out. FunRich 3.1.3 was used to enrich the expression sites of core prescriptions. Metascape was used to perform Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis of intersection targets. Cytoscape 3.6.0 was used to visualize the "Chinese medicine-active ingredient-core target-pathway" network. The results showed that 315 pieces of medical records in the treatment of edema by TCM masters were obtained and five core prescriptions were analyzed by association rules and k-means clustering. Core prescription 1 contained Poria, Atractylodis Macrocephalae Rhizoma, Astragali Radix, Alismatis Rhizoma, Glycyrrhizae Radix et Rhizoma, and Codonopsis Radix, involving 166 chemical components and 1 125 targets. Core prescription 2 contained Astragali Radix, Salviae Miltiorrhizae Radix et Rhizoma, Poria, Chuanxiong Rhizoma, Paeoniae Radix Rubra, and Angelicae Sinensis Radix, involving 138 chemical components and 1 112 targets. Core prescription 3 contained Poria, Salviae Miltiorrhizae Radix et Rhizoma, Astragali Radix, Atractylodis Macrocephalae Rhizoma, Alismatis Rhizoma, and Coicis Semen, involving 126 chemical components and 1 121 targets. Core prescription 4 contained Poria, Forsythiae Fructus, Atractylodis Macrocephalae Rhizoma, Imperatae Rhizoma, Cicadae Periostracum, and Coicis Semen, involving 58 chemical components and 820 targets. Core prescription 5 contained Poria, Atractylodis Macrocephalae Rhizoma, Astragali Radix, Alismatis Rhizoma, Trionycis Carapax, and Dioscoreae Rhizoma, involving 68 chemical components and 919 targets. The core targets of core prescriptions included AKT1, ALB, CASP3, MAPK3, EGFR, SRC, MAPK1, and TNF. The potential targets of core prescriptions in the treatment were highly expressed in the stomach, bladder, lung, and kidney. KEGG pathways were enriched in inflammation and cell cycle pathways, especially the inflammation-relation pathways. The therapeutic effect of core prescriptions on edema is presumedly achieved by tonifying the spleen, draining water, activating blood, and benefiting Qi to resist inflammation and regulate the immune system. This study is expected to provide references for the summary of TCM masters' experience and new drug development.

Administration of isoliquiritigenin prevents nonalcoholic fatty liver disease through a novel IQGAP2-CREB-SIRT1 axis.

Isoliquiritigenin (ISO) is a flavonoid extracted from the root of licorice, which serves various biological and pharmacological functions including antiinflammatory, antioxidation, liver protection, and heart protection. However, the mechanism of its action remains elusive and the direct target proteins of ISO have not been identified so far. Through cell-based screening, we identified ISO as a potent lipid-lowering compound. ISO treatment successfully ameliorated fatty acid-induced cellular lipid accumulation and improved nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) by increasing PPARα-dependent lipid oxidation and decreasing SREBPs-dependent lipid synthesis. Both these signaling required the activation of SIRT1. Knockdown of SIRT1 resulted in the reversal of ISO beneficiary effects suggesting that the lipid-lowering activity of ISO was regulated by SIRT1 expression. To identify the direct target of ISO, limited proteolysis combined with mass spectrometry (LiP-SMap) strategy was applied and IQGAP2 was identified as the direct target for ISO in regulating lipid homeostasis. In the presence of ISO, both mRNA and protein levels of SIRT1 were increased; however, this effect was abolished by blocking IQGAP2 expression using siRNA. To explore how IQGAP2 regulated the expression level of SIRT1, proteome profiler human phospho-kinase array kit was used to reveal possible phosphorylated kinases and signaling nodes that ISO affected. We found that through phosphorylation of CREB, ISO transduced signals from IQGAP2 to upregulate SIRT1 expression. Thus, we not only demonstrated the molecular basis of ISO in regulating lipid metabolism but also exhibited for the first time a novel IQGAP2-CREB-SIRT1 axis in treating NAFLD/NASH.

[Network pharmacology study of Yi medicine Jinweitai Capsules in treating gastrointestinal diseases].

The network pharmacology and molecular docking methods were used to explore the mechanism of Jinweitai Capsules in the treatment of acute and chronic gastritis, gastric and duodenal ulcers, and chronic colitis. The chemical components of herbs in Jinweitai Capsules were collected through TCMSP, CNKI and PubMed. Target prediction was performed through PubChem and SwissTargetPrediction databases; genes relating to acute and chronic gastritis, gastric and duodenal ulcers, chronic colitis were collected from OMIM database; potential targets of Jinweitai Capsules for relevant gastrointestinal diseases were obtained by Venny analysis; DAVID database was used to perform GO and KEGG enrichment analysis; protein interactions were obtained by STRING database and visua-lized by Cytoscape; AutoDockVina was used for molecular docking of AKT1, EGFR, PTPN11 and its reverse-selected chemical components. Potential mechanisms of Jinweitai Capsules in treating relevant gastrointestinal diseases were clarified according to the results of the docking. The results showed 86 potential active ingredients of Jinweitai Capsules and 268 potential targets for treatment of acute and chronic gastritis, gastric and duodenal ulcers, and chronic colitis. KEGG pathway enrichment analysis showed that 20 pathways relating to acute and chronic gastritis, gastric and duodenal ulcers, and chronic colitis mainly involved calcium signaling pathway and chemokine signaling pathway. Molecular docking showed a good binding activity between AKT1, EGFR, PTPN11 and its reverse screening chemical components. Jinweitai Capsules may exert an effect in the treatment of acute and chronic gastritis, gastric and duodenal ulcers, and chronic colitis by acting on AKT1, EGFR, PTPN11 and other targets in 15 signal pathways relating to cell inflammation and immunity, cell proliferation and apoptosis, Helicobacter pylori infection, and gastrointestinal tract.

Network pharmacology study of Yi medicine Jinweitai Capsules in treating gastrointestinal diseases / 中国中药杂志

The network pharmacology and molecular docking methods were used to explore the mechanism of Jinweitai Capsules in the treatment of acute and chronic gastritis, gastric and duodenal ulcers, and chronic colitis. The chemical components of herbs in Jinweitai Capsules were collected through TCMSP, CNKI and PubMed. Target prediction was performed through PubChem and SwissTargetPrediction databases; genes relating to acute and chronic gastritis, gastric and duodenal ulcers, chronic colitis were collected from OMIM database; potential targets of Jinweitai Capsules for relevant gastrointestinal diseases were obtained by Venny analysis; DAVID database was used to perform GO and KEGG enrichment analysis; protein interactions were obtained by STRING database and visua-lized by Cytoscape; AutoDockVina was used for molecular docking of AKT1, EGFR, PTPN11 and its reverse-selected chemical components. Potential mechanisms of Jinweitai Capsules in treating relevant gastrointestinal diseases were clarified according to the results of the docking. The results showed 86 potential active ingredients of Jinweitai Capsules and 268 potential targets for treatment of acute and chronic gastritis, gastric and duodenal ulcers, and chronic colitis. KEGG pathway enrichment analysis showed that 20 pathways relating to acute and chronic gastritis, gastric and duodenal ulcers, and chronic colitis mainly involved calcium signaling pathway and chemokine signaling pathway. Molecular docking showed a good binding activity between AKT1, EGFR, PTPN11 and its reverse screening chemical components. Jinweitai Capsules may exert an effect in the treatment of acute and chronic gastritis, gastric and duodenal ulcers, and chronic colitis by acting on AKT1, EGFR, PTPN11 and other targets in 15 signal pathways relating to cell inflammation and immunity, cell proliferation and apoptosis, Helicobacter pylori infection, and gastrointestinal tract.

[Discovery and study on potential effect of herbal pair of Uncariae Ramulus cum Uncis-Eucommiae Cortex on pregnancy hypertension based on network pharmacology and molecular docking].

This study aimed to explore the optimal indications and mechanism of Uncariae Ramulus cum Uncis(UR)-Eucommiae Cortex(EC) in lowering blood pressure based on network pharmacology and molecular docking. Chemical constituents were collected and screened by TCMSP database. Swiss Target Prediction platform was used to predict the related targets of the drug. OMIM, TCMIP and GeneCards databases were used to collect hypertension-related genes, and the intersections were taken to obtain potential targets for anti-hypertensive treatment of UR-EC. FunRich software was used to enrich the clinical phenotype and expression site of potential target of lowering blood pressure to analyze and predict the optimal indications of UR-EC. STRING database was used for KEGG pathway enrichment analysis, and Cytoscape 3.7.2 was used to construct the network of "composition-target-pathway". The key targets and their corresponding components in the network were analyzed and obtained, and then molecular docking was applied for preliminary verification. Twenty potential active components of UR and 24 potential active components of EC were respectively collected, and 92 anti-hypertensive potential targets of UR-EC were obtained. According to FunRich enrichment results, the optimal indication of UR-EC was pregnancy hypertension, which involved calcium signaling pathway, HIF-1 signaling pathway, neuroactive ligand receptor interaction, renin vascular tightening, VEGF signaling pathway, etc. In addition, AKT1, NOS2, ADRB2, F2, NOS3, SCN5 A, HTR2 A and JAK2 were considered as the key targets in the network. The molecular docking results showed that the screened potential active components had high binding activity with the key targets. This study preliminarily revealed that UR-EC may have therapeutic effects on pregnancy hypertension in terms of sedation, anti-hypertension, anti-inflammatory, anti-oxidation, improvement of vascular endothelial function and so on.

[Intervention mechanism of Qingwen Baidu Yin on cytokine storm based on network pharmacology].

The aim of this paper was to explore the intervention mechanism of Qingwen Baidu Yin in cytokine storm based on network pharmacology. TCMSP and TCMIP V2.0 server were used to predict all chemical components and action targets of Qingwen Baidu Yin. Diseases that could be treated by Qingwen Baidu Yin were predicted through Enrichr database. A compound target interaction(PPI) network diagram was constructed using STRING 11.0. OmicShare was used to analyzed the gene ontology(GO) enrichment and enrichment of the Kyoto encyclopedia of genes and genomes(KEGG) pathway of core targets. Component-target-path network diagram was constructed with Cytoscape 3.6.0 software. After analysis of the database, 267 compounds were screened for Qingwen Baidu Yin, involving 1 450 targets, and a protein interaction network was constructed. Total 219 core target proteins were predicted, such as NFKB1, STAT1, RAF1, IL2, JAK1, IL6, TNF, BCL2 and other important targets, and 221 core target pathways were enriched, including cancer pathway, Kaposi's sarcoma-associated herpes virus infection, chemokine signal pathway, PI3 K-AKT signal pathway, EB virus infection, virus carcinogenesis and T cell receptor signaling pathways, a collection of which were highly related to cytokine storms. GO annotation analysis suggested that Qingwen Baidu Yin Decoction may exert therapeutic effects by regulating protein phosphorylation, cell response to cytokine stimulation, cell proliferation, inflammatory response, transmembrane receptor protein tyrosine kinase signaling pathway, and cytokine-mediated signaling pathways. This study revealed potential active components of Qingwen Baidu Yin in defending against cytokine storm and its possible mechanism of action, and provided theoretical basis and technical support for further clinical application of this prescription.

Interpretation of Theory of Weiluo Tongxin and Its Potential Molecular Mechanism Based on Zhishi Xiebai Guizhitang / 中国实验方剂学杂志

The scientific interpretation of the connotation of traditional Chinese medicine （TCM） theory is an important part of the development of TCM. Combined ancient classic theories with modern science and technology is a new path for the innovative development of TCM theory. Based on this， taking Zhishi Xiebai Guizhitang as an example， the molecular mining technology of integrative pharmacology-based research platform of TCM V2.0 （TCMIP V2.0） was used to analyze the mechanism of Zhishi Xiebai Guizhitang in preventing and treating gastropathic stomachache. A total of 220 chemical components in Zhishi Xiebai Guizhitang were obtained， and 674 targets were involved， of which 12 core targets directly affected angina pectoris and gastroesophageal reflux disease， including insulin （INS）， glyceraldehyde-3-phosphate dehydrogenase （GAPDH）， RAC-α serine/threonine-protein kinase 1 （AKT1）， tumour protein p53 （TP53）， albumin （Alb）， mitogen-activated protein kinase 3 （MAPK3）， interleukin-6 （IL-6）， etc. And tumor necrosis factor （TNF） signaling pathway， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway， IL-17 signaling pathway， hypoxia-inducible factor-1 （HIF-1） signaling pathway and other 121 pathways involved in these related diseases. All of these are the biological basis of Weiluo Tongxin theory. Combing the classical theories of TCM combined with the exploring the molecular mechanism of representative prescriptions can provide a demonstration and reference for the scientific connotation research of TCM theory.

Discovery and study on potential effect of herbal pair of Uncariae Ramulus cum Uncis-Eucommiae Cortex on pregnancy hypertension based on network pharmacology and molecular docking / 中国中药杂志

This study aimed to explore the optimal indications and mechanism of Uncariae Ramulus cum Uncis(UR)-Eucommiae Cortex(EC) in lowering blood pressure based on network pharmacology and molecular docking. Chemical constituents were collected and screened by TCMSP database. Swiss Target Prediction platform was used to predict the related targets of the drug. OMIM, TCMIP and GeneCards databases were used to collect hypertension-related genes, and the intersections were taken to obtain potential targets for anti-hypertensive treatment of UR-EC. FunRich software was used to enrich the clinical phenotype and expression site of potential target of lowering blood pressure to analyze and predict the optimal indications of UR-EC. STRING database was used for KEGG pathway enrichment analysis, and Cytoscape 3.7.2 was used to construct the network of "composition-target-pathway". The key targets and their corresponding components in the network were analyzed and obtained, and then molecular docking was applied for preliminary verification. Twenty potential active components of UR and 24 potential active components of EC were respectively collected, and 92 anti-hypertensive potential targets of UR-EC were obtained. According to FunRich enrichment results, the optimal indication of UR-EC was pregnancy hypertension, which involved calcium signaling pathway, HIF-1 signaling pathway, neuroactive ligand receptor interaction, renin vascular tightening, VEGF signaling pathway, etc. In addition, AKT1, NOS2, ADRB2, F2, NOS3, SCN5 A, HTR2 A and JAK2 were considered as the key targets in the network. The molecular docking results showed that the screened potential active components had high binding activity with the key targets. This study preliminarily revealed that UR-EC may have therapeutic effects on pregnancy hypertension in terms of sedation, anti-hypertension, anti-inflammatory, anti-oxidation, improvement of vascular endothelial function and so on.

Characterization of Adult Canine Kidney Epithelial Stem Cells That Give Rise to Dome-Forming Tubular Cells.

Dome formation can occur in cultured tubular epithelial cells originating from various tissues, including the mammary gland and the kidney. The isolation and characterization of normal kidney epithelial stem cells that give rise to dome-forming tubular cells have never been reported. We attempted to isolate and characterize canine kidney epithelial stem cells using a simple cell culture method that we have previously used to isolate other adult human stem cells. Dome-forming kidney epithelial cells were derived from dissociated adult canine kidney tissues that were cultured in a modified keratinocyte serum-free medium supplemented with N-acetyl-l-cysteine, l-ascorbic acid 2-phosphate, nicotinamide, and fetal bovine serum. These cells exhibited high self-renewal capacity in long-term culture (growth for >13 months and 30 cumulative population doublings) and exhibited characteristics of stem cells, including (1) deficiency in gap junctional intercellular communication, (2) anchorage-independent growth, (3) expression of stem cell markers octamer-binding transcription factor 4 and SRY (sex determining region Y)-box 2, (4) expression of cell surface markers CD24 and CD133, and (5) multipotent differentiation into osteoblasts, adipocytes, chondrocytes, and dome-forming tubular cells. Most of these characteristics are shared by the well-known canine renal tubule-derived immortalized Madin-Darby Canine Kidney cell line. Furthermore, the putative canine kidney stem cells developed in this study formed budding tubule-like organoids on Matrigel and required high cell density (>4,000 cells/cm2) for sustained growth and confluency for dome formation. The signal transducer and activator of transcription-3 (STAT3) phosphorylation inhibitor, AG490, inhibited colony-forming efficiency and dome formation, whereas lipopolysaccharide, an activator of STAT3, increased colony-forming efficiency in a dose-dependent manner. These results are consistent with the hypothesis that high cell density induces STAT3 expression, which promotes both stem cell self-renewal and differentiation into tubular cells. Our novel cell culture method should be useful for the future development of normal human kidney stem cells for clinical applications and for studying mechanisms of nephrotoxicity.

Administration of methyl palmitate prevents non-alcoholic steatohepatitis (NASH) by induction of PPAR-α.

BACKGROUND AND AIMS: The lack of valid therapeutic approach that can ameliorate the manifestations of NASH is a barrier to therapeutic development. Therefore, we investigate the novel role of Methyl Palmitate (MP) in preventing NASH and the possible mechanism involved. METHODS: 50 Male C57BL/6 J mice were randomly divided into 5 groups (n = 10). The control group was fed control diet; model group was fed MCD diet; MP 1 group was fed MCD diet supplemented with MP (75 mg/kg/day); MP 2 group was fed MCD plus MP diet (150 mg/kg/day); and MP 3 group was fed MCD plus MP diet (300 mg/kg/day). Histological staining's, and commercially available kits for serum ALT and AST and hepatic contents of TG, TC, MDA, SOD, and GSH were used to assess NASH. Furthermore, relative liver protein and gene expression levels were determined by Western Blot and qPCR, respectively. RESULTS: Mice fed MCD diet developed NASH, which was markedly improved by MP in a dose-dependent manner. MP treatment improved hepatic content of TG, TC, MDA, SOD and GSH and serum levels of ALT and AST. In vivo studies showed that MP treatment activated PPARα expression, that in turns, promoted ß-oxidation protein and gene expressions, suppressed TNFα, MCP1, TGFß1 and Colla1 protein and gene expression levels, contributing to the prevention of NASH. CONCLUSIONS: Our results indicated that MP could successfully prevent NASH. This effect of MP was mediated through induction of PPARα pathway. This study provides a novel therapeutic target that plays pivotal role in the prevention of NASH.

Effect of Electroacupuncture on Inflammatory Response of Rats after Focal Cerebral Ischemia-reperfusion via Regulating IκB Kinases β Expression / 中国康复理论与实践

Objective:To observe the changes of inflammatory damage in the brain of rats after focal cerebral ischemia-reperfusion, and explore the effect of the initiation of IκB kinases β (IKKβ), which is the key protein of activating nuclear factor (NF)-kappa B signaling pathway in inflammatory response, and the mechanism of electroacupuncture inhibiting inflammatory damage. Methods:A total of 240 male Sprague-Dawley rats were randomly divided into sham group, ischemia-reperfusion group, electroacupuncture group, IKKβ silencing group, IKKβ overexpression group and IKKβ overexpression + electroacupuncture group, each group was further divided into six hours, twelve hours, 24 hours, 48 hours and 72 hours subgroups. The right middle cerebral artery occlusion reperfusion model was established by modified thread embolization. The IKKβ gene was intervened by gene silencing and gene overexpression technology. Results:Compared with the model group, the neurological function score increased (P < 0.05), the cerebral infarction volume decreased (P < 0.05), the activation of NF-κB p65 was inhibited, and the content of proinflammatory factors decreased (P < 0.05) in IKKβ silencing group. Compared with IKKβ silencing group, the above results were significantly worse in IKKβ overexpression group (P < 0.05), and microglia in cerebral ischemic cortex were significantly activated. The activation of microglia and activation of IKKβ were significantly inhibited in IKKβ overexpression + electroacupuncture group. Conclusion:IKKβ gene silencing could inhibit the inflammatory response of cerebral ischemic cortex mediated by NF-κB signaling pathway, and over-expression of IKKβ could lead to severe inflammatory damage in ischemic cortex. Electroacupuncture could inhibit the inflammatory damage after focal cerebral ischemia-reperfusion by regulating the activity of IKKβ.

Energy Analysis of a Complementary Heating System Combining Solar Energy and Coal for a Rural Residential Building in Northwest China.

In order to utilize solar energy to meet the heating demands of a rural residential building during the winter in the northwestern region of China, a hybrid heating system combining solar energy and coal was built. Multiple experiments to monitor its performance were conducted during the winter in 2014 and 2015. In this paper, we analyze the efficiency of the energy utilization of the system and describe a prototype model to determine the thermal efficiency of the coal stove in use. Multiple linear regression was adopted to present the dual function of multiple factors on the daily heat-collecting capacity of the solar water heater; the heat-loss coefficient of the storage tank was detected as well. The prototype model shows that the average thermal efficiency of the stove is 38%, which means that the energy input for the building is divided between the coal and solar energy, 39.5% and 60.5% energy, respectively. Additionally, the allocation of the radiation of solar energy projecting into the collecting area of the solar water heater was obtained which showed 49% loss with optics and 23% with the dissipation of heat, with only 28% being utilized effectively.

Effects of Antarctic krill oil on lipid and glucose metabolism in C57BL/6J mice fed with high fat diet.

BACKGROUND: Obesity and other metabolic diseases have become epidemic which greatly affect human health. Diets with healthy nutrition are efficient means to prevent this epidemic occurrence. Novel food resources and process technology were needed for these purpose. In this study, Antarctic krill oil (KO) extracted from a dry krill by a procedure of hot pump dehydration in combined with freezing-drying was used to investigate health effect in animals including the growth, lipid and glucose metabolism. METHODS: C57BL/6J mice were fed with a lard based high fat (HF) diet and substituted with KO for a period of 12 weeks in comparison with low fat normal control (NC) diet. Mice body weight and food consumption were recorded. Serum lipid metabolism - of C57BL/6J mice serum was measured. A glucose tolerance tests (GTTs) and pathology analysis of mice were performed at the end of the experiment. RESULTS: The KO fed mice had less body weight gain, less fat accumulation in tissue such as adipose and liver. Dyslipidemia induced by high fat diet was partially improved by KO feeding with significant reduction of serum low density lipoprotein-cholesterol (LDL-C) content. Furthermore, KO feeding also improved glucose metabolism in C57BL/6J mice including a glucose tolerance of about 22% vs. 32% of AUC (area under the curve) for KO vs HF diet and the fast blood glucose level of 8.5 mmol/L, 9.8 mmol/L and 9.3 mmol/L for NC, HF and KO diet groups, respectively. In addition, KO feeding also reduced oxidative damage in liver with a decrease of malondialdehyde (MDA) content and increase of superoxide dismutase (SOD) content. CONCLUSION: This study provided evidence of the beneficial effects of KO on animal health from the processed technology, particularly on lipid and glucose metabolism. This study confirmed that as the Antarctic krill was extracted with a procedure of efficient energy, it might make it possible for Krill oil to be available for food industry.

Effect of Melilotus officinalis extract on the apoptosis of brain tissues by altering cerebral thrombosis and inflammatory mediators in acute cerebral ischemia.

Present investigation evaluates the protective effect of Melilotus officinalis (MO) extract on the brain tissues in acute cerebral ischemia. Acute cerebral ischemia was induced by occlusion of carotid artery and rats with cerebral ischemia were treated with MO (100, 250 & 500mg/kg) for the duration of three days. Cerebral ischemia was confirmed by estimating infract volume and neurological deficit score. Moreover biochemical parameters in plasma such as 6-keto-PGF1α and TXB2 and concentration of cytokine, oxidative stress, apoptosis ratio and protein expressions of Bcl2 & Bax were estimated in the brain tissues. It was observed that treatment with MO significantly (p<0.01) decreases the infract volume and neurological deficit score than negative control group. There was significant decrease (p<0.01) in the oxidative stress and cytokine in the brain tissues and increase in the plasma concentration of 6-keto-PGF1α in MO treated group of rats compared to negative control group. Plasma concentration of TXB 2 was significantly enhanced in MO treated group compared to negative control group of rats. It was also found that treatment with MO ameliorates the apoptosis induced by cerebral ischemia. Present study concludes that MO ameliorates apoptosis of brain tissues in cerebral ischemic rats by decreasing cerebral thrombosis, oxidative stress and inflammatory mediators.

Asiatic acid exerts anticancer potential in human ovarian cancer cells via suppression of PI3K/Akt/mTOR signalling.

Context Asiatic acid, a triterpenoid compound extracted from the tropical medicinal plant Centella asiatica (Family: Apiaceae), has exhibited various biological activities. Objective This study was performed to investigate the cytotoxic effects of asiatic acid on human ovarian cancer cells. Materials and methods SKOV3 and OVCAR-3 ovarian cancer cells were exposed to different concentrations of asiatic acid (10-100 µg/mL) for 72 or 48 h. Cell viability, colony formation, cell cycle distribution, apoptotic response were examined. Involvement of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway was tested. Results At the concentration of 40 µg/mL, asiatic acid caused about 50% reduction in the viability of ovarian cancer cells, but had little effect on the viability of normal human ovarian epithelial cells. Asiatic acid at 10 µg/mL reduced colony formation of ovarian cancer cells by 25-30%. Asiatic acid-treated cells showed a cell cycle arrest at the G0/G1 phase and 7- to 10-fold increase in apoptosis. The phosphorylation levels of PI3K, Akt and mTOR were remarkably lower in asiatic acid-treated cells. Overexpression of constitutively active Akt partially reversed the cytotoxic effects of asiatic acid, as evidenced by increased cell viability and colony formation. Furthermore, knockdown of Akt mimicked the growth-suppressive activity of asiatic acid. Discussion and conclusion These results provide first the evidence for the anticancer potential of asiatic acid in ovarian cancer cells, partially via inactivation of the PI3K/Akt/mTOR pathway. Asiatic acid may represent a potential therapeutic agent for ovarian cancer.

Salvage chemotherapy followed by granulocyte colony-stimulating factor-primed donor leukocyte infusion with graft-vs.-host disease control for minimal residual disease in acute leukemia/myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation: prognostic factors and clinical outcomes.

This study investigated the prognostic factors and clinical outcomes of preemptive chemotherapy followed by granulocyte colony-stimulating factor-primed donor leukocyte infusion (Chemo-DLI) according to minimal residual disease (MRD) status in patients with acute leukemia and myelodysplastic syndromes who received allogeneic hematopoietic stem cell transplantation (HSCT) (n = 101). Patients received immunosuppressive drugs to prevent graft-vs.-host disease (GVHD) after Chemo-DLI. The 3-yr cumulative incidences of relapse, non-relapse mortality, and disease-free survival (DFS) after HSCT were 39.5%, 9.6%, and 51.7%, respectively. The cumulative incidences of relapse and DFS were significantly poorer in patients who exhibited early-onset MRD. Forty-four patients turned MRD negative 1 month after Chemo-DLI; their cumulative incidences of relapse and DFS were significantly better than those with persistent MRD 1 month after preemptive Chemo-DLI (relapse: 19.8% vs. 46.8%, P = 0.001; DFS: 69.6% vs. 46.4%, P = 0.004). The cumulative incidences of relapse and DFS after HSCT were significantly better in patients with chronic GVHD (cGVHD) than those without cGVHD (relapse: 19.6% vs. 63.7%, P < 0.001; DFS: 74.4% vs. 23.8%, P < 0.001). Early-onset MRD, persistent MRD after Chemo-DLI, and non-cGVHD after Chemo-DLI, which were associated with increased relapse and impaired DFS, suggest unsatisfactory response to preemptive Chemo-DLI.