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1.
Foods ; 13(8)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38672884

RESUMO

The effects of subcritical water microenvironment on the physiochemical properties, antioxidant activity and in vitro digestion of polysaccharides (SWESPs) from squash were investigated. After single-factor experiments, twenty samples were successfully prepared at different extraction temperatures (110, 130, 150, 170 and 190 °C) and extraction times (4, 8, 12 and 16 min). Under a low temperature environment, the whole process was mainly based on the extraction of SWESP. At this time, the color of SWESP was white or light gray and the molecular mass was high. When the temperature was 150 °C, since the extraction and degradation of SWESP reached equilibrium, the maximum extraction rate (18.67%) was reached at 150 °C (12 min). Compared with traditional methods, the yield of squash SWESP extracted by subcritical water was 3-4 times higher and less time consuming. Under high temperature conditions, SWESPs were degraded and their antioxidant capacity and viscosity were reduced. Meanwhile, Maillard and caramelization reactions turned the SWESPs yellow-brown and produced harmful substances. In addition, different SWESPs had different effects on in vitro digestion. In brief, SWESPs prepared under different conditions have different structures and physicochemical properties, allowing the obtainment of the required polysaccharide. Our results show that squash polysaccharides prepared in different subcritical water states had good development potential and application in the food industry.

2.
BMJ Open ; 14(2): e076579, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38423773

RESUMO

OBJECTIVES: Colorectal cancer (CRC) encompasses a spectrum of pathological types, each exhibiting distinct biological behaviours that challenge the conventional T-staging system's predictive efficiency. Thus, this study aims to explore the prognostic significance of the T stage across various CRC pathological types, seeking to unravel insights that could enhance prognostic assessment in this complex disease. STUDY DESIGN: We performed a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database for primary CRC cases from 2010 to 2017. SETTING: The SEER database, comprising data from various US regional and state cancer registries, identified 39 321 patients with CRC. Our analysis focused on the three most common CRC pathological types: adenocarcinoma (AC), mucinous adenocarcinoma (MC) and signet ring cell carcinoma (SR). PRIMARY OUTCOME MEASURES: The study used Cox regression models to evaluate how different pathological characteristics impact mortality risk in patients with CRC. Time-dependent receiver operating characteristic curves were also applied to assess the prognostic accuracy of various tumour node metastasis (TNM)/non-mucinous (NM) stages. RESULTS: We observed significant associations between T stage and mortality risk for patients with AC and MC. Notably, in comparison to those at T1 stage, patients with AC in the T4 stage demonstrated a 2.01-fold increase in mortality risk (HR=2.01, 95% CI: 1.89 to 2.15), while patients with MC at T4 stage showed a 1.42-fold increase (HR=1.42, 95% CI: 1.03 to 1.97). However, within the SR group, T stages did not independently impact survival, showing no significant distinction (HR=1.07, 95% CI: 0.59 to 1.95). Intriguingly, the traditional TNM staging systems demonstrated limited discriminatory power in predicting prognosis for patients with SR when compared with the more innovative NM staging systems. CONCLUSIONS: This study uncovers important insights about the prognostic significance of the T stage in different types of CRC, highlighting the need for personalised assessments based on specific histological subtypes.


Assuntos
Adenocarcinoma , Neoplasias Colorretais , Humanos , Prognóstico , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Colorretais/epidemiologia , Adenocarcinoma/patologia
3.
Medicine (Baltimore) ; 103(2): e36957, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38215151

RESUMO

Gastrointestinal (GI) cancers pose a significant challenge due to high prevalence and mortality. While advancements in detection and conventional treatments have been made, prognosis often remains poor, particularly for advanced-stage cancers. Immunotherapy has emerged as a transformative approach, leveraging the body immune system against cancer, including immune checkpoint inhibitors (ICIs), cancer vaccines, and adoptive cell transfer. These modalities have shown promise, achieving sustained responses and improved survival in some patients. However, their efficacy in GI cancers is less pronounced, hindered by drug resistance mechanisms that are either intrinsic or acquired over time. This review examines the latest understanding of immunotherapy in GI cancers, focusing on ICIs, cancer vaccines, and adoptive cell transfer, along with their associated outcomes and limitations. It delves into the mechanisms behind drug resistance, including alterations in immune checkpoints, the immunosuppressive tumor microenvironment, and genetic/epigenetic changes. The role of the gut microbiome is also considered as an emerging factor in resistance. To combat drug resistance, strategies such as enhancing immune response, targeting the tumor microenvironment, and modulating resistance mechanisms are explored. The review underscores the potential of ferroptosis induction as a novel approach. Looking forward, it highlights the need for personalized immunotherapies, understanding the influence of the gut microbiome, and further exploration of ferroptosis in overcoming resistance. While challenges persist, the continuous evolution in GI cancer immunotherapy research promises innovative treatments that could significantly improve patient outcomes.


Assuntos
Vacinas Anticâncer , Neoplasias Gastrointestinais , Humanos , Vacinas Anticâncer/uso terapêutico , Neoplasias Gastrointestinais/tratamento farmacológico , Imunoterapia , Resistência a Medicamentos , Microambiente Tumoral
4.
Front Oncol ; 13: 1234887, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38023163

RESUMO

Choline, a quintessential quaternary ammonium compound, plays a cardinal role in several pivotal biological mechanisms, chiefly in safeguarding cell membrane integrity, orchestrating methylation reactions, and synthesizing vital neurotransmitters. This systematic review meticulously dissects the complex interplay between choline metabolism and its profound implications in oncology. The exposition is stratified into three salient dimensions: Initially, we delve into the intricacies of choline metabolism, accentuating its indispensability in cellular physiology, the enzymatic labyrinth governing its flux, and the pivotal cellular import mechanisms. Subsequently, we elucidate the contemporary comprehension of choline metabolism in the cancer paradigm, traversing its influence from inception to the intricate metamorphosis during oncogenic progression, further compounded by dysregulated enzyme activities and aberrant signaling cascades. Conclusively, we illuminate the burgeoning potential of choline-centric metabolic imaging modalities, notably magnetic resonance spectroscopy (MRS) and positron emission tomography (PET), as avant-garde tools for cancer diagnostics and therapeutic trajectory monitoring. Synoptically, the nuanced perturbations in choline metabolism in neoplastic entities unfurl critical insights, potentially heralding paradigm shifts in diagnostic and therapeutic oncological stratagems. A deeper foray into this realm is anticipated to fortify our molecular understanding and refine intervention modalities in cancer theranostics.

5.
Pharm Biol ; 61(1): 1222-1233, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37565668

RESUMO

CONTEXT: Diabetic nephropathy (DN) is the main cause of end-stage renal disease. Modified Shen-Yan-Fang-Shuai formula (M-SYFSF) has excellent clinical efficacy in treating diabetic kidney disease. However, the potential mechanism of M-SYFSF remains unknown. OBJECTIVE: To investigate the mechanism of M-SYFSF against DN by network pharmacological analysis and biological experiments. MATERIALS AND METHODS: Utilizing a web-based pharmacology database, the potential mechanisms of M-SYFSF against DN were identified. In vivo experiments, male SD rats were injected with streptozotocin (50 mg/kg) and got uninephrectomy to construct a model of DN. M-SYFSF (11.34 g/kg/d) was gavaged once per day for 12 weeks after model establishment. In vitro experiments, human proximal tubular cells (HK-2) were performed with advanced glycation end-products (AGEs) (100 µg/mL), then intervened with M-SYFSF freeze-dried powder. Pathological staining, WB, IHC, ELISA were conducted to explore the mechanism of M-SYFSF against DN. RESULTS: Network pharmacological analysis showed that MAPK pathway was the potential pathway. Results showed that compared with the Model group, M-SYFSF significantly reduced 24h urine albumin, UACR, and serum creatinine levels (54.90 ± 26.67 vs. 111.78 ± 4.28, 8.87 ± 1.69 vs. 53.94 ± 16.01, 11.56 ± 1.70 vs. 118.70 ± 49.57, respectively), and improved renal pathological changes. Furthermore, the intervention of M-SYFSF reduced the expression of pro-inflammatory cytokines and inhibited the activation of MAPK pathway in AGEs-treated HK-2 cells. DISCUSSION AND CONCLUSION: M-SYFSF is likely to reduce inflammation in DN by inhibiting the MAPK pathway. It provides a theoretical basis for the clinical application of M-SYFSF in the treatment of DN.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Medicamentos de Ervas Chinesas , Ratos , Masculino , Humanos , Animais , Nefropatias Diabéticas/metabolismo , Farmacologia em Rede , Ratos Sprague-Dawley , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Produtos Finais de Glicação Avançada/metabolismo
6.
Sci Rep ; 13(1): 11758, 2023 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-37474552

RESUMO

The prognostic significance of radiotherapy (RT) for colorectal cancer (CRC) has shown conflicting results, particularly among different pathological subtypes, including adenocarcinoma (AC), mucinous adenocarcinoma (MC), and signet-ring cell carcinoma (SR). This study analyzed the prognosis of three pathological CRC types and focused on the prognostic significance of RT on three CRC histological subtypes. Patients diagnosed with AC (n = 54,174), MC (n = 3813), and SR (n = 664) in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database (2010-2017) were evaluated. Cox regression models and competitive risk models were built to assess the effect of RT on the risk of CRC-associated death. Potential interactions between RT and stratified variables including age, sex, and tumor location were examined by multiplicative models. Compared with AC patients, SR patients had the worst overall survival (OS) among 3 subtypes of CRC (log-rank test, p < 0.001). Compared with patients who did not receive radiotherapy, RT was associated with a 1.09-fold (HR = 1.09, 95%[CI]: 1.03, 1.15) elevated risk of death among AC patients. In the SR group, RT significantly reduced the risk of death by 39% (HR = 0.61, 95%[CI]: 0.39-0.95). However, RT did not appear to independently influence survival in the MC group (HR = 0.96, 95%[CI]: 0.77, 1.21). In the subgroup analysis, tumor location (colon and rectum) significantly modified the association between RT and the risk of death among the AC and SR patients (p for interaction < 0.05). SR patients exhibited a worse OS (overall survival) than AC patients, and the effect of RT varied according to CRC histological subtypes. This can ultimately lead to more personalized and effective treatment strategies for CRC patients.


Assuntos
Adenocarcinoma Mucinoso , Adenocarcinoma , Neoplasias Colorretais , Humanos , Prognóstico , Estadiamento de Neoplasias , Adenocarcinoma/patologia
7.
Front Oncol ; 12: 785345, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35957872

RESUMO

Epithelial-to-mesenchymal transition (EMT) and angiogenesis have emerged as two pivotal events in cancer progression. Paeoniflorin has been widely studied in experimental models and clinical trials for cancer treatment because of its anti-cancer property. However, the underlying mechanisms of paeoniflorin in EMT and angiogenesis in glioblastoma was not fully elucidated. The present study aimed to investigate whether paeoniflorin inhibits EMT and angiogenesis, which involving c-Met suppression, while exploring the potential ways of c-Met degradation. In our study, we found that paeoniflorin inhibited EMT via downregulating c-Met signaling in glioblastoma cells. Furthermore, overexpressing c-Met in glioblastoma cells abolished the effects of paeoniflorin on EMT. Moreover, paeoniflorin showed anti-angiogenic effects by suppressing cell proliferation, migration, invasion and tube formation through downregulating c-Met in human umbilical vein endothelial cells (HUVECs). And c-Met overexpression in HUVECs offset the effects of paeoniflorin on angiogenesis. Additionally, paeoniflorin induced autophagy activation involving mTOR/P70S6K/S6 signaling and promoted c-Met autophagic degradation, a process dependent on K63-linked c-Met polyubiquitination. Finally, paeoniflorin suppressed mesenchymal makers (snail, vimentin, N-cadherin) and inhibited angiogenesis via the identical mechanism in an orthotopic xenograft mouse model. The in vitro and in vivo experiments showed that paeoniflorin treatment inhibited EMT, angiogenesis and activated autophagy. What's more, for the first time, we identified c-Met may be a potential target of paeoniflorin and demonstrated paeoniflorin downregulated c-Met via K63-linked c-Met polyubiquitination-dependent autophagic degradation. Collectively, these findings indicated that paeoniflorin inhibits EMT and angiogenesis via K63-linked c-Met polyubiquitination-dependent autophagic degradation in human glioblastoma.

8.
Int J Biol Macromol ; 188: 729-739, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34389393

RESUMO

A neutral polysaccharide designated as CMDP-1a (molecular mass 9.263 kDa) was isolated from Cucurbita moschata Duch through hot water extraction, ethanol precipitation, and column chromatography. On the basis of methylation, fourier-transform infrared, monosaccharide composition, and one- and two-dimensional nuclear magnetic resonance spectroscopy analyses, the structure of CMDP-1a was determined to be a backbone composed of α-1,4 linked glucopyranosyl residues with α-Glcp residue linkage at backbone C-6. Atomic force microscopy and scanning electron microscopy analyses revealed that CMDP-1a had a spherical conformation in solution. In immunostimulation assays, CMDP-1a promoted the proliferation of RAW 264.7 macrophages and significantly enhanced their pinocytic and phagocytic capacity. Furthermore, CMDP-1a induced the M1 polarization of original macrophages and the conversion of macrophages from M2 to M1, thereby modulating the balance of M1/M2 macrophages. These results indicated that CMDP-1a might be a potential immunomodulator for food purposes.


Assuntos
Cucurbita/química , Fatores Imunológicos/farmacologia , Polissacarídeos/farmacologia , Animais , Polaridade Celular/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Espectroscopia de Ressonância Magnética , Metilação , Camundongos , Modelos Biológicos , Peso Molecular , Monossacarídeos/análise , Fagocitose/efeitos dos fármacos , Pinocitose/efeitos dos fármacos , Polissacarídeos/isolamento & purificação , Polissacarídeos/ultraestrutura , Células RAW 264.7 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier
9.
Carbohydr Polym ; 269: 118288, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34294314

RESUMO

A pectic polysaccharide (named CMDP-4b) with a molecular weight of 31.97 kDa was extracted from Cucurbita moschata Duch and purified by column chromatography. On the basis of methylation, Fourier-transform infrared, monosaccharide composition, and one- and two-dimensional nuclear magnetic resonance spectroscopy analyses, the structure of CMDP-4b was determined to be composed of an α-1,4-linked homogalacturonan backbone, which was slightly acetylated and highly methyl-esterified, and branched at the O-3 position of the →4)-α-D-GalpA-6-OMe-(1→. Immunomodulatory assays showed that CMDP-4b not only induced the secretion of nitrous oxide and cytokines (i.e. IL-1ß, TNF-α, and IL-6) but also promoted pinocytic and phagocytic activities of macrophages, suggesting that CMDP-4b possessed immunomodulatory activity. Moreover, toll-like receptor 4 and complement receptor 3 may play a critical role in CMDP-4b-induced macrophage activation through the NF-κB and the MAPKs signaling pathways. Our study provides the molecular basis for the potential use of CMDP-4b as a natural immunostimulant.


Assuntos
Cucurbita/química , Fatores Imunológicos/farmacologia , Pectinas/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Pectinas/química , Pectinas/isolamento & purificação , Fagocitose/efeitos dos fármacos , Pinocitose/efeitos dos fármacos , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
10.
Int J Biol Macromol ; 182: 1003-1014, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33892025

RESUMO

Pumpkin polysaccharides with various bioactivities are mainly taken orally, thus detailed knowledge of the intestinal transport of which are essential for understanding its bioactivities. The Caco-2 cells monolayer model (mimic intestinal epithelium) was successfully constructed and Cucurbia moschata polysaccharides (PPc-F) were successfully conjugated with fluorescein isothiocyanate (FITC) to evaluate the transcellular transport mechanism and subcellular localization of PPc. The transport process of PPc-F was energy-dependent, and a moderately-absorbed biological macromolecule according to the apparent permeability coefficients (Papp) value. The endocytosis process of PPc-F in Caco-2 cells included the clathrin- and caveolae (or lipid draft)-medicated routes. And the translocation process was related to endoplasmic reticulum (ER), golgi apparatus (GA), tubulin and the acidification of endosomes. As for the intracellular location of PPc-F, it was mainly accumulated in ER. The study provided an understanding of the transmembrane transport of PPc-F, and could help studying the mechanisms of its effects.


Assuntos
Cucurbita/química , Endocitose , Polissacarídeos/química , Células CACO-2 , Cavéolas/metabolismo , Retículo Endoplasmático/metabolismo , Fluoresceína/química , Humanos , Microdomínios da Membrana/metabolismo , Polissacarídeos/metabolismo , Transcitose
11.
Foods ; 10(1)2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33478048

RESUMO

In this paper, subcritical water (SCW) was applied to modify pumpkin (Cucurbita moschata Duchesne ex Poiret) polysaccharides, and the properties and antioxidant activity of pumpkin polysaccharides were investigated. SCW treatments at varying temperature led to changes in the rheological and emulsifying properties of pumpkin polysaccharides. SCW treatments efficiently degraded pumpkin polysaccharides and changed the molecular weight distribution. Decreases in intrinsic viscosity, viscosity-average molecular weight, and apparent viscosity were also observed, while the activation energy and flow behavior indices increased. The temperature of SCW treatment has a great influence on the linear viscoelastic properties and antioxidant activity of pumpkin polysaccharides. Pumpkin polysaccharides solution treated by SCW at 150 °C exhibited the highest emulsifying activity and antioxidant activity, which was probably due to a broader molecular mass distribution and more reducing ends exposed after treatment. Scanning electron microscopy showed that SCW treatment changed the microstructure of pumpkin polysaccharides, resulting in the exposure of bigger surface area. Our results suggest that SCW treatment is an effective approach to modify pumpkin polysaccharides to achieve improved solution properties and antioxidant activity.

12.
Carbohydr Polym ; 251: 117090, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33142631

RESUMO

The novel natural low-molecular-mass polysaccharide (SLWPP-3) from pumpkin (Cucurbia moschata) was separated from the waste supernatant after macromolecular polysaccharide production and purified using a DEAE cellulose-52 column and gel-filtration chromatography. Chemical and instrumental studies revealed that SLWPP-3 with a molecular mass of 3.5 kDa was composed of rhamnose, glucose, arabinose, galactose and uronic acid with a weight ratio of 1: 1: 4: 6: 15, and primarily contained →3,6)-ß-d-Galp-(1→, →4)-α-GalpA-(1→(OMe), →4)-α-GalpA-(1→, →2,4)-α-d-Rhap-(1→, →3)-ß-d-Galp-(1→, →4)-α-d-Glcp, and →4)-ß-d-Galp residues in the backbone. The branch chain passes were connected to the main chain through the O-4 atom of glucose and O-3 atom of arabinose. Physiologically, the ability of SLWPP-3 to inhibit carbohydrate-digesting enzymes and DPPH and ABTS radicals, as well as protect pancreatic ß cells from oxidative damage by decreasing MDA levels and increasing SOD activities, was confirmed. The findings elucidated the structural types of pumpkin polysaccharides and revealed a potential adjuvant natural product with hypoglycemic effects.


Assuntos
Antioxidantes/farmacologia , Cucurbita/química , Hipoglicemiantes/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Polissacarídeos/química , Polissacarídeos/farmacologia , Estreptozocina/toxicidade , Animais , Antibióticos Antineoplásicos/toxicidade , Antioxidantes/química , Linhagem Celular , Hipoglicemiantes/química , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Malondialdeído/metabolismo , Peso Molecular , Ratos , Superóxido Dismutase/metabolismo
13.
Neuroreport ; 31(10): 730-736, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32501888

RESUMO

We previously reported that intraspinal transplantation of human amniotic mesenchymal stem cells (hAMSCs) promotes functional recovery in a rat model of acute traumatic spinal cord injury (SCI). However, whether intravenous transplantation of hAMSCs also has therapeutic benefit remains uncertain. In this study, we assessed whether intravenous transplantation of hAMSCs improves outcomes in rats with acute traumatic SCI. In addition, the potential mechanisms underlying the possible benefits of this therapy were investigated. Adult female Sprague-Dawley rats were subjected to SCI using a weight drop device, and then hAMSCs or PBS were administered after 2 h via the tail vein. Our results indicated that transplanted hAMSCs could migrate to injured spinal cord lesion. Compared with the control group, hAMSCs transplantation significantly decreased the numbers of ED1 macrophages/microglia and caspase-3 cells, and reduced levels of inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-6 and IL-1ß. In addition, hAMSCs transplantation significantly attenuated Evans blue extravasation, promoted angiogenesis and axonal regeneration. hAMSCs transplantation also significantly improved functional recovery. These results suggest that intravenous administration of hAMSCs provides neuroprotective effects in rats after acute SCI, and could be an alternative therapeutic approach for the treatment of acute SCI.


Assuntos
Administração Intravenosa/métodos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia , Traumatismos da Medula Espinal/terapia , Líquido Amniótico/citologia , Animais , Apoptose , Células Cultivadas , Feminino , Humanos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/fisiopatologia
14.
Chem Res Toxicol ; 33(4): 933-939, 2020 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-32191437

RESUMO

To date, a safe and reliable treatment of osteoarthritis (OA) has not yet been announced. Inflammatory response and degradation of the articular extracellular matrix (ECM) induced by IL-1ß are important pathological characteristics of OA. Laquinimod is a quinoline-3-carboxamide and a novel oral immunomodulatory compound in clinical use. However, whether laquinimod has a beneficial effect in OA is not known. In our research, we found that laquinimod could ameliorate IL-1ß-induced generation of ROS and improve mitochondrial function by increasing mitochondrial membrane potential (ΔΨm). Furthermore, treatment with laquinimod suppressed IL-1ß-induced production of TNF-α and IL-6. Notably, laquinimod prevented the degradation of type II collagen by inhibiting MMP-3 and MMP-13. Meanwhile, the presence of laquinimod attenuated the reduction in aggrecan by mediating ADAMTS-4 and ADAMTS-5. Mechanistically, laquinimod ameliorated IL-1ß-induced inflammation and degeneration of ECM by suppressing the activation of NF-κB. Taken together, our findings reveal that laquinimod possesses a beneficial effect against IL-1ß insults in human chondrocytes, implying an important role of laquinimod in OA.


Assuntos
Anti-Inflamatórios/farmacologia , Cartilagem/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Interleucina-1beta/antagonistas & inibidores , Quinolonas/farmacologia , Cartilagem/metabolismo , Linhagem Celular , Condrócitos/metabolismo , Relação Dose-Resposta a Droga , Matriz Extracelular/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-1beta/metabolismo
15.
J Cell Physiol ; 235(3): 2232-2244, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31486078

RESUMO

Adult human mesenchymal stem cells have the potential to differentiate into osteoblast, which plays crucial roles in bone regeneration and repair. Some transcriptional factors (TFs), such as BMP-2 and RUNX2, have been demonstrated to control the differentiation processes. It is important to discover more key regulators in osteoblast differentiation. Recently, some studies found long noncoding RNAs (lncRNAs) participating in osteoblast differentiation, such as MALAT1, DANCR, and ANCR. In this study, we performed a network-based computational analysis to investigate the lncRNA-messenger RNA (mRNA) crosstalks via integrating microRNA (miRNA)-RNA interactions, gene coexpression, and protein-protein interactions. First, multiple topology analyses were performed to osteoblast-differentiation-related lncRNA-mRNA network (ODLMN). Several lncRNAs with central topology structures were identified as key regulators. Results showed that these lncRNAs participated in osteoblast differentiation via phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase, and Ras signals. Previous studies have demonstrated that lncRNAs exert functions by involving in close modules. Second, after performing module searching in ODLMN, two functional modules were identified, which played crucial roles through involving in PI3K/protein kinase B, cyclic adenosine 3',5'-monophosphate, and hypoxia-inducible factor 1 pathways. Third, a subset of core lncRNA-TF crosstalks that might form feedback loops to control the biological processes in osteoblast differentiation was identified. These core lncRNA-TF feedback loops showed more TF binding affinity than other lncRNAs. All these results can help us to uncover the molecular mechanism and provide new targets for bone regeneration and repair.


Assuntos
Diferenciação Celular/genética , Redes Reguladoras de Genes/genética , Osteoblastos/fisiologia , RNA Longo não Codificante/genética , Perfilação da Expressão Gênica/métodos , Humanos , Osteogênese/genética , Fosfatidilinositol 3-Quinases/genética , RNA Mensageiro/genética , Fatores de Transcrição/genética , Transcriptoma/genética
16.
Carbohydr Polym ; 229: 115534, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31826396

RESUMO

As a new platform of systems biology, metabolomics provides a powerful approach to discover therapeutic biomarkers and mechanism of metabolic disease. Type 2 diabetes mellitus (T2DM) is a global metabolic disease, thus, a urinary metabolomics profiling was analyzed to study the anti-diabetic effects and mechanism of stachyose (ST) on high-fat diet- and low dose streptozotocinc-induced T2DM rats. The results showed that ST treatment regulated the level of insulin, low-density lipoprotein cholesterol, and triglycerides, which demonstrates improvement in T2DM on ST treatment. Urinary samples from the ST and T2DM group were enrolled in metabolomics study, 21 differential metabolites were identified from urinary metabolomics analysis, indicating that the ST treatment partly exerted the anti-diabetes activity by regulating energy metabolism, gut microbiota changes and inflammation. A metabolomics strategy is both suitable and reliable for exploring the anti-diabetes effects and understanding the mechanisms of ST treatment against T2DM.


Assuntos
Biomarcadores/urina , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metabolômica , Oligossacarídeos/uso terapêutico , Animais , LDL-Colesterol/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/patologia , Dieta Hiperlipídica , Análise Discriminante , Metabolismo Energético/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Histamina/urina , Hipoglicemiantes/farmacologia , Insulina/sangue , Análise dos Mínimos Quadrados , Masculino , Oligossacarídeos/farmacologia , Análise de Componente Principal , Ratos , Ratos Wistar , Estreptozocina/toxicidade , Triglicerídeos/sangue
17.
Zhongguo Zhong Yao Za Zhi ; 44(11): 2403-2410, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359670

RESUMO

As the famous Chinese patent medicine, Yinhua Miyanling Tablets, which was derived from ancient prescription denominated Bazhengsan, has not only the effects in clearing away heat and purging pathogenic fire, removing dampness and relieving stranguria, but also have the functions of detoxifying and tonifying. A great number of scientific studies have demonstrated that Yinhua Mi-yanling Tablets played significant roles in destroying harmful microbes and resisting inflammatory and diuresis. Compared with antibiotics, traditional antibacterial Chinese patent medicine Yinhua Miyanling Tablets has the advantage in bacterial resistance in long-term use. Fundamental studies about the content of pharmaceutical ingredients and the modern pharmacology of Yinhua Miyanling Tablets were collected and summarized, which conduces to indicating the active ingredients of Yinhua Miyanling Tablets with the medicinal efficacy from the molecular level and the internal mechanism of Yinhua Miyanling Tablets in the treatment of urinary tract infection(UTI) from the scientific perspective. In the field of clinical research, literatures associated with Yinhua Miyanling Tablets for the treatment of UTI were summarized and analyzed in terms of treatment type, administration mode, dosage, frequency of medication, course, efficiency, side effects and whether combined with healthy lifestyle. These literatures confirmed the medicinal values and the application prospect of Yinhua Miyanling Tablets in treating UTI, especially acute UTI, which provides a scientific theoretical foundation and a correct direction for the clinical application of Yinhua Miyanling Tablets. In conclusion, this article contributes to the standardization of Yinhua Miyanling Tablets in the treatment of UTI, in the expectation of giving the scientific guidance for clinical practice.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Humanos , Medicina Tradicional Chinesa , Pesquisa , Comprimidos
18.
Biomed Res Int ; 2019: 9053295, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30886866

RESUMO

Paeoniflorin (PF), as one of the important valid natural compounds of the total glucosides of peony, has displayed a potential effect in cancer prevention and treatment. Aggressive migration and invasion, as an important process, can contribute to tumor progression through infiltrating the surround normal tissue. Actin cytoskeleton rearrangement plays a key role in cells migration and invasion, involving multiple signal pathways. HGF/c-Met signal, as an important couple of oncoprotein, has been demonstrated to regulate actin cytoskeleton rearrangement. In our study, we aim to explore whether paeoniflorin can inhibit migration and invasion and actin cytoskeleton rearrangement via regulation of HGF/c-Met/RhoA/ROCK signal. Various approaches were applied to demonstrate the mechanism of paeoniflorin-mediated anticancer effect, including cell wound healing assay, invasion assay, immunofluorescence staining and transfection, and western blotting. We observed that paeoniflorin inhibited HGF-induced migration and invasion and actin cytoskeleton rearrangement in glioblastoma cells. Furthermore, the inhibition of HGF-induced migration and invasion and actin cytoskeleton rearrangement involved c-Met-mediated RhoA/ROCK signaling in glioblastoma. Thus, our study proved that paeoniflorin could inhibit migration and invasion and actin cytoskeleton rearrangement through inhibition of HGF/c-Met/RhoA/ROCK signaling in glioblastoma, suggesting that paeoniflorin might be a candidate compound to treat glioblastoma.


Assuntos
Glioblastoma/tratamento farmacológico , Glucosídeos/farmacologia , Fator de Crescimento de Hepatócito/genética , Monoterpenos/farmacologia , Proteínas Proto-Oncogênicas c-met/genética , Proteína rhoA de Ligação ao GTP/genética , Citoesqueleto de Actina/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Invasividade Neoplásica/genética , Transdução de Sinais/efeitos dos fármacos , Quinases Associadas a rho/genética
19.
Z Orthop Unfall ; 157(1): 42-47, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29969810

RESUMO

OBJECTIVE: The aim of this study was to perform a cross-cultural adaption of the KOOS into Chinese and to evaluate its psychometric properties in patients with anterior cruciate ligament reconstruction (ACL reconstruction) in mainland China. DESIGN: A cross-sectional study. SETTING: Patients completed the Chinese version of the KOOS and the SF-36 questionnaire three times. We evaluated the reliability, checked the validity, and assessed the responsiveness. PARTICIPANTS: A total of 42 patients who had undergone ACL reconstruction. MAIN OUTCOME MEASURES: The results of the questionnaire survey. RESULTS: The Chinese version of the KOOS was well accepted, with ideal test-retest reliability and internal consistency. The test-retest reliability was significant, with high ICC values ranging from 0.888 to 0.941. Additionally, we found that the internal consistency was adequate, with Cronbach's alpha coefficient ranging from 0.740 to 0.975. All a priori hypotheses were supported by a high correlation between the KOOS and SF-36. Furthermore, responsiveness was demonstrated since the ES and SRM between subscales following ACL reconstruction was found in the expected pattern. CONCLUSIONS: The Chinese version of the KOOS showed psychometric properties demonstrating acceptable reliability and validity similar to the original version. We conclude that the Chinese version is a reliable and valid instrument for research and clinical assessments of ACL reconstruction patients in mainland China.


Assuntos
Reconstrução do Ligamento Cruzado Anterior/estatística & dados numéricos , Traumatismos do Joelho , Osteoartrite do Joelho , Adulto , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Traumatismos do Joelho/epidemiologia , Traumatismos do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/cirurgia , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários/normas , Traduções , Resultado do Tratamento
20.
Food Chem ; 277: 744-752, 2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-30502211

RESUMO

This study investigated an efficient and recyclable approach for purification of crude pumpkin oligosaccharide (POS) by macroporous resins. Five resins with different physical and chemical properties were tested for decoloration of POS. In virtue of its higher decoloration ratio (92.6%) and POS recovery ratio (81.3%), the macroporous resin DM28 was considered to a better selection. Depending on the changes of molecular weight, part of the monosaccharides in crude POS were removed simultaneously after decoloration by DM28. Operating conditions were also determined by the dynamic breakthrough and desorption curves. Moreover, UV/vis spectroscopy and Fourier transform infrared results revealed that most of the colored impurities and proteins can be removed, but the characteristic groups of the POS exhibited no significant difference. Compared with traditional methods, DM28 resin is superior in decoloration efficiency, pigment recovery and oligosaccharide recovery. This research contributes to further exploration on the structure and function of POS.


Assuntos
Cucurbita/metabolismo , Oligossacarídeos/química , Adsorção , Cor , Peso Molecular , Oligossacarídeos/isolamento & purificação , Extratos Vegetais/metabolismo , Porosidade , Resinas Vegetais/química , Espectrofotometria , Espectroscopia de Infravermelho com Transformada de Fourier
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