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1.
Chaos ; 34(10)2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39393184

RESUMEN

This paper is concerned with the limit cycle problem of a cubic reversible Hamiltonian system under perturbation of polynomials of degree n with a switching line x=0. The upper and lower bounds of the number of limit cycles are obtained using the first order Melnikov function and its expansion. The method for calculating the Melnikov function relies upon some iterative formulas, which differs from other approaches.

2.
Cancers (Basel) ; 16(16)2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39199578

RESUMEN

Despite major advances in non-small-cell lung cancer (NSCLC) treatment, the five-year survival rates for patients with non-oncogene-driven tumors remain low, necessitating combinatory approaches to improve outcomes. Our prior high-throughput RNAi screening identified Aurora kinase A (AURKA) as a potential key player in cisplatin resistance. In this study, we investigated AURKA's role in platinum and radiation sensitivity in multiple NSCLC cell lines and xenograft mouse models, as well as its effect on immune checkpoints, including PD-L1, B7x, B7-H3, and HHLA2. Of 94 NSCLC patient tumor specimens, 91.5% tested positive for AURKA expression, with 34% showing moderate-to-high levels. AURKA expression was upregulated following cisplatin treatment in NSCLC cell lines PC9 and A549. Both AURKA inhibition by alisertib and inducible AURKA knockdown potentiated the cytotoxic effects of cisplatin and radiation, leading to tumor regression in doxycycline-inducible xenograft mice. Co-treated cells exhibited increased DNA double-strand breaks, apoptosis, and senescence. Additionally, AURKA inhibition alone by alisertib increased PD-L1 and B7-H3 expression. In conclusion, our study demonstrates that AURKA inhibition enhances the efficacy of platinum-based chemotherapy in NSCLC cells and modulates the expression of multiple immune checkpoints. Therefore, combinatory regimens with AURKA inhibitors should be strategically designed and further studied within the evolving landscape of chemo-immunotherapy.

3.
Sensors (Basel) ; 24(16)2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39204996

RESUMEN

A three-dimensional magnetic probe system has been designed and implemented at the Space Plasma Environment Research Facility (SPERF). This system has been developed to measure the magnetic field with high spatial and temporal resolution, enabling studies of fundamental processes in space physics, such as magnetic reconnection at the Earth's magnetopause, on the basis of SPERF. The system utilizes inductive components as sensors, arranged in an array and soldered onto a printed circuit board (PCB), achieving a spatial resolution of 2.5 mm. The system's electrical parameters have been measured, and its amplitude-frequency response characteristics have been simulated. The system has demonstrated good performance with response capabilities below 50 kHz. The experimental setup and results are discussed, highlighting the system's effectiveness in accurately measuring weak magnetic signals and its suitability for magnetic reconnection experiments.

4.
Tuberculosis (Edinb) ; 148: 102530, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38857553

RESUMEN

OBJECTIVES: To determine the usefulness of LINC00152 and LARS2-AS1 as potential biomarkers for latent tuberculosis (LTB) and active tuberculosis (ATB), as well as their effect on Mycobacterium (Mtb) infection. METHODS: The expression levels of LINC00152 and LARS2-AS1 in the health, patients with LTB and ATB were detected by qRT-PCR. The ROC curves were constructed to show their potential as biomarkers. The intracellular survival assays for Mtb and the levels of immune-related cytokines were determined to discover the effect of LINC00152 and LARS2-AS1 on Mtb infection. The relationships of miR-485-5p with LINC00152 and LARS2-AS1 were explored. RESULTS: LINC00152 and LARS2-AS1 levels were significantly elevated in patients with ATB and LTB, and Mtb-infected macrophages. LINC00152 and LARS2-AS1 can distinguish the LTB from the health and ATB from LTB. LARS2-AS1 and LINC00152 knock-down reduced the intracellular Mtb survival and induced cellular immune response after Mtb challenge. miR-485-5p was a targeting miRNA for LINC00152 and LARS2-AS1. CONCLUSIONS: LINC00152 and LARS2-AS1 can be considered as potential biomarkers for tuberculosis disease. LINC00152 and LARS2-AS1 have anti-Mtb effects.


Asunto(s)
Macrófagos , MicroARNs , Mycobacterium tuberculosis , ARN Largo no Codificante , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Humanos , Macrófagos/inmunología , Macrófagos/microbiología , Macrófagos/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Mycobacterium tuberculosis/inmunología , Mycobacterium tuberculosis/genética , Masculino , Femenino , Tuberculosis Latente/inmunología , Tuberculosis Latente/genética , Tuberculosis Latente/microbiología , Tuberculosis Latente/diagnóstico , Tuberculosis/inmunología , Tuberculosis/genética , Tuberculosis/microbiología , Adulto , Estudios de Casos y Controles , Interacciones Huésped-Patógeno , Persona de Mediana Edad , Citocinas/metabolismo , Citocinas/genética , Valor Predictivo de las Pruebas , Biomarcadores/metabolismo
5.
Artículo en Inglés | MEDLINE | ID: mdl-38619108

RESUMEN

The accumulation of ice can pose numerous inconveniences and potential hazards, profoundly affecting both human productivity and daily life. To combat the challenges posed by icing, extensive research efforts have been dedicated to the development of low-ice adhesion surfaces. In this study, we harness the power of molecular dynamics simulations to delve into the intricate dynamics of polymer chains and their role in determining the modulus of the material. We present a novel strategy to prepare ultralow-modulus poly(dimethylsiloxane) (PDMS) elastomers with a molecular brush configuration as icephobic materials. The process involves grafting monohydride-terminated PDMS (H-PDMS) as side chains onto backbone chain PDMS with pendant vinyl functional groups to yield a molecular brush structure. The segments of this polymer structure effectively restrict interchain entanglement, thereby rendering a lower modulus compared to traditional linear structures at an equivalent cross-linking density. The developed soft coating exhibits a remarkably ultralow ice adhesion strength of 13.1 ± 1.1 kPa. Even after enduring 50 cycles of icing and deicing, the ice adhesion strength of this coating steadfastly stayed below 16 kPa, showing no notable increase. Importantly, the molecular brush coating applied to glass demonstrated an impressive light transmittance of 92.1% within the visible light spectrum, surpassing the transmittance of bare glass, which was measured at 91.3%. This icephobic coating with exceptional light transmittance offers a wide range of applications and holds significant potential as a practical icephobic material.

6.
Int J Biol Macromol ; 267(Pt 1): 131406, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38582472

RESUMEN

Starch and plant fibers are abundant natural polymers that offer biodegradability, making them potential substitutes for plastics in certain applications, but are usually limited by its high hydrophilicity, and low mechanical performance. To address this issue, polylactic acid (PLA) is blended with cellulose and chitosan to create a waterproof film that can be applied to starch-fiber foaming biodegradable composites to enhance their water resistance properties. Here, plant fibers as a reinforcement is incorporated to the modified starch by foaming mold at 260 °C, and PLA based hydrophobic film is coated onto the surface to prepare the novel hydrophobic bio-composites. The developed bio-composite exhibits comprehensive water barrier properties, which is significantly better than that of traditional starch and cellulose based materials. Introducing PLA films decreases water vapor permeability from 766.83 g/m2·24h to 664.89 g/m2·24h, and reduce hysteresis angles from 15.57° to 8.59° within the first five minutes after exposure to moisture. The water absorption rate of PLA films also decreases significantly from 12.3 % to 7.9 %. Additionally, incorporating hydrophobic films not only enhances overall waterproof performance but also improves mechanical properties of the bio-composites. The fabricated bio-composite demonstrates improved tensile strength from 2.09 MPa to 3.53 MPa.


Asunto(s)
Interacciones Hidrofóbicas e Hidrofílicas , Poliésteres , Almidón , Resistencia a la Tracción , Agua , Poliésteres/química , Almidón/química , Agua/química , Permeabilidad , Quitosano/química , Celulosa/química , Vapor , Propiedades de Superficie
7.
Horm Metab Res ; 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-38052232

RESUMEN

Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy threatening patients' life quality. Our previous study has demonstrated that inhibition of long non-coding RNA H19 (lncRNA h19; H19) blocks ATC growth and metastasis. The current study aimed to further explore the potential mechanism of H19 in ATC. Expression of H19, miR-454-3p, and BHLHE40 mRNA was measured using RT-qPCR in tissue samples and cell lines. The dual-luciferase reporter assay and Pearson correlation analysis were used to explore the interaction among H19, miR-454-3p, and BHLHE40. The biological process of proliferation, migration, and invasion was determined using loss- or gain-function CCK-8 and Transwell assays. Western blot assay was used to evaluate the changes in protein levels. H19 was elevated in ATC tissues and cell lines. Based on online prediction database results, miR-454-3p might be a target of H19, and BHLHE40 might be a direct target of miR-454-3p. miR-454-3p expression was decreased in ATC and had a negative interaction with H19. BHLHE40 mRNA expression was increased and has a negative correlation with miR-454-3p and a positive correlation with H19. Downregulation of miR-454-3p and upregulation of BHLHE40 could reverse the decreased cellular activities caused by si-H19. Moreover, the silence of H19 modulates BHLHE40 to affect the PI3K/AKT protein levels and apoptotic-related protein levels. The current study provided a potential detailed mechanism of H19 in ATC, and lncRNA H19-miR-454-3p-BHLHE40 interaction may be a new experimental basis for prognosis and targeted therapy for ATC patients.

8.
Cancers (Basel) ; 15(13)2023 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-37444481

RESUMEN

Immunotherapy has transformed lung cancer management, but PSC remains an aggressive subtype with a poor prognosis. This study investigates the differential expression of PD-L1 and alternative immune checkpoints (ICs; B7x, B7-H3, and HHLA2), and genetic alterations in PSCs. Tumor specimens of 41 PSC patients were evaluated. PD-L1, B7x, B7-H3, and HHLA2 were positive in 75.0%, 67.6%, 73.0%, and 91.9% of tumors, respectively. PD-L1 expression was significantly higher in the epithelial compared to the sarcomatoid component (median TPS: 50% vs. 0%, p = 0.010). Expression of PD-L1 in both components was only seen in 32.1% of patients. However, at least one IC was expressed in 92.9% of epithelial and 100% of sarcomatoid components. Furthermore, METex14 was detected in 19.5% of patients and was associated with a higher sarcomatoid percentage. Our preclinical studies revealed that METex14 induced PD-L1 expression via MAPK or PI3K/Akt pathways, and MET inhibitors decreased PD-L1 expression. Our findings demonstrate distinct expressions of ICs in PSC subcomponents. Thus, combination IC inhibition as a therapeutic strategy in PSC warrants further exploration. A high percentage of METex14 in PSC and its role in regulating PD-L1 expression reveal different therapeutic targets in this aggressive NSCLC subtype.

9.
J Neurosci ; 43(26): 4821-4836, 2023 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-37290936

RESUMEN

Relative motion breaks a camouflaged target from a same-textured background, thus eliciting discrimination of a motion-defined object. Ring (R) neurons are critical components in the Drosophila central complex, which has been implicated in multiple visually guided behaviors. Using two-photon calcium imaging with female flies, we demonstrated that a specific population of R neurons that innervate the superior domain of bulb neuropil, termed superior R neurons, encoded a motion-defined bar with high spatial frequency contents. Upstream superior tuberculo-bulbar (TuBu) neurons transmitted visual signals by releasing acetylcholine within synapses connected with superior R neurons. Blocking TuBu or R neurons impaired tracking performance of the bar, which reveals their importance in motion-defined feature encoding. Additionally, the presentation of a low spatial frequency luminance-defined bar evoked consistent excitation in R neurons of the superior bulb, whereas either excited or inhibited responses were evoked in the inferior bulb. The distinct properties of the responses to the two bar stimuli indicate there is a functional division between the bulb subdomains. Moreover, physiological and behavioral tests with restricted lines suggest that R4d neurons play a vital role in tracking motion-defined bars. We conclude that the central complex receives the motion-defined features via a visual pathway from superior TuBu to R neurons and might encode different visual features via distinct response patterns at the population level, thereby driving visually guided behaviors.SIGNIFICANCE STATEMENT Animals could discriminate a motion-defined object that is indistinguishable with a same-textured background until it moves, but little is known about the underlying neural mechanisms. In this study, we identified that R neurons and their upstream partners, TuBu neurons, innervating the superior bulb of Drosophila central brain are involved in the discrimination of high-frequency motion-defined bars. Our study provides new evidence that R neurons receive multiple visual inputs from distinct upstream neurons, indicating a population coding mechanism for the fly central brain to discriminate diverse visual features. These results build progress in unraveling neural substrates for visually guided behaviors.


Asunto(s)
Drosophila , Percepción de Movimiento , Humanos , Animales , Femenino , Vías Visuales/fisiología , Percepción de Movimiento/fisiología , Neuronas/fisiología , Encéfalo/fisiología
11.
Transl Lung Cancer Res ; 12(4): 808-823, 2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37197623

RESUMEN

Background: Tumor mutation burden (TMB) is one of the biomarkers for efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). Due to the potential of radiomic signatures to identify microscopic genetic and molecular differences, thus radiomics is considered a suitable tool for judging the TMB status probably. In this paper, the radiomics method was applied to analyze the TMB status of NSCLC patients, so as to construct a prediction model for distinguishing between TMB-high and TMB-low status. Methods: A total of 189 NSCLC patients with TMB detection result were retrospectively included between 30 November 2016 and 1 January 2021, and were divided into two groups: TMB-high (≥10/Mb, 46 patients) and TMB-low (<10/Mb, 143 patients). Some clinical features related to TMB status were screened out in 14 clinical features and 2,446 radiomic features were extracted. All patients were randomly divided into a training set (n=132) and a validation set (n=57). Univariate analysis and least absolute shrinkage and selection operator (LASSO) were used for radiomics feature screening. A clinical model, radiomics model, and nomogram were constructed with the above screened features and compared. Decision curve analysis (DCA) was used to evaluate the clinical value of the established models. Results: Two clinical features (smoking history, pathological type) and 10 radiomics features were significantly correlated with the TMB status. The prediction efficiency of the intra-tumoral model was better than that of the peritumoral model (AUC: 0.819 vs. 0.816; accuracy: 0.773 vs. 0.632, specificity: 0.767 vs. 0.558). The efficacy of the prediction model based on radiomic features was significantly better than that of the clinical model (AUC: 0.822 vs. 0.683; specificity: 0.786 vs. 0.643). The nomogram, established by combining smoking history, pathologic type, and rad-score, showed the best diagnostic efficacy (AUC =0.844) and had potential clinical value in assessing the TMB status of NSCLC. Conclusions: The radiomics model based on CT images of NSCLC patients performed well in distinguishing the status of TMB-high and TMB-low, and the nomogram could provide additional information on the timing and regimen of immunotherapy.

12.
Radiol Case Rep ; 18(5): 1796-1808, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36915609

RESUMEN

A subcutaneous abscess of the penis is a rare condition. It can be idiopathic or have an underlying cause, such as intracavernous injection therapy, foreign body, dilated perineal abscess, abnormal erection, or trauma. Clinical signs are mainly swelling in the penis, penile pain, and swelling. Conventional treatment is primarily surgical incision and drainage, followed by systemic antibiotic therapy. In recent years, with the development of medical technology, minimally invasive interventions and less invasive techniques, such as ultrasound-guided aspiration, are being developed. This article aims to report a case of ultrasound-guided successful diagnosis and treatment of an aseptic idiopathic subcutaneous abscess at the root of the penis and to review the literature on penile abscesses. The patient, a 61-year-old male, underwent ultrasound-guided puncture and drainage using a coaxial aspiration/flushing technique in combination with antibiotics to treat this rare urinary tract condition. The patient recovered well postoperatively and was discharged 3 days later. At a 2-week postoperative follow-up, an ultrasound showed a marked reduction in the penile abscess mass.

13.
Carbohydr Polym ; 307: 120627, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-36781278

RESUMEN

Starch is regarded as one of the most promising sustainable materials due to its abundant yield and excellent biodegradability. From the perspective of practical engineering applications, this paper systematically describes the development of starch-based bio-composites in the past decade. Packaging properties, processing characteristics, and current challenges for the efficient processing of starch-based bio-composites are reviewed in industrial packaging. Green coatings, binders, adsorbents, flocculants, flame retardants, and emulsifiers are used as examples to illustrate the versatility of starch-based bio-composites in chemical agent applications. In addition, the work compares the application of starch-based bio-composites in conventional spinning with emerging spinning technologies and describes the challenges of electrostatic spinning for preparing nanoscale starch-based fibers. In terms of flexible electronics, the starch-based bio-composites are regard as a solid polymer electrolyte and easily modified porous material. Moreover, we describe the applications of the starch-based gels in tissue engineering, controlled drug release, and medical dressings. Finally, the theoretical input and technical guidance in the advanced sustainable engineering application of the starch-based bio-composites are provided in the work.


Asunto(s)
Polímeros , Almidón , Almidón/química , Ingeniería de Tejidos
14.
Dig Dis Sci ; 68(1): 138-146, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35451710

RESUMEN

BACKGROUND AND AIMS: We have previously shown that gabexate mesylate-poloxamer 407 conjugate (GMTI) alleviates traumatic pancreatitis in rats. In this study, we evaluated the therapeutic effect of GMTI on sodium taurocholate-induced severe acute pancreatitis (SAP) in an optimized rat model. METHODS: An SAP rat model was established via microinjection of 3.5% sodium taurocholate and retention in the bile duct for 1 min. SAP rats were administered GMTI via tail vein injection (i.v.) or tail vein injection + intraperitoneal injection (i.v. + i.p.). All rats were sacrificed at 12 h after treatment. Biochemical approach and enzyme-linked immunosorbent assay were performed to measure the serum levels of amylase (AMY), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Hematoxylin and eosin staining and TUNEL assay were conducted to examine histopathology and acinar cell apoptosis in the rat pancreas. RESULTS: SAP was successfully induced in all model rats, as evidenced by progressively aggravating SAP symptoms and signs, pancreatic histopathological abnormalities, as well as elevated serum levels of TNF-α, IL-6, and AMY. The mortality rates at 1 h, 6 h, and 12 h were 0%, 0%, and 25%, respectively. GMTI therapy via i.v. or i.v. + i.p. significantly reduced pancreatic wet weights, ascites amounts, pathological scores, and circulating levels of TNF-α and IL-6 while promoting acinar cell apoptosis in SAP rats. GMTI therapy via i.v. + i.p. outperformed i.v. in improving pancreatic histology and reducing TNF-α and IL-6 serum levels in SAP rats. CONCLUSIONS: Our optimized SAP rat model is reliable and reproducible. GMTI therapy is a promising approach against SAP.


Asunto(s)
Gabexato , Pancreatitis , Ratas , Animales , Pancreatitis/inducido químicamente , Pancreatitis/tratamiento farmacológico , Pancreatitis/patología , Gabexato/efectos adversos , Poloxámero/farmacología , Interleucina-6 , Factor de Necrosis Tumoral alfa , Ratas Sprague-Dawley , Ácido Taurocólico , Enfermedad Aguda , Páncreas/patología
15.
Radiol Case Rep ; 17(10): 3595-3600, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35923338

RESUMEN

Segmental testicular infarction is a rare clinical condition most often seen as acute unilateral scrotal pain. Segmental testicular infarction should be suspected in patients with scrotal pain; when an ultrasound shows hypoechoic or mixed echogenic lesions within the testicular parenchyma; contrast-enhanced ultrasound shows a little or no contrast filling, along with negative multiple tumor markers. This report presents a 60-year-old male who presented with sudden onset of left testicular pain with no apparent cause. Emergency Doppler ultrasound, contrast-enhanced ultrasound, and laboratory tests showed findings characteristic of Segmental testicular infarction. The patient the final diagnosis was based on a combination of clinical findings (regression or cessation of symptoms, no tumor marker abnormalities, no palpable testicular mass) and ultrasound evidence of improvement (size reduction or shape change from oval to wedge) during a follow-up period of at least 3 months.

16.
Mol Imaging Biol ; 24(6): 909-919, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35705779

RESUMEN

PURPOSE: Sigma-1 receptor (Sig-1R), a chaperone that resides at the mitochondrion-associated endoplasmic reticulum (ER) membrane, is an ER stress biomarker. It is thought that ER stress plays a critical role in the progression of metabolic-associated fatty liver disease (MAFLD). The aim of this study was to evaluate a positron emission tomography (PET) tracer [18F]F-TZ3108 targeting Sig-1R for MAFLD. PROCEDURES: The mouse model of MAFLD was established by feeding high-fat diet (HFD) for 12 weeks. Dynamic (0-60 min) PET/CT scans were performed after intravenous injection of 2-deoxy-2[18F]fluoro-D-glucose ([18F]-FDG) and [18F]F-TZ3108. Tracer kinetic modeling was performed for quantification of the PET/CT imaging of the liver. Post-PET biodistribution, the liver tissue western blotting (WB), and immunofluorescence (IF) were performed to compare the expression of Sig-1R levels in the organs harvested from both MAFLD and age-matched control mice. RESULTS: The micro PET/CT imaging revealed a significantly decreased uptake of [18F]F-TZ3108 in the livers of the MAFLD group compared to the healthy controls, while the uptake of [18F]-FDG in the livers was not significantly different between the two groups. Based on the tracer kinetic modeling, the binding disassociate rate (k4) for [18F]F-TZ3108 was significantly increased in MAFLD group compared to healthy controls. The volume distribution (VT), and the non-displacement binding potential (BPND) revealed significantly decrease in MAFLD compared to healthy controls respectively. The post-PET biodistribution (%ID/g) of [18F]F-TZ3108 in the livers of MAFLD mice was significantly reduced nearly twofold than that in the livers of control mice. WB and IF experiments further confirmed the reduction of Sig-1R expression in the MAFLD group. CONCLUSIONS: The expression of Sig-1R in the liver, measured by the PET tracer, [18F]F-TZ3108, was significantly decreased in mouse model of MAFLD. The [18F]F-TZ3108 PET/CT imaging may provide a novel means of visualization for ER stress in MAFLD or other diseases in vivo.


Asunto(s)
Fluorodesoxiglucosa F18 , Hepatopatías , Animales , Ratones , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Distribución Tisular , Tomografía de Emisión de Positrones/métodos
17.
Transl Cancer Res ; 11(3): 559-568, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35402180

RESUMEN

Background: The aim of this study was to evaluate the effect of ligustrazine on the apoptosis of A549 cells and clarify the mechanism of ligustrazine-induced apoptosis. Methods: Ligustrazine was prepared with medium according to the gradient concentration. Based on a cytotoxicity test, 3 different concentrations of ligustrazine were selected to form low, medium, and high groups, with a 0 mg/mL dose used as the control. The apoptosis degree and Fas (Fas cell surface death receptor) and Fas-L (Fas Ligand) expression were detected by flow cytometry and quantitative polymerase chain reaction (qPCR), respectively; meanwhile, the activity of caspase 8 and caspase 3 was analyzed by enzyme-linked immunosorbent assay (ELISA) and qPCR, respectively. Results: After 24 hours of ligustrazine administration, the survival rate of A549 cells decreased with the increase of drug concentration, while the rate of apoptosis increased with the increase of drug concentration. Meanwhile, Fas and Fas-L expression was found to be significantly increased at both the gene and protein level, which was positively correlated with drug concentration. Furthermore, the expression of caspase 8 and caspase 3 was positively correlated with the concentration of ligustrazine, and there was significant difference compared with the control group. Conclusions: Ligustrazine can induce the apoptosis of A549 cells via the upregulation of Fas- and caspase-activating death receptor pathway expression.

18.
Cancer Cell Int ; 22(1): 21, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-35033072

RESUMEN

BACKGROUND: Molecular markers play an important role in predicting clinical outcomes in pancreatic adenocarcinoma (PAAD) patients. Analysis of the ferroptosis-related genes may provide novel potential targets for the prognosis and treatment of PAAD. METHODS: RNA-sequence and clinical data of PAAD was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) public databases. The PAAD samples were clustered by a non-negative matrix factorization (NMF) algorithm. The differentially expressed genes (DEGs) between different subtypes were used by "limma_3.42.2" package. The R software package clusterProfiler was used for functional enrichment analysis. Then, a multivariate Cox proportional and LASSO regression were used to develop a ferroptosis-related gene signature for pancreatic adenocarcinoma. A nomogram and corrected curves were constructed. Finally, the expression and function of these signature genes were explored by qRT-PCR, immunohistochemistry (IHC) and proliferation, migration and invasion assays. RESULTS: The 173 samples were divided into 3 categories (C1, C2, and C3) and a 3-gene signature model (ALOX5, ALOX12, and CISD1) was constructed. The prognostic model showed good independent prognostic ability in PAAD. In the GSE62452 external validation set, the molecular model also showed good risk prediction. KM-curve analysis showed that there were significant differences between the high and low-risk groups, samples with a high-risk score had a worse prognosis. The predictive efficiency of the 3-gene signature-based nomogram was significantly better than that of traditional clinical features. For comparison with other models, that our model, with a reasonable number of genes, yields a more effective result. The results obtained with qPCR and IHC assays showed that ALOX5 was highly expressed, whether ALOX12 and CISD1 were expressed at low levels in tissue samples. Finally, function assays results suggested that ALOX5 may be an oncogene and ALOX12 and CISD1 may be tumor suppressor genes. CONCLUSIONS: We present a novel prognostic molecular model for PAAD based on ferroptosis-related genes, which serves as a potentially effective tool for prognostic differentiation in pancreatic cancer patients.

19.
Ann Diagn Pathol ; 55: 151835, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34624626

RESUMEN

Juvenile hyaline fibromatosis (JHF) is an extremely rare autosomal recessive disease that typically presents in infancy or early childhood. Largely due to the rarity, JHF is still not widely recognized by clinicians and pathologists in China. It is not uncommonly to misdiagnose the disease as other types of disorders. In this study, we present our experience with five cases of JHF to enhance the recognition of this rare but distinctive entity. There were 4 males and 1 female, with age at presentation ranging from 5 to 44 years. All patients presented with multiple subcutaneous nodular lesions of varying size in various parts of the body since birth or early childhood. Three patients also had joint involvement. Pathologically, the lesions were poorly circumscribed, located mainly in the dermis and subcutis. All five cases were characterized by abundant homogeneous hyaline-like matrix that differs sharply from the adjacent connective tissue, which stained strongly with periodic acid-Schiff (PAS) and was diastase resistant. Embedded within the eosinophilic glassy matrix were cords or small clusters of plump spindled to epithelioid cells, frequently with clear cytoplasm. Familiarity with the characteristic features of JHF is not only important in avoiding misdiagnosis but also essential for clinical management and prognostic evaluation.


Asunto(s)
Síndrome de Fibromatosis Hialina , Adolescente , Adulto , Preescolar , China , Trastornos de los Cromosomas/diagnóstico , Trastornos de los Cromosomas/patología , Femenino , Humanos , Síndrome de Fibromatosis Hialina/diagnóstico , Síndrome de Fibromatosis Hialina/patología , Masculino , Pronóstico , Receptores de Péptidos/análisis , Receptores de Péptidos/metabolismo , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología
20.
J Neurochem ; 156(1): 59-75, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32383496

RESUMEN

Natural scenes contain complex visual cues with specific features, including color, motion, flicker, and position. It is critical to understand how different visual features are processed at the early stages of visual perception to elicit appropriate cellular responses, and even behavioral output. Here, we studied the visual orientation response induced by flickering stripes in a novel behavioral paradigm in Drosophila melanogaster. We found that free walking flies exhibited bandpass orientation response to flickering stripes of different frequencies. The most sensitive frequency spectrum was confined to low frequencies of 2-4 Hz. Through genetic silencing, we showed that lamina L1 and L2 neurons, which receive visual inputs from R1 to R6 neurons, were the main components in mediating flicker-induced orientation behavior. Moreover, specific blocking of different types of lamina feedback neurons Lawf1, Lawf2, C2, C3, and T1 modulated orientation responses to flickering stripes of particular frequencies, suggesting that bandpass orientation response was generated through cooperative modulation of lamina feedback neurons. Furthermore, we found that lamina feedback neurons Lawf1 were glutamatergic. Thermal activation of Lawf1 neurons could suppress neural activities in L1 and L2 neurons, which could be blocked by the glutamate-gated chloride channel inhibitor picrotoxin (PTX). In summary, lamina monopolar neurons L1 and L2 are the primary components in mediating flicker-induced orientation response. Meanwhile, lamina feedback neurons cooperatively modulate the orientation response in a frequency-dependent way, which might be achieved through modulating neural activities of L1 and L2 neurons.


Asunto(s)
Encéfalo/fisiología , Neuronas/fisiología , Orientación Espacial/fisiología , Percepción Visual/fisiología , Animales , Drosophila melanogaster , Retroalimentación , Estimulación Luminosa
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