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1.
J Org Chem ; 89(3): 1657-1668, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38241608

RESUMEN

Herein, we report a heterogeneous visible light-driven preparation of α-alkylated glycine derivatives. This approach employed a ß-ketoenamine-linked covalent organic framework (2D-COF-4) as the heterogeneous photocatalyst and N-hydroxy phthalimide (NHPI) esters as the alkyl radical sources. Numerous glycine derivatives, including dipeptides, were precisely and efficiently alkylated under visible light-driven reaction conditions. Based on the excellent photoactivity and organic reaction compatibility of 2D-COF-4, this alkylation could proceed flexibly in a green solvent (ethanol) without any other additives. The photocatalyst and phthalimide were fruitfully recycled with a simple workup procedure, revealing a high ecoscale value and low environmental factor (E-factor).

2.
Neuroimage ; 284: 120447, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37949257

RESUMEN

BACKGROUND AND AIMS: The pathophysiology of achalasia, which involves central nuclei abnormalities, remains unknown. We investigated the resting-state functional MRI (rs-fMRI) features of patients with achalasia. METHODS: We applied resting-state functional MRI (rs-fMRI) to investigate the brain features in patients with achalasia (n = 27), compared to healthy controls (n = 29). Focusing on three regions of interest (ROIs): the dorsal motor nucleus of the vagus (DMV), the nucleus ambiguus (NA), and the nucleus of the solitary tract (NTS), we analyzed variations in resting-state functional connectivity (rs-FC), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo). RESULTS: Achalasia patients demonstrated stronger functional connectivity between the NA and the right precentral gyrus, left postcentral gyrus, and left insula. No significant changes were found in the DMV or NTS. The fMRI analysis showed higher rs-FC values for NA-DMV and NA-NTS connections in achalasia patients. Achalasia patients exhibited decreased fALFF values in the NA, DMV, and NTS regions, as well as increased ReHo values in the NA and DMV regions. A positive correlation was observed between fALFF values in all six ROIs and the width of the barium meal. The NTS fALFF value and NA ReHo value displayed a positive correlation with integrated relaxation pressure (IRP), while the ReHo value in the right precentral gyrus showed an inverse correlation with the height of the barium meal. CONCLUSIONS: Abnormal rs-FC and regional brain activity was found in patients with achalasia. Our study provides new insights into the pathophysiology of achalasia and highlights the potential of rs-fMRI in improving the diagnosis and treatment of this condition.


Asunto(s)
Mapeo Encefálico , Acalasia del Esófago , Humanos , Acalasia del Esófago/diagnóstico por imagen , Bario , Encéfalo/diagnóstico por imagen , Núcleo Solitario , Imagen por Resonancia Magnética
3.
Cancer Immunol Immunother ; 72(3): 633-645, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36018370

RESUMEN

BACKGROUND: Programmed cell death protein 1 (PD-1) antibody has been approved for a variety of tumors, but its effective rate is unsatisfactory. New evidence suggests that mast cells are an important component of the tumor microenvironment and are associated with resistance to immunotherapy, but the underlying mechanism is not clear. METHODS: Bioinformatics analysis of patients with melanoma in TCGA-SKCM and GSE91061 was used to determine the prognostic value of mast cells and their association with anti-PD-1 immunotherapy. HMC-1 cells (mast cell line) and bone marrow-derived mast cells (BMMCs) were used to verify the effect of PD-1 antibody and cromolyn sodium in vitro. The mouse subcutaneous melanoma model was used to verify the effect of the PD-1 antibody on mast cells in vivo. RESULTS: Bioinformatics analysis showed that mast cells were a poor prognostic factor associated with resistance to anti-PD-1 immunotherapy. PD-1 was expressed on the mast cell membrane. The PD-1 antibody promoted the release of histamine and cytokines from mast cells via the PI3K/AKT pathway and calcium signaling pathway. The activation of mast cells induced by PD-1 antibody could be partially inhibited by cromolyn sodium. In vivo, cromolyn sodium increased the efficacy of PD-1 antibody and decreased the infiltration of mast cells and the density of microvessels. CONCLUSION: PD-1+ mast cell activated by PD-1 antibody plays a negative role in the tumor microenvironment via the enhanced function of releasing histamine and cytokines. Inhibition of mast cell may provide a new solution to solve the low response rate of anti-PD-1 immunotherapy.


Asunto(s)
Mastocitos , Melanoma , Ratones , Animales , Cromolin Sódico/metabolismo , Cromolin Sódico/farmacología , Histamina/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Citocinas/metabolismo , Melanoma/metabolismo , Inmunoterapia , Microambiente Tumoral
4.
Small ; 19(16): e2206083, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36683234

RESUMEN

The notorious shuttle effect and sluggish conversion of polysulfides seriously hinder the practical application of Lithium-sulfur (Li-S) batteries. In this study, a novel architecture of MoS2 /MoO3 heterostructure uniformly distributed on carbon nanotubes (MoS2 /MoO3 @CNT) is designed and introduced into Li-S batteries via decorating commercial separator to regulate the redox reactions of polysulfides. Systematic experiments and theoretical calculations showed that the heterostructure not only provides sufficient surface affinity to capture polysulfides and acts as an active catalyst to promote the conversion of polysulfides, but also the highly conductive CNT enables rapid electron/ion migration. As a result, Li-S batteries with the MoS2 /MoO3 @CNT-PP separator deliver an impressive reversible capacity (1015 mAh g-1 at 0.2 A g-1 after 100 cycles), excellent rate capacity (873 mAh g-1 at 5 A g-1 ), and low self-discharge capacity loss (94.6% capacity retention after 7 days of standing). Moreover, even at an elevated temperature of 70 °C, it still exhibits high-capacity retention (800 mAh g-1 at 1 A g-1 after 100 cycles). Encouragingly, when the sulfur load is increased to 8.7 mg cm-2 , the high reversible areal capacity of 6.61 mAh cm-2 can be stably maintained after 100 cycles, indicating a high potential for practical application.

5.
Soft Matter ; 19(25): 4651-4659, 2023 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-37284854

RESUMEN

The preparation of mixed-shell polymeric nanoparticles (MSPNs) and their stabilized non-aqueous Pickering emulsions was described in this study. Poly(methyl methacrylate)-poly(4-vinylpyridine) (PMMA-P4VP) diblock copolymer nanoparticles with different morphologies including spheres, worms and vesicles were first prepared via reversible addition-fragmentation chain transfer-based polymerization induced self-assembly in toluene. C18 alkyl chains were subsequently grafted onto the surfaces of the as-prepared PMMA-P4VP nanoparticles, affording C18/PMMA-P4VP MSPNs with P4VP blocks as the core and C18/PMMA chains as the mixed shells. MSPNs were utilized as Pickering emulsifiers to prepare non-aqueous Pickering emulsions, where [Bmim][PF6] and toluene oils were selected. Two kinds of different Pickering emulsions, [Bmim][PF6]-in-toluene and toluene-in-[Bmim][PF6], could be formed, depending on the initial location of MSPNs. However, neither of them could be generated when PMMA-P4VP diblock copolymer nanoparticles were adopted as Pickering emulsifiers, indicating MSPNs were better than diblock copolymer nanoparticle precursors in the aspect of stabilizing oil-oil interfaces. The formation mechanisms of different kinds of Pickering emulsions were unraveled in this study.

6.
J Clin Gastroenterol ; 56(5): 405-411, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-33852447

RESUMEN

BACKGROUND AND AIMS: High prevalence of minimal change lesion (MCL) in nonerosive reflux esophagitis (NERD) patients is commonly recognized by many endoscopists. However, it is difficult to detect MCL with conventional white-light imaging (WLI) endoscopy. Linked color imaging (LCI), a novel image-enhanced endoscopy technology with strong, unique color enhancement, is used for easy recognition of early gastric cancer and detection of Helicobacter pylori infection. The aim of the study was to compare the efficacy of LCI and WLI endoscopy in evaluating MCL in patients with NER. MATERIALS AND METHODS: Forty-one patients with NERD and 38 subjects with nongastroesophageal reflux disease (non-GERD) were recruited in this study between August 2017 and July 2018. During upper gastrointestinal endoscopy, the distal 5 cm of the esophageal mucosal morphology at the squamocolumnar junction was visualized using WLI followed by LCI. MCL was defined as areas of erythema, blurring of the Z-line, friability, decreased vascularity, white turbid discoloration, and edema or accentuation of the mucosal folds. Three experienced endoscopists evaluated the color patterns for MCL on WLI images and on WLI combined with LCI images in both groups. A biopsy was taken 2 cm above the esophagogastric junction. Histologic slides were scored by a pathologist in a blinded manner. RESULTS: The proportion of MCL was higher in the patients with NERD (70.7%, 29/41) than in patients with non-GERD (39.5%, 15/38) using WLI combined with LCI. In 12 patients with NERD, both WLI and LCI showed normal mucosa. The MCL detection rate was significantly higher when using WLI combined with LCI than when using WLI (70.7% vs. 51.2%, P=0.039) in patients with NERD. The histopathologic score of MCL (+) was significantly higher than that of MCL (-) patients in both the NERD group (4.59±0.32 vs. 2.36±0.34, P<0.01) and the non-GERD group (3.47±0.50 vs. 2.00±0.28, P<0.01). The intraobserver reproducibility levels and interobserver agreement were better with LCI than with WLI alone. CONCLUSIONS: Frequency of MCL was higher in patients with NERD than in those with non-GERD. MCL can be identified by using WLI combined with LCI in patients with NERD. By enhancing endoscopic images, LCI is more sensitive in detecting MCL compared with WLI.


Asunto(s)
Esofagitis Péptica , Infecciones por Helicobacter , Helicobacter pylori , Color , Endoscopía Gastrointestinal , Esofagitis Péptica/diagnóstico por imagen , Humanos , Reproducibilidad de los Resultados
7.
Neural Plast ; 2021: 9938566, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34367273

RESUMEN

Background: Parkinson's disease (PD) is a common neurological degenerative disease that cannot be completely cured, although drugs can improve or alleviate its symptoms. Optogenetic technology, which stimulates or inhibits neurons with excellent spatial and temporal resolution, provides a new idea and approach for the precise treatment of Parkinson's disease. However, the neural mechanism of photogenetic regulation remains unclear. Objective: In this paper, we want to study the nonlinear features of EEG signals in the striatum and globus pallidus through optogenetic stimulation of the substantia nigra compact part. Methods: Rotenone was injected stereotactically into the substantia nigra compact area and ventral tegmental area of SD rats to construct rotenone-treated rats. Then, for the optogenetic manipulation, we injected adeno-associated virus expressing channelrhodopsin to stimulate the globus pallidus and the striatum with a 1 mW blue light and collected LFP signals before, during, and after light stimulation. Finally, the collected LFP signals were analyzed by using nonlinear dynamic algorithms. Results: After observing the behavior and brain morphology, 16 models were finally determined to be successful. LFP results showed that approximate entropy and fractal dimension of rats in the control group were significantly greater than those in the experimental group after light treatment (p < 0.05). The LFP nonlinear features in the globus pallidus and striatum of rotenone-treated rats showed significant statistical differences before and after light stimulation (p < 0.05). Conclusion: Optogenetic technology can regulate the characteristic value of LFP signals in rotenone-treated rats to a certain extent. Approximate entropy and fractal dimension algorithm can be used as an effective index to study LFP changes in rotenone-treated rats.


Asunto(s)
Ganglios Basales/efectos de los fármacos , Potenciales de la Membrana/efectos de los fármacos , Neuronas/efectos de los fármacos , Optogenética/métodos , Rotenona/farmacología , Animales , Masculino , Ratas , Ratas Sprague-Dawley , Desacopladores/farmacología
8.
Mikrochim Acta ; 186(12): 796, 2019 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-31734770

RESUMEN

Exosomes represent a new generation of biomarkers for the early diagnosis of hepatic carcinoma. A fluorometric assay is presented that is based on the hybridization chain reaction and magnetic nanoparticles for the highly sensitive determination of exosome (from HepG2 cells). Antibody as the recognition element was modified on the surface of magnetic nanoparticles. Antibody was used to capture the exosome. The Probe 1 was consisted of aptamer sequence and trigger sequence. Aptamer sequence will bind with the surface protein of exosome. The trigger sequence will hybridize with the probe2 (FAM-labeled) and the probe3 (FAM-labeled). So the product of the hybridization chain reaction will present a strong fluorescence signal. The fluorescence product of hybridization chain reaction will link with magnetic nanoparticles through the 'magnetic nanoparticles-antibody-exosome-aptamer' structure. The product can be separated from the matrix due to the present of the magnetic nanoparticles. The excitation was set at 490 nm. The fluorescence value of the emission spectra at 519 nm was set as the signal response. The linear range of this assay is from 1000 to 107 particles·mL-1. The detection limit is 100 particles·mL-1. This assay was applied to the determination of exosome from the hepatic carcinoma cells. Graphical abstractIn the presence of exosmes, the hybridization chain reaction was triggered and strong green fluorescence will be produced. Moreover, the magnetic particles can separate the products from the matrix.


Asunto(s)
Aptámeros de Nucleótidos/química , Biomarcadores de Tumor/análisis , Exosomas/química , Nanopartículas del Metal/química , Anticuerpos/inmunología , Aptámeros de Nucleótidos/genética , Secuencia de Bases , Carcinoma Hepatocelular/diagnóstico , ADN/química , ADN/genética , Sondas de ADN/química , Sondas de ADN/genética , Exosomas/inmunología , Colorantes Fluorescentes/química , Células Hep G2 , Humanos , Separación Inmunomagnética , Límite de Detección , Técnicas de Amplificación de Ácido Nucleico , Hibridación de Ácido Nucleico , Espectrometría de Fluorescencia/métodos
9.
Bioprocess Biosyst Eng ; 42(9): 1507-1515, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31134336

RESUMEN

Advanced nitrogen removal without the addition of external carbon source is challenging in the conventional biological nitrogen removal processes. This study presented a novel anaerobic/aerobic/anoxic sequencing batch reactor (A/O/A SBR) based on endogenous nitrate (NO3--N) respiration to enhance nitrogen removal. The mean effluent total nitrogen (TN) in the A/O/A SBR could be reduced to as low as 3.5 mg/L, when the average influent TN and chemical oxygen demand (COD) were 52.7 and 235.4 mg/L, respectively. This advanced nitrogen removal was attributed to the post-denitrification, since 82.7% of TN removal was achieved in the post-anoxic stage. The post-denitrification rate with nitrite (NO2--N, 0.59 mg NO2--N/gMLVSS/h) was higher than that with NO3--N (0.35 mg NO3--N/gMLVSS/h). Therefore, the post-anoxic time could be further optimized by achieving denitrification via NO2--N. The A/O/A SBR has good potential in achieving advanced nitrogen removal, especially in nitrogen-sensitive rural areas.


Asunto(s)
Técnicas de Cultivo Celular por Lotes , Reactores Biológicos , Carbono/metabolismo , Desnitrificación , Modelos Biológicos , Nitrógeno/metabolismo , Aerobiosis , Anaerobiosis
10.
Biochem Biophys Res Commun ; 504(4): 878-884, 2018 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-30219235

RESUMEN

To investigate the effect of multi-kinase kinase inhibitors (sorafenib; regorafenib; lenvatinib) on the invasion and metastasis of human hepatocellular carcinoma (HCC) cells, and the outcome of this effect on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), yet unclarified. Cells were subjected to four different treatments: blank control group, sorafenib (10 µmol/L) treatment group, regorafenib (20 mmol/L) treatment group, and lenvatinib (4 µmol/L) treatment group. Anti-invasion and anti-metastasis effects were tested using the wound-healing assay and transwell invasion assay. Real-time PCR and Western blot analyses were used to determine the impact of sorafenib, regorafenib, and lenvatinib on the gene expression of MMPs and TIMPs in the two HCC lines (Hep3B and SMMC-7721). Results from the wound-healing and transwell invasion assays showed the three tested anti-cancer drugs to have a significant inhibitory effect on the metastasis and invasion of HCC cells. Real-time PCR and western blot analyses revealed that sorafenib down-regulated the expressions of MMP-7,10,16 and up-regulated those of TIMP-1,3,4, regorafenib down-regulated the expression of MMP-1 and up-regulated TIMP-3 gene expression, and lenvatinib down-regulated the expressions of MMP-1,2,7,9,10,16 and up-regulated those of TIMP-1,3,4. However, these three targeted anti-cancer drugs seem to have no significant regulatory effect on the expressions of other MMPs and TIMPs family genes. In conclusion, sorafenib, regorafenib, and lenvatinib inhibit the invasion and metastasis of HCC cells by regulating MMPs/TIMPs expression levels.


Asunto(s)
Antineoplásicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Metaloproteinasas de la Matriz/genética , Inhibidores Tisulares de Metaloproteinasas/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Metaloproteinasas de la Matriz/metabolismo , Terapia Molecular Dirigida/métodos , Familia de Multigenes , Compuestos de Fenilurea/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/farmacología , Quinolinas/farmacología , Sorafenib/farmacología , Inhibidores Tisulares de Metaloproteinasas/metabolismo
11.
Anticancer Drugs ; 29(3): 262-270, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29356692

RESUMEN

Histone acetylation is one of the most abundant post-translational modifications in eukaryotic cells; aberrant histone acetylation is related to a range of cancer types because of the dysregulation of histone deacetylases (HDACs). Inhibition of HDACs leads to suppression of tumor growth in multiple cancers, whereas the inhibitory effects of HDAC inhibitors remain incompletely understood in epidermal growth factor receptor (EGFR)-mutant lung cancers. In this study, the antitumor effects of HDACs inhibitor suberoylanilide hydroxamic acid (SAHA, vorinostat) were examined in EGFR-mutant lung cancer cell lines. The results of the present work showed that SAHA markedly inhibited cell viability and proliferation, induced cell apoptosis by arresting the cell cycle in the G2/M phase, and significantly reduced tumor growth in a xenograft model. Further study confirmed that the suppression function of SAHA might be mediated by regulating the ERK-dependent and/or the AKT-dependent pathway; meanwhile, angiogenesis abrogation induced by SAHA exerted effects on tumor regression in vivo. Taken together, our results identify the antitumor effects of HDACs inhibitor SAHA as an alternative therapeutic application for the epigenetic treatment of EGFR-mutant non-small-cell lung cancer.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/genética , Inhibidores de Histona Desacetilasas/farmacología , Ácidos Hidroxámicos/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Mutación , Animales , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/genética , Relación Dosis-Respuesta a Droga , Humanos , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Distribución Aleatoria , Vorinostat , Ensayos Antitumor por Modelo de Xenoinjerto
12.
Strahlenther Onkol ; 192(12): 944-950, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27300370

RESUMEN

BACKGROUND: Primary localized amyloidosis is characterized by the deposition of amyloid proteins restricted to one organ, without systemic involvement. Primary nasopharyngeal amyloidosis is an exceedingly rare condition, for which the standard treatment remains unknown. Because of its challenging anatomical position, surgery alone hardly results in complete resection of the localized amyloidosis. Therefore, an interdisciplinary planning board to design optimal treatment is of particular importance. PATIENT AND METHODS: A 39-year-old man presented with a several-week history of nasal obstruction and epistaxis. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed the presence of a retro-odontoid nonenhancing soft tissue mass. RESULTS: The endoscopic biopsy demonstrated that the mass was amyloid in nature. An extensive systemic workup revealed an absence of inflammatory process, systemic amyloidosis, or plasma cell dyscrasia. The patient was treated with a combination of surgery and radiotherapy, showing no evidence of recurrence or progression at his 1­year follow-up. CONCLUSION: Primary solitary amyloidosis is a rare form of amyloidosis. To the best of our knowledge, this is the first report of a nasopharyngeal amyloidosis case treated with excision and radiation leading to complete remission. Because of the difficulty for surgeons to achieve radical resection with such lesions, radiotherapy proved to be an excellent adjuvant treatment in this case.


Asunto(s)
Amiloidosis/patología , Amiloidosis/radioterapia , Enfermedades Nasofaríngeas/patología , Enfermedades Nasofaríngeas/radioterapia , Radioterapia Conformacional/métodos , Adulto , Amiloidosis/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Enfermedades Nasofaríngeas/diagnóstico por imagen , Dosificación Radioterapéutica , Resultado del Tratamiento
13.
Pancreatology ; 16(5): 733-8, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27324074

RESUMEN

BACKGROUND/OBJECTIVES: Pulmonary apoptosis is an important pathogenic mechanism of acute lung injury induced by many factors. This study aims to investigate whether the caspase inhibitor zVAD-fmk has a protective effect against lung injury in the severe acute pancreatitis model (SAP) in rats. METHODS: Seventy-two Sprague-Dawley rats were randomly divided into Sham, SAP, and SAP + zVAD-fmk groups. The SAP model was established by injection of 5% sodium taurocholate into the pancreatic duct. Animals were sacrificed at 3 h, 6 h, 12 h, and 24 h after operation and then HE staining analysis was performed to assess the lung injury. ELISA was used to detect the activity of myeloperoxidase (MPO) and the concentrations of tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß). Western blotting was used to detect the expression of cleaved caspase-3 in the lung tissues. RESULTS: Rats in SAP group showed obvious lung injury through pathologic examination. Pretreatment with zVAD-fmk significantly inhibited a post-SAP increase in the activation of MPO, TNF-α, IL-1ß, and caspase-3, and decreased lung injury induced by SAP as determined by the pathologic score. CONCLUSION: Our results suggest that apoptosis plays an important role in acute pancreatitis-associated lung injury (APALI), and inhibition of caspase activity may represent a new therapeutic approach for the treatment of APALI.


Asunto(s)
Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/prevención & control , Clorometilcetonas de Aminoácidos/uso terapéutico , Apoptosis/efectos de los fármacos , Inhibidores de Caspasas/uso terapéutico , Inflamación/etiología , Inflamación/prevención & control , Pancreatitis/complicaciones , Lesión Pulmonar Aguda/patología , Amilasas/sangre , Animales , Caspasa 3/biosíntesis , Interleucina-1beta/antagonistas & inhibidores , Masculino , Conductos Pancreáticos/patología , Pancreatitis/inducido químicamente , Pancreatitis/patología , Ratas , Ratas Sprague-Dawley , Ácido Taurocólico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores
14.
Chin J Traumatol ; 19(3): 146-50, 2016 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-27321294

RESUMEN

PURPOSE: This study aims to explore the biomechanical mechanism of lower limb injuries to the driver by establishing a finite element (FE) simulation model of collisions. METHODS: First a minibus FE model was integrated with a seat belt system. Then it was used to rebuild two collisions together with the total human model for safety (THUMS) provided by Toyota Motor Corporation: a rear-end collision between a minibus and a truck and a head-on collision of a minibus to a rigid wall. The impact velocities of both collisions were set at 56 km/h. The vehicle dynamic response, vehicle deceleration, and dashboard intrusion in the two collisions were compared. RESULTS: In the minibus rear-end truck collision, the peak values of the von Mises equivalent stress at the tibia and the femur were 133 MPa and 126 MPa respectively; while in the minibus head-on rigid wall collision, the data were 139 MPa and 99 MPa. Compared with the minibus head-on rigid wall collision, the vehicle deceleration was smaller and the dashboard intrusion was larger in the minibus rear-end truck collision. CONCLUSION: The results illustrate that a longer dashboard incursion distance corresponds to a higher von Mises equivalent stress at the femur. The simulation results are consistent with the driver's autopsy report on lower limbs injuries. These findings verify that FE simulation method is reliable and useful to analyze the mechanisms of lower limb injuries to the driver in minibus frontal collisions.


Asunto(s)
Accidentes de Tránsito , Conducción de Automóvil , Análisis de Elementos Finitos , Extremidad Inferior/lesiones , Fenómenos Biomecánicos , Humanos
15.
Zhonghua Gan Zang Bing Za Zhi ; 23(2): 130-3, 2015 Feb.
Artículo en Zh | MEDLINE | ID: mdl-25880980

RESUMEN

OBJECTIVE: To investigate the effects of activation of the GLP-1 receptor on the p38MAPK signaling pathway in hepatic stellate cells (HSCs). METHODS: HSCs were isolated and identified according to morphological features; the levels of GLP-1R protein were determined by western blotting.The HSCs were randomly divided into a control grouP (normal saline treatment) and experimental grouP(liraglutide treatment); after 120 hours, the expression of p38MAPK mRNA was examined by RT-PCR and of phosphorylated (p)-p38MAPK protein was detected by western blotting. RESULTS: GLP-1R proteins were detected in the HSCs. Compared with the control group, the experimental group showed significantly decreased p38MAPK mRNA and p-p38MAPK protein (both P < 0.01). CONCLUSION: The p38MAPK signaling pathway could be down-regulated when GLP-1R is activated in HSCs.


Asunto(s)
Células Estrelladas Hepáticas/metabolismo , Sistema de Señalización de MAP Quinasas , Receptores de Glucagón/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Células Cultivadas , Péptido 1 Similar al Glucagón/análogos & derivados , Péptido 1 Similar al Glucagón/farmacología , Receptor del Péptido 1 Similar al Glucagón , Humanos , Liraglutida , ARN Mensajero
16.
Org Biomol Chem ; 12(24): 4070-3, 2014 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-24817255

RESUMEN

A simple and practical copper-catalyzed approach to oxindole derivatives by copper-catalyzed bis-arylation of N-alkyl-N-phenylacrylamides with diaryliodonium triflates has been developed under mild conditions, and the method is of tolerance towards some functional groups in the substrates.


Asunto(s)
Alquenos/química , Cobre/química , Indoles/síntesis química , Catálisis , Indoles/química , Oxindoles
17.
J Biomech ; 165: 112024, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38412622

RESUMEN

Vulnerable Road users (VRUs) often suffer multiple fatal head injury types simultaneously in road accidents. In this study, a head-weighted injury criterion (HWIC4) was proposed for assessing the risk of head AIS 4+ injuries considering multiple injury types. Firstly, the kinematic characteristics of VRUs in the 50 in-depth accidents were reconstructed by using multi-body system models, and head injuries were reconstructed using eight head kinematic-based injury criteria and eight brain tissue injury criteria via the THUMS (Ver. 4.0.2) head finite element model. The predictive capability of each injury criterion to predict head AIS 4+ injuries was assessed and four better predictors (HIC15, angular acceleration, coup pressure, and maximum principal strain) were selected. The different head injury types and the weighting parameters for each injury type were taken into account in the development of HWIC4. Finally, the effectiveness and evaluation of HWIC4 for head AIS 4+ injury was validated based on the area under of receiver operating characteristic (AUROC) curve and reconstruction results from 10 additional selected accident cases. The results showed that HWIC4 has a good predictive capability for head AIS 4+ injuries with an AUROC of 0.983, which means that HWIC4 is superior and more reliable than a single head injury criterion. This knowledge further improves the capability of head injury criteria to predict head AIS 4+ injuries.


Asunto(s)
Lesiones Encefálicas , Traumatismos Craneocerebrales , Humanos , Accidentes de Tránsito , Fenómenos Biomecánicos , Aceleración
18.
J Control Release ; 365: 729-743, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38065412

RESUMEN

Radiation-induced ototoxicity is associated with inflammation response and excessive reactive oxygen species in the cochlea. However, the effectiveness of many drugs in clinical settings is limited due to anatomical barriers in the inner ear and pharmacokinetic instability. To address this issue, we developed an injectable hydrogel called RADA32-HRN-dexamethasone (RHD). The RHD hydrogel possesses self-anti-inflammatory properties and can self-assemble into nanofibrous structures, ensuring controlled and sustained release of dexamethasone in the local region. Flow cytometry analysis revealed that the uptake of FITC-conjugated RHD gel by hair cells increased in a time-dependent manner. Compared to free dexamethasone solutions, dexamethasone-loaded RHD gel achieved a longer and more controlled release profile of dexamethasone. Additionally, RHD gel effectively protected against the inflammatory response, reduced excessive reactive oxygen species production, and reversed the decline in mitochondrial membrane potentials induced by ionizing radiation, leading to attenuation of apoptosis and DNA damage. Moreover, RHD gel promoted the recovery of outer hair cells and partially restored auditory function in mice exposed to ionizing radiation. These findings validated the protective effects of RHD gel against radiation-induced ototoxicity in both cell cultures and animal models. Furthermore, RHD gel enhanced the activity of the mammalian target of rapamycin (mTOR) signaling pathway, which was inhibited by ionizing radiation, thereby promoting the survival of hair cells. Importantly, intratympanic injections of RHD gel exhibited excellent biosafety and do not interfere with the anti-tumor effects of radiotherapy. In summary, our study demonstrates the therapeutic potential of injectable dexamethasone-loaded RHD hydrogel for the treatment of radiation-induced hearing loss by regulating the mTOR signaling pathway.


Asunto(s)
Dexametasona , Ototoxicidad , Ratones , Animales , Dexametasona/farmacocinética , Hidrogeles/química , Especies Reactivas de Oxígeno , Ototoxicidad/tratamiento farmacológico , Transducción de Señal , Serina-Treonina Quinasas TOR , Mamíferos
19.
Immun Inflamm Dis ; 12(1): e1129, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38270295

RESUMEN

BACKGROUND: Non-coding RNAs (ncRNAs) are a group of RNAs that cannot synthesize proteins, but are critical in gene expression regulation. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), the two major family members, are intimately involved in controlling immune response, cell proliferation, apoptosis, differentiation and polarization, and cytokine secretion. Their interactions significantly influence lung inflammatory diseases and could be potential therapeutic targets. OBJECTIVES: The review aims to elucidate the role of ncRNAs, especially the interactions between lncRNA and miRNA in lung diseases, including acute and chronic lung inflammatory diseases, as well as lung cancer. And provide novel insights into disease mechanisms and potential therapeutic methods. METHODS: We conducted a comprehensive review of the latest studies on lncRNA and miRNA in lung inflammatory diseases. Our research involved searching through electronic databases like PubMed, Web of Science, and Scopus. RESULTS: We explain the fundamental characteristics and functions of miRNA and lncRNA, their potential interaction mechanisms, and summarize the newly explorations on the role of lncRNA and miRNA interactions in lung inflammatory diseases. CONCLUSIONS: Numerous lncRNAs and miRNAs have been found to partipicate in all stages of lung inflammatory diseases. While ncRNA-based therapies have been validated and developed, there remain challenges in developing more stable and effective drugs for clinical use.


Asunto(s)
Neoplasias Pulmonares , MicroARNs , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , MicroARNs/genética , Apoptosis , Pulmón
20.
Front Plant Sci ; 15: 1371435, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38660445

RESUMEN

Introduction: Low-light-stress is a common meteorological disaster that can result in slender seedlings. The photoreceptors play a crucial role in perceiving and regulating plants' tolerance to low-light-stress. However, the low-light-stress tolerance of cucumber has not been effectively evaluated, and the functions of these photoreceptor genes in cucumber, particularly under low-light-stress conditions, are not clear. Methods: Herein, we evaluated the growth characteristics of cucumber seedlings under various LED light treatment. The low-light-stress tolerant cucumber CR and intolerant cucumber CR were used as plant materials for gene expression analysis, and then the function of CsCRY1 was analyzed. Results: The results revealed that light treatment below 40 µmol m-2 s-1 can quickly and effectively induce low-light-stress response. Then, cucumber CR exhibited remarkable tolerance to low-light-stress was screened. Moreover, a total of 11 photoreceptor genes were identified and evaluated. Among them, the cryptochrome 1 (CRY1) had the highest expression level and was only induced in the low-light sensitive cucumber CS. The transcript CsaV3_3G047490.1 is predicted to encode a previously unknown CsCRY1 protein, which lacks 70 amino acids at its C-terminus due to alternative 5' splice sites within the final intron of the CsCRY1 gene. Discussion: CRY1 is a crucial photoreceptor that plays pivotal roles in regulating plants' tolerance to low-light stress. In this study, we discovered that alternative splicing of CsCRY1 generates multiple transcripts encoding distinct CsCRY1 protein variants, providing valuable insights for future exploration and utilization of CsCRY1 in cucumber.

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