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1.
Mol Genet Genomics ; 299(1): 50, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38734849

RESUMEN

Intracerebral hemorrhage (ICH) is one of the major causes of death and disability, and hypertensive ICH (HICH) is the most common type of ICH. Currently, the outcomes of HICH patients remain poor after treatment, and early prognosis prediction of HICH is important. However, there are limited effective clinical treatments and biomarkers for HICH patients. Although circRNA has been widely studied in diseases, the role of plasma exosomal circRNAs in HICH remains unknown. The present study was conducted to investigate the characteristics and function of plasma exosomal circRNAs in six HICH patients using circRNA microarray and bioinformatics analysis. The results showed that there were 499 differentially expressed exosomal circRNAs between the HICH patients and control subjects. According to GO annotation and KEGG pathway analyses, the targets regulated by differentially expressed exosomal circRNAs were tightly related to the development of HICH via nerve/neuronal growth, neuroinflammation and endothelial homeostasis. And the differentially expressed exosomal circRNAs could mainly bind to four RNA-binding proteins (EIF4A3, FMRP, AGO2 and HUR). Moreover, of differentially expressed exosomal circRNAs, hsa_circ_00054843, hsa_circ_0010493 and hsa_circ_00090516 were significantly associated with bleeding volume and Glasgow Coma Scale score of the subjects. Our findings firstly revealed that the plasma exosomal circRNAs are significantly involved in the progression of HICH, and could be potent biomarkers for HICH. This provides the basis for further research to pinpoint the best biomarkers and illustrate the mechanism of exosomal circRNAs in HICH.


Asunto(s)
Exosomas , ARN Circular , Humanos , ARN Circular/genética , ARN Circular/sangre , Exosomas/genética , Exosomas/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Anciano , Hemorragia Intracraneal Hipertensiva/genética , Hemorragia Intracraneal Hipertensiva/sangre , Biomarcadores/sangre , Biología Computacional/métodos , Perfilación de la Expresión Génica , Hemorragia Cerebral/genética , Hemorragia Cerebral/sangre , Redes Reguladoras de Genes
2.
Small ; 20(16): e2304318, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38018305

RESUMEN

The long-term inflammatory microenvironment is one of the main obstacles to inhibit acute spinal cord injury (SCI) repair. The natural adipose tissue-derived extracellular matrix hydrogel shows effective anti-inflammatory regulation because of its unique protein components. However, the rapid degradation rate and removal of functional proteins during the decellularization process impair the lasting anti-inflammation function of the adipose tissue-derived hydrogel. To address this problem, adipose tissue lysate provides an effective way for SCI repair due to its abundance of anti-inflammatory and nerve regeneration-related proteins. Thereby, human adipose tissue lysate-based hydrogel (HATLH) with an appropriate degradation rate is developed, which aims to in situ long-term recruit and induce anti-inflammatory M2 macrophages through sustainedly released proteins. HATLH can recruit and polarize M2 macrophages while inhibiting pro-inflammatory M1 macrophages regardless of human or mouse-originated. The axonal growth of neuronal cells also can be effectively improved by HATLH and HATLH-induced M2 macrophages. In vivo experiments reveal that HATLH promotes endogenous M2 macrophages infiltration in large numbers (3.5 × 105/100 µL hydrogel) and maintains a long duration for over a month. In a mouse SCI model, HATLH significantly inhibits local inflammatory response, improves neuron and oligodendrocyte differentiation, enhances axonal growth and remyelination, as well as accelerates neurological function restoration.


Asunto(s)
Hidrogeles , Traumatismos de la Médula Espinal , Humanos , Ratones , Animales , Hidrogeles/farmacología , Traumatismos de la Médula Espinal/tratamiento farmacológico , Neuronas/metabolismo , Macrófagos/metabolismo , Antiinflamatorios/uso terapéutico
3.
J Bioenerg Biomembr ; 56(3): 261-271, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38421527

RESUMEN

Downregulation of circ_0044226 has been demonstrated to reduce pulmonary fibrosis, but the role of circ_0044226 in liver fibrosis remains to be explored. In this work, we found that circ_0044226 expression was upregulated during liver fibrosis. Knockdown of circ_0044226 inhibited proliferation, promoted autophagy and apoptosis of hepatic stellate cell LX-2. Bioinformatic analysis and dual luciferase reporter assays confirmed the interaction between circ_0044226, miR-4677-3p and SEC61G. Mechanistically, knockdown of circ_0044226 suppressed SEC61G expression by releasing miR-4677-3p, thereby enhancing endoplasmic reticulum stress. Overexpression of SEC61G or endoplasmic reticulum stress inhibitor 4-phenylbutiric acid partially reversed the effect of knockdown circ_0044226 on LX-2 cell function. In vivo experiments showed that inhibition of circ_0044226 attenuated CCL4-induced liver fibrosis in mice. These imply that circ_0044226 may be a potential target for the treatment of liver fibrosis.


Asunto(s)
Apoptosis , Autofagia , Estrés del Retículo Endoplásmico , Células Estrelladas Hepáticas , MicroARNs , ARN Circular , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Autofagia/fisiología , MicroARNs/metabolismo , MicroARNs/genética , Animales , Ratones , ARN Circular/genética , ARN Circular/metabolismo , Humanos , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Cirrosis Hepática/genética , Masculino
4.
J Nanobiotechnology ; 22(1): 201, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38659058

RESUMEN

The utilization of extracellular vesicles (EV) in immunotherapy, aiming at suppressing peripheral immune cells responsible for inflammation, has demonstrated significant efficacy in treating various inflammatory diseases. However, the clinical application of EV has faced challenges due to their inadequate targeting ability. In addition, most of the circulating EV would be cleared by the liver, resulting in a short biological half-life after systemic administration. Inspired by the natural microvesicles (MV, as a subset of large size EV) are originated and shed from the plasma membrane, we developed the immunosuppressive MV-mimetic (MVM) from endotoxin tolerant dendritic cells (DC) by a straightforward and effective extrusion approach, in which DC surface proteins were inherited for providing the homing ability to the spleen, while αCD3 antibodies were conjugated to the MVM membranes for specific targeting of T cells. The engineered MVM carried a large number of bioactive cargos from the parental cells, which exhibited a remarkable ability to promote the induction of regulatory T cells (Treg) and polarization of anti-inflammatory M2 macrophages. Mechanistically, the elevated Treg level by MVM was mediated due to the upregulation of miR-155-3p. Furthermore, it was observed that systemic and local immunosuppression was induced by MVM in models of sepsis and rheumatoid arthritis through the improvement of Treg and M2 macrophages. These findings reveal a promising cell-free strategy for managing inflammatory responses to infections or tissue injury, thereby maintaining immune homeostasis.


Asunto(s)
Micropartículas Derivadas de Células , Células Dendríticas , Inflamación , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Animales , Ratones , Inflamación/tratamiento farmacológico , Micropartículas Derivadas de Células/metabolismo , Ratones Endogámicos C57BL , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Vesículas Extracelulares , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/inmunología , Sepsis/inmunología , Sepsis/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inmunología , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Humanos , Inmunoterapia/métodos
5.
Angew Chem Int Ed Engl ; 63(28): e202404329, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38683742

RESUMEN

A hitherto unknown class of C4-symmetric Caryl-Cß (C3, C8, C13, C18) axially chiral porphyrins has been synthesized and the application of their iridium (Ir) complexes in catalytic asymmetric C(sp3)-H functionalization is documented. Cyclotetramerization of enantioenriched axially chiral 2-hydroxymethyl-3-naphthyl pyrroles under mild acidic conditions affords, after oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), the C4-symmetric α,α,α,α-atropenantiomer as an only isolable diastereomer. Both regioisomeric Ir(Por*)(CO)(Cl) complexes catalyze the carbene C-H insertion reaction affording the same enantiomer, albeit with slight difference in enantioselectivity. With the optimum Ir-complex 3 e, the 2-substituted arylacetic acid derivatives were generated from diazo compounds and cyclohexadiene in excellent yields and enantioselectivities.

6.
Microb Pathog ; 174: 105937, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36496058

RESUMEN

Helicobacter pylori (H. pylori), a gram-negative bacterial microbiological carcinogen, has been identified as the leading jeopardy feature for developing human gastric cancer (GC). As a result, inhibiting H. pylori growth has been identified as an effective and critical technique for preventing GC development. In this study, geraniol inhibits H. pylori-induced gastric carcinogen signalling in human gastric epithelial cells (GES-1). Geraniol prevents cytotoxicity, ROS and apoptosis in H. pylori-induced GES-1 cells. Furthermore, geraniol protects against H. -induced antioxidant depletion caused by malondialdehyde, damage of reactive DNA and nuclear fragmentation. Geraniol significantly reduced the expression of phosphorylated mitogen activated protein kinases (MAPKs) proteins such as p38 MAPK, extracellular signal-regulated kinase-1 (ERK1), c-Jun N-terminal kinase (c-JNK), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2) in GES-1 infected with H. pylori. Furthermore, geraniol increased the antioxidant protein peroxiredoxin-1 (Prdx-1) in H. pylori-infected cells. Geraniol thus protects H. pylori-concomitant infection, and its resistance may be a possible method in preventing gastric cancer caused by H. pylori.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Antioxidantes/farmacología , Antioxidantes/metabolismo , Carcinógenos/metabolismo , Carcinógenos/farmacología , Células Epiteliales , Mucosa Gástrica/patología , Infecciones por Helicobacter/microbiología , Neoplasias Gástricas/patología
7.
BMC Cardiovasc Disord ; 23(1): 617, 2023 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-38097977

RESUMEN

BACKGROUND: To analyze the association of serum Asprosin concentrations with heart failure (HF). METHODS: A total of 103 patients with HF were included in the HF group, and 103 patients with health checkups were included in the non-HF group. The serum Asprosin levels of the two groups were measured, and relevant clinical data were collected for statistical analysis. RESULTS: Compared with the non-HF group, the serum Asprosin concentration was significantly higher in the HF group, and the difference was statistically significant (P < 0.001). According to the serum Asprosin levels, we divided all the subjects into three quartiles. We found that the prevalence of HF increased with increasing serum Asprosin levels in the three groups (P < 0.001). Serum Asprosin levels were positively correlated with NT-ProBNP (P < 0.05) and negatively correlated with LVEF (P < 0.001). Dichotomous logistic regression analysis found Asprosin and age to be independent risk factors for HF (OR = 1.010, 95% CI: 1.003-1.018; OR = 1.058, 95% CI:1.004-1.665, respectively). Combining Asprosin and NT-proBNP indicators to draw ROC curves can improve the specificity and sensitivity of HF diagnosis. CONCLUSIONS: Serum Asprosin levels were significantly elevated in HF patients. The serum Asprosin level is an independent risk factor for HF, and the combined detection of Asprosin and NT-proBNP levels can improve the accuracy of HF diagnosis.


Asunto(s)
Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/diagnóstico , Curva ROC , Factores de Riesgo , Péptido Natriurético Encefálico , Fragmentos de Péptidos , Biomarcadores
8.
Small ; 18(24): e2200020, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35429137

RESUMEN

Luminescent Janus nanoparticles refer to a special category of Janus-based nanomaterials that not only exhibit dual-asymmetric surface nature but also attractive optical properties. The introduction of luminescence has endowed conventional Janus nanoparticles with many alluring light-responsive functionalities and broadens their applications in imaging, sensing, nanomotors, photo-based therapy, etc. The past few decades have witnessed significant achievements in this field. This review first summarizes well-established strategies to design and prepare luminescent Janus nanoparticles and then discusses optical properties of luminescent Janus nanoparticles based on downconversion and upconversion photoluminescence mechanisms. Various emerging applications of luminescent Janus nanoparticles are also introduced. Finally, opportunities and future challenges are highlighted with respect to the development of next-generation luminescent Janus nanoparticles with diverse applications.


Asunto(s)
Nanopartículas Multifuncionales , Nanopartículas , Nanoestructuras , Luminiscencia
9.
Exp Cell Res ; 405(2): 112706, 2021 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-34146541

RESUMEN

Angiopoietin like 4 (ANGPTL4) has been proved to play an important role in lipid and glucose metabolism disorders and related cardiovascular diseases, but its role in the formation of cirrhosis still needs to be further explored. Therefore, the aim of this study was to investigate the role of ANGPTL4 in the development of liver cirrhosis and its mechanism, as well as its effect on Kupffer cell polarization and hepatic stellate cell activation. The ELISA and RT-qPCR assay were used to detect the content of ANGPTL4 in serum and mRNA expression in cells and tissues respectively. The expression of ANGPTL4, Arg1 and Mrc2 in Kupffer cells was measured by Western blot. The percentage of CD163+ and CD206+ cells was measured by flow cytometry. Mice cirrhosis model was established, and the expression of ANGPTL4 was interfered by injecting sh-ANGPTL4 lentiviral vector into caudal vein. The results revealed that ANGPTL4 was significantly up-regulated in liver cirrhosis patients and HBV induced liver injury cell models. Further studies found that interference with ANGPTL4 regulated CD163 and inhibited the polarization and proinflammatory effects of KCs,as well as inhibited the activation of hepatic stellate cells (HSCs) and fibrosis. More importantly, Interference with ANGPTL4 inhibits the progression of liver cirrhosis in mice. What's more, TLR4/NF-κB pathway was involved in the molecular mechanism of ANGPTL4 on Kupffer cells and hepatic stellate cells. It is suggested that the mechanism of sh-ANGPTL4 suppressing the polarization of KCs and the activation of hepatic stellate cells (HSCs) is to regulate the TLR4/NF-κB signaling pathways.


Asunto(s)
Angiopoyetinas/metabolismo , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Macrófagos del Hígado/metabolismo , FN-kappa B/metabolismo , Receptores de Superficie Celular/metabolismo , Proteína 4 Similar a la Angiopoyetina/farmacología , Animales , Células Estrelladas Hepáticas/metabolismo , Lipopolisacáridos/farmacología , Cirrosis Hepática/patología , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismo
10.
Mikrochim Acta ; 189(3): 120, 2022 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-35201432

RESUMEN

Although upconversion photodynamic therapy (PDT) has gained extensive interests in disease treatment, the intracellular migration pathway of upconversion photosensitizers and underlying cell-particle interaction mechanism is still largely unexplored. In this work photoswitchable upconversion nanoparticles (UCNPs) are reported  that can release orthogonal emissions excited by two near-infrared lights, i.e., red color of 980-nm and green color of 808-nm light excitation. Taking advantage of the dual-emissive property, a methodology based on Pearson's correlation analysis is proposed to verify the accuracy of upconversion luminescence signals under different excitation lights, which has been previously neglected. Meanwhile, we have designed a near-infrared mediated bioimaging nanoplatform that can generate reactive oxygen species (ROS) using one light and simultaneously track the location of upconversion photosensitizers using another excitation light. Our study not only depicts the migration pathway of upconversion photosensitizers, but also demonstrates the organelle escape of these upconversion nanoparticles via PCI (photochemical internalization) process. It is believed that our results inspire more efficient synergistic therapy by combining PDT with other modalities in a programmable manner.


Asunto(s)
Nanopartículas , Intervención Coronaria Percutánea , Fotoquimioterapia , Rayos Infrarrojos , Nanopartículas/química , Fármacos Fotosensibilizantes/química
11.
Ren Fail ; 44(1): 398-406, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35225149

RESUMEN

BACKGROUND & AIMS: Acute kidney injury (AKI) is conventionally evaluated by a dynamic change of serum creatinine (Scr). Cystatin C (CysC) seems to be a more accurate biomarker for assessing kidney function. This retrospective multicenter study aims to evaluate whether AKI re-defined by CysC can predict the in-hospital outcomes of patients with liver cirrhosis and acute gastrointestinal bleeding. METHODS: Overall, 677 cirrhotic patients with acute gastrointestinal bleeding, in whom both Scr and CysC levels were detected at admissions, were screened. eGFRScr, eGFRCysC, and eGFRScr-CysC were calculated. MELD-Na score and AKI were re-evaluated by CysC instead of Scr. Odds ratios (ORs) were calculated in the logistic regression analyses. The receiver operating characteristic (ROC) curve analyses were performed. RESULTS: Univariate logistic regression analyses demonstrated that baseline Scr and CysC levels, eGFRScr, eGFRCysC, eGFRScr-CysC, original MELD-Na score defined by Scr, MELD-Na score re-defined by CysC, and AKI re-defined by CysC, but not conventional AKI defined by Scr, were significantly associated with in-hospital death. ROC analyses showed that baseline CysC level, eGFRScr, eGFRCysC, eGFRScr-CysC, original MELD-Na score defined by Scr, and MELD-Na score re-defined by CysC, but not baseline Scr level, could significantly predict the risk of in-hospital death. CONCLUSIONS: AKI re-defined by CysC may be superior for predicting the in-hospital mortality of cirrhotic patients with acute gastrointestinal bleeding.


Asunto(s)
Lesión Renal Aguda , Creatinina/sangre , Cistatina C/sangre , Hemorragia Gastrointestinal , Cirrosis Hepática/complicaciones , Lesión Renal Aguda/sangre , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Biomarcadores/sangre , China/epidemiología , Femenino , Hemorragia Gastrointestinal/sangre , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/mortalidad , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos
12.
Chem Rec ; 21(7): 1681-1696, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34145731

RESUMEN

Photopolymerization refers to a type of polymerization process in which light is utilized as excitation source to initiate polymerization of monomers and oligomers. Despite great progress, photopolymerization is typically induced by ultraviolet or visible light, which still greatly restrains its applications. Upconversion nanoparticles (UCNPs) represent a class of optical nanomaterials that are able to convert low-energy near-infrared (NIR) light into high-energy ultraviolet (or visible light) emissions. In this context, UCNP-assisted photopolymerization has recently attracted extensive attentions due to its unique advantages. In this account, recent advances in the fundamentals, optimization and emerging applications of UCNP-based photopolymerization are reviewed. Fundamental theories of upconversion luminescence and photopolymerization will be introduced first. Various optimization approaches to improve UCNP-assisted photopolymerization are then summarized, followed by diverse emerging applications. Challenges and future perspectives in this area will be provided as a conclusion.

13.
BMC Gastroenterol ; 21(1): 253, 2021 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-34098892

RESUMEN

BACKGROUND AND AIM: Hemostasis profile is often complicated in liver cirrhosis. Thromboelastography is a global viscoelastic test recommended by the current practice guideline and consensus. This cross-sectional study aimed to evaluate the association of thromboelastography profile with severity of liver cirrhosis and presence of portal venous system thrombosis (PVST). METHODS: Overall, 116 and 50 cirrhotic patients were included in the Shenyang and Xi'an cohorts, respectively. Thromboelastography parameters were compared between cirrhotic patients with Child-Pugh class A and B/C, those with and without decompensated events, and those with and without PVST. Hypercoagulability would be considered if at least two of the following thromboelastography parameters were met: shortened reactive time (R), shortened coagulation time (K), increased angle, and increased maximum amplitude (MA). RESULTS: In the Shenyang cohort, 16 patients had shortened R, of whom seven (43.75%) had prolonged K and 11 (68.75%) decreased MA. In the Xi'an cohort, 24 patients had shortened R, of whom seven (29.17%) had prolonged K and 15 (62.50%) decreased MA. In the Shenyang cohort, the prevalence of hypercoagulability was not significantly different between cirrhotic patients with Child-Pugh class A and B/C (3.85% vs. 6.25%, P = 0.873), those with and without decompensated events (5.49% vs. 4.00%, P = 1.000), and those with and without PVST (4.17% vs. 5.88%, P = 1.000), which were similar to the results obtained in the Xi'an cohort. CONCLUSION: There is a high rate of discordance between R and other thromboelastography parameters. In addition, hypercoagulability may not be related to more advanced stage of liver cirrhosis or presence of PVST.


Asunto(s)
Trombosis , Trombosis de la Vena , Estudios Transversales , Humanos , Cirrosis Hepática/complicaciones , Tromboelastografía , Trombosis/epidemiología , Trombosis de la Vena/complicaciones , Trombosis de la Vena/epidemiología
14.
Int J Mol Sci ; 23(1)2021 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-35008465

RESUMEN

Benzodiazepines (BZDs) produce versatile pharmacological actions through positive modulation of GABAA receptors (GABAARs). A previous study has demonstrated that high concentrations of diazepam potentiate GABA currents on the α1ß2γ2 and α1ß2 GABAARs in a flumazenil-insensitive manner. In this study, the high-concentration effects of BZDs and their sensitivity to flumazenil were determined on synaptic (α1ß2γ2, α2ß2γ2, α5ß2γ2) and extra-synaptic (α4ß2δ) GABAARs using the voltage-clamp electrophysiology technique. The in vivo evaluation of flumazenil-insensitive BZD effects was conducted in mice via the loss of righting reflex (LORR) test. Diazepam induced biphasic potentiation on the α1ß2γ2, α2ß2γ2 and α5ß2γ2 GABAARs, but did not affect the α4ß2δ receptor. In contrast to the nanomolar component of potentiation, the second potentiation elicited by micromolar diazepam was insensitive to flumazenil. Midazolam, clonazepam, and lorazepam at 200 µM exhibited similar flumazenil-insensitive effects on the α1ß2γ2, α2ß2γ2 and α5ß2γ2 receptors, whereas the potentiation induced by 200 µM zolpidem or triazolam was abolished by flumazenil. Both the GABAAR antagonist pentylenetetrazol and Fa173, a proposed transmembrane site antagonist, abolished the potentiation induced by 200 µM diazepam. Consistent with the in vitro results, flumazenil antagonized the zolpidem-induced LORR, but not that induced by diazepam or midazolam. Pentylenetetrazol and Fa173 antagonized the diazepam-induced LORR. These findings support the existence of non-classical BZD binding sites on certain GABAAR subtypes and indicate that the flumazenil-insensitive effects depend on the chemical structures of BZD ligands.


Asunto(s)
Benzodiazepinas/farmacología , Flumazenil/farmacología , Receptores de GABA-A/metabolismo , Animales , Animales no Consanguíneos , Clonazepam/farmacología , Diazepam/farmacología , Femenino , Antagonistas del GABA/farmacología , Masculino , Ratones , Midazolam/farmacología , Xenopus laevis/metabolismo , Ácido gamma-Aminobutírico/metabolismo
15.
Chin Med Sci J ; 36(4): 323-332, 2021 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-34986969

RESUMEN

To get an optimal product of orthopaedic implant or regenerative medicine needs to follow trial-and-error analyses to investigate suitable product's material, structure, mechanical properites etc. The whole process from in vivo tests to clinical trials is expensive and time-consuming. Computational model is seen as a useful analysis tool to make the product development. A series of models for simulating tissue engineering process from cell attachment to tissue regeneration are reviewed. The challenging is that models for simulating tissue engineering processes are developed separately. From cell to tissue regeneration, it would go through blood injection after moving out the defect; to cell disperse and attach on the scaffold; to proliferation, migration and differentiation; and to the final part-becoming mature tissues. This paper reviewed models that related to tissue engineering process, aiming to provide an opportunity for researchers to develop a mature model for whole tissue engineering process. This article focuses on the model analysis methods of cell adhesion, nutrient transport and cell proliferation, differentiation and migration in tissue engineering. In cell adhesion model, one of the most accurate method is to use discrete phase model to govern cell movement and use Stanton-Rutland model for simulating cell attachment. As for nutrient transport model, numerical model coupling with volume of fluid model and species transport model together is suitable for predicting nutrient transport process. For cell proliferation, differentiation and migration, finite element method with random-walk algorithm is one the most advanced way to simulate these processes. Most of the model analysis methods require further experiments to verify the accuracy and effectiveness. Due to the lack of technology to detect the rate of nutrient diffusion, there are especially few researches on model analysis methods in the area of blood coagulation. Therefore, there is still a lot of work to be done in the research of the whole process model method of tissue engineering. In the future, the numerical model would be seen as an optimal way to investigate tissue engineering products bioperformance and also enable to optimize the parameters and material types of the tissue engineering products.


Asunto(s)
Ingeniería de Tejidos , Diferenciación Celular , Movimiento Celular , Proliferación Celular , Simulación por Computador
16.
J Cell Physiol ; 235(3): 2071-2079, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31347172

RESUMEN

Human chromosomal segregation 1-like (CSE1L) gene functions as a key molecular mediator in cellular proliferation, invasion, and apoptosis. The association of CSE1L with tumor progression has been reported in diverse human cancers. A greater understanding of CSE1L molecular mechanism is beneficial for cancer treatment. In the current study, we show that CSE1L was highly expressed in gastric cancer (GC) cell lines. CSE1L silence promoted apoptosis and inhibited cell proliferation and invasion. Overexpression of glycoprotein nonmetastatic melanoma protein B (GPNMB) reversed the anticancer effect of CSE1L inhibition. CSE1L inhibition decreased GPNMB by microphthalmia-associated transcription factor (MITF). Moreover, GPNMB regulates the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway. Taken together, our study revealed that CSE1L inhibition decreased MITF and suppressed GPNMB expression, thereby activating the PI3K/Akt/mTOR and MEK/ERK signaling pathway, ultimately inhibiting the tumor growth and metastasis in GC.


Asunto(s)
Proliferación Celular/fisiología , Proteína de Susceptibilidad a Apoptosis Celular/metabolismo , Glicoproteínas de Membrana/metabolismo , Factor de Transcripción Asociado a Microftalmía/metabolismo , Metástasis de la Neoplasia/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Apoptosis/fisiología , Línea Celular , Línea Celular Tumoral , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Sistema de Señalización de MAP Quinasas/fisiología , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo
17.
J Oral Pathol Med ; 49(4): 305-310, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31397922

RESUMEN

BACKGROUND: Oral submucous fibrosis (OSF) is a potentially malignant lesion characterized by epithelial-mesenchymal transition (EMT). Bone morphogenetic protein 4 (BMP4) promotes EMT in fibrotic diseases, but the underlying mechanisms and its potential role in OSF are unclear. This study investigates whether BMP4 plays a role in the pathogenesis of OSF and explores the underlying mechanisms. METHODS: The expression of BMP4 and the EMT proteins E-cadherin and vimentin was investigated in OSF specimens by immunohistochemical staining. Pearson's correlation analysis was conducted to explore the correlation between BMP4 and the EMT markers. Western blotting and RT-PCR assays were used to analyze the effect of arecoline (a known EMT-promoting pathogenic factor in OSF) on BMP4 and identify the transcription factor involved. Confocal microscopy was used to observe the intracellular sublocalization of the identified transcription factor, Yes-associated protein 1 (YAP1). Finally, siRNA silencing of BMP4 was used to determine its effect on YAP1 activation and arecoline-induced EMT. RESULTS: BMP4 is overexpressed in OSF and plays a role in EMT, as its expression correlates with the expression of E-cadherin and vimentin. Arecoline induces BMP4 expression via the activation of YAP1 (through its nuclear translocation). Furthermore, the YAP1/BMP4 mechanism is the main molecular event in arecoline-induced EMT, as knockdown of BMP4 expression affects expression of the EMT markers and inhibits extracellular matrix accumulation. CONCLUSIONS: Arecoline induces EMT in OSF via the YAP1/BMP4 pathway. Thus, BMP4 could be considered as a potential therapeutic target for the treatment of OSF.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Arecolina/farmacología , Proteína Morfogenética Ósea 4/metabolismo , Transición Epitelial-Mesenquimal , Fibrosis de la Submucosa Bucal/patología , Factores de Transcripción/metabolismo , Antígenos CD/metabolismo , Cadherinas/metabolismo , Humanos , Fibrosis de la Submucosa Bucal/metabolismo , Vimentina/metabolismo , Proteínas Señalizadoras YAP
18.
BMC Bioinformatics ; 20(Suppl 15): 481, 2019 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-31874606

RESUMEN

BACKGROUND: Cognitive decline has emerged as a significant threat to both public health and personal welfare, and mild cognitive decline/impairment (MCI) can further develop into Dementia/Alzheimer's disease. While treatment of Dementia/Alzheimer's disease can be expensive and ineffective sometimes, the prevention of MCI by identifying modifiable risk factors is a complementary and effective strategy. RESULTS: In this study, based on the data collected by Centers for Disease Control and Prevention (CDC) through the nationwide telephone survey, we apply a data-driven approach to re-exam the previously founded risk factors and discover new risk factors. We found that depression, physical health, cigarette usage, education level, and sleep time play an important role in cognitive decline, which is consistent with the previous discovery. Besides that, the first time, we point out that other factors such as arthritis, pulmonary disease, stroke, asthma, marital status also contribute to MCI risk, which is less exploited previously. We also incorporate some machine learning and deep learning algorithms to weigh the importance of various factors contributed to MCI and predicted cognitive declined. CONCLUSION: By incorporating the data-driven approach, we can determine that risk factors significantly correlated with diseases. These correlations could also be expanded to another medical diagnosis besides MCI.


Asunto(s)
Disfunción Cognitiva/diagnóstico , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Ciencia de los Datos , Humanos , Aprendizaje Automático , Persona de Mediana Edad , Factores de Riesgo
19.
J Oral Maxillofac Surg ; 77(11): 2259-2268, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31260674

RESUMEN

PURPOSE: We used a single-variable method to analyze the influence of the guide sleeve height of a conventional template on implantation accuracy in vitro and improve the function of short-sleeve templates by adding a visual direction-indicating guide (VDING). MATERIALS AND METHODS: We created 100 copies of a volunteer's dentition plaster model. The normal template (NT) and the VDING template (VT) were made with guide sleeves 2, 5, 8, and 10 mm in height. Additionally, a freehand (FH) group and a group with an FH-based visual guide were used. Simulated implantation in an emulated head model was performed in each group. After surgery, cone-beam computed tomography images of the plaster were used for registration, and the accuracy was compared among the groups. RESULTS: When the NT sleeve height was 5 mm or less, increased deviation was found, and the results for some of the accuracy indicators were not different from those in the FH group. The accuracy of sleeves 5 mm or less in height was better in the VT group than in the NT or FH group. CONCLUSIONS: Use of the NT with a guide sleeve height of 5 mm or less can introduce large deviations in implantation, which can be prevented by the VT. However, the use of the VDING alone was not sufficient.


Asunto(s)
Tomografía Computarizada de Haz Cónico , Implantes Dentales , Cirugía Asistida por Computador , Diseño Asistido por Computadora , Implantación Dental Endoósea , Humanos , Imagenología Tridimensional
20.
Zhongguo Zhong Yao Za Zhi ; 44(8): 1537-1544, 2019 Apr.
Artículo en Zh | MEDLINE | ID: mdl-31090316

RESUMEN

Because the red and bright color of corolla is the main indicator for the quality assessment of good safflower,the dyed safflower is sometimes found at the herbal market,what is influence on this herb quality and efficacy. A total of 127 safflower samples was therefore collected from different cultivating areas and herbal markets in China to develop a rapid method to identify the dyed safflower. Near-infrared spectroscopy(NIRS) combined with characteristic identification,high performance liquid chromatography(HPLC),principal component analysis(PCA) and partial least squares regression analysis(PLS) were employed to differentiate safflower from dyed safflower samples,and further quantify the levels of the 6 dyes,i.e. tartrazine,carmine,sunset yellow,azorubine,acid red 73 and orange Ⅱ in the dyed safflower. The results indicated that the 50 safflower samples and 77 dyed safflower samples were located at different regions in PCA cluster diagram by NIR spectra. Tartrazine,carmineand and sunset yellow were found in the 77 dyed safflower samples with the amounts of 0. 60-3. 66,0. 11-1. 37,0. 10-0. 71 mg·g-1,respectively. It indicated that the three dyes were the common and main dyes in the dyed safflower. However,azorubine,acid red 73 and orange Ⅱ were not detected in all herb samples. A total of 62 dyed safflower samples were chosen as calibration samples to develop the model for estimating the amount of dyes in dyed safflower. The estimating accuracy was verified by another 15 dyed safflower samples. The values of tartrazine,carmine and sunset yellow in dyed safflower samples were compared between the NIRS and HPLC methods. Each value of mean absolute difference(MAD) was less than 5%. The correlation coefficients of tartrazine,carmineand and sunset yellow were 0. 970,0. 975,0. 971,respectively. It indicated the data quantified by NIRS and HPLC were consistence. It is concluded that NIRS can not only differentiate safflower from dyed safflower,but also quantify the amount of the dyes. NIRS is suitable for rapidly identify the quality of safflower.


Asunto(s)
Carthamus tinctorius/química , Colorantes/análisis , Espectroscopía Infrarroja Corta , Compuestos Azo , Bencenosulfonatos , Carmín , China , Naftalenosulfonatos , Tartrazina
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