Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 30
Filtrar
1.
Materials (Basel) ; 17(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38730762

RESUMO

X80 pipeline steel has played a vital role in oil and gas transportation in recent years. However, hydrogen-related issues frequently lead to pipeline failures during service, resulting in significant losses of properties and lives. Three heat treatment processes (furnace cooling (FC), air cooling (AC), and water cooling (WC)) were carried out to investigate the effect of different microstructures on hydrogen-induced cracking (HIC) susceptibility of X80 pipeline steel. The WC sample demonstrated the highest hydrogen embrittlement index, registering at 21.9%, while the AC and FC samples exhibited progressively lower values of 15.45% and 10.98%, respectively. Under equivalent hydrogen charging durations, crack dimensions with a maximum length exceeding 30 µm in the WC sample generally exceed those in the FC sample and AC sample. The variation is attributed to the difference in microstructures of the samples, predominantly lath bainite (LB) in water-cooled samples, granular bainite (GB) in air-cooled samples, and ferrite/pearlite (F/P) in FC samples. The research results demonstrate that the sensitivity of lath bainite (LB) to HIC is significantly higher than that of pearlite, ferrite, and granular bainite (GB). The presence of a large amount of martensite/austenite (M/A) constituents within bainite results in a multitude of hydrogen trap sites. HIC cracks in bainite generally propagate along the profiles of M/A constituents, showing both intergranular and transgranular cracking modes.

2.
Int J Biol Macromol ; 268(Pt 1): 131593, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38631571

RESUMO

Asparagus officinalis L. is a horticultural crop that contains a variety of bioactive compounds with anti-inflammatory effects. Aqueous extracts of A. officinalis can noticeably improve the learning and memory function of model mice. Herein, a pectin-arabinoglucuronogalactan complex (AOPB-1-1) with a relative molecular weight of 90.8 kDa was isolated from A. officinalis. The repeating structural unit of AOPB-1-1 was identified through monosaccharide composition, methylation analysis, uronic acid reduction, partial acid hydrolysis, and nuclear magnetic resonance spectroscopy. AOPB-1-1 contains the rhamnogalacturonan-I (RG-I) domain of pectin polysaccharides (PPs) and arabinoglucuronogalactan (AGG) regions. The backbone of the AGG region is composed of →3,6)-ß-D-Galp-(1→ and →4)-ß-D-Glcp-(1→ residues substituted at the 4-position to the →4)-α-D-GalAp-(1→ residues of the RG-I main chain. The anti-neuroinflammatory activity of AOPB-1-1 suggests that it can significantly reduce the content of inflammatory cytokines, including nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and inhibit the expression of inflammatory genes including cyclooxygenase-2 (COX2), nitric oxide synthase (iNOS), TNF-α, IL-6, and interleukin-1ß (IL-1ß) in LPS-stimulated BV2 cells. Furthermore, its inhibitory effects on TNF-α and IL-6 levels were even better than those of minocycline. The significant anti-neuroinflammatory activity of AOPB-1-1 suggests its applicability as a therapeutic option for the treatment of Alzheimer's disease.


Assuntos
Anti-Inflamatórios , Asparagus , Pectinas , Pectinas/farmacologia , Pectinas/química , Pectinas/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Asparagus/química , Animais , Camundongos , Galactanos/farmacologia , Galactanos/química , Galactanos/isolamento & purificação , Citocinas/metabolismo , Óxido Nítrico/metabolismo , Peso Molecular
3.
Int J Biol Macromol ; 269(Pt 1): 131903, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38688342

RESUMO

Ganoderma sinense, known as Lingzhi in China, is a medicinal fungus with anti-tumor properties. Herein, crude polysaccharides (GSB) extracted from G. sinense fruiting bodies were used to selectively inhibit triple-negative breast cancer (TNBC) cells. GSBP-2 was purified from GSB, with a molecular weight of 11.5 kDa and a composition of α-l-Fucp-(1→, ß-d-Glcp-(1→, ß-d-GlcpA-(1→, →3)-ß-d-Glcp-(1→, →3)-ß-d-GlcpA-(1→, →4)-α-d-Galp-(1→,→6)-ß-d-Manp-(1→, and →3,6)-ß-d-Glcp-(1→ at a ratio of 1.0:6.3:1.7:5.5:1.5:4.3:8.0:7.9. The anti-MDA-MB-231 cell activity of GSBP-2 was determined by methyl thiazolyl tetrazolium, colony formation, scratch wound healing, and transwell migration assays. The results showed that GSBP-2 could selectively inhibit the proliferation, migration, and invasion of MDA-MB-231 cells through the regulation of genes targeting epithelial-mesenchymal transition (i.e., Snail1, ZEB1, VIM, CDH1, CDH2, and MMP9) in the MDA-MB-231 cells. Furthermore, Western blotting results indicated that GSBP-2 could restrict epithelial-mesenchymal transition by increasing E-cadherin and decreasing N-cadherin expression through the PI3K/Akt pathway. GSBP-2 also suppressed the angiogenesis of human umbilical vein endothelial cells. In conclusion, GSBP-2 could inhibit the proliferation, migration, and invasion of MDA-MB-231 cells and showed significant anti-angiogenic ability. These findings indicate that GSBP-2 is a promising therapeutic adjuvant for TNBC.


Assuntos
Movimento Celular , Ganoderma , Neoplasias de Mama Triplo Negativas , Humanos , Ganoderma/química , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Movimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Invasividade Neoplásica , Feminino , Antineoplásicos/farmacologia , Antineoplásicos/química , Transição Epitelial-Mesenquimal/efeitos dos fármacos
4.
Mol Ther Oncolytics ; 31: 100752, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38130701

RESUMO

Extracellular vesicles (EVs) carry DNA, RNA, protein, and other substances involved in intercellular crosstalk and can be used for the targeted delivery of drugs. Triple-negative breast cancer (TNBC) is rich in recurrent and metastatic disease and lacks therapeutic targets. Studies have proved the role of EVs in the different stages of the genesis and development of TNBC. Cancer cells actively secrete various biomolecules, which play a significant part establishing the tumor microenvironment via EVs. In this article, we describe the roles of EVs in the tumor immune microenvironment, metabolic microenvironment, and vascular remodeling, and summarize the application of EVs for objective delivery of chemotherapeutic drugs, immune antigens, and cancer vaccine adjuvants. EVs-based therapy may represent the next-generation tool for targeted drug delivery for the cure of a variety of diseases lacking effective drug treatment.

5.
Antiviral Res ; 219: 105720, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37748652

RESUMO

Immune checkpoint blockade-based therapies are effective against a sorts of cancers. However, drug resistance is a problem that cannot be ignored. This review intends to elucidate the mechanisms underlying drug tolerance induced by PD-1/PD-L1 inhibitors, as well as to outline proposed mechanism-based combination therapies and small molecule drugs that target intrinsic immunity and immune checkpoints. According to the differences of patients and types of cancer, the optimization of individualized combination therapy will help to enhance PD-1/PD-L1-mediated immunoregulation, reduce chemotherapy resistance, and provide new ideas for chemotherapy-resistant cancer.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1 , Neoplasias/tratamento farmacológico
6.
Mol Ther Oncolytics ; 28: 212-229, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36860815

RESUMO

Breast cancer is the leading cause of cancer-related deaths in females worldwide, and the liver is one of the most common sites of distant metastases in breast cancer patients. Patients with breast cancer liver metastases face limited treatment options, and drug resistance is highly prevalent, leading to a poor prognosis and a short survival. Liver metastases respond extremely poorly to immunotherapy and have shown resistance to treatments such as chemotherapy and targeted therapies. Therefore, to develop and to optimize treatment strategies as well as to explore potential therapeutic approaches, it is crucial to understand the mechanisms of drug resistance in breast cancer liver metastases patients. In this review, we summarize recent advances in the research of drug resistance mechanisms in breast cancer liver metastases and discuss their therapeutic potential for improving patient prognoses and outcomes.

7.
Int J Biol Macromol ; 219: 1284-1296, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36037912

RESUMO

Polygala tenuifolia is extensively used to treat amnesia in traditional Chinese medicine, and pharmacological studies have reported the beneficial effects of P. tenuifolia on intelligence and cognition. In the present study, the crude polysaccharide alkali-extracted from P. tenuifolia roots (PTB) inhibited lipopolysaccharide-induced microglia/astrocyte activation and significantly improved the learning and memory ability of Alzheimer's disease (AD) rats. To determine its bioactive components, a heteropolysaccharide (PTBP-1-3) was isolated from PTB. Structural analysis showed that PTBP-1-3 was composed of α-L-Araf-(1→, â†’3)-α-L-Araf-(1→, →5)-α-L-Araf-(1→, →3,5)-α-L-Araf-(1→, →2,5)-α-L-Araf-(1→, ß-D-Xylp-(1→, →2,3,4)-ß-D-Xylp-(1→, α-L-Rhap-(1→, ß-D-Galp-(1→, →4)-α-D-Galp-(1→, →6)-α-D-Galp-(1→, →6)-α-D-Glcp-(1→, →3,6)-α-D-Glcp-(1→, →6)-α-D-Manp-(1→, and →2,4)-ß-D-Manp-(1→ residues. PTBP-1-3 decreased the production of NO, TNF-α, and IL-1ß in lipopolysaccharide-activated BV2 microglia cells in a manner similar to that of minocycline. In conclusion, PTBP-1-3 exhibited a potent inhibitory effect on neuroinflammation, and could be one of the bioactive ingredients in PTB for anti-neuroinflammation. PTB and PTBP-1-3 may be potential therapeutic agents for the treatment of AD.


Assuntos
Polygala , Álcalis , Animais , Lipopolissacarídeos/farmacologia , Minociclina , Polygala/química , Polissacarídeos/química , Ratos , Fator de Necrose Tumoral alfa
8.
Heliyon ; 8(6): e09660, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35706933

RESUMO

Recent research efforts have shown that tea has activities against SARS-CoV-2. However, the active compounds and the action mechanisms are largely unknown. Here we study the inhibitory potential of L-theanine from tea and its semi-synthesized derivative, a small-molecule fluorescent compound, ethyl 6-bromocoumarin-3-carboxylyl L-theanine (TBrC) against infection and replication of SARS-CoV-2 and the underlying mechanisms of action. We reveal that TBrC has potential activities against SARS-CoV-2 in addition to its activity against lung cancer. TBrC showed extracellular inhibition of SARS-CoV-2 Mpro/3CL and the host cell receptor ACE2 while interacting with the viral spike glycoproteins (wild-type, Delta, and Omicron mutants). Moreover, TBrC and L-theanine significantly suppressed growth and TNFα-induced nuclear transcriptional activation of NF-κB in human lung cancer cells without affecting the viability of normal lung cells, suggesting a potential protection of TBrC and L-theanine from pulmonary damages in SARS-CoV-2 infected patients, especially for lung cancer patients with SARS-CoV-2 infection.

9.
Front Pharmacol ; 12: 764602, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803708

RESUMO

Alhagi pseudalhagi Desv. Extract (APE) is the major active fraction extracted from the aerial part of Alhagi pseudalhagi Desv. In view of its application in Uyghur medicine, it may be beneficial for the treatment of ulcerative colitis (UC). The aim of the present study was to investigate the possible beneficial effects of APE on UC mice and detect the possible mechanisms underlying these effects. Methods: An acute UC model was established in mice using dextran sulfate sodium. Sixty mice were randomly divided into six groups: normal, UC model, sulfasalazine (200 mg/kg), high-dose APE (APE-H, 2.82 g/kg), middle-dose APE (APE-M, 1.41 g/kg), and low-dose APE (APE-L, 0.70 g/kg) groups. Drugs were administered by gavage for 10 days after the induction of colitis. Serum and colon tissue samples were collected from the mice during the experiment, and survival signs, body weight changes, disease activity index (DAI), colon length, and colon wet weight in mice were determined after the treatment. UC-induced damage, including inflammation and ulceration of colon mucosa, were observed by the naked eye as well as using hematoxylin and eosin staining (H&E) and scanning electron microscopy and scored according to Wallace and Keean's criteria. We measured the levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, IL-6, and IL-10 in the serum and colon tissues using ELISA. Additionally, the relative protein levels of toll-like receptor 4 (TLR4), nuclear factor-kappa B p65 (NF-κB p65), phosphorylated NF-κB p65 at Ser536 (p-p65 Ser536), inhibitor kappa B-kinase ß (IK-Kß), and phosphorylated IK-Kß (Ser176/180) (p-IK-Kß) in colonic mucosal epithelial tissues were detected using western blotting. The main functional components of APE were analyzed and confirmed by UPLC-MS/MS. Results: APE treatment repaired the UC-induced colon mucosa injury, reduced the weight loss, attenuated DAI, colon macroscopic damage index, and histological inflammation, and significantly downregulated the levels of inflammatory markers, including TNF-α, IL-1ß, and IL-6, in the serum and colon tissues. Additionally, APE treatment reduced the levels of TLR4 and phosphorylation of p-NF-κB and p-IK-Kß. The main components of APE are taxifolin, 3,5-dihydroxy-2-(4-hydroxyphenyl)-7-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl) oxan-2-yl] oxychromen-4-one, hyperoside, rutin, kaempferol, isorhamnetin, 7,8-dihydroxyflavone, and kaempferide. Conclusions: To the best of our knowledge, the present study is first to demonstrate that APE exerts a protective effect against intestinal inflammation in UC by affecting TLR4-dependent NF-κB signaling pathways.

10.
Front Oncol ; 11: 705059, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745938

RESUMO

The discovery of circular RNA (circRNA) greatly complements the traditional gene expression theory. CircRNA is a class of non-coding RNA with a stable cyclic structure. They are highly expressed, spatiotemporal-specific and conservative across species. Importantly, circRNA participates in the occurrence of many kinds of tumors and regulates the tumor development. Glioma is featured by limited therapy and grim prognosis. Cancer-associated circRNA compromises original function or creates new effects in glioma, thus contributing to oncogenesis. Therefore, this article reviews the biogenesis, metabolism, functions and properties of circRNA as a novel potential biomarker for gliomas. We elaborate the expression characteristics, interaction between circRNA and other molecules, aiming to identify new targets for early diagnosis and treatment of gliomas.

11.
Carbohydr Polym ; 259: 117553, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33674023

RESUMO

Achyranthes bidentata is a species of flowering plant that is mainly distributed in China. The A. bidentata rhizome is a famous traditional Chinese medicine that has been widely used to treat lumbago, arthritis, and bone hyperplasia. In this work, A. bidentata rhizome was isolated and purified to obtain a pectic polysaccharide (ABPB-4). Chemical and spectral analyses showed that ABPB-4 had a main chain of →4)-α-d-GalpA-(1→ and →2,4)-α-l-Rhap-(1→, and the branch chains included →4)-ß-d-Galp-(1→, →6)-ß-d-Galp-(1→, →3,6)-ß-d-Galp-(1→, →5)-α-l-Araf-(1→ and →3,5)-α-l-Araf-(1→, and it was terminated with α-l-Araf-(1→ and ß-d-Galp-(1→. At concentrations of 0.01, 0.02, and 0.04 µmol/L, ABPB-4 significantly promotes the proliferation, differentiation, and mineralization of MC3T3-E1 cells in vitro, and it appreciably enhances the mRNA expression levels of osteogenic-related genes in these cells. Overall, the results reported herein indicate that ABPB-4 has outstanding osteogenic activity, and that it may be used as an anti-osteoporosis agent in the future.


Assuntos
Achyranthes/metabolismo , Polissacarídeos/química , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Peso Molecular , Osteogênese/efeitos dos fármacos , Polissacarídeos/análise , Polissacarídeos/farmacologia , Rizoma/metabolismo , Fator de Transcrição Sp7/genética , Fator de Transcrição Sp7/metabolismo
12.
Int J Biol Macromol ; 163: 464-475, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32621930

RESUMO

Our previous study has indicated that a crude polysaccharide derived from Acorus tatarinowii, AT50, remarkably improves learning and memory in scopolamine-induced amnesic mice and prevents the release of inflammatory mediators. To further explore the bioactive constituents of AT50, a novel polysaccharide (ATP50-3) was purified, and its anti-neuroinflammatory effects and underlying mechanisms were investigated. ATP50-3 significantly reduced abnormal elevation of inflammatory mediators in lipopolysaccharide (LPS)-induced proinflammatory BV2 cells in vitro and inhibited the activation of nuclear factor kappa B (NF-κB). Moreover, ATP50-3 down-regulated LPS-induced protein levels of Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein (MyD88), p-PI3K (phosphoinositide 3-kinase), and p-Akt (protein kinase B). Further experiments demonstrated that TAK242 (a TLR4 inhibitor) and LY294002 (a PI3K inhibitor) remarkably augmented ATP50-3's down-regulation on LPS-induced proinflammatory mediators. Importantly, ATP50-3 provided neuroprotection against neuroinflammation-induced neurotoxicity in primary cortical and hippocampal neurons by mitigating overproduction of reactive oxygen species and damage to the mitochondrial membrane potential (MMP). Taken together, our findings suggest that ATP50-3 exerts anti-neuroinflammatory and neuroprotective effects through modulation of TLR4-mediated MyD88/NF-κB and PI3K/Akt signaling pathways.


Assuntos
Acorus/química , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Polissacarídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Técnicas de Cultura de Células , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Camundongos , Microglia/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Células Piramidais/metabolismo
13.
Carbohydr Polym ; 229: 115405, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31826414

RESUMO

The fruit of Alpinia oxyphylla is often used in traditional Chinese medicine to treat dementia and memory defects. In this study, we isolated a novel acidic polysaccharide (AOP70-2-1) from A. oxyphylla fruit. Structural analysis showed that AOP70-2-1 consists of ß-D-GlcAp-(1→, →2,3,6)-α-D-Galp-(1→, α-L-Araf-(1→, →2,5)-α-L-Araf-(1→, →4)-α-D-Glcp-(1→, →3,4)-α-D-Xylp-(1→, →3,6)-ß-D-Manp-(1→, and α-L-Rhap-(1→. Morphological analysis indicated that AOP70-2-1 had an irregular sheet structure. The crude polysaccharide (AOP70) from A. oxyphylla significantly improved learning and memory ability of Alzheimer's disease (AD) mice, and AOP70 exhibited comparable or even better effects than huperzine A. Most important, AOP70 reduced NO, IL-1ß, TNF-α, and PGE-2 concentrations to normal levels. AOP70-2-1 significantly inhibited NO production in lipopolysaccharide stimulated BV2 microglial cells. Note that the effect of 2.6 µM AOP70-2-1 was superior to indomethacin. AOP70-2-1 also remarkably decreased the values of IL-6 and TNF-α. AOP70-2-1 may be a bioactive component of AOP70 and has the potential for the treatment of AD.


Assuntos
Alpinia , Doença de Alzheimer/tratamento farmacológico , Anti-Inflamatórios , Fármacos Neuroprotetores , Polissacarídeos , Doença de Alzheimer/sangue , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Linhagem Celular , Dinoprostona/sangue , Frutas , Interleucina-1beta/sangue , Masculino , Camundongos , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico/sangue , Polissacarídeos/química , Polissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/sangue
14.
Carbohydr Polym ; 219: 219-228, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31151520

RESUMO

Coreopsis tinctoria is being widely cultivated in Xinjiang of China, whose consumption is known to prevent diabetes and neurodegenerative diseases. To elucidate the bioactive ingredients responsible for these benefits, the alkaline soluble crude polysaccharide (CTB) was isolated from C. tinctoria. In vitro experiments showed that the inhibition of α-amylase and α-glucosidase by CTB was 13407-fold and 906-fold higher than that by positive control, respectively. Then, a novel arabinogalactan, CTBP-1, was isolated and purified from CTB. Structural analysis showed that CTBP-1 possessed a 1,6-linked ß-d-Galp and 1,5-linked α-l-Araf backbone with branches substituted at the C-3 position of the 1,6-linked ß-d-Galp, and the side chains included 1,5-linked α-l-Araf, T-linked ß-d-Galp and T-linked α-l-Araf. The inhibitory effects of CTBP-1 on α-amylase and α-glucosidase were 2.7 and 17.9 times that of acarbose, respectively. CTBP-1 could avoid indigestion and similar side effects. In addition, CTBP-1 remarkably inhibited the release of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. In summary, CTBP-1 is a novel arabinogalactan with great potential as a treatment for type 2 diabetes and Alzheimer's disease.


Assuntos
Coreopsis/metabolismo , Galactanos , Inibidores de Glicosídeo Hidrolases/farmacologia , Microglia , Extratos Vegetais/química , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/metabolismo , Células Cultivadas , China , Galactanos/química , Galactanos/farmacologia , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Microglia/citologia , Microglia/efeitos dos fármacos , Óxido Nítrico/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
15.
Cell Physiol Biochem ; 49(5): 2047-2059, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30244247

RESUMO

BACKGROUND/AIMS: Thyroid cancer is the most common malignancy in human endocrine system. Smad ubiquitination regulatory factor 1 (Smurf1) is an E3 ubiquitin-protein ligase in ubiquitin-proteasome pathway (UPP) system. This study aimed to investigate the effects of Smurf1 on thyroid cancer proliferation and metastasis, as well as underlying potential mechanism. METHODS: The expression levels of Smurf1 in thyroid tumor tissues and thyroid cancer cells were detected by western blotting and qRT-PCR. Then, the effects of up-regulation or down-regulation of Smurf1 on thyroid cancer cell viability, migration, invasion, proliferation and apoptosis were measured using trypan blue exclusion assay, two-chamber migration (invasion) assay, cell colony formation assay and Guava Nexin assay, respectively. The ubiquitination of kisspeptin-1 (KISS-1) was assessed by protein ubiquitination assay. Finally, the effects of KISS-1 overexpression on activity of nuclear factor-kappa B (NF-κB) signaling pathway, as well as thyroid cancer cell viability, migration, invasion, proliferation and apoptosis were also detected, respectively. RESULTS: Smurf1 was highly expressed in thyroid tumor tissues and thyroid cancer cells. Up-regulation of Smurf1 promoted the viability, migration, invasion and proliferation of thyroid cancer cells. Knockdown of Smurf1 had opposite effects. Moreover, smurf1 promoted the ubiquitination of KISS-1. Overexpression of KISS-1 inactivated NF-κB pathway, suppressed thyroid cancer cell viability, migration, invasion and proliferation, and induced cell apoptosis. CONCLUSION: Up-regulation of Smurf1 exerted important roles in thyroid cancer formation and development by promoting thyroid cancer proliferation and metastasis. The ubiquitin-dependent degradation of KISS-1 induced by Smurf1 and the activation of NF-κB signaling pathway might be involved in this process. Smurf1 could be an effective therapy target and biomarker for thyroid cancer treatment.


Assuntos
Kisspeptinas/metabolismo , Neoplasias da Glândula Tireoide/patologia , Ubiquitina-Proteína Ligases/metabolismo , Adulto , Apoptose , Caspase 3/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Kisspeptinas/genética , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Neoplasias da Glândula Tireoide/metabolismo , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Proteína X Associada a bcl-2/metabolismo
16.
Biochim Biophys Acta Mol Basis Dis ; 1863(12): 3190-3201, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28847514

RESUMO

Alcohol exposure induces adipose hyperlipolysis and causes excess fatty acid influx into the liver, leading to alcoholic steatosis. The impacts of omega-3 polyunsaturated fatty acids (n-3 PUFA) on ethanol-induced fatty liver are well documented. However, the role of n-3 PUFA in ethanol-induced adipose lipolysis has not been sufficiently addressed. In this study, the fat-1 transgenic mice that synthesizes endogenous n-3 from n-6 PUFA and their wild type littermates with an exogenous n-3 PUFA enriched diet were subjected to a chronic ethanol feeding plus a single binge as model to induce liver injury with adipose lipolysis. Additionally, the differentiated adipocytes from 3T3-L1 cells were treated with docosahexaenoic acid or eicosapentaenoic acid for mechanism studies. Our results demonstrated that endogenous and exogenous n-3 PUFA enrichment ameliorates ethanol-stimulated adipose lipolysis by increasing PDE3B activity and reducing cAMP accumulation in adipocyte, which was associated with activation of GPR120 and regulation of Ca2+/CaMKKß/AMPK signaling, resultantly blocking fatty acid trafficking from adipose tissue to the liver, which contributing to ameliorating ethanol-induced adipose dysfunction and liver injury. Our findings identify that endogenous and exogenous n-3 PUFA enrichment ameliorated alcoholic liver injury by activation of GPR120 to suppress ethanol-stimulated adipose lipolysis, which provides the new insight to the hepatoprotective effect of n-3 PUFA against alcoholic liver disease.


Assuntos
Adiposidade/efeitos dos fármacos , Etanol/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Hepatopatias Alcoólicas/prevenção & controle , Substâncias Protetoras/farmacologia , Células 3T3-L1 , Quinases Proteína-Quinases Ativadas por AMP , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/patologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo , AMP Cíclico/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 3/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Fígado Gorduroso Alcoólico/prevenção & controle , Feminino , Lipólise/efeitos dos fármacos , Hepatopatias Alcoólicas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Quinases/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais
17.
J Ethnopharmacol ; 199: 119-127, 2017 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-28163112

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Type 2 diabetes mellitus (T2DM) is becoming a serious threat to human health. The fruit of Morus alba L. is widely used as a traditional Chinese medicine for the treatment of DM, dizziness, tinnitus, insomnia, and premature graying, as well as to protect the liver and kidneys. Several studies have demonstrated that the aqueous extracts of the roots bark, leaves, and ramuli of mulberry, which are known to contain polyphenols and polysaccharides, have antihyperglycemic and antihyperlipidemic activities. The aim of the present study was to further investigate the active polysaccharides from M. alba fruit by evaluating the antidiabetic activities of different fractions on T2DM rats and elucidate the mechanism underlying these activities. MATERIALS AND METHODS: Diabetic rats were treated with two fractions of M. alba fruit polysaccharides (MFP50 and MFP90). The disease models were induced by a high-fat diet and low dose injection of streptozotocin and were compared to normal rats and metformin-treated diabetic rats. After seven weeks, the fasting blood glucose (FBG), oral glucose tolerance test (OGTT), fasting serum insulin (FINS) levels, homeostasis model of assessment-insulin resistance (HOMA-IR), glycated serum protein (GSP), and serum alanine transaminase (ALT) levels, as well as serum lipid profiles and histopathological changes in the pancreas were measured. Next, the expressions of the insulin signaling pathway were measured by western blot analysis to elucidate the potential mechanism underlying these antidiabetic activities. RESULTS: After seven weeks of treatment, a significant reduction in the FBG levels, OGTT-area under the curve (OGTT-AUC), FINS, HOMA-IR, ALT, and triglyceride (TG) values of the MFP50 group was observed. On the other hand, in the MFP90 group, the FBG, OGTT-AUC, FINS, HOMA-IR, GSP, and TG levels were significantly reduced. The level of high-density lipoprotein cholesterol (HDL-c) and the proportion of HDL-c to total cholesterol (TC) significantly increased in the MFP50 group. Moreover, MFP50 and MFP90 induced repair of damaged pancreatic tissues of the diabetic rats. The hypoglycemic effect of MFP50 was more stable than MFP90, whereas the hypolipidemic effect of MFP90 was slightly better than MFP50. Moreover, the expression levels of InsR, IRS-2, Akt and GLUT4 in the MFP90 group significantly increased relative to that of the T2DM group. CONCLUSIONS: MFP50 and MFP90 have markedly antihyperglycemic and antihyperlipidemic effects and can clearly relieve diabetes symptoms in the T2DM rat model. The M. alba fruit polysaccharides may potentially be utilized as an effective treatment for T2DM. Further research into the structures of active M. alba fruit polysaccharides and their mechanisms in promoting antidiabetic effects are underway.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , Frutas , Hipoglicemiantes/uso terapêutico , Morus , Polissacarídeos/uso terapêutico , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Hipoglicemiantes/isolamento & purificação , Masculino , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Polissacarídeos/isolamento & purificação , Ratos , Ratos Wistar , Estreptozocina , Resultado do Tratamento
18.
Carbohydr Polym ; 147: 365-371, 2016 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-27178942

RESUMO

A novel polysaccharide, designated GCPB-1b, was obtained from the alkaline extract of the submerged fermentation culturing mycelium powder of Boshuzhi, Ganoderma capense. This polysaccharide was purified by ion-exchange and gel-permeation column chromatography and is a glucan (MW 2847Da). GCPB-1b has a specific optical rotation of [α]D(25)=+154° (c 1.0, H2O). Based on monosaccharide analysis, partial acid hydrolysis, periodic acid oxidation-Smith degradation, methylation analysis, Fourier transform-infrared spectroscopy (FT-IR), gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectroscopy, the backbone of GCPB-1b was composed of (1→4)-linked-α-d-glucose residues and (1→4,6)-linked-α-d-glucose residues. Furthermore, GCPB-1b had 1-diphenyl-2-picryl-hydrazyl (DPPH) radical-scavenging ability (EC50 3.23µM) according to antioxidant activity tests which was greater than other antioxidants. These data suggest that GCPB-1b holds promise as an anti-aging functional food.


Assuntos
Ganoderma/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Antioxidantes/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Oxirredução/efeitos dos fármacos , Polissacarídeos/isolamento & purificação , Espectroscopia de Infravermelho com Transformada de Fourier
20.
Hepatogastroenterology ; 61(136): 2196-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25699349

RESUMO

BACKGROUND/AIMS: To investigate acute hypervolemic hemodilution effect on oxygen metabolism and blood pharmacokinetics in patients undergoing acute laparotomy during Induction of general anesthesia. METHODOLOGY: Forty ASA I-II patients undergoing acute laparotomy were randomly divided into 2 groups (n=20 each): Patients of group A received Voluven 7 ml/kg in 20 mins before induction and 8 ml/kg after induction. Patients of group B received 6 ml/kg/h Plasmalyte A. Hemodynamic parameters MAP, HR and CVP were collected at 6 set points during the surgery: T1: before AHH; T2: before anesthesia induction; T3: right intubation; T4: 10 min after intubation; T5: 20 min after intubation; T6: skin incision. Arterial and venous blood samples were taken for blood gas analysis and determination of lactic acid, Hb and Hct: T1: before AHH, T2: right after AHH, T3: 0.5 h after AHH, T4: l h after AHH. Arterial Oxygen Content (Ca02), Central Venous Oxygen Content (Ccv02) and Oxygen Extraction Ratio (ER02) were calculated. RESULTS: The hemodynamic parameters were maintained within normal limits during operation in group A (P <0.05). CaO2, CcvO2, ERO2 and Lac between the two groups were no significant difference (P> 0.05). Compared with T1, CaO2/CcvO2 atT 2~4 reduced in both groups (P <0.05). Compared with group A, Hb and Hct in group B increased at T2~4 (P <0.05). CONCLUSIONS: Acute hypervolemic hemodilution in patients undergoing acute laparotomy during Induction of general anesthesia have some preventive hypotension effect, more conducive to the smooth blood pharmacokinetics; Voluven induced expansion of applications is safe and effective, and has no effect on the body's metabolic rate of oxygen.


Assuntos
Anestesia Geral , Hemodiluição , Laparotomia , Oxigênio/metabolismo , Idoso , Feminino , Hemodinâmica , Humanos , Ácido Láctico/metabolismo , Masculino , Pessoa de Meia-Idade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA