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1.
Transl Oncol ; 50: 102130, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39303357

RESUMEN

Ovarian cancer is a highly heterogeneous tumor with a poor prognosis. The lack of reliable and efficient research models that can accurately mimic heterogeneity has impeded in-depth investigations and hindered the clinical translation of research findings in ovarian cancer. Organoid models have emerged as a promising in vitro approach, demonstrating remarkable fidelity to the histological, molecular, genomic, and transcriptomic features of their tissues of origin. In recent years, organoids have contributed to advancing our understanding of ovarian cancer initiation, metastasis, and drug resistance mechanisms, as well as facilitating clinical screening of effective therapeutic agents. The establishment of high-throughput organoid culture systems, coupled with cutting-edge technologies such as organ-on-a-chip, genetic engineering, and 3D printing, has tremendous potential for accelerating ovarian cancer research translation. In this review, we present a comprehensive overview of the latest exploration of organoids in basic ovarian cancer research and clinical translation. Furthermore, we discuss the prospects and challenges associated with the use of organoids and related novel technologies in the context of ovarian cancer. This review provides insights into the application of organoids in ovarian cancer.

2.
Cell ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39243765

RESUMEN

Sneezing and coughing are primary symptoms of many respiratory viral infections and allergies. It is generally assumed that sneezing and coughing involve common sensory receptors and molecular neurotransmission mechanisms. Here, we show that the nasal mucosa is innervated by several discrete populations of sensory neurons, but only one population (MrgprC11+MrgprA3-) mediates sneezing responses to a multitude of nasal irritants, allergens, and viruses. Although this population also innervates the trachea, it does not mediate coughing, as revealed by our newly established cough model. Instead, a distinct sensory population (somatostatin [SST+]) mediates coughing but not sneezing, unraveling an unforeseen sensory difference between sneezing and coughing. At the circuit level, sneeze and cough signals are transmitted and modulated by divergent neuropathways. Together, our study reveals the difference in sensory receptors and neurotransmission/modulation mechanisms between sneezing and coughing, offering neuronal drug targets for symptom management in respiratory viral infections and allergies.

3.
Adv Mater ; : e2406296, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39233551

RESUMEN

Li-TFSI doped spiro-OMeTAD is widely recognized as a beneficial hole transport layer (HTL) in perovskite solar cells (PSCs), contributing to high device efficiencies. However, the uncontrolled migration of lithium ions (Li+) during device operation has impeded its broad adoption in scalable and stable photovoltaic modules. Herein, an additive strategy is proposed by employing ferrocenium hexafluorophosphate (FcPF6) as a relay medium to enhance the hole extraction capability of the spiro-OMeTAD via the instant oxidation function. Besides, the novel Fc-Li interaction effectively restricts the movement of Li+. Simultaneously, the dissociative hexafluorophosphate group is cleverly exploited to regulate the unstable iodide species on the perovskite surface, further inhibiting the formation of migration channels and stabilizing the interfaces. This modification leads to power conversion efficiencies (PCEs) reaching 22.13% and 20.27% in 36 cm2 (active area of 18 cm2) and 100 cm2 (active area of 56 cm2) perovskite solar modules (PSMs), respectively, with exceptional operational stability obtained for over 1000 h under the ISOS-L-1 procedure. The novel FcPF6-based engineering approach is pivotal for advancing the industrialization of PSCs, particularly those relying on high-performance spiro-OMeTAD- based HTLs.

4.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(9): 986-988, 2024.
Artículo en Chino | MEDLINE | ID: mdl-39267516

RESUMEN

Patient 1, a 12-day-old female infant, presented with fever, cough, dyspnea, and elevated infection markers, requiring respiratory support. Metagenomic next-generation sequencing (mNGS) of blood and bronchoalveolar lavage fluid revealed Legionella pneumophila (LP), leading to diagnoses of LP pneumonia and LP sepsis. The patient was treated with erythromycin for 15 days and azithromycin for 5 days, resulting in recovery and discharge. Patient 2, an 11-day-old female infant, presented with dyspnea, fever, elevated infection markers, and multiple organ dysfunction, requiring mechanical ventilation. mNGS of blood and cerebrospinal fluid indicated LP, leading to diagnoses of LP pneumonia, LP sepsis, and LP intracranial infection. The patient was treated with erythromycin for 19 days and was discharged after recovery. Neonatal LP pneumonia lacks specific clinical symptoms, and azithromycin is the preferred antimicrobial agent. The use of mNGS can provide early and definitive diagnosis for severe neonatal pneumonia of unknown origin.


Asunto(s)
Enfermedad de los Legionarios , Humanos , Femenino , Recién Nacido , Enfermedad de los Legionarios/diagnóstico , Enfermedad de los Legionarios/tratamiento farmacológico
5.
Artículo en Inglés | MEDLINE | ID: mdl-39288064

RESUMEN

The Dunning-Kruger Effect (DKE) is a metacognitive phenomenon where low-skilled individuals tend to overestimate their competence while high-skilled individuals tend to underestimate their competence. This effect has been observed in a number of domains including humor, grammar, and logic. In this paper, we explore if and how DKE manifests in visual reasoning and judgment tasks. Across two online user studies involving (1) a sliding puzzle game and (2) a scatterplot-based categorization task, we demonstrate that individuals are susceptible to DKE in visual reasoning and judgment tasks: those who performed best underestimated their performance, while bottom performers overestimated their performance. In addition, we contribute novel analyses that correlate susceptibility of DKE with personality traits and user interactions. Our findings pave the way for novel modes of bias detection via interaction patterns and establish promising directions towards interventions tailored to an individual's personality traits. All materials and analyses are in supplemental materials: https://github.com/CAV-Lab/DKE_supplemental.git.

6.
Ther Adv Med Oncol ; 16: 17588359241271845, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39246808

RESUMEN

Background: Genetic studies of ovarian cancer (OC) have historically focused on BRCA1/2 mutations, lacking other studies of homologous recombination repair (HRR). Poly (ADP-ribose) polymerase inhibitors (PARPi) exploit synthetic lethality to significantly improve OC treatment outcomes, especially in BRCA1/2 deficiency patients. Objectives: Our study aims to construct a mutation map of HRR genes in OC and identify factors influencing the efficacy of PARPi. Design: A retrospective observational analysis of HRR gene variation data from 695 OC patients from March 2019 to February 2022 was performed. Methods: The HRR gene variation data of 695 OC patients who underwent next-generation sequencing (NGS) in the First Affiliated Hospital of Zhengzhou University were retrospectively collected. Clinical data on the use of PARPi in these patients were also gathered to identify factors that may interfere with the efficacy of PARPi. Results: Out of 127 pathogenic variants in the BRCA1/2 genes, 104 (81.9%) were BRCA1 mutations, and 23 (18.1%) were BRCA2 mutations. Among the 59 variants of uncertain significance (VUS), 20 (33.9%) were BRCA1, while 39 (66.1%) were BRCA2 mutations. In addition to BRCA1/2, HRR gene results showed that 9 (69%) of 13 were HRR pathway pathogenic variants; and 16 (1.7%) of 116 VUS were Food and Drug Administration (FDA)-approved mutated HRR genes. Notably, the treatment regimen significantly influenced the effectiveness of PARPi, especially when using first-line maintenance therapy, leading to enhanced progression-free survival (PFS) compared to alternative protocols. Conclusion: Focusing on HRR gene mutations and supporting clinical research about PARPi in OC patients is crucial for developing precision treatment strategies and enhancing prognosis.

7.
Eur J Med Chem ; 277: 116753, 2024 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-39142150

RESUMEN

Previously, we reported a novel natural scaffold compound, isobavachin (4',7-dihydroxy-8-prenylflavanone), as a highly potent hURAT1 inhibitor with anti-hyperuricemia effect. However, the structure-activity relationship remains unknown and the poor pharmacokinetic (PK) parameters may limit further clinical use. Herein, a series of isobavachin derivatives were rationally designed and synthesized to explore the structure-activity relationship of isobavachin target hURAT1, and to improve their PK properties. Among them, compounds 15d, 15f, 15g, 27b and 27d showed promising hURAT1 inhibitory activities, which could comparable to that of isobavachin (IC50 = 0.24 µM). In addition, 27b also inhibited another urate reabsorption transporter GLUT9 with an IC50 of 4.47 µM. Compound 27b displayed greater urate-lowering activity in a hyperuricemia mouse model at a dose of 10 mg/kg compared to isobavachin and lesinurad. Overall, our results suggest that compound 27b represents a novel, safe hURAT1 and GLUT9 dual-target inhibitor with excellent drug availability and is worthy of further investigation as an anti-hyperuricemia agent.


Asunto(s)
Diseño de Fármacos , Hiperuricemia , Animales , Humanos , Masculino , Ratones , Relación Dosis-Respuesta a Droga , Hiperuricemia/tratamiento farmacológico , Estructura Molecular , Transportadores de Anión Orgánico/antagonistas & inhibidores , Transportadores de Anión Orgánico/metabolismo , Proteínas de Transporte de Catión Orgánico/antagonistas & inhibidores , Proteínas de Transporte de Catión Orgánico/metabolismo , Relación Estructura-Actividad , Ácido Úrico/sangre
8.
Spectrochim Acta A Mol Biomol Spectrosc ; 322: 124828, 2024 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-39029204

RESUMEN

Zn2+ plays a vital role in regulating various life processes, such as gene expression, cell signaling, and brain function. In this study, a near-infrared fluorescent probe AXS was synthesized to detect Zn2+ with good fluorescence specificity, high selectivity, and high sensitivity; the detection limit of Zn2+ was 6.924 × 10-11 M. The mechanism of Zn2+ recognition by the AXS probe was investigated by 1H nuclear magnetic resonance titrations, UV-visible spectroscopy, fluorescence spectroscopy, Fourier-transform infrared spectroscopy, and high-resolution mass spectrometry. Test paper experiments showed that the AXS probe could detect Zn2+ in real samples. In addition, quantitative and qualitative detection of Zn2+ in common foodstuffs was achieved. For portable Zn2+ detection, a smartphone detection platform was also developed based on the AXS probe. Importantly, the AXS probe showed good bioimaging capabilities in Caenorhabditis elegans and mice.


Asunto(s)
Caenorhabditis elegans , Colorantes Fluorescentes , Zinc , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Animales , Zinc/análisis , Ratones , Espectrometría de Fluorescencia/métodos , Límite de Detección , Teléfono Inteligente , Imagen Óptica/métodos
9.
J Vis Exp ; (207)2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38829124

RESUMEN

Functional genomics screening offers a powerful approach to probe gene function and relies on the construction of genome-wide plasmid libraries. Conventional approaches for plasmid library construction are time-consuming and laborious. Therefore, we recently developed a simple and efficient method, CRISPR-based modular assembly (CRISPRmass), for high-throughput construction of a genome-wide upstream activating sequence-complementary DNA/open reading frame (UAS-cDNA/ORF) plasmid library. Here, we present a protocol for CRISPRmass, taking as an example the construction of a GAL4/UAS-based UAS-cDNA/ORF plasmid library. The protocol includes massively parallel two-step test tube reactions followed by bacterial transformation. The first step is to linearize the existing complementary DNA (cDNA) or open reading frame (ORF) cDNA or ORF library plasmids by cutting the shared upstream vector sequences adjacent to the 5' end of cDNAs or ORFs using CRISPR/Cas9 together with single guide RNA (sgRNA), and the second step is to insert a UAS module into the linearized cDNA or ORF plasmids using a single step reaction. CRISPRmass allows the simple, fast, efficient, and cost-effective construction of various plasmid libraries. The UAS-cDNA/ORF plasmid library can be utilized for gain-of-function screening in cultured cells and for constructing a genome-wide transgenic UAS-cDNA/ORF library in Drosophila.


Asunto(s)
Sistemas CRISPR-Cas , Biblioteca de Genes , Sistemas de Lectura Abierta , Plásmidos , Plásmidos/genética , Animales , Sistemas CRISPR-Cas/genética , Sistemas de Lectura Abierta/genética , ADN Complementario/genética , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , Drosophila melanogaster/genética
10.
ACS Appl Mater Interfaces ; 16(22): 28193-28208, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38776411

RESUMEN

Ferroptosis therapy and immunotherapy have been widely used in cancer treatment. However, nonselective induction of ferroptosis in tumors is prone to immunosuppression, limiting the therapeutic effect of ferroptosis cancer treatment. To address this issue, this study reports a customized hybrid nanovesicle composed of NK cell-derived extracellular versicles and RSL3-loaded liposomes (hNRVs), aiming to establish a positive cycle between ferroptosis therapy and immunotherapy. Thanks to the enhanced permeability and retention effect and the tumor homing characteristics of NK exosomes, our data indicate that hNRVs can actively accumulate in tumors and enhance cellular uptake. FASL, IFN-γ, and RSL3 are released into the tumor microenvironment, where FASL derived from NK cells effectively lyses tumor cells. RSL3 downregulates the expression of GPX4 in the tumor, leading to the accumulation of LPO and ROS, and promotes ferroptosis in tumor cells. The accumulation of IFN-γ and TNF-α stimulates the maturation of dendritic cells and effectively induces the inactivation of GPX4, promoting lipid peroxidation, making them sensitive to ferroptosis and indirectly promoting the occurrence of ferroptosis. This study highlights the role of the customized hNRV platform in enhancing the effectiveness of synergistic treatment with selective delivery of ferroptosis inducers and immune activation against glioma without causing additional side effects on healthy organs.


Asunto(s)
Exosomas , Ferroptosis , Glioma , Inmunoterapia , Células Asesinas Naturales , Liposomas , Ferroptosis/efectos de los fármacos , Exosomas/metabolismo , Exosomas/química , Liposomas/química , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Células Asesinas Naturales/efectos de los fármacos , Animales , Ratones , Glioma/terapia , Glioma/patología , Glioma/tratamiento farmacológico , Glioma/inmunología , Glioma/metabolismo , Humanos , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Línea Celular Tumoral , Interferón gamma/metabolismo , Microambiente Tumoral/efectos de los fármacos , Ratones Endogámicos C57BL , Especies Reactivas de Oxígeno/metabolismo , Carbolinas
11.
ChemSusChem ; : e202400266, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38777790

RESUMEN

Herein, we propose a simple and effective fluoride (F-) ions post-treatment method to improve the solar water splitting performance of monoclinic BiVO4 (abbreviated as BVO). The surface modification of BVO with functional F- ions not only facilitates the transfer and separation efficiency of carriers at the electrode/electrolyte interface but also promotes the adsorption and activation of water, resulting in a photocurrent of 3.2 mA/cm2 at a bias voltage of 1.2 VRHE. Furthermore, the transfer and separation of carriers in the bulk and on the surface are further regulated by the oxygen vacancies induced by F- ions, thereby enhancing the PEC water splitting performance of BVO. Notably, the experimental findings demonstrate that the introduce of F- ions into the KBi electrolyte enhances the photo-charging process of BVO. Specifically, at a bias voltage of 0.6 VRHE, the BVO-0.12F sample exhibits a stable photocurrent of 1.2 mA/cm2, which is twice as high as that of the initial BVO sample. Remarkably, our study unveils that the addition of F- ions into the KBi electrolyte solution plays a pivotal role in facilitating the separation of charge carriers and promoting interfacial charge transport. Consequently, this further leads to a substantial enhancement in the solar water splitting performance for BVO-0.12F photoanode.

12.
BMC Med Educ ; 24(1): 405, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605345

RESUMEN

BACKGROUND: In medical imaging courses, due to the complexity of anatomical relationships, limited number of practical course hours and instructors, how to improve the teaching quality of practical skills and self-directed learning ability has always been a challenge for higher medical education. Artificial intelligence-assisted diagnostic (AISD) software based on volume data reconstruction (VDR) technique is gradually entering radiology. It converts two-dimensional images into three-dimensional images, and AI can assist in image diagnosis. However, the application of artificial intelligence in medical education is still in its early stages. The purpose of this study is to explore the application value of AISD software based on VDR technique in medical imaging practical teaching, and to provide a basis for improving medical imaging practical teaching. METHODS: Totally 41 students majoring in clinical medicine in 2017 were enrolled as the experiment group. AISD software based on VDR was used in practical teaching of medical imaging to display 3D images and mark lesions with AISD. Then annotations were provided and diagnostic suggestions were given. Also 43 students majoring in clinical medicine from 2016 were chosen as the control group, who were taught with the conventional film and multimedia teaching methods. The exam results and evaluation scales were compared statistically between groups. RESULTS: The total skill scores of the test group were significantly higher compared with the control group (84.51 ± 3.81 vs. 80.67 ± 5.43). The scores of computed tomography (CT) diagnosis (49.93 ± 3.59 vs. 46.60 ± 4.89) and magnetic resonance (MR) diagnosis (17.41 ± 1.00 vs. 16.93 ± 1.14) of the experiment group were both significantly higher. The scores of academic self-efficacy (82.17 ± 4.67) and self-directed learning ability (235.56 ± 13.50) of the group were significantly higher compared with the control group (78.93 ± 6.29, 226.35 ± 13.90). CONCLUSIONS: Applying AISD software based on VDR to medical imaging practice teaching can enable students to timely obtain AI annotated lesion information and 3D images, which may help improve their image reading skills and enhance their academic self-efficacy and self-directed learning abilities.


Asunto(s)
Inteligencia Artificial , Educación Médica , Humanos , Programas Informáticos , Aprendizaje , Tomografía Computarizada por Rayos X , Enseñanza
13.
J Hazard Mater ; 469: 133968, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38452682

RESUMEN

Pb2+ is a heavy metal ion pollutant that poses a serious threat to human health and ecosystems. The conventional methods for detecting Pb2+ have several limitations. In this study, we introduce a novel fluorescent probe that enables the detection of Pb2+ in the near-infrared region, free from interference from other common ions. A unique characteristic of this probe is its ability to rapidly and accurately identify Pb2+ through ratiometric measurements accompanied by a large Stokes shift of 201 nm. The limit of detection achieved by probe was remarkably low, surpassing the standards set by the World Health Organization, and outperforming previously reported probes. To the best of our knowledge, this is the first organic small-molecule fluorescent probe with both near-infrared emission and ratiometric properties for the detection of Pb2+. We present a triple-mode sensing platform constructed using a probe that allows for the sensitive and selective recognition of Pb2+ in common food items. Furthermore, we successfully conducted high-quality fluorescence imaging of Pb2+ in various samples from common edible plants, HeLa cells, Caenorhabditis elegans, and mice. Importantly, the probe-Pb2+ complex exhibited tumour-targeting capabilities. Overall, this study presents a novel approach for the development of fluorescent probes for Pb2+ detection.


Asunto(s)
Colorantes Fluorescentes , Plomo , Humanos , Animales , Ratones , Células HeLa , Ecosistema
14.
Front Cardiovasc Med ; 11: 1303529, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38390440

RESUMEN

Background: In this study, we aim to investigate the relationship between the attenuation of peri-coronary adipose tissue (PCAT) in patients with suspected coronary artery disease (CAD) and the assessment of coronary vascular functions using coronary flow reserve (CFR). Methods: We included 364 patients who underwent 13N-NH3 positron emission tomography/computed tomography and coronary computed tomography angiography (CCTA). We determined the relationship between fat attenuation index (FAI), PCAT volume, and other qualitative CT-derived anatomic parameters with CFR. Results: We detected a decrease in CFR (<2.5) in 206 (57%) patients. At the patient level, those with reduced CFR showed a significantly higher prevalence of diffused atherosclerosis (41% vs. 23%; P < 0.001) and higher FAI (-75.5 HU vs. -77.1 HU; P = 0.014). In patients without obstructive CAD, FAI was significantly higher in those with reduced CFR (-75.5 HU vs. -77.7 HU, P = 0.026). On the vessel level, 1,092 vessels were analyzed, and 642 (59%) exhibited reduced CFR. The vessels with reduced CFR presented a significantly higher prevalence of obstructive CAD (37% vs. 26%; P < 0.001), diffused atherosclerosis (22% vs. 11%; P < 0.001), low-attenuation plaque (6% vs. 3%; P = 0.030), and positive remodeling (7% vs. 2%; P = 0.001). FAI was higher in vessels with reduced CFR (-80.8 HU vs. -81.8 HU; P = 0.045) than in normal CFR. In the patient-level analysis, obstructive CAD, diffused atherosclerosis, and FAI were independently linked with CFR. FAI was still associated with global CFR after adjusting for traditional risk factors (age, hypertension, diabetes, hyperlipidemia, and smoking). FAI remained independently associated with reduced CFR in patients without obstructive CAD. Conclusions: Coronary perivascular inflammation evaluated by CCTA was independently associated with coronary vascular function. In patients without obstructive CAD, FAI was higher in the presence of reduced CFR. Altogether, FAI can help reveal microcirculatory damage in patients who do not exhibit epicardial artery stenosis.

15.
J Phys Chem Lett ; 15(9): 2453-2461, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38407025

RESUMEN

The organic-inorganic halide perovskite has become one of the most promising candidates for next-generation memory devices, i.e. memristors, with excellent performance and solution-processable preparation. Yet, the mechanism of resistive switching in perovskite-based memristors remains ambiguous due to a lack of in situ visualized characterization methods. Here, we directly observe the switching process of perovskite memristors with in situ photoluminescence (PL) imaging microscopy under an external electric field. Furthermore, the corresponding element composition of conductive filaments (CFs) is studied, indicating that the metallic CFs with respect to the activity of the top electrode are essential for device performance. Finally, electrochemical impedance spectroscopy (EIS) is conducted to reveal that the transition of ion states is associated with the formation of metallic CFs. This study provides in-depth insights into the switching mechanism of perovskite memristors, paving a pathway to develop and optimize high-performance perovskite memristors for large-scale applications.

16.
J Biomed Mater Res A ; 112(5): 700-709, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-37962013

RESUMEN

Sensorineural hearing loss (SNHL) is caused by the loss of sensory hair cells (HCs) and/or connected spiral ganglion neurons (SGNs). The current clinical conventional treatment for SNHL is cochlear implantation (CI). The principle of CI is to bypass degenerated auditory HCs and directly electrically stimulate SGNs to restore hearing. However, the effectiveness of CI is limited when SGNs are severely damaged. In the present study, oriented nanofiber scaffolds were fabricated using electrospinning technology to mimic the SGN spatial microenvironment in the inner ear. Meanwhile, different proportions of polyaniline (PANI), poly-l-lactide (PLLA), gelatin (Gel) were composited to mimic the composition and mechanical properties of auditory basement membrane. The effects of oriented PANI/PLLA/Gel biomimetic nanofiber scaffolds for neurite outgrowth were analyzed. The results showed the SGNs grew in an orientation along the fiber direction, and the length of the protrusions increased significantly on PANI/PLLA/Gel scaffold groups. The 2% PANI/PLLA/Gel group showed best effects for promoting SGN adhesion and nerve fiber extension. In conclusion, the biomimetic oriented nanofiber scaffolds can simulate the microenvironment of SGNs as well as promote neurite outgrowth in vitro, which may provide a feasible research idea for SGN regeneration and even therapeutic treatments of SNHL in future.


Asunto(s)
Compuestos de Anilina , Nanofibras , Poliésteres , Ganglio Espiral de la Cóclea , Ganglio Espiral de la Cóclea/fisiología , Gelatina/farmacología , Neuronas
17.
Radiat Oncol ; 18(1): 183, 2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-37936130

RESUMEN

BACKGROUND: Radiotherapy is widely used in treating cervical cancer patients, however, radioresistance unavoidably occurs and seriously affects the treatment effect. It is well known that hypoxia plays an important role in promoting radioresistance in tumor microenvironment, yet our understanding of the effect of small extracellular vesicles miRNA on cervical cancer radiosensitivity in hypoxic environment is still limited. METHODS: Small extracellular vesicles extracted from hypoxic and normoxic cultured cervical cancer cells were evaluated for their effects on radioresistance. miR-152-3p was found to be a potential effector in hypoxia-derived extracellular vesicles by searching the GEO database. Its downstream substrate was confirmed by double luciferase report, which was KLF15. The role of miR-152-3p and KLF15 in regulating cervical cancer radioresistance was detected by cell activity assays. The findings were confirmed in vivo by animal models. The expression of miR-152-3p was quantified by qRT-PCR and its prognostic significance was evaluated. RESULTS: Hypoxic environment promoted the secretion of small extracellular vesicles, and reduced the apoptosis and DNA damage caused by radiation, accompanied by increased expression of small extracellular vesicles miR-152-3p from hypoxic cervical cancer cells. Furthermore, small extracellular vesicles miR-152-3p promoted Hela xenograft growth and reduced the radiosensitivity vivo. Mechanism studies revealed that KLF15 protein was the downstream target of miR-152-3p in regulating radioresistance. CONCLUSION: Our findings suggest that small extracellular vesicles miR-152-3p affects the therapeutic effect of radiotherapy and holds potential as a biomarker or therapeutic target for cervical cancer prognosis and improving radiotherapy.


Asunto(s)
MicroARNs , Neoplasias del Cuello Uterino , Femenino , Animales , Humanos , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Apoptosis/genética , Células HeLa , Hipoxia/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/genética , Microambiente Tumoral , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo
18.
ACS Biomater Sci Eng ; 9(12): 6610-6622, 2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-37988580

RESUMEN

Spinal tumors often lead to more complex complications than other bone tumors. Nerve injuries, dura mater defect, and subsequent cerebrospinal fluid (CSF) leakage generally appear in spinal tumor surgeries and are followed by serious adverse outcomes such as infections and even death. The use of suitable dura mater replacements to achieve multifunctionality in fluid leakage plugging, preventing adhesions, and dural reconstruction is a promising therapeutic approach. Although there have been innovative endeavors to manage dura mater defects, only a handful of materials have realized the targeted multifunctionality. Here, we review recent advances in dura repair materials and techniques and discuss the relative merits in both preclinical and clinical trials as well as future therapeutic options. With these advances, spinal tumor patients with dura mater defects may be able to benefit from novel treatments.


Asunto(s)
Neoplasias de la Columna Vertebral , Humanos , Neoplasias de la Columna Vertebral/etiología , Neoplasias de la Columna Vertebral/cirugía , Pérdida de Líquido Cefalorraquídeo/cirugía , Pérdida de Líquido Cefalorraquídeo/etiología , Pérdida de Líquido Cefalorraquídeo/prevención & control , Procedimientos Neuroquirúrgicos/efectos adversos , Procedimientos Neuroquirúrgicos/métodos , Duramadre/cirugía , Duramadre/lesiones
19.
Cancer Biol Ther ; 24(1): 2287128, 2023 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-38010897

RESUMEN

Radioresistance is the major obstacle that affects the efficacy of radiotherapy which is an important treatment for cervical cancer. By analyzing the databases, we found that aldolase A (ALDOA), which is a key enzyme in metabolic reprogramming, has a higher expression in cervical cancer patients and is associated with poor prognosis. We detected the expression of ALDOA in the constructed cervical cancer radioresistance (RR) cells by repetitive irradiation and found that it was upregulated compared to the control cells. Functional assays were conducted and the results showed that the knockdown of ALDOA in cervical cancer RR cells inhibited the proliferation, migration, and clonogenic abilities by regulating the cell glycolysis. In addition, downregulation of ALDOA enhanced radiation-induced apoptosis and DNA damage by causing G2/M phase arrest and further promoted radiosensitivity of cervical cancer cells. The functions of ALDOA in regulating tumor radiosensitivity were also verified by the mouse tumor transplantation model in vivo. Therefore, our study provides new insights into the functions of ALDOA in regulating the efficacy of radiotherapy and indicates that ALDOA might be a promising target for enhancing radiosensitivity in treating cervical cancer patients.


Asunto(s)
Fructosa-Bifosfato Aldolasa , Neoplasias del Cuello Uterino , Animales , Femenino , Humanos , Ratones , Línea Celular Tumoral , Proliferación Celular/genética , Daño del ADN , Fructosa-Bifosfato Aldolasa/genética , Fructosa-Bifosfato Aldolasa/metabolismo , Regulación Neoplásica de la Expresión Génica , Glucólisis , Tolerancia a Radiación/genética , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/patología
20.
PeerJ ; 11: e16412, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38025749

RESUMEN

Background: Pyroptosis, a lytic form of programmed cell death initiated by inflammasomes, has been reported to be closely associated with tumor proliferation, invasion and metastasis. However, the roles of pyroptosis genes (PGs) in low-grade glioma (LGG) remain unclear. Methods: We obtained information for 1,681 samples, including the mRNA expression profiles of LGGs and normal brain tissues and the relevant corresponding clinical information from two public datasets, TCGA and GTEx, and identified 45 differentially expressed pyroptosis genes (DEPGs). Among these DEPGs, nine hub pyroptosis genes (HPGs) were identified and used to construct a genetic risk scoring model. A total of 476 patients, selected as the training group, were divided into low-risk and high-risk groups according to the risk score. The area under the curve (AUC) values of the receiver operating characteristic (ROC) curves verified the accuracy of the model, and a nomogram combining the risk score and clinicopathological characteristics was used to predict the overall survival (OS) of LGG patients. In addition, a cohort from the Gene Expression Omnibus (GEO) database was selected as a validation group to verify the stability of the model. qRT-PCR was used to analyze the gene expression levels of nine HPGs in paracancerous and tumor tissues from 10 LGG patients. Results: Survival analysis showed that, compared with patients in the low-risk group, patients in the high-risk group had a poorer prognosis. A risk score model combining PG expression levels with clinical features was considered an independent risk factor. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that immune-related genes were enriched among the DEPGs and that immune activity was increased in the high-risk group. Conclusion: In summary, we successfully constructed a model to predict the prognosis of LGG patients, which will help to promote individualized treatment and provide potential new targets for immunotherapy.


Asunto(s)
Glioma , Piroptosis , Humanos , Pronóstico , Glioma/genética , Nomogramas , Factores de Riesgo
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