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1.
Int J Biol Macromol ; 261(Pt 1): 129670, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38280697

RESUMO

The oxidative microenvironment in fibrotic livers often diminishes the effectiveness of mesenchymal stem cells (MSCs)-based therapy. Recent research suggests that pharmacological pre-treatment could enhance the therapeutic performance of MSCs. In this study, we assessed the impact of Arctium lappa L. polysaccharides (ALP) on the biological properties of nasal ectomesenchymal stem cells (EMSCs) and investigated the augmenting effect of ALP pretreatment on EMSCs (ALP-EMSCs) for the treatment of liver fibrosis. ALP treatment demonstrated multiple biological impacts on EMSC functions regarding liver fibrosis: firstly, it maintained the stemness of the cells while boosting the EMSCs' paracrine effects; secondly, it increased the expression of anti-inflammatory and antioxidant factors; thirdly, it inhibited the activation of hepatic stellate cells (HSCs) and liver collagen build-up by modulating the Wnt/ß-catenin signaling pathways. Collectively, these effects helped to halt the progression of liver fibrosis. Therefore, the use of ALP-EMSCs presents an innovative and promising approach for treating hepatic fibrosis in clinical scenarios.


Assuntos
Arctium , Células-Tronco Mesenquimais , Humanos , beta Catenina/metabolismo , Via de Sinalização Wnt , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo
2.
Anal Biochem ; 684: 115360, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37865269

RESUMO

CONTEXT: Echinacoside (ECH) is a natural anti-cancer compound and is of great value in cancer treatment. However, the mechanism underlying this effect on breast cancer (BC) was unclear. OBJECTIVE: To explore the mechanism of ECH treating BC by network pharmacology and experimental validation. MATERIALS & METHODS: Several databases were searched to screen potential targets of ECH and obtain information on targets related to BC. STRING was applied to construct a Protein-protein interaction (PPI) network. DAVID was applied for Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Gene Expression Profiling Interactive Analysis (GEPIA) was searched for the relationship between the expression profile and overall survival of major targets in normal breast and BC tissues. Finally, the results of network pharmacology analysis were validated by experiments. RESULTS: Seventeen targets of ECH overlapped with targets in BC. Ten hub targets were determined through PPI. By GO and KEGG analysis 15 entries and 25 pathways were obtained, in which phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), hypoxia inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) played greater roles. Validation of key targets in the GEPIA database showed that PIK3R1 and PIK3CD remained consistent with the results of the study. Experiments in vitro showed ECH inhibited proliferation, induced apoptosis and reduced mRNA levels and protein expression of PI3K, AKT, hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (VEGFA) in MCF-7 cells. Furthermore, experiments in vivo revealed that ECH significantly reduced tumor growth, promoted apoptosis and decreased the related mRNA levels and protein expression, suggesting ECH works on BC by regulating PI3K/AKT/HIF-1α/VEGF signaling pathway. DISCUSSION & CONCLUSION: In summary, ECH played an important role in anti-BC by regulating PI3K/AKT/HIF-1α/VEGF signaling pathway. Furthermore, ECH had multi-target and multi-pathway effects, which may be a promising natural compound for treating BC.


Assuntos
Neoplasias da Mama , Proteínas Proto-Oncogênicas c-akt , Feminino , Humanos , Neoplasias da Mama/metabolismo , Proliferação de Células , Hipóxia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fatores de Crescimento do Endotélio Vascular
3.
Zhongguo Zhong Yao Za Zhi ; 48(7): 1760-1769, 2023 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-37282950

RESUMO

The present study aimed to investigate the effect of diosgenin on mammalian target of rapamycin(mTOR), fatty acid synthase(FASN), hypoxia inducible factor-1α(HIF-1α), and vascular endothelial growth factor A(VEGFA) expression in liver tissues of rats with non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin on lipogenesis and inflammation in NAFLD. Forty male SD rats were divided into a normal group(n=8) fed on the normal diet and an experimental group(n=32) fed on the high-fat diet(HFD) for the induction of the NAFLD model. After modeling, the rats in the experimental group were randomly divided into an HFD group, a low-dose diosgenin group(150 mg·kg~(-1)·d~(-1)), a high-dose diosgenin group(300 mg·kg~(-1)·d~(-1)), and a simvastatin group(4 mg·kg~(-1)·d~(-1)), with eight rats in each group. The drugs were continuously given by gavage for eight weeks. The levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were detected by the biochemical method. The content of TG and TC in the liver was detected by the enzyme method. Enzyme-linked immunosorbent assay(ELISA) was used to measure interleukin 1ß(IL-1ß) and tumor necrosis factor α(TNF-α) in the serum. Lipid accumulation in the liver was detected by oil red O staining. Pathological changes of liver tissues were detected by hematoxylin-eosin(HE) staining. The mRNA and protein expression levels of mTOR, FASN, HIF-1α, and VEGFA in the liver of rats were detected by real-time fluorescence-based quantitative polymerase chain reaction(PCR) and Western blot, respectively. Compared with the normal group, the HFD group showed elevated body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1ß, and TNF-α(P<0.01), increased lipid accumulation in the liver(P<0.01), obvious liver steatosis, up-regulated mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.01), and increased protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). Compared with the HFD group, the groups with drug treatment showed lowered body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1ß, and TNF-α(P<0.05, P<0.01), reduced lipid accumulation in the liver(P<0.01), improved liver steatosis, decreased mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.05, P<0.01), and declining protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). The therapeutic effect of the high-dose diosgenin group was superior to that of the low-dose diosgenin group and the simvastatin group. Diosgenin may reduce liver lipid synthesis and inflammation and potentiate by down-regulating the mTOR, FASN, HIF-1α, and VEGFA expression, playing an active role in preventing and treating NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Ratos , Masculino , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , LDL-Colesterol , Ratos Sprague-Dawley , Fígado , Inflamação/metabolismo , Dieta Hiperlipídica/efeitos adversos , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , RNA Mensageiro/metabolismo , Peso Corporal , Mamíferos
4.
Brain Sci ; 12(10)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36291216

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the rehabilitation effects of four common interventions (BA: body acupuncture, SA: scalp acupuncture, TA: tongue acupuncture, SLT: speech and language training) used singly or in combination with language function in patients with post-stroke aphasia (PSA). DESIGN: We systematically searched PubMed, EMBASE, Cochrane Library, Ovid, Web of Science, CNKI, VIP, and Wanfang from inception to 4 April 2022. Only randomized controlled trials that met the eligibility criteria were included. The risk of bias of studies included was assessed using the RoB-2 tool. The effects of different interventions for PSA patients were analyzed and ranked according to the surface under the cumulative ranking (SUCRA) analysis. RESULTS: A total of 69 RCTs were included, including 5097 total participants. According to the results of the SUCRA curves, TA ranked highest in improving overall efficacy (SUCRA = 86%) and oral expression score (SUCRA = 86%). BA + TA ranked highest in increasing the comprehension score (SUCRA = 74.9%). BA + SA ranked highest in improving aphasia patients' repetition (SUCRA = 89.2%) and denomination scores (SUCRA = 93%). CONCLUSIONS: Results of our network meta-analysis and SUCRA ranking showed that tongue acupuncture, body acupuncture + tongue acupuncture, and body acupuncture + scalp acupuncture seem to offer better advantages than other interventions for improving the language function in PSA patients. Moreover, it is noteworthy that our results are limited to the Chinese population, since all eligible studies are from China. Future well-designed studies with larger sample sizes and more ethnic groups are required to further verify these findings.

5.
Drug Dev Res ; 83(8): 1725-1738, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36126194

RESUMO

Diosgenin, a steroidal saponin, is a natural product found in many plants. Diosgenin has a wide range of pharmacological activities, and has been used to treat cancer, nervous system diseases, inflammation, and infections. Numerous studies have shown that diosgenin has potential therapeutic value for lipid metabolism diseases via various pathways and mechanisms, such as controlling lipid synthesis, absorption, and inhibition of oxidative stress. These mechanisms and pathways have provided ideas for researchers to develop related drugs. In this review, we focus on data from animal and clinical studies, summarizing the toxicity of diosgenin, its pharmacological mechanism, recent research advances, and the related mechanisms of diosgenin as a drug for the treatment of lipid metabolism, especially in obesity, hyperlipidemia, nonalcoholic fatty liver disease, atherosclerosis, and diabetes. This systematic review will briefly describe the advantages of diosgenin as a potential therapeutic drug and seek to enhance our understanding of the pharmacological mechanism, recipe-construction, and the development of novel therapeutics against lipid metabolism diseases.


Assuntos
Diosgenina , Animais , Diosgenina/farmacologia , Diosgenina/uso terapêutico , Metabolismo dos Lipídeos , Estresse Oxidativo , Antioxidantes/farmacologia , Inflamação/tratamento farmacológico
6.
Ultrason Sonochem ; 63: 104946, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31945567

RESUMO

The existence of sulfur compounds in crude oil will bring many problems such as corrosion, catalyst poisoning and pollution to the petroleum processing process. Therefore, how to reduce the sulfur content as much as possible in the process of crude oil processing has become an important research topic in the petroleum processing industry. In this paper, ultrasonic-oxidative desulfurization is studied. The effects of reaction temperature, reaction time, amount of oxidant and demulsifier on desulfurization rate are investigated. And the effect of oxidative desulfurization and single oxidative desulfurization under ultrasonic treatment are compared. It is found that the addition of ultrasonic treatment can enhance the desulfurization effect of desulfurizer, the desulfurization efficiency can be increased by about 10% under ultrasonic treatment (100 W, 70 kHz); ultrasonic wave plays an auxiliary role in the system, it can promote heterogeneous reactions, improve the activity of oxidants, and promote the degradation of macromolecular compounds. Finally, physical desulfurization, chemical desulfurization and biological desulfurization technologies are compared.

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