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Article ; Online: Study of workshop network stability based on pinning control in disturbance environment.

Li, Xiaojuan / Cui, Gaojian / Li, Shunmin / Zhang, Fangyuan

2023 Volume 13, Issue 1, Page(s) 5382

Abstract: In the production process, the manufacturing behavior and all the essential factors are affected by several disturbance factors, showing a complex dynamic fluctuation law. It makes the stability control process a difficult problem in environmental ... ...

Abstract	In the production process, the manufacturing behavior and all the essential factors are affected by several disturbance factors, showing a complex dynamic fluctuation law. It makes the stability control process a difficult problem in environmental constraints. In this paper, the workshop production process is considered, and an improved coupled map lattice workshop production network state model is proposed. On this basis, the controller with the function of resource load protection is designed, and the network state model of the workshop based on the pinning control is developed. Three kinds of stability control strategies, SAC (Self-adaption Control) , SC (Self-acting Control) and PC (Pinning Control) , are designed based on disturbance triggering behavior and node state transition rules. In addition, two control effect evaluation indexes, RTS (Recovery Time Steps) and NFT (Node Failure Times) are designed. Considering the actual production data of diesel fuel injection system parts production workshop as example, the model is simulated and verified. The results show that under different disturbance intensities, compared with the SAC strategy, the RTS-Average value of the PC strategy is reduced by 29.83% on average, and the NFT-Average values are reduced by 46.9% on average. This proves that the pinning control strategy has certain advantages in controlling time length and propagation scale of disturbance propagation.
Language	English
Publishing date	2023-04-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-32562-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: JinChan YiShen TongLuo Formula ameliorate mitochondrial dysfunction and apoptosis in diabetic nephropathy through the HIF-1α-PINK1-Parkin pathway.

Qiyan Zheng / Zhang, Xueqin / Guo, Jing / Wang, Yahui / Jiang, Yuhua / Li, Shunmin / Liu, Yu Ning / Liu, Wei Jing

Journal of ethnopharmacology

2024 Volume 328, Page(s) 117863

Abstract: Ethnopharmacological relevance: The JinChan YiShen TongLuo (JCYSTL) formula, a traditional Chinese medicine (TCM), has been used clinically for decades to treat diabetic nephropathy (DN). TCM believes that the core pathogenesis of DN is "kidney ... ...

Abstract	Ethnopharmacological relevance: The JinChan YiShen TongLuo (JCYSTL) formula, a traditional Chinese medicine (TCM), has been used clinically for decades to treat diabetic nephropathy (DN). TCM believes that the core pathogenesis of DN is "kidney deficiency and collateral obstruction," and JCYSTL has the effect of "tonifying kidney and clearing collateral," thus alleviating the damage to kidney structure and function caused by diabetes. From the perspective of modern medicine, mitochondrial damage is an important factor in DN pathogenesis. Our study suggests that the regulation of mitophagy and mitochondrial function by JCYSTL may be one of the internal mechanisms underlying its good clinical efficacy. Aim of the study: This study aimed to investigate the mechanisms underlying the renoprotective effects of JCYSTL. Materials and methods: Unilateral nephrectomy combined with low-dose streptozotocin intraperitoneally injected in a DN rat model and high glucose (HG) plus hypoxia-induced HK-2 cells were used to explore the effects of JCYSTL on the HIF-1α/mitophagy pathway, mitochondrial function and apoptosis. Results: JCYSTL treatment significantly decreased albuminuria, serum creatinine, blood urea nitrogen, and uric acid levels and increased creatinine clearance levels in DN rats. In vitro, medicated serum containing JCYSTL formula increased mitochondrial membrane potential (MMP); improved activities of mitochondrial respiratory chain complexes I, III, and IV; decreased the apoptotic cell percentage and apoptotic protein Bax expression; and increased anti-apoptotic protein Bcl-2 expression in HG/hypoxia-induced HK-2 cells. The treatment group exhibited increased accumulation of PINK1, Parkin, and LC3-II and reduced P62 levels in HG/hypoxia-induced HK-2 cells, whereas in PINK1 knockdown HK-2 cells, JCYSTL did not improve the HG/hypoxia-induced changes in Parkin, LC3-II, and P62. When mitophagy was impaired by PINK1 knockdown, the inhibitory effect of JCYSTL on Bax and its promoting effect on MMP and Bcl-2 disappeared. The JCYSTL-treated group displayed significantly higher HIF-1α expression than the model group in vivo, which was comparable to the effects of FG-4592 in DN rats. PINK1 knockdown did not affect HIF-1α accumulation in JCYSTL-treated HK-2 cells exposed to HG/hypoxia. Both JCYSTL and FG-4592 ameliorated mitochondrial morphological abnormalities and reduced the mitochondrial respiratory chain complex activity in the renal tubules of DN rats. Mitochondrial apoptosis signals in DN rats, such as increased Bax and Caspase-3 expression and apoptosis ratio, were weakened by JCYSTL or FG-4592 administration. Conclusion: This study demonstrates that the JCYSTL formula activates PINK1/Parkin-mediated mitophagy by stabilizing HIF-1α to protect renal tubules from mitochondrial dysfunction and apoptosis in diabetic conditions, presenting a promising therapy for the treatment of DN.
MeSH term(s)	Rats ; Animals ; Diabetic Nephropathies/pathology ; bcl-2-Associated X Protein ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2 ; Ubiquitin-Protein Ligases/metabolism ; Hypoxia ; Protein Kinases/metabolism ; Mitochondrial Diseases ; Diabetes Mellitus ; Drugs, Chinese Herbal
Chemical Substances	yishen ; tongluo ; bcl-2-Associated X Protein ; Proto-Oncogene Proteins c-bcl-2 ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Protein Kinases (EC 2.7.-) ; Drugs, Chinese Herbal
Language	English
Publishing date	2024-02-05
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2024.117863
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Article ; Online: A novel enzyme-based functional correlation algorithm for multi-omics reveals the potential mechanisms of traditional Chinese medicines: Taking Jian-Pi-Yi-Shen formula as an example.

Yin, Ying-Hao / Li, Chang-Hui / Huang, Hai-Piao / Zhang, Chi / Zhang, Shang-Bin / Li, Shun-Min / Chen, Jianping

Journal of pharmaceutical and biomedical analysis

2024 Volume 241, Page(s) 115973

Abstract: The integrated analysis of host metabolome and intestinal microbiome is an opportunity to explore the complex therapeutic mechanisms of traditional Chinese medicines. Currently, researchers mainly employ various statistical correlation analytical methods ...

Abstract	The integrated analysis of host metabolome and intestinal microbiome is an opportunity to explore the complex therapeutic mechanisms of traditional Chinese medicines. Currently, researchers mainly employ various statistical correlation analytical methods to investigate metabolome-microbiome correlations. However, these conventional correlation techniques often focus on statistical correlations and their biological meanings are always ignored, especially the functional relevance between them. Here, we developed a novel enzyme-based functional correlation (EBFC) algorithm to further improve the interpretability and the identified scope of microbe-metabolite correlations based on the conventional Spearman's analysis. The proposed EBFC algorithm is successfully utilized to reveal the therapeutic mechanisms of Jian-Pi-Yi-Shen (JPYS) formula on the treatment of adenine-induced chronic kidney disease (CKD) rats. JPYS, a TCM formula for treating CKD, has beneficial clinical effects. We tentatively revealed the potential mechanism of JPYS for treating CKD rats from the perspective of the serum metabolome, gut microbiome, and their interactions. Specifically, 11 metabolites and 19 bacterial genera in the CKD rats were significantly regulated to approaching normal status after JPYS treatment, suggesting that JPYS could ameliorate the pathological symptoms of CKD rats by reshaping the disturbed metabolome and gut microbiota. Further correlation analysis between the significantly perturbed metabolites, microbiota, and the related enzymes provided more strong evidence for the study of host metabolism-microbiota interactions and the therapeutic mechanism of JPYS on CKD rats. In conclusion, these findings will help us to deeply understand the pathogenesis of CKD and provide new insights into the therapeutic mechanism of JPYS.
MeSH term(s)	Rats ; Animals ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use ; Multiomics ; Medicine, Chinese Traditional/methods ; Renal Insufficiency, Chronic/metabolism ; Metabolome
Chemical Substances	Drugs, Chinese Herbal
Language	English
Publishing date	2024-01-11
Publishing country	England
Document type	Journal Article
ZDB-ID	604917-5
ISSN	1873-264X ; 0731-7085
ISSN (online)	1873-264X
ISSN	0731-7085
DOI	10.1016/j.jpba.2024.115973
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Article ; Online: Effects of hypoxia-inducible factor prolyl hydroxylase inhibitors versus erythropoiesis-stimulating agents on iron metabolism and inflammation in patients undergoing dialysis: A systematic review and meta-analysis

Zheng, Qiyan / Zhang, Pingna / Yang, Huisheng / Geng, Yunling / Tang, Jingyi / Kang, Yi / Qi, Airong / Li, Shunmin

Heliyon. 2023 Apr., v. 9, no. 4 p.e15310-

2023

Abstract: This study aimed to evaluate the effects of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) on iron metabolism and inflammation in dialysis-dependent chronic kidney disease (DD-CKD) patients. PubMed, Embase, Web of Science, Cochrane ... ...

Abstract	This study aimed to evaluate the effects of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) on iron metabolism and inflammation in dialysis-dependent chronic kidney disease (DD-CKD) patients. PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov websites were searched for randomized controlled trials (RCTs) investigating HIF-PHIs versus ESAs for DD-CKD patients. Twenty studies with 14,737 participants were included in the meta-analysis, which demonstrated no significant difference in the effect of transferrin saturation and ferritin between HIF-PHIs and the ESAs group (MD, 0.65; 95%CI, −0.45 to 1.75; very low certainty; SMD, −0.03; 95% CI, −0.13 to 0.07; low certainty). However, HIF-PHIs significantly increased the iron (MD, 2.30; 95% CI, 1.40 to 3.20; low certainty), total iron-binding capacity (SMD, 0.82; 95% CI, 0.66 to 0.98; low certainty), and transferrin (SMD, 0.90; 95%CI, 0.74 to 1.05; moderate certainty) levels when compared with the ESAs group. In contrast, the hepcidin level and dosage of intravenous iron were significantly decreased in the HIF-PHIs group compared with the ESAs group (MD, −15.06, 95%CI, −21.96 to −8.16; low certainty; MD, −18.07; 95% CI, −30.05 to −6.09; low certainty). The maintenance dose requirements of roxadustat were independent of baseline CRP or hsCRP levels with respect to the effect on inflammation. HIF-PHIs promote iron utilization and reduce the use of intravenous iron therapy. Furthermore, HIF-PHIs, such as roxadustat, maintain the erythropoietic response independent of the inflammatory state. Thus, HIF-PHIs may be an alternative treatment strategy for anemia in DD-CKD patients, where ESA is hyporesponsive due to iron deficiency and inflammation.
Keywords	Internet ; anemia ; dialysis ; ferritin ; hepcidin ; inflammation ; intravenous injection ; iron ; iron absorption ; kidney diseases ; meta-analysis ; procollagen-proline dioxygenase ; systematic review ; transferrin ; Hypoxia-inducible factor prolyl hydroxylase inhibitors ; Chronic kidney disease ; Iron metabolism ; HIF-PHIs: ; DD-CKD: ; RCTs: ; ESAs: ; rhEPO: ; Hb: ; EPO: ; TSAT: ; TIBC: ; CRP: ; hsCRP: ; PHD:
Language	English
Dates of publication	2023-04
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Use and reproduction
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e15310
Database	NAL-Catalogue (AGRICOLA)

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Article: Lipidomics reveals the potential mechanism of honokiol against adenine-induced chronic kidney disease.

Liu, Xinhui / Gao, Liwen / Huang, Xi / Deng, Ruyu / Wei, Xian / Lu, Jiandong / Li, Shunmin

Frontiers in pharmacology

2022 Volume 13, Page(s) 1019629

Abstract: Honokiol (HKL), a biphenolic compound, is derived from the bark ... ...

Abstract	Honokiol (HKL), a biphenolic compound, is derived from the bark of
Language	English
Publishing date	2022-10-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.1019629
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Article: Network Pharmacology and Experimental Verification Strategies to Illustrate the Mechanism of Jian-Pi-Yi-Shen Formula in Suppressing Epithelial-Mesenchymal Transition.

Zhao, Yuan / Li, Xiangbin / Wang, Fochang / Huang, Shiying / Du, Hanqian / Li, Shunmin / Chen, Jianping

Frontiers in pharmacology

2022 Volume 13, Page(s) 873023

Abstract: Jian-Pi-Yi-Shen formula (JPYSF), a traditional Chinese medicine, has been recommended to treat renal fibrosis for decades. Previous studies had shown that JPYSF could inhibit epithelial-mesenchymal transition (EMT), an important regulatory role in renal ... ...

Abstract	Jian-Pi-Yi-Shen formula (JPYSF), a traditional Chinese medicine, has been recommended to treat renal fibrosis for decades. Previous studies had shown that JPYSF could inhibit epithelial-mesenchymal transition (EMT), an important regulatory role in renal fibrosis. However, the mechanism of JPYSF action is largely unknown. In this study, network pharmacology and experimental verification were combined to elucidate and identify the potential mechanism of JPYSF against renal fibrosis by suppressing EMT at molecular and pathway levels. Network pharmacology was first performed to explore the mechanism of JPYSF against renal fibrosis targeting EMT, and then a 5/6 nephrectomy (5/6 Nx)-induced rat model of renal fibrosis was selected to verify the predictive results by Masson's trichrome stains and western blot analysis. Two hundred and thirty-two compounds in JPYSF were selected for the network approach analysis, which identified 137 candidate targets of JPYSF and 4,796 known therapeutic targets of EMT. The results of the Gene Ontology (GO) function enrichment analysis included 2098, 88, and 133 GO terms for biological processes (BPs), molecular functions (MFs), and cell component entries, respectively. The top 10 enrichment items of BP annotations included a response to a steroid hormone, a metal ion, oxygen levels, and so on. Cellular composition (CC) is mainly enriched in membrane raft, membrane microdomain, membrane region, etc. The MF of JPYSF analysis on EMT was predominately involved in proximal promoter sequence-specific DNA binding, protein heterodimerization activity, RNA polymerase II proximal promoter sequence-specific DNA binding, and so on. The involvement signaling pathway of JPYSF in the treatment of renal fibrosis targeting EMT was associated with anti-fibrosis, anti-inflammation, podocyte protection, and metabolism regulation. Furthermore, the
Language	English
Publishing date	2022-05-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.873023
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Article ; Online: The effects of natural products and bioactive ingredients of traditional Chinese medicine on apoptosis of ovarian granulosa cells.

Zhong, Lulu / Luo, Yue / Zhou, Feng / Yang, Xuebin / Tan, Yang / Li, Shunmin / Pei, Gang

Journal of applied toxicology : JAT

2022 Volume 43, Issue 6, Page(s) 772–788

Abstract: Abnormal ovarian function is the main manifestation of female reproductive toxicity. Granulosa cells (GCs) play an important role in determining the fate of follicles and are the main effector cells of the female reproductive system. Excessive apoptosis ... ...

Abstract	Abnormal ovarian function is the main manifestation of female reproductive toxicity. Granulosa cells (GCs) play an important role in determining the fate of follicles and are the main effector cells of the female reproductive system. Excessive apoptosis of GCs leads to pathological folliculogenesis and further reproductive damage. However, drugs available for treatment of female reproductive toxicity are limited. Recent studies have confirmed that various natural products and bioactive ingredients of traditional Chinese medicine (TCM) can inhibit apoptosis of GCs and protect ovarian function. In this review, the mechanisms underlying the proapoptotic and antiapoptotic effects of natural products and bioactive ingredients of TCM on the proliferation, function, and apoptosis of GCs are summarized based on the findings of reports published over the past 10 years as reference for the treatment of female reproductive toxicity.
MeSH term(s)	Female ; Humans ; Ovarian Follicle ; Medicine, Chinese Traditional ; Granulosa Cells ; Apoptosis
Language	English
Publishing date	2022-11-22
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	604625-3
ISSN	1099-1263 ; 0260-437X
ISSN (online)	1099-1263
ISSN	0260-437X
DOI	10.1002/jat.4406
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Article: Effects of hypoxia-inducible factor prolyl hydroxylase inhibitors versus erythropoiesis-stimulating agents on iron metabolism and inflammation in patients undergoing dialysis: A systematic review and meta-analysis.

Zheng, Qiyan / Zhang, Pingna / Yang, Huisheng / Geng, Yunling / Tang, Jingyi / Kang, Yi / Qi, Airong / Li, Shunmin

Heliyon

2023 Volume 9, Issue 4, Page(s) e15310

Abstract: Aims: This study aimed to evaluate the effects of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) on iron metabolism and inflammation in dialysis-dependent chronic kidney disease (DD-CKD) patients.: Methods: PubMed, Embase, Web of ... ...

Abstract	Aims: This study aimed to evaluate the effects of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) on iron metabolism and inflammation in dialysis-dependent chronic kidney disease (DD-CKD) patients. Methods: PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov websites were searched for randomized controlled trials (RCTs) investigating HIF-PHIs versus ESAs for DD-CKD patients. Key findings: Twenty studies with 14,737 participants were included in the meta-analysis, which demonstrated no significant difference in the effect of transferrin saturation and ferritin between HIF-PHIs and the ESAs group (MD, 0.65; 95%CI, -0.45 to 1.75; very low certainty; SMD, -0.03; 95% CI, -0.13 to 0.07; low certainty). However, HIF-PHIs significantly increased the iron (MD, 2.30; 95% CI, 1.40 to 3.20; low certainty), total iron-binding capacity (SMD, 0.82; 95% CI, 0.66 to 0.98; low certainty), and transferrin (SMD, 0.90; 95%CI, 0.74 to 1.05; moderate certainty) levels when compared with the ESAs group. In contrast, the hepcidin level and dosage of intravenous iron were significantly decreased in the HIF-PHIs group compared with the ESAs group (MD, -15.06, 95%CI, -21.96 to -8.16; low certainty; MD, -18.07; 95% CI, -30.05 to -6.09; low certainty). The maintenance dose requirements of roxadustat were independent of baseline CRP or hsCRP levels with respect to the effect on inflammation. Significance: HIF-PHIs promote iron utilization and reduce the use of intravenous iron therapy. Furthermore, HIF-PHIs, such as roxadustat, maintain the erythropoietic response independent of the inflammatory state. Thus, HIF-PHIs may be an alternative treatment strategy for anemia in DD-CKD patients, where ESA is hyporesponsive due to iron deficiency and inflammation.
Language	English
Publishing date	2023-04-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e15310
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Article ; Online: Jian-Pi-Yi-Shen formula restores iron metabolism from dysregulation in anemic rats with adenine-induced nephropathy.

Li, Changhui / Huang, Haipiao / Wang, Rui / Zhang, Chi / Huang, Shiying / Wu, Jinru / Mo, Pingli / Yu, Huimin / Li, Shunmin / Chen, Jianping

Journal of ethnopharmacology

2023 Volume 312, Page(s) 116526

Abstract: Ethnopharmacological relevance: Jian-Pi-Yi-Shen (JPYS) is a herbal decoction being used to relieve the symptoms of chronic kidney disease (CKD) and its complications, including anemia, for over twenty years. Nonetheless, it is unclear how JPYS ... ...

Abstract	Ethnopharmacological relevance: Jian-Pi-Yi-Shen (JPYS) is a herbal decoction being used to relieve the symptoms of chronic kidney disease (CKD) and its complications, including anemia, for over twenty years. Nonetheless, it is unclear how JPYS influences renal anemia and iron metabolism. Aim of the study: An analysis of network pharmacology, chemical profiling, and in vivo experiments was conducted to identify the impact of JPYS on JAK2-STAT3 pathway and iron utilization in renal anemia and CKD. Materials and methods: The chemical properties of JPYS and its exposed ingredients were detected in vivo. And based on the aforesaid chemical compounds, the potential targets and signaling pathways of JPYS for renal anemia treatment were predicted by network pharmacology. Afterward, an adenine-feeding animal model of CKD-related anemia was developed to verify the mechanism by which JPYS modulates iron recycling to treat renal anemia. Renal injury was estimated by serum creatinine (Scr), blood urea nitrogen (BUN), histopathological examinations and fibrosis degree. Western blot, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry approaches were utilized to assess the levels of JAK2, STAT3 and iron metabolism-related factors. Results: There were 164 active ingredients identified in JPYS, including prototypes and metabolites in vivo were identified in JPYS, and 21 core targets were found through network pharmacology based on topological characteristics. Combined with the core targets and pathway enrichment analysis, the majority of the candidate targets were associated with the JAK2-STAT3 signaling pathways. Experimental results indicated that JPYS treatment significantly decreased the expression of BUN and Scr, restored renal pathological damage, down-regulated fibrosis degree, and improved hematological parameters such as red blood cell, hemoglobin and hematocrit in CKD rats. Furthermore, JPYS significantly restored iron metabolism from dysregulation by increasing the levels of iron and ferritin in the serum, inhibiting the production of hepcidin in liver and serum, and regulating transferrin receptor 1 in bone marrow. Meanwhile, the expression of JAK2 and STAT3 was suppressed by JPYS treatment. Conclusions: Based on these results, JPYS reduces hepcidin levels by inhibiting the activation of JAK2-STAT3 signaling, thereby protecting against iron deficiency anemia.
MeSH term(s)	Rats ; Animals ; Hepcidins/metabolism ; Adenine ; Anemia/drug therapy ; Iron ; Renal Insufficiency, Chronic/chemically induced ; Renal Insufficiency, Chronic/drug therapy ; Fibrosis
Chemical Substances	Hepcidins ; Adenine (JAC85A2161) ; Iron (E1UOL152H7)
Language	English
Publishing date	2023-04-23
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2023.116526
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Article ; Online: Effects of honokiol protects against chronic kidney disease via BNIP3/NIX and FUNDC1-mediated mitophagy and AMPK pathways.

Wei, Xian / Wang, Yuzhi / Lao, Yunlan / Weng, Jiali / Deng, Ruyu / Li, Shunmin / Lu, Jiandong / Yang, Shudong / Liu, Xinhui

Molecular biology reports

2023 Volume 50, Issue 8, Page(s) 6557–6568

Abstract: Background: Chronic kidney disease (CKD) is a serious health threat worldwide. Defective mitophagy has been reported to induce mitochondrial dysfunction, which is closely associated with CKD pathogenesis. Honokiol (HKL) is a bioactive component of ... ...

Abstract	Background: Chronic kidney disease (CKD) is a serious health threat worldwide. Defective mitophagy has been reported to induce mitochondrial dysfunction, which is closely associated with CKD pathogenesis. Honokiol (HKL) is a bioactive component of Magnolia officinalis that has multiple efficacies. Our study aimed to investigate the effect of HKL on a CKD rat model and explore the possible mechanisms of mitophagy mediated by Bcl-2 interacting protein 3 and BNIP3-like (NIX) (also known as the BNIP3/NIX pathway) and FUN14 domain-containing 1 (the FUNDC1 pathway) and the role of the AMP-activated protein kinase (AMPK) pathway. Methods: A CKD rat model was established by feeding the animals dietary adenine (0.75% w/w, 3 weeks). Simultaneously, the treatment group was given HKL (5 mg/kg/day, 4 weeks) by gavage. Renal function was assessed by measuring serum creatinine (Scr) and blood urea nitrogen (BUN) levels. Pathological changes were analyzed by periodic acid-Schiff (PAS) and Masson's trichrome staining. Protein expression was evaluated by Western blotting and immunohistochemistry. Results: HKL treatment ameliorated the decline in renal function and reduced tubular lesions and interstitial fibrosis in CKD rats. Accordingly, the renal fibrosis markers Col-IV and α-SMA were decreased by HKL. Moreover, HKL suppressed the upregulation of the proapoptotic proteins Bad and Bax and Cleaved caspase-3 expression in CKD rats. Furthermore, HKL suppressed BNIP3, NIX and FUNDC1 expression, leading to the reduction of excessive mitophagy in CKD rats. Additionally, AMPK was activated by adenine, and HKL reversed this change and significantly decreased the level of activated AMPK (phosphorylated AMPK, P-AMPK). Conclusion: HKL exerted a renoprotective effect on CKD rats, which was possibly associated with BNIP3/NIX and FUNDC1-mediated mitophagy and the AMPK pathway.
MeSH term(s)	Rats ; Animals ; Mitophagy ; AMP-Activated Protein Kinases/metabolism ; Mitochondria/metabolism ; Renal Insufficiency, Chronic/drug therapy ; Renal Insufficiency, Chronic/metabolism ; Mitochondrial Proteins/metabolism ; Membrane Proteins/metabolism
Chemical Substances	AMP-Activated Protein Kinases (EC 2.7.11.31) ; honokiol (11513CCO0N) ; Mitochondrial Proteins ; BNIP3 protein, rat ; Membrane Proteins ; FUNDC1 protein, rat
Language	English
Publishing date	2023-06-20
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-023-08592-1
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