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1.
Nucleic Acids Res ; 52(W1): W248-W255, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38738636

RESUMEN

Knowledge of protein function is essential for elucidating disease mechanisms and discovering new drug targets. However, there is a widening gap between the exponential growth of protein sequences and their limited function annotations. In our prior studies, we have developed a series of methods including GraphPPIS, GraphSite, LMetalSite and SPROF-GO for protein function annotations at residue or protein level. To further enhance their applicability and performance, we now present GPSFun, a versatile web server for Geometry-aware Protein Sequence Function annotations, which equips our previous tools with language models and geometric deep learning. Specifically, GPSFun employs large language models to efficiently predict 3D conformations of the input protein sequences and extract informative sequence embeddings. Subsequently, geometric graph neural networks are utilized to capture the sequence and structure patterns in the protein graphs, facilitating various downstream predictions including protein-ligand binding sites, gene ontologies, subcellular locations and protein solubility. Notably, GPSFun achieves superior performance to state-of-the-art methods across diverse tasks without requiring multiple sequence alignments or experimental protein structures. GPSFun is freely available to all users at https://bio-web1.nscc-gz.cn/app/GPSFun with user-friendly interfaces and rich visualizations.


Asunto(s)
Proteínas , Programas Informáticos , Proteínas/química , Proteínas/metabolismo , Conformación Proteica , Análisis de Secuencia de Proteína , Aprendizaje Profundo , Sitios de Unión , Anotación de Secuencia Molecular , Redes Neurales de la Computación , Secuencia de Aminoácidos , Humanos , Internet
2.
J Cell Mol Med ; 28(8): e18256, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38527290

RESUMEN

Acute myeloid leukaemia (AML) is a prevalent haematological malignancy in which various immune and stromal cells in the bone marrow microenvironment have instrumental roles and substantially influence its progression. KIR2DL is a member of the immunoglobulin-like receptor family and a natural killer (NK) cell surface-specific receptor. However, its impact on immune infiltration regarding AML has not been addressed. We aimed to explore molecular markers associated with the immune microenvironment and prognosis of AML with a particular focus on KIR2DL family members. Analysis of data from The Cancer Genome Atlas and Genotype-Tissue Expression databases revealed that KIR2DL1, KIR2DL3 and KIR2DL4 expression were significantly upregulated in AML and associated with decreased overall survival (OS). Moreover, univariate Cox analysis implicated KIR2DL genes as independent prognostic markers of OS. Functional enrichment analysis revealed that KIR2DL genes were associated with immune cells, the immune microenvironment and NK cell-mediated cytotoxicity. Additionally, immune infiltration analyses revealed that KIR2DL upregulation was associated with stronger immune infiltration. Finally, we performed drug sensitivity profiling of KIR2DL genes using the Cellminer database. Collectively, our findings suggest that KIR2DL1, KIR2DL3 and KIR2DL4 have critical roles in AML and may represent novel biomarker genes for disease prognosis and immune infiltration.


Asunto(s)
Leucemia Mieloide Aguda , Humanos , Pronóstico , Leucemia Mieloide Aguda/patología , Médula Ósea/patología , Microambiente Tumoral/genética
3.
Mol Carcinog ; 63(8): 1611-1620, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38780147

RESUMEN

Sulforaphane (SFN) exerts anticancer effect on various cancers including gastric cancer. However, the regulatory effect of SFN on programmed death-ligand 1 (PD-L1) and checkpoint blockade therapy in gastric cancer have not been elucidated. Here we demonstrated that SFN suppressed gastric cancer cell growth both in vitro and in vivo study. SFN upregulated PD-L1 expression through activating ΔNP63α in gastric cancer cells. Further, we found that SFN impaired the anticancer effect of anti-PD-L1 monoclonal antibody (α-PD-L1 mab) on gastric cancer cells. These results uncover a novel PD-L1 regulatory mechanism and the double-edged role of SFN in gastric cancer intervention.


Asunto(s)
Antígeno B7-H1 , Inhibidores de Puntos de Control Inmunológico , Isotiocianatos , Neoplasias Gástricas , Sulfóxidos , Factores de Transcripción , Isotiocianatos/farmacología , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , Antígeno B7-H1/metabolismo , Sulfóxidos/farmacología , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Animales , Ratones , Línea Celular Tumoral , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/metabolismo , Proteínas Supresoras de Tumor/genética , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Desnudos
4.
Artículo en Inglés | MEDLINE | ID: mdl-38607219

RESUMEN

Background: Ropivacaine (Ropi) is a widely utilized anesthetic in cesarean sections (CS), however its optimal dosage remains controversial. Objective: To assess the efficacy and safety of varying doses (10mg, 5mg, 4mg, and 3mg) of Ropi in subarachnoid block (SA) for CS. Methods: A prospective cohort study was conducted, and a total of 74 pregnant women undergoing CS at Nantong Maternal and Child Health Care Hospital between January and June 2023 were selected as the study population. Participants were stratified into groups based on Ropivacaine dosage: Group A (10 mg, n=18), Group B (5 mg, n=26), Group C (4 mg, n=15), and Group D (3 mg, n=15). The total Ropivacaine dosage administered via SA was consistently 10 mg across all groups. We measured anesthetic efficacy, safety profiles, abdominal wall muscle relaxation, pre- and post-anesthesia stress and inflammatory responses before and after anesthesia and compared among the four groups. Results: Group A exhibited the shortest onset time for block initiation and longest recovery duration (P < .05). Group D displayed the highest incidence of patients requiring additional anesthetics and experiencing adverse reactions, whereas the utilization rate of vasopressors was most pronounced in Group A (P < .05). Notably, Group D reported the lowest satisfaction rate regarding abdominal wall muscle relaxation (P < .05). Stress responses were significantly lower in Groups A, B, and C compared to Group D, while the levels of inflammatory factors in Groups B and C were higher than those in Group A but lower than those in Group D (P < .05). Conclusions: Administration of 4 mg hyperbaric Ropi in SA can achieve an optimal anesthesia effect in CS with a high level of safety, along with inducing mild abdominal wall muscle relaxation and attenuating stress and inflammatory responses pre- and post-anesthesia. Thus, it is recommended for clinical application.

5.
Chem Biodivers ; 21(3): e202400017, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38321767

RESUMEN

Three undescribed isosteroidal alkaloids, przewalskines A-C (1-3), as well as seven known alkaloids (4-10) were obtained from Fritillaria przewalskii bulbs. Their structures were deduced by extensive HRESIMS, 1D NMR, and 2D NMR analyses, and their bioactivities were evaluated involving the anti-inflammatory and inhibitory potencies on AChE, BChE, and Aß aggregation. Compound 4 revealed the potent effect on inhibiting Aß aggregation activity with IC50 value of 33.1 µM, AChE activity with IC50 value of 6.9 µM, and also showed NO release inhibitory acitivity with IC50 value of 32.6 µM. These findings contribute new multi-.target anti-AD agents and embody the chemical diversity of F. przewalskii.


Asunto(s)
Alcaloides , Fritillaria , Fritillaria/química , Alcaloides/farmacología , Alcaloides/química
6.
Sensors (Basel) ; 24(4)2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38400355

RESUMEN

The frequent occurrence of extreme climate events has a significant impact on people's lives. Heavy rainfall can lead to an increase of regional Terrestrial Water Storage (TWS), which will cause land subsidence due to the influence of hydrological load. At present, regional TWS is mostly obtained from Gravity Recovery and Climate Experiment (GRACE) data, but the method has limitations for small areas. This paper used water level and flow data as hydrological signals to study the land subsidence caused by heavy rainfall in the Chaohu Lake area of East China (June 2016-August 2016). Pearson's correlation coefficient was used to study the interconnection between water resource changes and Global Navigation Satellites System (GNSS) vertical displacement. Meanwhile, to address the reliability of the research results, combined with the Coefficient of determination method, the research findings were validated by using different institutional models. The results showed that: (1) During heavy rainfall, the vertical displacement caused by atmospheric load was larger than non-tidal oceanic load, and the influence trends of the two were opposite. (2) The rapidly increasing hydrologic load in the Chaohu Lake area resulted in greater subsidence displacement at the closer CORS station (CHCH station) than the more distant CORS station (LALA station). The Pearson correlation coefficients between the vertical displacement and water level were as high as -0.80 and -0.64, respectively. The phenomenon confirmed the elastic deformation principle of disc load. (3) Although there was a systematic bias between the different environmental load deformation models, the deformation trends were generally consistent with the GNSS monitoring results. The average Coefficients of determination between the different models and the GNSS results were 0.63 and 0.77, respectively. The results demonstrated the effectiveness of GNSS in monitoring short-term hydrological load. This study reveals the spatial-temporal evolution of land deformation during heavy rainfall around Chaohu Lake, which is of reference significance for water resource management and infrastructure maintenance in this area.

7.
Int J Mol Sci ; 24(13)2023 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-37445854

RESUMEN

Dried distiller's grains with solubles (DDGS) are rich in nutrients and can enhance animals' growth and immunity. However, there are few reports on the effects of a diet of DDGS on plasma metabolism and the related action pathways in domestic animals. In this study, groups of Guanling yellow cattle (GY) and Guanling crossbred cattle (GC) having a basal diet served as the control groups (GY-CG and GC-CG), and DDGS replacing 25% of the diet of GY and GC served as the replacement groups (GY-RG and GC-RG), with three cattle in each group. Plasma samples were prepared for metabolomic analysis. Based on multivariate statistical and univariate analyses, differential metabolites and metabolic pathways were explored. Twenty-nine significantly different metabolites (p < 0.05) were screened in GY-RG compared with those in GY-CG and were found to be enriched in the metabolic pathways, including choline metabolism in cancer, linolenic acid metabolism, and amino acid metabolism. Nine metabolites showed significant differences (p < 0.05) between GC-RG and GC-CG and were mainly distributed in the metabolic pathways of choline metabolism in cancer, glycerophospholipid metabolism, prostate cancer metabolism, and gonadotropin-releasing hormone (GnRH) secretion. These results suggest that a DDGS diet may promote healthy growth and development of experimental cattle by modulating these metabolic pathways. Our findings not only shed light on the nutritional effects of the DDGS diet and its underlying mechanisms related to metabolism but also provide scientific reference for the feed utilization of DDGS.


Asunto(s)
Alimentación Animal , Fitomejoramiento , Masculino , Bovinos , Animales , Alimentación Animal/análisis , Dieta/veterinaria , Animales Domésticos , Colina , Zea mays/química , Fenómenos Fisiológicos Nutricionales de los Animales , Grano Comestible/química
8.
Gut ; 70(12): 2261-2272, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33441378

RESUMEN

OBJECTIVE: As a canonical membrane tethering factor, the function of synbindin has been expanding and indicated in immune response. Here, we investigated the role of synbindin in the regulation of toll-like receptor 4 (TLR4) signalling and macrophage response to microbiota during colitis. DESIGN: Three distinct mouse models allowing global, myeloid-specific or intestinal epithelial cell-specific synbindin heterozygous deletion were constructed and applied to reveal the function of synbindin during dextran sodium sulfate (DSS) colitis. Effects of synbindin on TLR4 signalling and macrophage activation in response to bacterial lipopolysaccharide (LPS) or Fusobacterium nucleatum were evaluated. The colocalisation and interaction between synbindin and Rab7b were determined by immunofluorescence and coimmunoprecipitation. Synbindin expression in circulating monocytes and intestinal mucosal macrophages of patients with active IBD was detected. RESULTS: Global synbindin haploinsufficiency greatly exacerbated DSS-induced intestinal inflammation. The increased susceptibility to DSS was abolished by gut microbiota depletion, while phenocopied by specific synbindin heterozygous deletion in myeloid cells rather than intestinal epithelial cells. Profoundly aberrant proinflammatory gene signatures and excessive TLR4 signalling were observed in macrophages with synbindin interference in response to bacterial LPS or Fusobacterium nucleatum. Synbindin was significantly increased in intestinal mucosal macrophages and circulating monocytes from both mice with DSS colitis and patients with active IBD. Interleukin 23 and granulocyte-macrophage colony-stimulating factor were identified to induce synbindin expression. Mechanistic characterisation indicated that synbindin colocalised and directly interacted with Rab7b, which coordinated the endosomal degradation pathway of TLR4 for signalling termination. CONCLUSION: Synbindin was a key regulator of TLR4 signalling and restrained the proinflammatory macrophage activation against microbiota during colitis.


Asunto(s)
Colitis/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Activación de Macrófagos/efectos de los fármacos , Proteínas del Tejido Nervioso/farmacología , Receptor Toll-Like 4/efectos de los fármacos , Proteínas de Transporte Vesicular/farmacología , Animales , Modelos Animales de Enfermedad , Humanos , Ratones , Transducción de Señal , Proteínas de Unión a GTP rab7/efectos de los fármacos
9.
Dig Dis Sci ; 66(5): 1658-1668, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-32524415

RESUMEN

BACKGROUND AND AIMS: Information concerning deep radiological healing of perianal fistulas in Chinese patients with CD is limited. The present study aimed to establish the effectiveness of infliximab on CD-related perianal fistulas using magnetic resonance imaging (MRI) and identify predictors of deep radiological remission of fistulas. METHODS: We retrospectively reviewed patients with CD with draining perianal fistulas treated with infliximab and included only those who underwent clinical assessment and MRI before and after infliximab therapy. RESULTS: Among 178 patients who underwent repeated MRI and clinical assessment, 65.2% had complex fistulas. Post-infliximab therapy, 55.1% of patients with perianal fistulizing CD showed clinical remission and 26.4% presented a clinical response; 38.2% had deep radiological remission, and 34.3% had a partial response based on the Ng score; the Van Assche scores decreased obviously compared with baseline. Prolonged infliximab infusion (18 times) presented higher radiological remission rates in patients with CD with complex fistulas. Concomitant treatment with azathioprine increased the fistula healing rate compared with infliximab alone (50% vs. 36.9%, P < 0.001). Younger age at diagnosis of CD, proctitis and requiring perianal surgery were identified as predictors of poor deep radiological remission of fistulas. Eight of ten patients who stopped infliximab and switched to an alternative agent retained a status of fistula healing in the first year of follow-up. CONCLUSIONS: Infliximab induced deep radiological remission of perianal fistulas in Chinese patients with CD. Routine MRI should be used to monitor fistula healing. Patients with younger age at diagnosis of CD, proctitis, and/or requiring perianal surgery should receive combined therapy and careful monitoring.


Asunto(s)
Enfermedad de Crohn/tratamiento farmacológico , Infliximab/uso terapéutico , Imagen por Resonancia Magnética , Fístula Rectal/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos , Adulto , Factores de Edad , China , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico por imagen , Femenino , Humanos , Infliximab/efectos adversos , Masculino , Valor Predictivo de las Pruebas , Fístula Rectal/diagnóstico por imagen , Fístula Rectal/etiología , Inducción de Remisión , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Adulto Joven
10.
J Sci Food Agric ; 101(5): 1901-1909, 2021 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-32895910

RESUMEN

BACKGROUND: Fusarium head blight (FHB) is one of the disasters that seriously harm wheat and other small grain crops. It causes spoilage and mildew of the grain leading to a significant decline in the yield and quality of the grain. This research aimed to isolate antagonistic bacteria to purify antifungal proteins. A strain was isolated from the rhizosphere of healthy wheat in a wheat field affected by a severe FHB epidemic. This isolated strain was tentatively identified as Paenibacillus polymyxa 7F1, which displayed a strong inhibitory effect against several other pathogens. One novel antifungal protein was purified from the P. polymyxa 7F1 and successfully expressed. RESULTS: A crude culture of P. polymyxa 7F1 demonstrated antifungal activity that was stable at a temperature range of 60-90 °C and a pH range of 2.6-9.0. However, the antifungal activity of the P. polymyxa 7F1 was inhibited with proteinase K, trypsin, and neutral protease treatment. A 36 kDa protein with broad-spectrum antifungal activity was purified from the P. polymyxa 7F1. A glycosyl hydrolase domain was identified from this protein through liquid chromatography-mass spectrometry (LC-MS) analysis. A recombinant plasmid pET32a(+)/36kd for prokaryotic expression was constructed, and the renatured p36kd protein demonstrated similar antifungal activity to the 36 kDa protein purified from the P. polymyxa 7F1. CONCLUSION: A novel antifungal protein produced by P. polymyxa 7F1 was purified and expressed. The recombinant protein showed good antifungal activity as the novel purified protein. The novel antifungal protein provides an effective way to control the Fusarium head blight. © 2020 Society of Chemical Industry.


Asunto(s)
Fungicidas Industriales/farmacología , Paenibacillus polymyxa/química , Paenibacillus polymyxa/metabolismo , Triticum/crecimiento & desarrollo , Fungicidas Industriales/química , Fungicidas Industriales/aislamiento & purificación , Fungicidas Industriales/metabolismo , Fusarium/efectos de los fármacos , Fusarium/fisiología , Paenibacillus polymyxa/genética , Paenibacillus polymyxa/aislamiento & purificación , Enfermedades de las Plantas/microbiología , Rizosfera , Microbiología del Suelo
11.
J Food Sci Technol ; 58(6): 2258-2264, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33967322

RESUMEN

The objective of this study was to evaluate relationship with aggregation, secondary structures and gel properties of pork myofibrillar protein with different sodium chloride (1%, 2% and 3%). When the sodium chloride increased from 1 to 3%, the active sulfhydryl, surface hydrophobicity, hardness and cooking yield of myofibrillar protein were increased significantly (p < 0.05), the particle size, total sulfhydryl and Zeta potential were decreased significantly (p < 0.05), these meant the aggregations of pork myofibrillar protein were decreased. The changes of proteins aggregation induced the strongest intensity band of Amide I shifted up from 1660 cm-1 to 1661 cm-1, meanwhile, the ß-sheet structure content was increased significantly (p < 0.05) with the sodium chloride increased. From the above, the lower proteins aggregation and higher ß-sheet structure content could improve the water holding capacity and texture of pork myofibrillar protein gel.

12.
J Neuroinflammation ; 17(1): 18, 2020 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-31926553

RESUMEN

BACKGROUND: Microglial activation is a prominent feature of neuroinflammation, which is present in almost all neurodegenerative diseases. While an initial inflammatory response mediated by microglia is considered to be protective, excessive pro-inflammatory response of microglia contributes to the pathogenesis of neurodegeneration. Although autophagy is involved in the suppression of inflammation, its role and mechanism in microglia are unclear. METHODS: In the present study, we studied the mechanism by which lipopolysaccharide (LPS) affects microglial autophagy and the effects of autophagy on the production of pro-inflammatory factors in microglial cells by western blotting, immunocytochemistry, transfection, transmission electron microscopy (TEM), and real-time PCR. In a mouse model of neuroinflammation, generated by intraventricular injection of LPS (5 µg/animal), we induced autophagy by rapamycin injection and investigated the effects of enhanced autophagy on microglial activation by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. RESULTS: We found that autophagic flux was suppressed in LPS-stimulated N9 microglial cells, as evidenced by decreased expression of the autophagy marker LC3-II (lipidated form of MAP1LC3), as well as increased levels of the autophagy adaptor protein SQSTM1. LPS significantly decreased Vps34 expression in N9 microglial cells by activating the PI3KI/AKT/MTOR pathway without affecting the levels of lysosome-associated proteins and enzymes. More importantly, overexpression of Vps34 significantly enhanced the autophagic flux and decreased the accumulation of SQSTM1 in LPS-stimulated N9 microglial cells. Moreover, our results revealed that an LPS-induced reduction in the level of Vps34 prevented the maturation of omegasomes to phagophores. Furthermore, LPS-induced neuroinflammation was significantly ameliorated by treatment with the autophagy inducer rapamycin both in vitro and in vivo. CONCLUSIONS: These data reveal that LPS-induced neuroinflammation in N9 microglial cells is associated with the inhibition of autophagic flux through the activation of the PI3KI/AKT/MTOR pathway, while enhanced microglial autophagy downregulates LPS-induced neuroinflammation. Thus, this study suggests that promoting the early stages of autophagy might be a potential therapeutic approach for neuroinflammation-associated diseases.


Asunto(s)
Autofagosomas/inmunología , Fosfatidilinositol 3-Quinasas Clase III/metabolismo , Inflamación/inmunología , Microglía/inmunología , Serina-Treonina Quinasas TOR/metabolismo , Animales , Autofagosomas/efectos de los fármacos , Autofagia/efectos de los fármacos , Autofagia/inmunología , Línea Celular , Fosfatidilinositol 3-Quinasas Clase III/inmunología , Regulación hacia Abajo , Inflamación/inducido químicamente , Inflamación/metabolismo , Lipopolisacáridos/toxicidad , Masculino , Ratones , Ratones Endogámicos C57BL , Microglía/efectos de los fármacos , Microglía/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Serina-Treonina Quinasas TOR/inmunología
13.
BMC Gastroenterol ; 20(1): 421, 2020 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-33308166

RESUMEN

BACKGROUND: Clinicians aim to prevent progression of Crohn's disease (CD); however, many patients require surgical resection because of cumulative bowel damage. The aim of this study was to evaluate the impact of early intervention on bowel damage in patients with CD using the Lémann Index and to identify bowel resection predictors. METHODS: We analyzed consecutive patients with CD retrospectively. The Lémann Index was determined at the point of inclusion and at follow-up termination. The Paris definition was used to subdivide patients into early and late CD groups. RESULTS: We included 154 patients, comprising 70 with early CD and 84 with late CD. After follow-up for 17.0 months, more patients experienced a decrease in the Lémann Index (61.4% vs. 42.9%), and fewer patients showed an increase in the Lémann Index (20% vs. 35.7%) in the early compared with the late CD group. Infliximab and other therapies reversed bowel damage to a greater extent in early CD patients than in late CD patients. Twenty-two patients underwent intestinal surgery, involving 5 patients in the early CD group and 17 patients in the late CD group. Three independent predictors of bowel resection were identified: baseline Lémann index ≥ 8.99, disease behavior B1, and history of intestinal surgery. CONCLUSIONS: Early intervention within 18 months after CD diagnosis could reverse bowel damage and decrease short-term intestinal resection. Patients with CD with a history of intestinal surgery, and/or a Lémann index > 8.99 should be treated aggressively and monitored carefully to prevent progressive bowel damage.


Asunto(s)
Enfermedad de Crohn , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/cirugía , Humanos , Infliximab , Intestinos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
14.
Phytother Res ; 34(4): 817-824, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31782192

RESUMEN

Cancer stem cells (CSCs) are considered as the origin and driving cells of cancer, and play a key role in the progress of cancer. Studies have shown that capsaicin exerted inhibitory effect on prostate cancer cells, however, the effects of capsaicin on prostate CSCs remain undefined. In the present study, we showed that capsaicin could downregulate prostate CSCs markers and inhibit the growth of PC-3 and DU145 prostate cancer stem cells. Further, we found capsaicin suppressed the expression of Wnt-2, p-GSK3ß and ß-catenin, along with downregulation of Wnt/ß-catenin pathway target genes c-myc and cyclinD1. Using LiCl, a activator of Wnt/ß-catenin pathway, we found activation of Wnt/ß-catenin pathway could ameliorate the downregulation of prostate CSCs markers and the growth inhibition induced by capsaicin in prostate cancer stem cells. Those data suggested that the inhibition effect of capsaicin on prostate cancer stem cells and the anti-cancer effect of capsaicin on prostate cancer stem cell may be mediated by Wnt/ß-catenin pathway. Findings from this study reveals for the first time the potential role and mechanisms of capsaicin on prostate cancer stem cells.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Capsaicina/farmacología , Células Madre Neoplásicas/efectos de los fármacos , Neoplasias de la Próstata/patología , Vía de Señalización Wnt/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/fisiología , Células PC-3 , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Células Tumorales Cultivadas , Vía de Señalización Wnt/genética , beta Catenina/efectos de los fármacos , beta Catenina/metabolismo
15.
J Cell Biochem ; 120(9): 15616-15624, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31042325

RESUMEN

Curcumin is a phytochemical which exhibits significant inhibitory effect in multiple cancers including prostate cancer. MicroRNA-34a (miR-34a) was found to be a master tumor suppressor miRNA and regulated the growth of cancer cells. To date, however, the role of miR-34a in the anticancer action of curcumin against prostate cancer has been rarely reported. In the present study, we showed that curcumin altered the expression of cell cycle-related genes (cyclin D1, PCNA, and p21) and inhibited the proliferation of prostate cancer cells. Furthermore, we found that curcumin significantly upregulated the expression of miR-34a, along with the downregulated expression of ß-catenin and c-myc in three prostate cancer cell lines. Inhibition of miR-34a activated ß-catenin/c-myc axis, altered cell cycle-related genes expression and significantly suppressed the antiproliferation effect of curcumin in prostate cancer cells. Findings from this study revealed that miR-34a plays an important role in the antiproliferation effect of curcumin in prostate cancer.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Curcumina/farmacología , MicroARNs/genética , Neoplasias de la Próstata/tratamiento farmacológico , Animales , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones , Próstata/efectos de los fármacos , Próstata/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Ensayos Antitumor por Modelo de Xenoinjerto
16.
J Neuroinflammation ; 16(1): 188, 2019 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-31623610

RESUMEN

BACKGROUND: The glial response in multiple sclerosis (MS), especially for recruitment and differentiation of oligodendrocyte progenitor cells (OPCs), predicts the success of remyelination of MS plaques and return of function. As a central player in neuroinflammation, activation and polarization of microglia/macrophages (M/M) that modulate the inflammatory niche and cytokine components in demyelination lesions may impact the OPC response and progression of demyelination and remyelination. However, the dynamic behaviors of M/M and OPCs during demyelination and spontaneous remyelination are poorly understood, and the complex role of neuroinflammation in the demyelination-remyelination process is not well known. In this study, we utilized two focal demyelination models with different dynamic patterns of M/M to investigate the correlation between M/M polarization and the demyelination-remyelination process. METHODS: The temporal and spatial features of M/M activation/polarization and OPC response in two focal demyelination models induced by lysolecithin (LPC) and lipopolysaccharide (LPS) were examined in mice. Detailed discrimination of morphology, sensorimotor function, diffusion tensor imaging (DTI), inflammation-relevant cytokines, and glial responses between these two models were analyzed at different phases. RESULTS: The results show that LPC and LPS induced distinctive temporal and spatial lesion patterns. LPS produced diffuse demyelination lesions, with a delayed peak of demyelination and functional decline compared to LPC. Oligodendrocytes, astrocytes, and M/M were scattered throughout the LPS-induced demyelination lesions but were distributed in a layer-like pattern throughout the LPC-induced lesion. The specific M/M polarization was tightly correlated to the lesion pattern associated with balance beam function. CONCLUSIONS: This study elaborated on the spatial and temporal features of neuroinflammation mediators and glial response during the demyelination-remyelination processes in two focal demyelination models. Specific M/M polarization is highly correlated to the demyelination-remyelination process probably via modulations of the inflammatory niche, cytokine components, and OPC response. These findings not only provide a basis for understanding the complex and dynamic glial phenotypes and behaviors but also reveal potential targets to promote/inhibit certain M/M phenotypes at the appropriate time for efficient remyelination.


Asunto(s)
Enfermedades Desmielinizantes/diagnóstico por imagen , Enfermedades Desmielinizantes/metabolismo , Macrófagos/metabolismo , Microglía/metabolismo , Animales , Femenino , Fuerza de la Mano/fisiología , Imagen por Resonancia Magnética/métodos , Ratones , Ratones Endogámicos C57BL
17.
Phys Chem Chem Phys ; 21(27): 15089-15096, 2019 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-31241078

RESUMEN

In2S3, having a suitable bandgap and tunable magnetism, is a promising material for spintronic applications. Herein, we report that pristine In2S3 and In2S3:Gd3+ nanoparticles, with room temperature ferromagnetism, were synthesized by a gas-liquid phase chemical deposition method. The bandgap value, photoluminescence (PL) intensity and magnetic properties of In2S3:Gd3+ nanoparticles can be tuned by regulating the Gd3+ dopant concentration. In addition, the measured saturation magnetization in undoped In2S3 nanoparticles is 0.011 emu g-1 and the maximum saturation magnetization observed in In2S3:Gd3+ nanoparticles is 0.035 emu g-1; the corresponding magnetic mechanism is explicated based on bound-magnetic-polaron (BMP) theory. First-principles DFT calculations reveal that In vacancy and Gd3+ ion doping can induce intrinsic ferromagnetism. Finally, the results obtained from experiment and theory suggest the potential of Gd-doped In2S3 for application in spintronic devices.

18.
Int Ophthalmol ; 39(2): 419-429, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29392638

RESUMEN

PURPOSE: To observe the long-term changes in dry eye symptoms and vision-related quality of life in age-related cataract patients after phacoemulsification. METHODS: A total of 101 cataract patients after phacoemulsification combined with IOL implantation (Ph-IOL) in one eye were enrolled. Visual acuity, tear film breakup time (BUT), and Schirmer test 1 (ST1) were measured before and 1, 3, and 6 months after surgery. Ocular Surface Disease Index (OSDI) scores were used to evaluate the severity of dry eye symptoms. Utility values were assessed by the time trade-off (TTO), standard gamble for death (SGD), standard gamble for blindness (SGB) and rating scale (RS). RESULTS: The average LogMAR visual acuity in the operated eye was 1.35 ± 0.50 and increased rapidly after Ph-IOL, approaching a peak at 3 months (0.26 ± 0.15). The BUT and ST1 results decreased abruptly 1 month after surgery and gradually recovered until 6 months. OSDI scores increased significantly after surgery and gradually decreased until 6 months. Utility values evaluated by TTO, SGD, SGB and RS before surgery were 0.67 ± 0.19, 0.75 ± 0.15, 0.67 ± 0.20 and 0.2 ± 0.18, respectively, and increased to 0.91 ± 0.06, 0.98 ± 0.04, 0.92 ± 0.52 and 0.91 ± 0.06, 6 months after. Utility values measured with TTO, SGB or RS correlated significantly (P < 0.05) with visual acuity and OSDI scores pre- and postoperatively. CONCLUSIONS: Dry eye symptoms persist more than 3 months after Ph-IOL. Utility values were negatively influenced by dry eye symptoms.


Asunto(s)
Síndromes de Ojo Seco/etiología , Facoemulsificación/efectos adversos , Complicaciones Posoperatorias/etiología , Calidad de Vida , Agudeza Visual , Adulto , Anciano , Anciano de 80 o más Años , China/epidemiología , Síndromes de Ojo Seco/epidemiología , Síndromes de Ojo Seco/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/fisiopatología , Estudios Prospectivos , Encuestas y Cuestionarios , Factores de Tiempo
19.
Sensors (Basel) ; 18(10)2018 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-30360433

RESUMEN

Images captured by sensors in unpleasant environment like low illumination condition are usually degraded, which means low visibility, low brightness, and low contrast. In order to improve this kind of images, in this paper, a low-light sensor image enhancement algorithm based on HSI color model is proposed. At first, we propose a dataset generation method based on the Retinex model to overcome the shortage of sample data. Then, the original low-light image is transformed from RGB to HSI color space. The segmentation exponential method is used to process the saturation (S) and the specially designed Deep Convolutional Neural Network is applied to enhance the intensity component (I). At the end, we back into the original RGB space to get the final improved image. Experimental results show that the proposed algorithm not only enhances the image brightness and contrast significantly, but also avoids color distortion and over-enhancement in comparison with some other state-of-the-art research papers. So, it effectively improves the quality of sensor images.

20.
Sensors (Basel) ; 18(8)2018 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-30081575

RESUMEN

Contour is a very important feature in biological visual cognition and has been extensively investigated as a fundamental vision problem. In connection with the limitations of conventional models in detecting image contours in complex scenes, a hierarchical image contour extraction method is proposed based on the biological vision mechanism that draws on the perceptual characteristics of the early vision for features such as edges, shapes, and colours. By simulating the information processing mechanisms of the cells' receptive fields in the early stages of the biological visual system, we put forward a computational model that combines feedforward, lateral, and feedback neural connections to decode and obtain the image contours. Our model simulations and their results show that the established hierarchical contour detection model can adequately fit the characteristics of the biological experiment, quickly and effectively detect the salient contours in complex scenes, and better suppress the unwanted textures.


Asunto(s)
Biomimética , Percepción de Forma , Modelos Neurológicos , Retroalimentación , Neuronas/fisiología , Corteza Visual/citología , Corteza Visual/fisiología
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