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Article ; Online: Ling Zhi-8, a fungal immunomodulatory protein in

Li, Ju-Pi / Chu, Ching-Liang / Chao, Wan-Ru / Yeh, Cheng-Siang / Lee, Yi-Ju / Chen, Dz-Chi / Yang, Shun-Fa / Chao, Yu-Hua

Aging

2023 Volume 15, Issue 9, Page(s) 3621–3634

Abstract: ... for its clinical utility. Ling Zhi-8 (LZ-8), a fungal immunomodulatory protein in ...

Abstract	CPT-11 (Irinotecan) remains an important chemotherapeutic agent against various solid tumors nowadays. Potential adverse effects, especially gastrointestinal toxicities, are the main limiting factor for its clinical utility. Ling Zhi-8 (LZ-8), a fungal immunomodulatory protein in
MeSH term(s)	Mice ; Animals ; Reishi ; Irinotecan ; Claudin-1/genetics
Chemical Substances	Irinotecan (7673326042) ; Claudin-1
Language	English
Publishing date	2023-05-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.204695
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Article ; Online: Ling-Gui-Zhu-Gan decoction ameliorates nonalcoholic fatty liver disease via modulating the gut microbiota.

Chen, Lu-Ping / Zhang, Lin-Fang / Liu, Shuang / Hua, Hua / Zhang, Lei / Liu, Bao-Cheng / Wang, Rui-Rui

Microbiology spectrum

2024 , Page(s) e0197923

Abstract: ... with gut microbiota dysbiosis. Ling-Gui-Zhu-Gan decoction (LG) has been clinically used to treat NAFLD ... Importance: Until now, there has still been no study on the gut microbiota and metabolomics of Ling-Gui-Zhu ...

Abstract	Numerous studies have supported that nonalcoholic fatty liver disease (NAFLD) is highly associated with gut microbiota dysbiosis. Ling-Gui-Zhu-Gan decoction (LG) has been clinically used to treat NAFLD, but the underlying mechanism remains unknown. This study investigated the therapeutic effect and mechanisms of LG in mice with NAFLD induced by a high-fat diet (HD). An HD-induced NAFLD mice model was established to evaluate the efficacy of LG followed by biochemical and histopathological analysis. Metagenomics, metabolomics, and transcriptomics were used to explore the structure and metabolism of the gut microbiota. LG significantly improved hepatic function and decreased lipid droplet accumulation in HD-induced NAFLD mice. LG reversed the structure of the gut microbiota that is damaged by HD and improved intestinal barrier function. Meanwhile, the LG group showed a lower total blood bile acids (BAs) concentration, a shifted BAs composition, and a higher fecal short-chain fatty acids (SCFAs) concentration. Furthermore, LG could regulate the hepatic expression of genes associated with the primary BAs biosynthesis pathway and peroxisome proliferator-activated receptor (PPAR) signaling pathway. Our study suggested that LG could ameliorate NAFLD by altering the structure and metabolism of gut microbiota, while BAs and SCFAs are considered possible mediating substances. Importance: Until now, there has still been no study on the gut microbiota and metabolomics of Ling-Gui-Zhu-Gan decoction (LG) in nonalcoholic fatty liver disease (NAFLD) mouse models. Our study is the first to report on the reshaping of the structure and metabolism of the gut microbiota by LG, as well as explore the potential mechanism underlying the improvement of NAFLD. Specifically, our study demonstrates the potential of gut microbial-derived short-chain fatty acids (SCFAs) and blood bile acids (BAs) as mediators of LG therapy for NAFLD in animal models. Based on the results of transcriptomics, we further verified that LG attenuates NAFLD by restoring the metabolic disorder of BAs via the up-regulation of Fgf15/FXR in the ileum and down-regulation of CYP7A1/FXR in the liver. LG also reduces lipogenesis in NAFLD mice by mediating the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which then contributes to reducing hepatic inflammation and improving intestinal barrier function to treat NAFLD.
Language	English
Publishing date	2024-04-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.01979-23
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Article ; Online: Inhibition of estrogen sulfation by Xian-Ling-Gu-Bao capsule.

He, Liangliang / Chen, Chanjuan / Duan, Shuyi / Li, Yang / Li, Chuan / Yao, Xinsheng / Gonzalez, Frank J / Qin, Zifei / Yao, Zhihong

The Journal of steroid biochemistry and molecular biology

2022 Volume 225, Page(s) 106182

Abstract: Xian-Ling-Gu-Bao capsule (XLGB) is a widely prescribed traditional Chinese medicine used ...

Abstract	Xian-Ling-Gu-Bao capsule (XLGB) is a widely prescribed traditional Chinese medicine used for the treatment of osteoporosis. However, it significantly elevates levels of serum estrogens. Here we aimed to assess the dominant contributors of sulfotransferase (SULT) enzymes to the sulfation of estrogens and identify the effective inhibitors of this pathway in XLGB. First, estrone, 17β-estradiol, and estriol underwent sulfation in human liver S9 extracts. Phenotyping reactions and enzyme kinetics assays revealed that SULT1A1, 1A2, 1A3, 1C4, 1E1, and 2A1 all participated in estrogen sulfation, with SULT1E1 and 1A1 as the most important contributors. The incubation system for these two active enzymes were optimized with Tris-HCl buffer, DL-Dithiothreitol (DTT), MgCl
MeSH term(s)	Humans ; Molecular Docking Simulation ; Sulfotransferases/metabolism ; Polyphenols ; Estrogens
Chemical Substances	Sulfotransferases (EC 2.8.2.-) ; Polyphenols ; Estrogens
Language	English
Publishing date	2022-09-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1049188-0
ISSN	1879-1220 ; 0960-0760
ISSN (online)	1879-1220
ISSN	0960-0760
DOI	10.1016/j.jsbmb.2022.106182
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Article: Comparison of pharmacokinetic profiles of seven major bioactive components in normal and non-alcoholic fatty liver disease (NAFLD) rats after oral administration of Ling-Gui-Zhu-Gan decoction by UPLC-MS/MS.

Nie, Wenlong / Yang, Yang / Li, Ling / Ding, Yue / Chen, Xingmi / Li, Ming / He, Ning / Ji, Guang / Zhang, Yong / Kang, Ping / Zhang, Tong

Frontiers in pharmacology

2023 Volume 14, Page(s) 1174742

Abstract: ... in the plasma of rats after the oral administration of Ling-Gui-Zhu-Gan decoction (LGZGD). Besides, this very ...

Abstract	A sensitive and rapid ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was hereby developed for the determination of seven components, namely, glycyrrhizic acid, glycyrrhetinic acid, dehydrotumulosic acid, isoliquiritin, liquiritin, atractylenolide III, and cinnamic acid, in the plasma of rats after the oral administration of Ling-Gui-Zhu-Gan decoction (LGZGD). Besides, this very method was methodologically validated for specificity, linearity, inter-day and intra-day precision, accuracy, matrix effect, extraction recovery, and stability. It was also successfully used for the first time to compare the pharmacokinetic characteristics of the seven components after oral administration of LGZGD to normal rats and non-alcoholic fatty liver disease (NAFLD) rats. The results indicated significant differences between the pharmacokinetic characteristics of normal and NAFLD rats. To further reveal the different pharmacokinetic behaviors, the expressions of enzymes and transporters in the liver of normal and NAFLD rats were detected using UPLC-MS/MS. In the NAFLD rats, UDP-glucuronosyltransferase 1-1 (UGT1A1) and nine transporters were significantly inhibited and a positive correlation was observed between them and the AUC of the major components. The present results indicate that the pharmacokinetic differences between the normal and NAFLD rats might be attributed to the significant lower expression levels of both the metabolic enzyme UGT1A1 and nine transporter proteins in the NAFLD rats than in the normal rats. Meanwhile, UGT1A1 and the nine transporter proteins might be used as potential biomarkers to assess the ameliorative effect of LGZGD on NAFLD, which could provide useful information to guide the clinical application of LGZGD.
Language	English
Publishing date	2023-05-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2023.1174742
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Article: Ling-Ling Chen: Linking Long Noncoding RNA Processing and Function to RNA Biology.

Chen, Ling-Ling

Trends in biochemical sciences

2016 Volume 41, Issue 9, Page(s) 733–734

Language	English
Publishing date	2016-09
Publishing country	England
Document type	Journal Article
ZDB-ID	194216-5
ISSN	1362-4326 ; 0968-0004 ; 0376-5067
ISSN (online)	1362-4326
ISSN	0968-0004 ; 0376-5067
DOI	10.1016/j.tibs.2016.07.006
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Zs.A 1207: Show issues

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bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article: Qing-Kai-Ling oral liquid alleviated pneumonia via regulation of intestinal flora and metabolites in rats.

Chen, Hongying / Li, Siju / Pan, Biyan / Liu, Kun / Yu, Hansheng / Ma, Chong / Qi, Huiyuan / Zhang, Yuefeng / Huang, Xinyi / Ouyang, Dongsheng / Xie, Zhiyong

Frontiers in microbiology

2023 Volume 14, Page(s) 1194401

Abstract: Background: Qing-Kai-Ling (QKL) oral liquid, evolving from a classical Chinese formula known ...

Abstract	Background: Qing-Kai-Ling (QKL) oral liquid, evolving from a classical Chinese formula known as An-Gong-Niu-Huang pills, is a well-established treatment for pneumonia with its mechanism remaining muddled. Studies have shown that the regulation of both intestinal flora and host-microbiota co-metabolism may contribute to preventing and treating pneumonia. The study aimed to investigate the potential mechanism by which QKL alleviates pneumonia from the perspective of 'microbiota-metabolites-host' interaction. Methods: We evaluated the therapeutic effects of QKL on lipopolysaccharide (LPS)-induced pneumonia rats. To explore the protective mechanism of QKL treatment, a multi-omics analysis that included 16S rDNA sequencing for disclosing the key intestinal flora, the fecal metabolome to discover the differential metabolites, and whole transcriptome sequencing of lung tissue to obtain the differentially expressed genes was carried out. Then, a Spearman correlation was employed to investigate the association between the intestinal flora, the fecal metabolome and inflammation-related indices. Results: The study demonstrated that pneumonia symptoms were significantly attenuated in QKL-treated rats, including decreased TNF-α, NO levels and increased SOD level. Furthermore, QKL was effective in alleviating pneumonia and provided protection equivalent to that of the positive drug dexamethasone. Compared with the Model group, QKL treatment significantly increased the richness and αlpha diversity of intestinal flora, and restored multiple intestinal genera (e.g., Conclusion: Our findings indicated that QKL could potentially modulate intestinal flora dysbiosis, improve host-microbiota co-metabolism dysregulation and regulate gene expression in the lungs, thereby mitigating LPS-induced pneumonia in rats. The study may provide new ideas for the clinical application and further development of QKL.
Language	English
Publishing date	2023-06-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2023.1194401
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Article: Zhoushi Qi Ling decoction inhibits the progression of castration-resistant prostate cancer in vivo by regulating macrophage infiltration via IL6-STAT3 signaling.

Cao, Hongwen / Wang, Dan / Gao, Renjie / Chen, Lei / Feng, Yigeng / Sun, Peng

Journal of traditional and complementary medicine

2023 Volume 14, Issue 1, Page(s) 19–25

Abstract: ... Western blot.: Results and conclusion: Zhoushi Qi Ling decoction (ZQD) treatment significantly reduced PC3 ...

Abstract	Background and aim: Prostate cancer is a leading malignant tumor in men, associated with a high rate of mortality. Androgen deprivation therapy is commonly used to treat prostate cancer, which contributes to the progression of castration-resistant prostate cancer (CRPC). The current therapy has a low survival rate in patients with CRPC. Our study aims to develop a novel effective approach for CRPC treatment and improve survival benefits. Experimental procedure: CRPC cell line PC-3-Luc expressing luciferase and the CRPC cell line PC-3-IL6-Luc stably overexpressing IL-6 were used to establish the xenograft tumor mouse model. The tumor was monitored weekly using Bioluminescence imaging. Infiltrated macrophages were quantified by fluorescence-activated cell sorting using flow cytometry. IL6 mRNA level was determined using quantitative real-time PCR. The protein levels of total STAT3 and phosphorylated STAT3 were determined using Western blot. Results and conclusion: Zhoushi Qi Ling decoction (ZQD) treatment significantly reduced PC3 the xenograft tumor progression and the number of infiltrated macrophages when compared with saline treatment. IL6 mRNA level was remarkedly suppressed by ZQD treatment. Notably, the protein level of phosphorylated STAT3 was significantly decreased in PC3 the xenograft tumor treated with ZQD compared to saline treatment. Our findings demonstrated that ZQD treatment significantly reduced the progression of prostate cancer, evidenced by the reduced population of infiltrated macrophages and the inhibition of the IL6/STAT3 pathway.
Language	English
Publishing date	2023-06-07
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2709698-1
ISSN	2225-4110
ISSN	2225-4110
DOI	10.1016/j.jtcme.2023.05.005
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Article ; Online: Qi Ling decreases paclitaxel resistance in the human prostate cancer by reversing tumor-associated macrophages function.

Cao, Hongwen / Wang, Dan / Gao, Renjie / Feng, Yigeng / Chen, Lei

Aging

2022 Volume 14, Issue 4, Page(s) 1812–1821

Abstract: ... study, we evaluated the effects of Qi Ling (QL), a traditional Chinese medicine on paclitaxel resistance ... of QL-serum were abolished in the presence of IL-6. Qi Ling re-programmed TAMs and decreases paclitaxel ...

Abstract	Tumor-associated macrophages (TAMs) are critical immune cells infiltrated into tumor. In present study, we evaluated the effects of Qi Ling (QL), a traditional Chinese medicine on paclitaxel resistance in prostate cancer cells and explored the underlying mechanisms. We administrated QL to rats and collected the serum from QL-treated rats (QL-serum). We established the co-culture system of TAMs/paclitaxel resistant prostate cancer cells. We treated the TAMs with QL-serum and measured the viability of paclitaxel resistant prostate cancer cells after exposing to paclitaxel. We monitored the expression of M1 and M2 markers, the expression and activation of IL-6/STAT3 signaling pathways in TAMs after QL treatment. We treated TAMs with QL-serum together with interleukin (IL)-6, measured the expression of M1 and M2 markers, and the viability of paclitaxel resistant prostate cancer cells. In co-culture system, QL-serum-treated TAMs decreased the paclitaxel resistance in the human prostate cancer cells. QL-serum treatment significantly up-regulated the expression of M1 markers inducible nitric oxide synthase and tumor necrosis factor α while decreased the expression of M2 markers IL-10 and chemokine (C-C motif) ligand 22. QL-serum suppressed the activation of IL-6/ signal transducer and activator of transcription 3 signaling pathway. All these effects of QL-serum were abolished in the presence of IL-6. Qi Ling re-programmed TAMs and decreases paclitaxel resistance in prostate cancer cells.
MeSH term(s)	Animals ; Humans ; Interleukin-6/metabolism ; Male ; Paclitaxel/pharmacology ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/metabolism ; Qi ; Rats ; Tumor-Associated Macrophages
Chemical Substances	Interleukin-6 ; Paclitaxel (P88XT4IS4D)
Language	English
Publishing date	2022-02-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.203904
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Article ; Online: Qi Ling decoction enhances abiraterone treatment via suppression of autophagy in castration resistant prostate cancer.

Feng, Yigeng / Cao, Hongwen / Song, Zixi / Chen, Lei / Wang, Dan / Gao, Renjie

Aging

2022 Volume 14, Issue 24, Page(s) 9942–9950

Abstract: ... we aim to explore the potential of Qi Ling decoction (QLD), a traditional Chinese medicine ...

Abstract	Abiraterone acetate has exhibited impressive results in improving progression-free survival of patients with metastatic castration-resistant prostate cancer. However, many patients may develop abiraterone resistance with a variable duration of response. Hence, identifying a remedy to overcome abiraterone resistance is critical for patients with castration-resistant prostate cancer. In this study, we aim to explore the potential of Qi Ling decoction (QLD), a traditional Chinese medicine, in attenuating abiraterone resistance in prostate cancer. Cell viability and apoptosis were respectively measured by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. The protein levels were assessed by Western blotting assay. Autophagosome formation was quantified by counting LC3 puncta. We found that QLD was capable of promoting abiraterone-induced apoptosis and cell death of PC3-AbiR and DU145-AbiR cells
MeSH term(s)	Male ; Humans ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/pathology ; Qi ; Androstenes/pharmacology ; Androstenes/therapeutic use ; Autophagy
Chemical Substances	abiraterone (G819A456D0) ; Androstenes
Language	English
Publishing date	2022-12-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.204427
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Article ; Online: Mitochondrial toxicants in Xian-Ling-Gu-Bao induce liver injury by regulating the PI3K/mTOR signaling pathway: an in vitro study.

Piao, Shujuan / Lin, Hongwei / Tao, Xia / Chen, Wansheng

BMC complementary medicine and therapies

2022 Volume 22, Issue 1, Page(s) 317

Abstract: ... hepatotoxicity. Xian-Ling-Gu-Bao (XLGB) oral preparation is a commonly used drug for osteoporosis in China ...

Abstract	Background: Drug-induced mitochondrial toxicity is thought to be a common mechanism of drug hepatotoxicity. Xian-Ling-Gu-Bao (XLGB) oral preparation is a commonly used drug for osteoporosis in China. Classical safety evaluation studies have shown that the entire preparation and six Chinese herbal medicines have high safety, but the incidence of drug-induced liver damage due to XLGB remains high, the mechanism and toxic substances causing liver injury are still unclear. The purpose of this study is to identify compounds with potential mitochondrial liabilities in XLGB, and to clarify their underlying mechanisms and related pathways. Methods: The mitochondrial function analysis was performed using an extracellular flux assay, which simultaneously monitored both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Through network pharmacology and in vitro experimental verification, the potential protein targets, signaling pathways and molecular mechanism of mitochondrial toxicity have been studied. Results: We observed a significant decrease in mitochondrial respiration of Psoraleae Fructus and its five compounds in fundamental bioenergetics parameters such as basal respiration, ATP-linked production and maximal respiration, indicating mitochondrial dysfunction. The network pharmacology results showed that the influence of XLGB on mitochondrial dysfunction was closely related to PI3K-Akt signaling pathway, mTOR signaling pathway and Apoptosis. Western blot showed that the levels of mTOR, p-mTOR (Ser2448), Raptor, PI3K (p110α), Beclin 1, ATG5 and Caspase-9 were up-regulated after treatment with psoralidin, psoralen and bavachin, and the expression of Bcl-2 was down-regulated after bavachinin treatment. Conclusions: The hepatotoxicity of XLGB is associated with mitochondrial dysfunction. Five compounds in Psoraleae Fructus showed mitochondrial damage, they are psoralidin, isobavachalcone, bavachinin, bavachin and psoralen, especially psoralidin showed significant reduction in reserve capacity and respiratory control ratios. The molecular mechanism is related to the activation of PI3K/mTOR signaling pathway to inhibit autophagy and induce mitochondrial apoptosis.
MeSH term(s)	Humans ; Phosphatidylinositol 3-Kinases ; TOR Serine-Threonine Kinases ; Mitochondria ; Signal Transduction ; Chemical and Drug Induced Liver Injury ; Furocoumarins
Chemical Substances	Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; Furocoumarins ; MTOR protein, human (EC 2.7.1.1)
Language	English
Publishing date	2022-12-01
Publishing country	England
Document type	Journal Article
ISSN	2662-7671
ISSN (online)	2662-7671
DOI	10.1186/s12906-022-03798-5
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