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1.
Analyst ; 148(12): 2809-2817, 2023 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-37219873

RESUMEN

The weak signal strength of Raman imaging leads to long imaging times. To increase the speed of Raman imaging, line scanning and compressed Raman imaging methods have been proposed. Here we combine both line scanning and compressed sensing to further increase the speed. However, the direct combination leads to poor reconstruction results due to the missed coverage of the sample. To avoid this issue, "full-coverage" Compressed Line-scan Raman Imaging (FC-CLRI) is proposed, where line positions are random but constrained to measure each line position of the sample at least once. In proof-of-concept studies of polymer beads and yeast cells, FC-CLRI achieved reasonable image quality while making only 20-40% of the measurements of a fully-sampled line-scan image, achieving 640 µm2 FOV imaging in <2 min with 1.5 mW µm-2 laser power. Furthermore, we critically evaluate the CLRI method through comparison with simple downsampling, and have found that FC-CLRI preserves spatial resolution better while naïve downsampling provides an overall higher image quality for complex samples.

2.
J Am Chem Soc ; 144(33): 15314-15323, 2022 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-35969674

RESUMEN

Small-molecule Raman probes for cellular imaging have attracted great attention owing to their sharp peaks that are sensitive to environmental changes. The small cross section of molecular Raman scattering limits dynamic cellular Raman imaging to expensive and complex coherent approaches that acquire single-channel images and lose hyperspectral Raman information. We introduce a new method, dynamic azo-enhanced Raman imaging (DAERI), to couple the new class of azo-enhanced Raman probes with a high-speed line-scan Raman imaging system. DAERI achieved high-resolution low-power imaging of fast cellular dynamics resolved at ∼270 nm along the confocal direction, 75 µW/µm2 and 3.5 s/frame. Based on the azo-enhanced Raman probes with characteristic signals 102-104 stronger than classic Raman labels, DAERI was not restricted to the cellular Raman-silent region as in prior work and enabled multiplex visualization of organelle motions and interactions. We anticipate DAERI to be a powerful tool for future studies in biophysics and cell biology.


Asunto(s)
Espectrometría Raman , Espectrometría Raman/métodos
3.
Anal Chem ; 94(31): 11000-11007, 2022 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-35895976

RESUMEN

Microscopic imaging and imaging flow cytometry have wide potential in point-of-care assays; however, their narrow depth of focus necessitates precise mechanical or fluidic focus control of a sample in order to acquire high-quality images that can be used for downstream analysis, increasing the cost and complexity of the imaging system. This complexity represents a barrier to miniaturization and translation of point-of-care assays based on microscopic imaging or imaging flow cytometry. To address this challenge, we present a simple drop-in phase mask with a physics-informed, circularly symmetric asphere phase profile that extends the depth of focus by >5-fold while largely preserving the image quality compared to other depth extending methods. We show that such a focus-extended system overcomes manufacturing tolerances in low-cost sample chambers, enlarges the useable field-of-view of low-cost objectives, and permits increased throughput and precision in flow imaging systems without the need for complex flow-focusing. As the image quality is preserved without the need for postacquisition image restoration, our solution is also highly appropriate for on-line applications such as cell sorting.


Asunto(s)
Microfluídica , Pruebas en el Punto de Atención , Separación Celular , Análisis Costo-Beneficio , Citometría de Flujo/métodos , Sistemas de Atención de Punto
4.
Anal Chem ; 94(41): 14232-14241, 2022 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-36202399

RESUMEN

Laser tweezers Raman spectroscopy enables multiplexed, quantitative chemical and morphological analysis of individual bionanoparticles such as drug-loaded nanoliposomes, yet it requires minutes-scale acquisition times per particle, leading to a lack of statistical power in typical small-sized data sets. The long acquisition times present a bottleneck not only in measurement time but also in the analytical throughput, as particle concentration (and thus throughput) must be kept low enough to avoid swarm measurement. The only effective way to improve this situation is to reduce the exposure time, which comes at the expense of increased noise. Here, we present a hybrid principal component analysis (PCA) denoising method, where a small number (∼30 spectra) of high signal-to-noise ratio (SNR) training data construct an effective principal component subspace into which low SNR test data are projected. Simulations and experiments prove the method outperforms traditional denoising methods such as the wavelet transform or traditional PCA. On experimental liposome samples, denoising accelerated data acquisition from 90 to 3 s, with an overall 4.5-fold improvement in particle throughput. The denoised data retained the ability to accurately determine complex morphochemical parameters such as lamellarity of individual nanoliposomes, as confirmed by comparison with cryo-EM imaging. We therefore show that hybrid PCA denoising is an efficient and effective tool for denoising spectral data sets with limited chemical variability and that the RR-NTA technique offers an ideal path for studying the multidimensional heterogeneity of nanoliposomes and other micro/nanoscale bioparticles.


Asunto(s)
Algoritmos , Liposomas , Análisis de Componente Principal , Relación Señal-Ruido , Espectrometría Raman
5.
Opt Lett ; 47(22): 5949-5952, 2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37219144

RESUMEN

Traditional line-scan Raman imaging features a rapid imaging speed while preserving complete spectral information, yet has diffraction-limited resolution. Sinusoidally structured line excitation can yield an improvement in the lateral resolution of the Raman image along the line's direction. However, given the need for the line and spectrometer slit to be aligned, the resolution in the perpendicular direction remains diffraction limited. To overcome this, we present here a galvo-modulated structured line imaging system, where a system of three galvos can arbitrarily orient the structured line on the sample plane, while keeping the beam aligned to the spectrometer slit in the detection plane. Thus, a two-fold isotropic improvement in the lateral resolution fold is possible. We demonstrate the feasibility using mixtures of microspheres as chemical and size standards. The results prove an improvement in the lateral resolution of 1.8-fold (limited by line contrast at higher frequencies), while preserving complete spectral information of the sample.

6.
Pharmacol Res ; 179: 106200, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35367344

RESUMEN

Intracerebral hemorrhage (ICH) refers to hemorrhage caused by non-traumatic vascular rupture in the brain parenchyma, which is characterized by acute onset, severe illness, and high mortality and disability. The influx of blood into the brain tissue after cerebrovascular rupture causes severe brain damage, including primary injury caused by persistent hemorrhage and secondary brain injury (SBI) induced by hematoma. The mechanism of brain injury is complicated and is a significant cause of disability after ICH. Therefore, it is essential to understand the mechanism of brain injury after ICH to develop drugs to prevent and treat ICH. Studies have confirmed that many traditional Chinese medicines (TCM) can reduce brain injury by improving neurotoxicity, inflammation, oxidative stress (OS), blood-brain barrier (BBB), apoptosis, and neurological dysfunction after ICH. Starting from the pathophysiological process of brain injury after ICH, this paper summarizes the mechanisms by which TCM improves cerebral injury after ICH and its comparison with conventional western medicine, so as to provide clues and a reference for the clinical application of TCM in the prevention and treatment of hemorrhagic stroke and further research and development of new drugs.


Asunto(s)
Edema Encefálico , Lesiones Encefálicas , Animales , Hemorragia Cerebral/tratamiento farmacológico , Modelos Animales de Enfermedad , Humanos , Medicina Tradicional China/efectos adversos , Estrés Oxidativo
7.
BMC Med ; 17(1): 150, 2019 07 29.
Artículo en Inglés | MEDLINE | ID: mdl-31352904

RESUMEN

BACKGROUND: Colorectal cancer is the third most common cancer in the world. In this study, we assessed the long-term survival characteristics and prognostic associations and potential time-varying effects of clinico-demographic variables and two molecular markers (microsatellite instability (MSI) and BRAF Val600Glu mutation) in a population-based patient cohort followed up to ~ 19 years. METHODS: The patient cohort included 738 incident cases diagnosed between 1999 and 2003. Cox models were used to analyze the association between the variables and a set of survival outcome measures (overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), metastasis-free survival (MFS), recurrence/metastasis-free survival (RMFS), and event-free survival (EFS)). Cox proportional hazard (PH) assumption was tested for all variables, and Cox models with time-varying effects were used if any departure from the PH assumption was detected. RESULTS: During the follow-up, ~ 61% patients died from any cause, ~ 26% died from colorectal cancer, and ~ 10% and ~ 20% experienced recurrences and distant metastases, respectively. Stage IV disease and post-diagnostic recurrence or metastasis were strongly linked to risk of death from colorectal cancer. If a patient had survived the first 6 years without any disease-related event (i.e., recurrence, metastasis, or death from colorectal cancer), their risks became very minimal after this time period. Distinct sets of markers were associated with different outcome measures. In some cases, the effects by variables were constant throughout the follow-up. For example, MSI-high tumor phenotype and older age at diagnosis predicted longer MFS times consistently over the follow-up. However, in some other cases, the effects of the variables varied with time. For example, adjuvant radiotherapy treatment was associated with increased risk of metastasis in patients who received this treatment after 5.5 years post-diagnosis, but not before that. CONCLUSIONS: This study describes the long-term survival characteristics of a prospective cohort of colorectal cancer patients, relationships between baseline variables and a detailed set of patient outcomes over a long time, and time-varying effects of a group of variables. The results presented advance our understanding of the long-term prognostic characteristics in colorectal cancer and are expected to inspire future studies and clinical care strategies.


Asunto(s)
Supervivientes de Cáncer/estadística & datos numéricos , Neoplasias Colorrectales/mortalidad , Adulto , Anciano , Estudios de Cohortes , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Inestabilidad de Microsatélites , Persona de Mediana Edad , Mutación Missense , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/genética , Fenotipo , Pronóstico , Proteínas Proto-Oncogénicas B-raf/genética , Análisis de Supervivencia , Factores de Tiempo , Adulto Joven
8.
Opt Express ; 24(10): 10391-401, 2016 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-27409863

RESUMEN

A sensor system based on a continuous wave, external-cavity quantum-cascade laser (CW EC-QCL) was demonstrated for simultaneous detection of atmospheric H2O, HDO, N2O and CH4 using a compact, dense pattern multi-pass gas cell with an effective path-length of 57.6 m. The EC-QCL with a mode-hop-free spectral range of 1225-1285 cm-1 operating at ~7.8 µm was scanned covering four neighboring absorption lines, for H2O at 1281.161 cm-1, HDO at 1281.455 cm-1, N2O at 1281.53 cm-1 and CH4 at 1281.61 cm-1. A first-harmonic-normalized wavelength modulation spectroscopy with second-harmonic detection (WMS-2f/1f) strategy was employed for data processing. An Allan-Werle deviation analysis indicated that minimum detection limits of 1.77 ppmv for H2O, 3.92 ppbv for HDO, 1.43 ppbv for N2O, and 2.2 ppbv for CH4 were achieved with integration times of 50-s, 50-s, 100-s and 129-s, respectively. Experimental measurements of ambient air are also reported.

9.
Opt Express ; 24(6): A528-35, 2016 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-27136873

RESUMEN

Two compact TDLAS sensor systems based on different structural optical cores were developed. The two optical cores combine two recent developments, gallium antimonide (GaSb)-based ICL and a compact multipass gas cell (MPGC) with the goal to create compact TDLAS based sensors for the mid-IR gas detection with high detection sensitivity and low power consumption. The sensors achieved minimum detection limits of ~5 ppbv and ~8 ppbv, respectively, for CH4 and C2H6 concentration measurements with a 3.7-W power consumption.

10.
Appl Microbiol Biotechnol ; 100(9): 4027-34, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26767987

RESUMEN

Cloning of new toxic genes from Bacillus thuringiensis (Bt) and construction of Bt engineered strains are two key strategies for bio-control of coleopteran pests in agriculture and forestry. In this study, we cloned a new cry3Aa-type gene, cry3Aa8, from wild Bt strain YC-03 against coleopteran, and constructed a Bt engineered strain, ACE-38, containing insecticidal protein-encoding gene cry3Aa8. The engineered strain, with almost four times of Cry3Aa yield compared with strain YC-03, was an antibiotic marker-free strain. Though no selective pressure was presented in the medium, cry3Aa8 in the engineered strain ACE-38 remained stable. The yield of Cry3Aa by strain ACE-38 reached 2.09 mg/ml in the optimized fermentation medium. The activity of strain ACE-38 against Plagiodera versicolora was tested, and the LC50 of ACE-38 cultures in the optimized fermentation medium was 1.13 µl/ml. Strain ACE-38 is a non-antibiotic Bt engineered strain with high Chrysomelidae toxicity and exhibits good fermentation property. The modified indigenous site-specific recombination system constructed in this study might be useful for the construction of Bt engineered strains containing genes that cannot be expressed in the indigenous site-specific recombination system using plasmid pBMB1205R.


Asunto(s)
Bacillus thuringiensis/genética , Bacillus thuringiensis/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/toxicidad , Escarabajos/microbiología , Escarabajos/fisiología , Endotoxinas/metabolismo , Endotoxinas/toxicidad , Proteínas Hemolisinas/metabolismo , Proteínas Hemolisinas/toxicidad , Animales , Bacillus thuringiensis/crecimiento & desarrollo , Toxinas de Bacillus thuringiensis , Proteínas Bacterianas/genética , Bioensayo , Clonación Molecular , Endotoxinas/genética , Inestabilidad Genómica , Proteínas Hemolisinas/genética , Organismos Modificados Genéticamente/genética , Organismos Modificados Genéticamente/crecimiento & desarrollo , Organismos Modificados Genéticamente/metabolismo , Control Biológico de Vectores/métodos , Análisis de Supervivencia
11.
Opt Express ; 23(15): 19821-30, 2015 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-26367641

RESUMEN

A ppb-level formaldehyde (H2CO) sensor was developed using a thermoelectrically cooled (TEC), continuous-wave (CW) room temperature interband cascade laser (ICL) emitting at 3.59 µm and a miniature dense pattern multipass gas cell with >50 m optical path length. Performance of the sensor was investigated with two measurement schemes: direct absorption (DAS) and wavelength modulation spectroscopy (WMS). With an integration time of less than 1.5 second, a detection limit of ~3 ppbv for H2CO measurement with precision of 1.25 ppbv for DAS and 0.58 ppbv for WMS, respectively, was achieved without zero air based background subtraction. An Allan-Werle variance analysis indicated that the precisions can be further improved to 0.26 ppbv @ 300s for DAS and 69 pptv @ 90 s for WMS, respectively. A side-by-side comparison between two measurement schemes is also discussed in detail.

12.
Int J Syst Evol Microbiol ; 64(Pt 9): 3320-3324, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24994779

RESUMEN

A Gram-stain-positive, rod-shaped, endospore-forming bacterium, strain D45(T), was isolated from soil in Nanjing, China. The organism grew optimally at 30 °C, pH 7.0 and with 0 % NaCl (w/v). The 16S rRNA gene sequence of the isolate showed similarities lower than 97 % with respect to species of the genus Cohnella. The predominant respiratory quinone was MK-7, with MK-6 present as a minor component; anteiso-C15 : 0 and iso-C16 : 0 were the major fatty acids. The polar lipids of strain D45(T) were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two aminophospholipids, four phospholipids, two glycolipids, one aminolipid and two lipids. The DNA G+C content was 59.5 mol%. DNA-DNA hybridization of the isolate with two reference strains showed relatedness values of 33.4 % with Cohnella ginsengisoli DSM 18997(T) and 25.8 % with Cohnella thermotolerans DSM 17683(T). The phylogenetic, chemotaxonomic and phenotypic data supported the classification of strain D45(T) as a representative of a novel species of the genus Cohnella, for which the name Cohnella nanjingensis sp. nov. is proposed. The type strain is D45(T) ( = CCTCC AB 2014067(T) = DSM 28246(T)).


Asunto(s)
Bacillales/clasificación , Filogenia , Microbiología del Suelo , Bacillales/genética , Bacillales/aislamiento & purificación , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , Peptidoglicano/química , Fosfolípidos/química , Polisacáridos Bacterianos/biosíntesis , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/química
13.
Int J Syst Evol Microbiol ; 64(Pt 12): 3958-3963, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25205797

RESUMEN

A Gram-stain-positive, rod-shaped, endospore-forming, aerobic bacterial strain, designated M327(T), was isolated from the weathered surfaces of rock (mica schist) from Susong, Anhui Province, PR China. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain M327(T) belonged to the genus Paenibacillus and was related most closely to Paenibacillus terrigena A35(T) (98.6 % similarity) and Paenibacillus selenitireducens ES3-24(T) (98.3 %). Strain M327(T) contained meso-diaminopimelic acid in the cell wall and MK-7 as the major menaquinone. The main fatty acids of strain M327(T) were anteiso-C15 : 0 and iso-C16 : 0. The polar lipid profile contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, three unknown aminophospholipids and an unknown lipid. The total DNA G+C content of strain M327(T) was 48.6 mol%. Based on the low level of DNA-DNA relatedness (ranging from 26.6 to 33.1 %) to these type strains of species of the genus Paenibacillus and unique phenotypic characteristics, it is suggested that strain M327(T) represents a novel species of the genus Paenibacillus, for which the name Paenibacillus susongensis sp. nov. is proposed. The type strain is M327(T) ( = CCTCC AB 2014058(T) = LMG 28236(T) = JCM 19951(T)).


Asunto(s)
Paenibacillus/clasificación , Filogenia , Microbiología del Suelo , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Grasos/química , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , Paenibacillus/genética , Paenibacillus/aislamiento & purificación , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/química
14.
Mitochondrial DNA B Resour ; 9(7): 865-870, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39010881

RESUMEN

Amorphophallus paeoniifolius (Dennst.) Nicolson, 1885, often known as elephant foot yam, is a tropical tuber crop that originates from south-east Asia and belongs to the Araceae family. It is known for its high production potential and popularity as a medicinal plant. However, the phylogeny and genes for this species are still unavailable. In this study, the first complete chloroplast genome of A. paeoniifolius was reported and phylogenetic analysis was conducted with Araceae species. The chloroplast genome was 176,258 bp in length with 34.80% overall GC content and includes a large single-copy (LSC) region (93,951 bp), a small single-copy (SSC) region (15,013 bp), and a pair of inverted repeat (IRs) regions (33,647 bp). The chloroplast genome has 130 genes, which include 85 protein-coding genes, 37 tRNA genes, and eight rRNA genes. A maximum-likelihood (ML) phylogenetic analysis indicated that all Amorphophallus species formed a single monophyletic clade with a high bootstrap value and A. paeoniifolius was closely related to A. konjac, A. albus, A. krausei, and A. titanum. The chloroplast genome reported in this study will be useful for further taxonomic and evolutionary studies of Amorphophallus.

15.
Mater Today Bio ; 24: 100895, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38179430

RESUMEN

Rapid advances in nanomedicine have enabled potential applications in cancer therapy. The enhanced permeability and retention (EPR) effect is the primary rationale for the passive targeting of nanoparticles in oncology. However, growing evidence indicates that the accumulation of nanomaterials via the EPR effect could be more efficient. Inspired by our clinical observation of the Gap Junction connecpion between folliculostellate cells and pituitary adenoma cells, we designed a novel drug delivery system that targets tumours by coating folliculostellate cell (FS) membranes onto PLGA nanoparticles (NPs). The resulting FSNPs, inheriting membrane proteins from the folliculostellate cell membrane, significantly enhanced the EPR effect compared to nanoparticles without cancer cell membranes. We further demonstrated that mitotane encapsulation improved the therapeutic efficacy of mitotane in both heterotopic and orthotopic pituitary adenoma models. Owing to its significant efficacy, our FS cell membrane-coated nanoplatforms has the potential to be translated into clinical applications for the treatment of invasive pituitary adenoma.

16.
Biomater Sci ; 11(7): 2543-2550, 2023 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-36780398

RESUMEN

Histopathology evaluation and lymphadenectomy of node-positive patients is the usual procedure in clinical therapy. However, it requires days for the histopathology result analysis, which impedes intraoperative decision-making and immediate treatment. Noninvasive real-time imaging of metastatic lymph nodes can overcome these defects and help medical workers evaluate lymph nodes and make the operation decision more efficiently. Herein we developed iridium(III)-cyanine complex/bovine serum albumin (BSA)-based nanoparticles which are conjugated with folic acid (FA) (IrCy-FA NPs). The synthesized IrCy-FA NPs exhibit good biocompatibility, strong near-infrared absorption, and impressive lymph node accumulation and can serve as a photoacoustic (PA) imaging probe for lymph node imaging. Besides, the lymph nodes enriched with IrCy-FA NPs showing green color are easily visible to the naked eye, suggesting their potential as an intraoperative indicator. The real-time PA imaging with excellent contrast and high spatial resolution can promote efficient and reliable quantitative analysis of lymph nodes in vivo. By employing IrCy-FA NPs as the PA agent for lymph node imaging, we achieve effective pre-operative and post-operative evaluations of metastatic lymph nodes in lymphadenectomy. This study may provide helpful information for PA imaging guided colocalization and evaluation of lymph nodes and facilitate this method towards clinical trials.


Asunto(s)
Nanopartículas , Técnicas Fotoacústicas , Humanos , Iridio , Técnicas Fotoacústicas/métodos , Ganglios Linfáticos/diagnóstico por imagen , Escisión del Ganglio Linfático , Nanopartículas/uso terapéutico
17.
Front Oncol ; 13: 1122229, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36998434

RESUMEN

Background: Interactions among genetic variants are rarely studied but may explain a part of the variability in patient outcomes. Objectives: In this study, we aimed to identify 1 to 3 way interactions among SNPs from five Wnt protein interaction networks that predict the 5-year recurrence risk in a cohort of stage I-III colorectal cancer patients. Methods: 423 patients recruited to the Newfoundland Familial Colorectal Cancer Registry were included. Five Wnt family member proteins (Wnt1, Wnt2, Wnt5a, Wnt5b, and Wnt11) were selected. The BioGRID database was used to identify the proteins interacting with each of these proteins. Genotypes of the SNPs located in the interaction network genes were retrieved from a genome-wide SNP genotype data previously obtained in the patient cohort. The GMDR 0.9 program was utilized to examine 1-, 2-, and 3-SNP interactions using a 5-fold cross validation step. Top GMDR 0.9 models were assessed by permutation testing and, if significant, prognostic associations were verified by multivariable logistic regression models. Results: GMDR 0.9 has identified novel 1, 2, and 3-way SNP interactions associated with 5-year recurrence risk in colorectal cancer. Nine of these interactions were multi loci interactions (2-way or 3-way). Identified interaction models were able to distinguish patients based on their 5-year recurrence-free status in multivariable regression models. The significance of interactions was the highest in the 3-SNP models. Several of the identified SNPs were eQTLs, indicating potential biological roles of the genes they were associated with in colorectal cancer recurrence. Conclusions: We identified novel interacting genetic variants that associate with 5-year recurrence risk in colorectal cancer. A significant portion of the genes identified were previously linked to colorectal cancer pathogenesis or progression. These variants and genes are of interest for future functional and prognostic studies. Our results provide further evidence for the utility of GMDR models in identifying novel prognostic biomarkers and the biological importance of the Wnt pathways in colorectal cancer.

18.
JCI Insight ; 8(16)2023 08 22.
Artículo en Inglés | MEDLINE | ID: mdl-37432746

RESUMEN

Myeloid RNA regulator of Bim-induced death (Morrbid) is a newly identified leukocyte-specific long noncoding RNA (lncRNA). However, the expression and biological functions of Morrbid in cardiomyocytes and heart disease are currently unclear. This study was meant to determine the role of cardiac Morrbid in acute myocardial infarction (AMI) and to identify the potential cellular and molecular mechanisms involved. We found that both human and mouse cardiomyocytes could express a significant amount of Morrbid and that its expression was increased in cardiomyocytes with hypoxia or oxidative stress as well as in mouse hearts with AMI. Overexpression of Morrbid reduced the myocardial infarct size and cardiac dysfunction, whereas the infarct size and cardiac dysfunction deteriorated in cardiomyocyte-specific Morrbid-KO (Morrbidfl/fl/Myh6-Cre) mice. We identified that Morrbid had a protective effect against hypoxia- or H2O2-induced apoptosis; this was also confirmed in vivo in mouse hearts after AMI. We further discovered that serpine1 was a direct target gene of Morrbid that was involved in the Morrbid-mediated protective effect on cardiomyocytes. In summary, we have found, for the first time to our knowledge, that the cardiac Morrbid is a stress-enhanced lncRNA that protects hearts from AMI via antiapoptosis through its target gene serpine1. Morrbid may be a novel promising therapeutic target for ischemic heart diseases such as AMI.


Asunto(s)
Infarto del Miocardio , Isquemia Miocárdica , ARN Largo no Codificante , Humanos , Ratones , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Peróxido de Hidrógeno , Hipoxia
19.
Front Genet ; 13: 902217, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35991579

RESUMEN

Background: SNP interactions may explain the variable outcome risk among colorectal cancer patients. Examining SNP interactions is challenging, especially with large datasets. Multifactor Dimensionality Reduction (MDR)-based programs may address this problem. Objectives: 1) To compare two MDR-based programs for their utility; and 2) to apply these programs to sets of MMP and VEGF-family gene SNPs in order to examine their interactions in relation to colorectal cancer survival outcomes. Methods: This study applied two data reduction methods, Cox-MDR and GMDR 0.9, to study one to three way SNP interactions. Both programs were run using a 5-fold cross validation step and the top models were verified by permutation testing. Prognostic associations of the SNP interactions were verified using multivariable regression methods. Eight datasets, including SNPs from MMP family genes (n = 201) and seven sets of VEGF-family interaction networks (n = 1,517 SNPs) were examined. Results: ∼90 million potential interactions were examined. Analyses in the MMP and VEGF gene family datasets found several novel 1- to 3-way SNP interactions. These interactions were able to distinguish between the patients with different outcome risks (regression p-values 0.03-2.2E-09). The strongest association was detected for a 3-way interaction including CHRM3.rs665159_EPN1.rs6509955_PTGER3.rs1327460 variants. Conclusion: Our work demonstrates the utility of data reduction methods while identifying potential prognostic markers in colorectal cancer.

20.
Brain Res ; 1792: 148021, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-35878660

RESUMEN

Storax is a traditional Chinese herb that is widely applied in stroke treatment. However, its neuroprotective effects and mechanisms are yet to be fully elucidated. This study aimed to elucidate the neuroprotective effects and underlying mechanisms of storax on oxygen-glucose deprivation/reoxygenation (OGD/R) in injured cortical neurons. The cortical neurons of Wistar rats were primarily cultured in vitro. TheTUNELmethod and CM-H2DCFDA probe were used to detect cell apoptosis and reactive oxygen species (ROS) expression. Enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, and Western blot were used to detect the expression of inflammatory cytokines and proteins of the TLR4/TRAF6/NF-κB signaling pathway. Immunofluorescence was used to measure NF-κB nuclear translocation. Transfection of TLR4 siRNA was used to detect the potential anti-inflammatory mechanisms of storax. The present results have shown that storax protected primary cortical neurons from OGD/R-induced injury by suppressing ROS generation and cell apoptosis; alleviating HMGB-1, TNF-α, IL-1ß, and ICAM-1 expression; and promoting IL-10 expression. In addition, storax inhibited the activation of TLR4, TRAF6, IκBα, IKKß, and NF-κBp65 caused by OGD/R. It is suggested that storax prevents OGD/R-induced primary cortical neuron injury by inhibiting the TLR4/TRAF6/NF-κB signaling pathway.


Asunto(s)
Fármacos Neuroprotectores , Daño por Reperfusión , Animales , Glucosa/metabolismo , FN-kappa B/metabolismo , Neuronas/metabolismo , Fármacos Neuroprotectores/farmacología , Oxígeno/metabolismo , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/metabolismo , Transducción de Señal , Factor 6 Asociado a Receptor de TNF/metabolismo , Receptor Toll-Like 4/metabolismo
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