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1.
Bioorg Chem ; 150: 107539, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38861912

RESUMO

Hepatocellular carcinoma (HCC) is a malignant tumor that occurs in the liver, with a high degree of malignancy and relatively poor prognosis. Gypenoside L has inhibitory effects on liver cancer cells. However, its mechanism of action is still unclear. This study aims to investigate the inhibitory effects of gypenoside L on HCC in vitro and in vivo, and explore its potential mechanisms. The results showed that gypenoside L reduced the cholesterol and triglyceride content in HepG2 and Huh-7 cells, inhibited cell proliferation, invasion and metastasis, arrested cell cycle at G0/G1 phase, promoted cell apoptosis. Mechanistically, it targeted the transcription factor SREPB2 to inhibit the expression of HMGCS1 protein and inhibited the downstream proteins HMGCR and MVK, thereby regulating the mevalonate (MVA) pathway. Overexpression HMGCS1 led to significant alterations in the cholesterol metabolism pathway of HCC, which mediated HCC cell proliferation and conferred resistance to the therapeutic effect of gypenoside L. In vivo, gypenoside L effectively suppressed HCC growth in tumor-bearing mice by reducing cholesterol production, exhibiting favorable safety profiles and minimal toxic side effects. Gypenoside L modulated cholesterol homeostasis, enhanced expression of inflammatory factors by regulating MHC I pathway-related proteins to augment anticancer immune responses. Clinical samples from HCC patients also exhibited high expression levels of MVA pathway-related genes in tumor tissues. These findings highlight gypenoside L as a promising agent for targeting cholesterol metabolism in HCC while emphasizing the effectiveness of regulating the SREBP2-HMGCS1 axis as a therapeutic strategy.

2.
Front Pharmacol ; 14: 1215150, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37822878

RESUMO

Glucose metabolic disorders (GMD) can promote insulin resistance (IR) and diabetes, and damage liver and kidney. Gynostemma pentaphyllum is commonly used in the clinical treatment of diabetes, but the research on its main active constituents and GMD has not been reported yet. This study explores the therapeutic potential of gypenosides of heat-processed Gynostemma pentaphyllum (HGyp) on high-fat diet-induced GMD in mice. HGyp was administered at different doses for 12 weeks. The investigation encompassed an array of parameters, including body weight, blood lipids, blood glucose, and liver tissue components. Metabolomic and network analyses were conducted to uncover potential targets and pathways associated with HGyp treatment. The results revealed that HGyp alleviated GMD by reducing body weight, blood glucose, and improving blood lipids levels, while increasing liver glycogen and antioxidant enzyme levels. Additionally, HGyp exhibited protective effects on liver and kidney health by reducing tissue damage. Fourteen blood components were detected by LC-MS. Metabolomic and network analyses indicated the potential engagement of the AGE-RAGE signaling pathway in the therapeutic effects of HGyp.Furthermore, Western blot and ELISA assays confirmed that HGyp upregulated GLO1 and GLUT4 while down-regulating AGEs and RAGE expression in liver tissue. In light of these findings, HGyp demonstrates promise as a potential therapeutic candidate for combating GMD, warranting further exploration in the development of therapeutic strategies or functional products.

3.
Molecules ; 28(17)2023 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-37687242

RESUMO

Ginsenoside Rg3, Rk1, and Rg5, rare ginsenosides from Panax ginseng, have many pharmacological effects, which have attracted extensive attention. They can be obtained through the heat treatment of Gynostemma pentaphyllum. In this study, scanning electron microscopy (SEM) and thermal gravity-differential thermal gravity (TG-DTG) were employed to investigate this process and the content change in ginsenosides was analyzed using liquid chromatography-mass spectrometry (LC-MS). SEM and TG-DTG were used to compare the changes in the ginsenosides before and after treatment. In SEM, the presence of hydrogen bond rearrangement was indicated by the observed deformation of vascular bundles and ducts. The before-and-after changes in the peak patterns and peaks values in TG-DTG indicated that the content of different kinds of compounds produced changes, which all revealed that the formation of new saponins before and after the heat treatment was due to the breakage or rearrangement of chemical bonds. Additionally, the deformation of vascular bundles and vessels indicated the presence of hydrogen bond rearrangement. The glycosidic bond at the 20 positions could be cleaved by ginsenoside Rb3 to form ginsenoside Rd, which, in turn, gave rise to ginsenoside Rg3(S) and Rg3(R). They were further dehydrated to form ginsenoside Rk1 and Rg5. This transformation process occurs in a weak acidic environment provided by G. pentaphyllum itself, without the involvement of endogenous enzymes. In addition, the LC-MS analysis results showed that the content of ginsenoside Rb3 decreased from 2.25 mg/g to 1.80 mg/g, while the contents of ginsenoside Rk1 and Rg5 increased from 0.08 and 0.01 mg/g to 3.36 and 3.35 mg/g, respectively. Ginsenoside Rg3(S) and Rg3(R) were almost not detected in G. pentaphyllum, and the contents of them increased to 0.035 and 0.23 mg/g after heat treatment. Therefore, the rare ginsenosides Rg3(S), Rg3(R), Rk1, and Rg5 can be obtained from G. pentaphyllum via heat treatment.


Assuntos
Ginsenosídeos , Gynostemma , Temperatura Alta
4.
Chem Biol Interact ; 383: 110674, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37604220

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high morbidity and mortality. Targeting abnormal cholesterol metabolism is a potential therapeutic direction. Therefore, more natural drugs targeting cholesterol in HCC need to be developed. Gypenosides (Gyp), the major constituent of Gynostemma pentaphyllum, has been demonstrated to have pharmacological properties on anti-cancer, anti-obesity, and hepatoprotective. We investigated whether Gyp, isolated and purified by our lab, could inhibit HCC progression by inhibiting cholesterol synthesis. The present research showed that Gyp inhibited proliferation and migration, and induced apoptosis in Huh-7 and Hep3B cells. Metabolomics, transcriptomics, and target prediction all suggested that lipid metabolism and cholesterol biosynthesis were the mechanisms of Gyp. Gyp could limit the production of cholesterol and target HMGCS1, the cholesterol synthesis-related protein. Downregulation of HMGCS1 could suppress the progression and abnormal cholesterol metabolism of HCC. In terms of mechanism, Gyp suppressed mevalonate (MVA) pathway mediated cholesterol synthesis by inhibiting HMGCS1 transcription factor SREBP2. And the high expression of HMGCS1 in HCC human specimens was correlated with poor clinical prognosis. The data suggested that Gyp could be a promising cholesterol-lowering drug for the prevention and treatment of HCC. And targeting SREBP2-HMGCS1 axis in MVA pathway might be an effective HCC therapeutic strategy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Gynostemma , Ácido Mevalônico , Neoplasias Hepáticas/tratamento farmacológico , Hidroximetilglutaril-CoA Sintase
5.
Front Neurorobot ; 17: 1161652, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36925626

RESUMO

[This corrects the article DOI: 10.3389/fnbot.2022.1074862.].

6.
Comput Intell Neurosci ; 2022: 8289934, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110911

RESUMO

This paper studies the staring imaging attitude tracking and control for satellite videos based on image information. An improved temporal-spatial context learning algorithm is employed to extract the image information. Based on this, a hyperbolic tangent fuzzy sliding mode control law is proposed to achieve the attitude tracking and control. Furthermore, the hyperbolic tangent function and fuzzy logic system are introduced into the sliding mode controller. In the experiments, the improved temporal-spatial context learning algorithm is applied for the image information of the space target video sequence captured by Jilin-1 in orbit, where the image information is used as the input of the control loop. Moreover, the proposed method is realized through simulation. Besides, the image change caused by attitude adjustment is achieved successfully, and the target imaging can be located in the center of the image plane to realize the gaze tracking control of the space target effectively.

7.
Front Chem ; 10: 868063, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35350774

RESUMO

Although research on the treatment of atherosclerosis has progressed recently, challenges remain in developing more effective, safer and transformative strategies for the treatment of atherosclerosis. Nanomaterials have recently played a unique role in many fields, including atherosclerosis treatment. Platelets are common component in the blood. Due to their inherent properties, platelets can target and adhere to atherosclerotic plaques. Ultrasound-targeted microbubble destruction (UTMD) shows great prospects in promoting the efficiency of drug delivery in treating solid tumors. In this study, we explored the possibility that UTMD assists platelet biomimetic rapamycin (RAP)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (RAP@PLT NPs) in the treatment of atherosclerosis. The biomimetic nano-formulations exhibit better targeting ability to plaques when administered in vivo. Targeted destruction of Sonovue™ in the aortic area further improved the efficiency of targeting plaques. Moreover, the progression of atherosclerotic plaques was inhibited, and the stability of plaques was improved. Together, our study established a novel strategy for targeted delivery of nanoparticles in atherosclerotic plaques, by combining the advantages of the ultrasonic cavitation effect and biomimicking nanoparticles in drug delivery.

8.
J Clin Lab Anal ; 36(5): e24367, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35334492

RESUMO

BACKGROUND: The pathogenesis of connective tissue disease-associated interstitial lung disease (CTD-ILD) is unclear. This study aims to identify differentially expressed proteins (DEPs) in CTD-ILD to determine the potential role of these DEPs that may play in the pathogenesis of CTD-ILD and to offer potential therapeutic targets. METHODS: Bronchoalveolar lavage fluid (BALF) samples were collected from four patients with CTD-ILD and four patients without CTD-ILD. Label-free mass spectrometry-based relative quantification was used to identify the DEPs. Bioinformatics were used to determine the potential biological processes and signaling pathways associated with these DEPs. RESULTS: We found 65 upregulated DEPs including SFTPD, CADM1, ACSL4, TSTD1, CD163, LUM, SIGLEC1, CPB2, TGFBI and HGD, and 67 downregulated DEPs including SGSH, WIPF1, SIL1, RAB20, OAS3, GMPR2, PLBD1, DNAJC3, RNASET2 and OAS2. The results of GO functional annotation for the DEPs showed that the DEPS were mainly enriched in the binding, cellular anatomical entity, cellular processes, and biological regulation GO terms. The results of KEGG analyses showed that the pathways most annotated with the DEPs were complement and coagulation cascades, metabolic pathways, pathways in cancer, and PPAR signaling pathway. COG analyses further informed the functions associated with these DEPs, with most focused on signal transduction mechanisms; posttranslational modification, protein turnover, chaperones; intracellular trafficking, secretion, and vesicular transport; amino acid transport and metabolism; and lipid transport and metabolism. CONCLUSIONS: DEPs identified between patients with vs. without CTD-ILD may play important roles in the development of CTD-ILD and are potential new biomarkers for early diagnosis of CTD-ILD.


Assuntos
Doenças do Tecido Conjuntivo , Doenças Pulmonares Intersticiais , Biomarcadores , Líquido da Lavagem Broncoalveolar , Molécula 1 de Adesão Celular , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/diagnóstico , Proteínas do Citoesqueleto , Fatores de Troca do Nucleotídeo Guanina , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/etiologia , Espectrometria de Massas , Proteínas rab de Ligação ao GTP
9.
Front Neurorobot ; 16: 1074862, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36923945

RESUMO

Introduction: Small target detection with remote sensing images is a challenging topic due to the small size of the targets, complex, and fuzzy backgrounds. Methods: In this study, a new detection algorithm is proposed based on the YOLOv5s algorithm for small target detection. The data enhancement strategy based on the mosaic operation is applied to expand the remote image training sets so as to diversify the datasets. First, the lightweight and stable feature extraction module (LSM) and C3 modules are combined to form the feature extraction module, called as LCB module, to extract more features in the remote sensing images. Multi-scale feature fusion is realized based on the Res 2 unit, Dres 2, and Spatial Pyramid Pooling Small (SPPS) models, so that the receptive field can be increased to obtain more multi-scale global information based on Dres2 and retain the obtained feature information of the small targets accordingly. Furthermore, the input size and output size of the network are increased and set in different scales considering the relatively less target features in the remote images. Besides, the Efficient Intersection over Union (EIoU) loss is used as the loss function to increase the training convergence velocity of the model and improve the accurate regression of the model. Results and discussion: The DIOR-VAS and Visdrone2019 datasets are selected in the experiments, while the ablation and comparison experiments are performed with five popular target detection algorithms to verify the effectiveness of the proposed small target detection method.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34239591

RESUMO

Irritable bowel syndrome (IBS) is a functional gastrointestinal disease characterized by visceral hypersensitivity-related abdominal pain, in which diarrhea-predominant IBS (IBS-D) is the main subtype and has a high clinical incidence. Tongxie Anchang Decoction (TXACD) has been proved to significantly improve abdominal pain in patients with IBS-D, but its underlying therapeutic mechanism still remains unclear. In the present study, IBS-D model rats were induced by neonatal maternal separation (NMS) combined with restraint stress (RS). The therapeutic effect of TXACD was evaluated by fecal characteristics and abdominal withdrawal reflex (AWR) scores. After 14 days of intragastric administration, the colonic tissues of rats were collected to detect the protein and gene level of the NGF, TrkA, and TRPV1 using Western blotting and real-time polymerase chain reaction, respectively, and detect mast cells infiltration using toluidine blue staining. The abdominal aorta blood centrifuged was collected for detecting serum levels of SP, 5-HT, and CGRP with ELISA. The results revealed that TXACD could significantly improve visceral hypersensitivity in IBS-D rats, reflected in the decrease of AWR score and the serum levels of SP, 5-HT, and CGRP. In addition, TXACD treatment could alleviate mast cells infiltration. Moreover, the expression levels of the NGF, TrkA, and TRPV1 were repressed by TXACD. The findings of the present study indicated that the therapeutic effect of TXACD on visceral hypersensitivity might be closely related to the downregulation of the NGF/TrkA signaling pathway, the reversal of TRPV1 expression and mast cells infiltration, and the decreased release of neuroendocrine factors SP, 5-HT, and CGRP.

11.
Biomed Pharmacother ; 141: 111803, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34146854

RESUMO

The antipsychotic drug olanzapine was reported to induce nonalcoholic fatty liver disease (NAFLD), whereas the underlying mechanism remains incompletely understood. This study investigated whether apolipoprotein A5 (apoA5) and sortilin, two interactive factors involved in NAFLD pathogenesis, are implicated in olanzapine-induced NAFLD. In our study, at week 8, olanzapine treatment successfully induced hepatic steatosis in female C57 BL/6 J mice, which was independent of body weight gain. Likewise, olanzapine effectively mediated hepatocyte steatosis in HepG2 cells characterized by substantially elevated intracellular lipid droplets. Increased plasma triglyceride concentration and decreased plasma apoA5 levels were observed in mice treated with 8-week olanzapine. Surprisingly, olanzapine markedly enhanced hepatic apoA5 protein levels in mice, without a significant effect on rodent hepatic ApoA5 mRNA. Our in vitro study showed that olanzapine reduced apoA5 protein levels in the medium and enhanced apoA5 protein levels in hepatocytes, whereas this drug exerted no effect on hepatocyte APOA5 mRNA. By transfecting APOA5 siRNA into HepG2 cells, it was demonstrated that APOA5 knockdown effectively reversed olanzapine-induced hepatocyte steatosis in vitro. In addition, olanzapine drastically increased sortilin mRNA and protein levels in vivo and in vitro. Interestingly, SORT1 knockdown reduced intracellular apoA5 protein levels and increased medium apoA5 protein levels in vitro, without affecting intracellular APOA5 mRNA levels. Furthermore, SORT1 knockdown greatly ameliorated hepatocyte steatosis in vitro. This study provides the first evidence that sortilin inhibits the hepatic apoA5 secretion that is attributable to olanzapine-induced NAFLD, which provides new insight into effective strategies against NAFLD for patients with schizophrenia administered olanzapine.


Assuntos
Antipsicóticos/toxicidade , Apolipoproteína A-V/antagonistas & inibidores , Apolipoproteína A-V/biossíntese , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/metabolismo , Olanzapina/toxicidade , Animais , Feminino , Técnicas de Silenciamento de Genes/métodos , Células Hep G2 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
12.
Front Bioeng Biotechnol ; 8: 599107, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33304893

RESUMO

Accurate diagnosis, providing guidance for early treatment, can greatly improve the survival rate of cancer patients. However, there are still some difficulties with the existing diagnostic technology and early treatment methods. Here, near-infrared responsive phase-shifted nanoparticles (NRPNs) have been designed for magnetically targeted MR/US imaging and photothermal therapy of tumors. In this study, we fabricated a multifunctional polymer nanoparticle encapsulating indocyanine green (ICG), magnetic Fe3O4 nanoparticles and perfluoropentane (PFP). Under laser irradiation, the NRPNs, which trigger a phase-shifted expansion effect due to the quick conversion from light to heat by ICG and Fe3O4, can be used for ultrasound (US) imaging. At the same time, such nanoparticles can kill cancer cells via photothermal therapy (PTT). As a kind of negative enhancement agent, magnetic Fe3O4 nanoparticles in NRPNs showed high spatial resolution in MR imaging. Moreover, with the help of the magnetic field, the NRPNs nanoparticles showed high cellular uptake and high tumor accumulation, indicating their magnetic targeting property without biosafety concerns. Therefore, we present a strategy for magnetically targeted MR/US imaging guided photothermal therapy for the accurate diagnosis and efficient treatment of tumors.

13.
Int J Nanomedicine ; 15: 10151-10167, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33363371

RESUMO

BACKGROUND: Traditional nanoparticle-based drug delivery systems suffer from several limitations, such as easy clearance from blood and inaccurate targeting. MATERIALS AND METHODS: Here, we developed platelet membrane-coated nanoparticles (PM-NPs) to improve the precise delivery of drugs to tumor sites and enable a more efficient photothermal therapy (PTT) treatment. RESULTS: Mimicking the natural platelet membrane, nanoparticles containing drugs and photothermal agents were not recognized and cleared by the immune system; they could circulate in the blood for a long time and accumulate more efficiently at the tumor site, thus releasing more antitumor drugs and achieving better PTT effects. It is worth mentioning that, in this study, we found that tumors in mice treated with the platelet-mimicking nanoparticles were completely eliminated without recurrence during the observation period (up to 18 days). CONCLUSION: This study provides a new strategy to design delivery systems of drugs or photothermal agents, whether in biotherapy or other fields.


Assuntos
Antineoplásicos/uso terapêutico , Plaquetas/metabolismo , Neoplasias da Mama/terapia , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Terapia Fototérmica , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Proliferação de Células/efeitos dos fármacos , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Nanopartículas/ultraestrutura , Células RAW 264.7
14.
Medicine (Baltimore) ; 99(52): e23868, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33350782

RESUMO

BACKGROUND: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a kind of functional gastrointestinal disorder with obscure pathogenesis, and exploration about differential gene expression and cell heterogeneity of T lymphocytes in peripheral blood in IBS-D patients still remains unknown. Clinicians tend to use symptomatic treatment, but the efficacy is unstable and symptoms are prone to relapse. Traditional Chinese Medicine (TCM) is used frequently in IBS-D with stable and lower adverse effects. Tong-Xie-An-Chang Decoction (TXACD) has been proven to be effective in the treatment of IBS-D. However, the underlying therapeutic mechanism remains unclear. This trial aims to evaluate the clinical efficacy and safety of TXACD in IBS-D and elucidate the gene-level mechanism of IBS-D and therapeutic targets of TXACD based on single-cell sequencing technology. METHODS/DESIGN: This is a randomized controlled, double-blind, double-simulation clinical trial in which 72 eligible participants with IBS-D and TCM syndrome of liver depression and spleen deficiency will be randomly allocated in the ratio of 1:1 to two groups: the experimental group and the control group. The experimental group receives Tong-Xie-An-Chang Decoction (TXACD) and Pinaverium bromide tablets placebo; the control group receives pinaverium bromide tablets and TXACD placebo. Each group will be treated for 4 weeks. The primary outcome: the rate of IBS-Symptom Severity Score (IBS-SSS). The secondary outcomes: TCM syndrome score, adequate relief and IBS-Quality of Life Questionnaire (IBS-QOL). Mechanistic outcome is the single-cell sequencing profiling of the T lymphocytes in peripheral blood from IBS-D participants before and after the treatment and healthy individuals. DISCUSSION: This trial will prove the efficacy and safety of TXACD with high-quality evidence and provide a comprehensive perspective on the molecular mechanism of IBS-D by single-cell sequencing profiling, which makes us pinpoint specific biomarkers of IBS-D and therapeutic targets of TXACD.


Assuntos
Diarreia , Medicamentos de Ervas Chinesas , Síndrome do Intestino Irritável , Qualidade de Vida , Adulto , Misturas Complexas/administração & dosagem , Misturas Complexas/efeitos adversos , Diarreia/tratamento farmacológico , Diarreia/etiologia , Diarreia/psicologia , Método Duplo-Cego , Monitoramento de Medicamentos/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Síndrome do Intestino Irritável/sangue , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/tratamento farmacológico , Síndrome do Intestino Irritável/fisiopatologia , Masculino , Medicina Tradicional Chinesa/métodos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Avaliação de Sintomas , Linfócitos T , Resultado do Tratamento
15.
Artigo em Inglês | MEDLINE | ID: mdl-33281910

RESUMO

AIM: This study aims to uncover the pharmacological mechanism of Tongxie Anchang Decoction (TXACD), a new and effective traditional Chinese medicine (TCM) prescription, for treating irritable bowel syndrome with diarrhea predominant (IBS-D) using network pharmacology. METHODS: The active compounds and putative targets of TXACD were retrieved from TCMSP database and published literature; related target genes of IBS-D were retrieved from GeneCards; PPI network of the common target hub gene was constructed by STRING. Furthermore, these hub genes were analyzed using gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. RESULTS: A total of 54 active compounds and 639 targets were identified through a database search. The compound-target network was constructed, and the key compounds were screened out according to the degree. By using the PPI and GO and KEGG enrichment analyses, the pharmacological mechanism network of TXACD in the treatment of IBS-D was constructed. CONCLUSIONS: This study revealed the possible mechanisms by which TXACD treatment alleviated IBS-D involvement in the modulation of multiple targets and multiple pathways, including the immune regulation, inflammatory response, and oxidative stress. These findings provide novel insights into the regulatory role of TXACD in the prevention and treatment of IBS-D and hold promise for herb-based complementary and alternative therapy.

16.
Int J Nanomedicine ; 15: 8641-8658, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33177823

RESUMO

BACKGROUND: Although photothermal therapy (PTT) and photodynamics therapy (PDT) have both made excellent progress in tumor therapy, the effectiveness of using PTT or PDT alone is dissatisfactory due to the limitations of the penetration depth in PTT and the hypoxic microenvironment of tumors for PDT. Combination phototherapy has currently become a burgeoning cancer treatment. METHODS AND MATERIALS: In this work, a mitochondria-targeting liquid perfluorocarbon (PFC)-based oxygen delivery system was developed for the synergistic PDT/photothermal therapy (PTT) of cancer through image guiding. RESULTS: Importantly, these nanoparticles (NPs) can effectively and accurately accumulate in the target tumor via the enhanced permeability and retention (EPR) effect. CONCLUSION: This approach offers a novel technique to achieve outstanding antitumor efficacy by an unprecedented design with tumor mitochondria targeting, oxygen delivery, and synergistic PDT/PTT with dual-imaging guidance.


Assuntos
Fluorocarbonos/química , Mitocôndrias/efeitos dos fármacos , Nanopartículas/administração & dosagem , Neoplasias Experimentais/terapia , Oxigênio/administração & dosagem , Fototerapia/métodos , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Mitocôndrias/patologia , Nanopartículas/química , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/patologia , Oxigênio/química , Oxigênio/farmacocinética , Oxigênio Singlete/farmacocinética , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Front Microbiol ; 11: 731, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32425906

RESUMO

Ulcerative colitis is a gastrointestinal disorder intricately associated with intestinal dysbiosis, but effective treatments are currently limited. Indigo naturalis, a traditional Chinese medicine derived from indigo plants, has been widely used in the treatment of ulcerative colitis. However, the specific mechanisms have not yet been identified. Accordingly, in this study, we evaluated the effects and mechanisms of indigo naturalis on dextran sulfate sodium (DSS)-induced colitis in rats. Our results showed that indigo naturalis potently alleviated DSS-induced colitis in rats, and reversed DSS-induced intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing. The protective effects of indigo naturalis were gut microbiota dependent, as demonstrated by antibiotic treatments and fecal microbiota transplantation. Depletion of the gut microbiota through a combination of antibiotic treatments blocked the anti-inflammatory effect of indigo naturalis on the DSS-induced colitis, and the recipients of the gut microbiota from indigo naturalis-treated rats displayed a significantly attenuated intestinal inflammation, which was actively responsive to therapeutic interventions with indigo naturalis. Notably, supplement with indigo naturalis greatly increased the levels of feces butyrate, which was positively correlated with the relative abundances of Ruminococcus_1 and Butyricicoccus. We further showed that indigo naturalis-dependent attenuation of colitis was associated with elevated expression of short-chain fatty acid-associated receptors GPR41 and GPR43. Collectively, these results suggested that indigo naturalis alleviates DSS-induced colitis in rats through a mechanism of the microbiota-butyrate axis, particularly alterations in Ruminococcus_1 and Butyricicoccus abundances, and target-specific microbial species may have unique therapeutic promise for ulcerative colitis.

18.
Front Chem ; 8: 358, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32411675

RESUMO

Modulation of hypoxia is an essential factor for enhancing the effects of antitumor therapies, especially sonodynamic therapy and chemotherapy. To improve the efficacy of combination therapy by reversing the hypoxic tumor microenvironment, we developed shell-core structured PPID-NPs, which were designed with a polymer shell onto the sonosensitizer and a chemotherapeutic drug were loaded and a perfluorocarbon core loaded with oxygen. The perfluorocarbon core provides sufficient oxygen not only for causing the sonosensitizer to produce more singlet oxygen to induce cell apoptosis but also for reducing drug resistance to enhance therapeutic efficacy. Furthermore, the release of chemotherapeutic drugs at the tumor site can be controlled. Thus, PPID-NPs can efficiently inhibit the growth of breast cancer by synergistic therapy under ultrasound exposure. We believe that our oxygen-sufficient nanoplatform could be an ideal therapeutic system for hypoxic tumors.

19.
J Mater Chem B ; 8(18): 4132-4142, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32270160

RESUMO

Combination photothermal therapy (PTT)/chemotherapy has become an emerging cancer treatment strategy in recent years. However, one of the important challenges in the development of nanomedicines is escaping immune recognition and the phagocytosis by the reticuloendothelial system (RES) to ultimately maximize tumor accumulation. In this work, a cell membrane-coated magnetically targeted drug delivery nanosystem was developed for synergistic PTT/chemotherapy of cancer. Importantly, this nanosystem can cleverly escape identification and clearance from the immune system, effectively prolong the blood circulation time and accurately accumulate in the target tumor tissues. This provides a new strategy to realize extraordinary antitumor effect by a unique design with cell membrane cloaking, magnetic targeting, drug delivery and synergistic PTT/chemotherapy.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Membrana Eritrocítica/química , Nanopartículas/química , Fototerapia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Antibióticos Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Fenômenos Magnéticos , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Imagem Óptica , Tamanho da Partícula , Propriedades de Superfície
20.
Front Chem ; 7: 781, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31799240

RESUMO

PhGs are the major active compounds of Cistanche tubulosa, and it is extremely desirable for obtaining high purification of PhGs by adsorption from their extracts. To explore highly efficient adsorption of PhGs, a novel adsorption material for the efficient separation and purification of phenylethanoid glycosides (PhGs) from Cistanche tubulosa was explored. The three mesoporous carbons of ordered mesoporous carbon (CMK-3), disordered mesoporous carbon (DMC), and three-dimensional cubic mesoporous carbon (CMK-8) were compared for adsorption of PhGs. Meanwhile, adsorption isotherms, adsorption kinetics, and the optimization of adsorption conditions were investigated. The results indicated that CMK-3 showed the highest adsorption capacity of 358.09 ± 4.13 mg/g due to its high specific surface area, large pore volume and oxygen-containing functional groups. The experimental data can be accurately described using the Langmuir model and pseudo-second-order model. The intra-particle diffusion model suggested that the rate-limiting steps of adsorption were intra-particle diffusion.

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