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1.
Angew Chem Int Ed Engl ; 63(18): e202401924, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38366134

RESUMEN

Nitrate electroreduction reaction (eNO3 -RR) to ammonia (NH3) provides a promising strategy for nitrogen utilization, while achieving high selectivity and durability at an industrial scale has remained challenging. Herein, we demonstrated that the performance of eNO3 -RR could be significantly boosted by introducing two-dimensional Cu plates as electrocatalysts and eliminating the general carrier gas to construct a steady fluid field. The developed eNO3 -RR setup provided superior NH3 Faradaic efficiency (FE) of 99 %, exceptional long-term electrolysis for 120 h at 200 mA cm-2, and a record-high yield rate of 3.14 mmol cm-2 h-1. Furthermore, the proposed strategy was successfully extended to the Zn-nitrate battery system, providing a power density of 12.09 mW cm-2 and NH3 FE of 85.4 %, outperforming the state-of-the-art eNO3 -RR catalysts. Coupled with the COMSOL multiphysics simulations and in situ infrared spectroscopy, the main contributor for the high-efficiency NH3 production could be the steady fluid field to timely rejuvenate the electrocatalyst surface during the electrocatalysis.

2.
Neurobiol Dis ; 188: 106344, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37926169

RESUMEN

Epilepsy, a common complication of diffuse low-grade gliomas (DLGGs; diffuse oligodendroglioma and astrocytoma collectively), severely compromises the quality of life of patients. DLGG epileptogenicity may primarily be generated by interactions between the tumor and the neocortex. Neuronal uptake of dysfunctional mitochondria from the extracellular environment can lead to abnormal neuronal discharge. Mitochondrial dysfunction is frequently observed in gliomas that can transmigrate across the plasma membranes. Here, we examined the role of the Rho GTPase-activating protein 44 (RICH2) in mitochondrial dynamics and DLGG-related epilepsy. We investigated the association between mitochondrial and RICH2 expression in human DLGG tissues using immunohistochemistry. We examined the association between RICH2 and epilepsy in nude mouse glioma models by electrophysiology. The effect of RICH2 on mitochondrial morphology and calcium motility were assessed by single cell fluorescence microscopy. Quantitative RT-PCR (qRT-PCR) and Western blot analysis were performed to characterize RICH2 induced expression changes in the genes related to mitochondrial dynamics, mitogenesis and mitochondrial function. We found that RICH2 expression was higher in oligodendroglioma than in astrocytoma and was correlated with better prognosis and higher epilepsy rate in patients. The expression of mitochondria may be associated with clinical DLGG-related epilepsy and reduced by RICH2 overexpression. And RICH2 could promote DLGG-related epilepsy in tumorigenic nude mice. RICH2 overexpression decreased calcium flow and the mitochondria released from glioma cells (SW1088 and U251) into the extracellular environment, potentially via downregulation of MFN-1/MFN-2 levels which suggests reduced mitochondrial fusion. In addition, we observed decreased mitochondrial trafficking into neurons (released from glioma cells and trafficked into neurons), which could explain the higher incidence of DLGG-related epilepsy due to reduced neuroprotection. Furthermore, RICH2 downregulated MAPK/ERK/HIF-1 pathway. In conclusion, these results suggest that RICH2 could promote epilepsy by (i) inhibiting mitochondrial fusion via MFN downregulation and Drp-1 upregulation; (ii) altering the MAPK/ERK/Hif-1 signaling axis. RICH2 may be a potential target in the treatment of DLGG-related epilepsy.


Asunto(s)
Astrocitoma , Glioma , Oligodendroglioma , Animales , Ratones , Humanos , Calcio , Ratones Desnudos , Calidad de Vida , Mitocondrias
3.
Cell Mol Neurobiol ; 42(7): 2157-2170, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33837492

RESUMEN

MiR-499a-5p was significantly downregulated in degenerative tissues and correlated with apoptosis. Nonetheless, the biological function of miR-499a-5p in acute ischemic stroke has been still unclear. In this study, we found that the plasma levels of miR-499a-5p were significantly downregulated in 64 ischemic stroke patients and negatively correlated with the National Institutes of Health Stroke Scale score. Then, we constructed cerebral ischemia/reperfusion (I/R) injury in rats after middle cerebral artery occlusion and subsequent reperfusion and oxygen-glucose deprivation and reoxygenation (OGD/R)-treated SH-SY5Y cell model. Transfection with miR-499a-5p mimic was accomplished by intracerebroventricular injection in the in vivo I/R injury model. We further found that miR-499a-5p overexpression decreased infarct volumes and cell apoptosis in the in vivo I/R stroke model using TTC and TUNEL staining. PDCD4 was a direct target of miR-499a-5p by luciferase report assay and Western blotting. Knockdown of PDCD4 reduced the infarct damage and cortical neuron apoptosis caused by I/R injury. MiR-499a-5p exerted neuroprotective roles mainly through inhibiting PDCD4-mediated apoptosis by CCK-8 assay, LDH release assay, and flow cytometry analysis. These findings suggest that miR-499a-5p might represent a novel target that regulates brain injury by inhibiting PDCD4-mediating apoptosis.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , MicroARNs/genética , Neuroblastoma , Daño por Reperfusión , Animales , Apoptosis , Proteínas Reguladoras de la Apoptosis , Glucosa , Humanos , Infarto de la Arteria Cerebral Media , Proteínas de Unión al ARN , Ratas , Regulación hacia Arriba
4.
BMC Cancer ; 21(1): 512, 2021 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-33962579

RESUMEN

BACKGROUND: Definitive radiation therapy (dRT) is an effective initial treatment of intermediate-risk (IR) and high-risk (HR) prostate cancer (PCa). PSMA PET/CT is superior to standard of care imaging (CT, MRI, bone scan) for detecting regional and distant metastatic PCa. PSMA PET/CT thus has the potential to guide patient selection and the planning for dRT and improve patient outcomes. METHODS: This is a multicenter randomized phase 3 trial (NCT04457245). We will randomize 312 patients to proceed with standard dRT (control Arm, n = 150), or undergo a PSMA PET/CT scan at the study site (both 18F-DCFPyL and 68Ga-PSMA-11 can be used) prior to dRT planning (intervention arm, n = 162). dRT will be performed at the treating radiation oncologist facility. In the control arm, dRT will be performed as routinely planned. In the intervention arm, the treating radiation oncologist can incorporate PSMA PET/CT findings into the RT planning. Androgen deprivation therapy (ADT) is administered per discretion of the treating radiation oncologist and may be modified as a result of the PSMA PET/CT results. We assume that approximately 8% of subjects randomized to the PSMA PET arm will be found to have M1 disease and thus will be more appropriate candidates for long-term systemic or multimodal therapy, rather than curative intent dRT. PET M1 patients will thus not be included in the primary endpoint analysis. The primary endpoint is the success rate of patients with unfavorable IR and HR PCa after standard dRT versus PSMA PET-based dRT. Secondary Endpoints (whole cohort) include progression free survival (PFS), metastasis-free survival after initiation of RT, overall survival (OS), % of change in initial treatment intent and Safety. DISCUSSION: This is the first randomized phase 3 prospective trial designed to determine whether PSMA PET/CT molecular imaging can improve outcomes in patients with PCa who receive dRT. In this trial the incorporation of PSMA PET/CT may improve the success rate of curative intent radiotherapy in two ways: to optimize patient selection as a biomarker and to personalizes the radiotherapy plan. CLINICAL TRIAL REGISTRATION: UCLA IND#147591 ○ Submission: 02.27.2020 ○ Safe-to-proceed letter issued by FDA: 04.01.2020 UCLA IRB #20-000378 ClinicalTrials.gov Identifier NCT04457245 . Date of Registry: 07.07.2020. Essen EudraCT 2020-003526-23.


Asunto(s)
Antígenos de Superficie/análisis , Glutamato Carboxipeptidasa II/análisis , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata/radioterapia , Humanos , Masculino , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/mortalidad , Planificación de la Radioterapia Asistida por Computador
5.
BMC Health Serv Res ; 21(1): 1067, 2021 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-34627239

RESUMEN

BACKGROUND: In the development of artificial intelligence in ophthalmology, the ophthalmic AI-related recognition issues are prominent, but there is a lack of research into people's familiarity with and their attitudes toward ophthalmic AI. This survey aims to assess medical workers' and other professional technicians' familiarity with, attitudes toward, and concerns about AI in ophthalmology. METHODS: This is a cross-sectional study design study. An electronic questionnaire was designed through the app Questionnaire Star, and was sent to respondents through WeChat, China's version of Facebook or WhatsApp. The participation was voluntary and anonymous. The questionnaire consisted of four parts, namely the respondents' background, their basic understanding of AI, their attitudes toward AI, and their concerns about AI. A total of 562 respondents were counted, with 562 valid questionnaires returned. The results of the questionnaires are displayed in an Excel 2003 form. RESULTS: There were 291 medical workers and 271 other professional technicians completed the questionnaire. About 1/3 of the respondents understood AI and ophthalmic AI. The percentages of people who understood ophthalmic AI among medical workers and other professional technicians were about 42.6 % and 15.6 %, respectively. About 66.0 % of the respondents thought that AI in ophthalmology would partly replace doctors, about 59.07 % having a relatively high acceptance level of ophthalmic AI. Meanwhile, among those with AI in ophthalmology application experiences (30.6 %), above 70 % of respondents held a full acceptance attitude toward AI in ophthalmology. The respondents expressed medical ethics concerns about AI in ophthalmology. And among the respondents who understood AI in ophthalmology, almost all the people said that there was a need to increase the study of medical ethics issues in the ophthalmic AI field. CONCLUSIONS: The survey results revealed that the medical workers had a higher understanding level of AI in ophthalmology than other professional technicians, making it necessary to popularize ophthalmic AI education among other professional technicians. Most of the respondents did not have any experience in ophthalmic AI but generally had a relatively high acceptance level of AI in ophthalmology, and there was a need to strengthen research into medical ethics issues.


Asunto(s)
Oftalmología , Inteligencia Artificial , Actitud del Personal de Salud , Estudios Transversales , Humanos , Encuestas y Cuestionarios
6.
BMC Cardiovasc Disord ; 20(1): 368, 2020 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-32795304

RESUMEN

BACKGROUND: Left ventricular mural thrombus (LVMT) is a life-threatening complication in patients with left ventricular dysfunction. CASE PRESENTATION: A 67-year-old man had a history of penetrating myocardial infarction and left ventricular aneurysm (LVA). The patient was scheduled for a non-cardiac surgery and stopped aspirin for 10 days to reduce the risk of bleeding. Fresh LVMT was revealed via the transesophageal echocardiography (TEE) after the preoperative discontinuation of aspirin. CONCLUSIONS: Perioperative repeated evaluation for the thrombosis by echocardiography is essential in cases of patients with cardiovascular disease undergoing non-cardiac surgery. In high risk patient, during temporary interruption of antiplatelets, bridging with perioperative low-molecular-weight heparin is advisable.


Asunto(s)
Aspirina/administración & dosificación , Procedimientos Quirúrgicos Electivos/efectos adversos , Fibrinolíticos/administración & dosificación , Aneurisma Cardíaco/tratamiento farmacológico , Trombosis/prevención & control , Anciano , Esquema de Medicación , Aneurisma Cardíaco/complicaciones , Aneurisma Cardíaco/diagnóstico por imagen , Humanos , Masculino , Factores de Riesgo , Trombosis/diagnóstico por imagen , Trombosis/etiología , Resultado del Tratamiento
7.
J Cell Physiol ; 233(10): 6975-6985, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29693251

RESUMEN

Notch signal has complex roles in human malignancies, which might be attributed to the diversity of Notch receptors. Here, we set out to identify the association of NOTCH4 with colorectal cancer (CRC). In the hospital-based study cohort, we investigated NOTCH4 mRNA levels in primary CRC, as well as its association with clinicopathologic characteristics. Besides, NOTCH4 cDNA and siRNA was transfected into colorectal cancer cell line to elucidate its impact on tumor cell proliferation and migration. Results revealed a statistically significant lower expression of NOTCH4 mRNA in tumor specimens compared with that in control. NOTCH4 level in CRC was found to be related to tumor differentiation, invasion, and node metastasis. Moreover, it was demonstrated that NOTCH4 mRNA level could be an independent prognostic factor for both disease-free and overall survival of CRC patients. Overexpression of NOTCH4 in CRC cell lines suppressed tumor cell proliferation, migration, and invasion, while induced apoptosis. In the opposite, the malignant behavior of CRC cells was enhanced by NOTCH4 knockdown. These results demonstrated for the first time that NOTCH4 expression was decreased in CRC, which could determine tumor proliferation, relapse, and prognosis.


Asunto(s)
Proliferación Celular/fisiología , Neoplasias Colorrectales/metabolismo , Receptor Notch4/metabolismo , Apoptosis/genética , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Movimiento Celular/genética , Movimiento Celular/fisiología , Proliferación Celular/genética , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/genética
8.
Mol Carcinog ; 57(6): 762-771, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29500881

RESUMEN

As a novel candidate tumor suppressor, NDRG4 is largely unstudied in human malignancies. In this study, we investigated the protein expression level of NDRG4 in gastric cancer and its association with outcome of patients. In the present study, we recruited 286 patients with gastric cancer and investigated the protein and mRNA expression of NDRG4 in cancer and adjacent normal specimens by immunohistochemistry assay and real-time PCR. The association of NDRG4 level with clinicopathological characteristics was investigated by appropriate statistical analysis. NDRG4 overexpression and knockdown cell lines were established in order to detect its impact on proliferation and apoptosis. Significant decreased protein and mRNA expression of NDRG4 was found in gastric cancer, compared with adjacent normal specimens. Besides, it was found that NDRG4 protein expression in gastric cancer was significantly associated with tumor differentiation, invasion, metastasis, and stage. Patients with tumors of decreased NDRG4 level were more likely to have unfavorable disease-free and overall survival, in both univariate and multivariate analysis. In addition, overexpression of NDRG4 suppressed cell proliferation of gastric cancer cells in vitro; conversely, the proliferation of gastric cancer cells were enhanced by knockdown of NDRG4. These results proved for the first time that NDRG4 could be a potential tumor suppressor and prognostic marker of gastric cancer.


Asunto(s)
Biomarcadores de Tumor/genética , Proliferación Celular/genética , Proteínas Musculares/genética , Proteínas del Tejido Nervioso/genética , Neoplasias Gástricas/genética , Apoptosis/genética , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Proteínas Musculares/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Pronóstico , Interferencia de ARN , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/cirugía
9.
BMC Cancer ; 16(1): 806, 2016 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-27756250

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is a lethal disease, while the precise underlying molecular mechanisms of HCC pathogenesis remain to be defined. MicroRNA (miRNA), a class of non-coding small RNAs, can post-transcriptionally regulate gene expression. Altered miRNA expression has been reported in HCCs. This study assessed expression and the oncogenic activity of miRNA-10b (miR-10b) in HCC. METHODS: Forty-five paired human HCC and adjacent non-tumor tissues were collected for qRT-PCR and immunohistochemistry analysis of miR-10b and CUB and Sushi multiple domains 1 (CSMD1), respectively. We analyzed the clinicopathological data from these patients to further determine if there was an association between miR-10b and CSMD1. HCC cell lines were used to assess the effects of miR-10b mimics or inhibitors on cell viability, migration, invasion, cell cycle distribution, and colony formation. Luciferase assay was used to assess miR-10b binding to the 3'-untranslated region (3'-UTR) of CSMD1. RESULTS: miR-10b was highly expressed in HCC tissues compared to normal tissues. In vitro, overexpression of miR-10b enhanced HCC cell viability, migration, and invasion; whereas, downregulation of miR-10b expression suppressed these properties in HCC cells. Injection of miR-10b mimics into tumor cell xenografts also promoted xenograft growth in nude mice. Bioinformatics and luciferase reporter assay demonstrated that CSMD1 was the target gene of miR-10b. Immunocytochemical, immunohistochemical, and qRT-PCR data indicated that miR-10b decreased CSMD1 expression in HCC cells. CONCLUSIONS: We showed that miR-10b is overexpressed in HCC tissues and miR-10b mimics promoted HCC cell viability and invasion via targeting CSMD1 expression. Our findings suggest that miR-10b acts as an oncogene by targeting the tumor suppressor gene, CSMD1, in HCC.


Asunto(s)
Carcinoma Hepatocelular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/genética , Proteínas de la Membrana/genética , MicroARNs/genética , Regiones no Traducidas 3'/genética , Animales , Carcinogénesis/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular , Supervivencia Celular/genética , Femenino , Células Hep G2 , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Proteínas de la Membrana/metabolismo , Ratones Desnudos , Persona de Mediana Edad , Oncogenes/genética , Interferencia de ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Trasplante Heterólogo , Proteínas Supresoras de Tumor
10.
Proc Natl Acad Sci U S A ; 110(11): 4339-44, 2013 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-23440206

RESUMEN

Despite their nearly universal activation of mammalian target of rapamycin (mTOR) signaling, glioblastomas (GBMs) are strikingly resistant to mTOR-targeted therapy. We analyzed GBM cell lines, patient-derived tumor cell cultures, and clinical samples from patients in phase 1 clinical trials, and find that the promyelocytic leukemia (PML) gene mediates resistance to mTOR-targeted therapies. Direct mTOR inhibitors and EGF receptor (EGFR) inhibitors that block downstream mTOR signaling promote nuclear PML expression in GBMs, and genetic overexpression and knockdown approaches demonstrate that PML prevents mTOR and EGFR inhibitor-dependent cell death. Low doses of the PML inhibitor, arsenic trioxide, abrogate PML expression and reverse mTOR kinase inhibitor resistance in vivo, thus markedly inhibiting tumor growth and promoting tumor cell death in mice. These results identify a unique role for PML in mTOR and EGFR inhibitor resistance and provide a strong rationale for a combination therapeutic strategy to overcome it.


Asunto(s)
Antineoplásicos/farmacología , Arsenicales/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioblastoma/metabolismo , Proteínas Nucleares/metabolismo , Óxidos/farmacología , Serina-Treonina Quinasas TOR/biosíntesis , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Animales , Trióxido de Arsénico , Línea Celular Tumoral , Receptores ErbB/biosíntesis , Femenino , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Glioblastoma/patología , Humanos , Masculino , Ratones , Proteínas Nucleares/genética , Proteína de la Leucemia Promielocítica , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/genética , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/genética
11.
Tumour Biol ; 36(11): 8593-600, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26040769

RESUMEN

Cutaneous melanoma is the most malignant form of skin cancer characterized by aggressive invasion. Matrix metalloproteinases play essential roles in tumor invasion due to their ECM degrading capacity. However, the clinical significance of matrix metalloproteinasis (MMP)-12 in human cutaneous melanoma has not been addressed yet. In the present study, we investigated MMP-12 expression level in 298 patients with cutaneous melanoma and 60 normal skin tissue specimens by immunohistochemistry assay. Appropriate statistical analysis was utilized to determine the association of MMP-12 with clinical features and prognosis of melanoma. Results showed that MMP-12 expression was increased in cutaneous melanoma compared with that in normal skin. It was also found that MMP-12 expression in melanoma was significantly associated with tumor invasion and metastasis. Univariate survival analysis indicated that patients with melanoma of high MMP-12 expression had unfavorable overall survival compared with those of low MMP-12 expression. Cox's proportional hazards analysis showed that MMP-12 expression was an independent prognostic marker of overall survival for patients with cutaneous melanoma. These results proved that MMP-12 expression was increased in cutaneous melanoma and associated with tumor progression. It also provided the first evidence that MMP-12 level could be an independent prognostic marker for patients with cutaneous melanoma.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , Metaloproteinasa 12 de la Matriz/biosíntesis , Melanoma/genética , Neoplasias Cutáneas/genética , Adulto , Anciano , Biomarcadores de Tumor/genética , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Metaloproteinasa 12 de la Matriz/genética , Melanoma/patología , Persona de Mediana Edad , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Pronóstico , Neoplasias Cutáneas/patología , Melanoma Cutáneo Maligno
12.
Hepatol Res ; 45(1): 97-106, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24593119

RESUMEN

AIM: HAb18G/CD147 is an important factor in invasion and metastasis of hepatocellular carcinoma (HCC). However, the clinical implications of HAb18G/CD147 expression in HCC are still unclear. In this study, we clarify the clinical significance of HAb18G/CD147. We characterize the association between HAb18G/CD147 expression and presentation of fibrosis or chronic hepatitis B, as well as its effect on HCC development. METHODS: The expression of HAb18G/CD147 in human hepatocarcinoma cell lines was analyzed by reverse transcription polymerase chain reaction and western blotting. Tumor tissues were obtained from HCC patients who underwent surgical resection between 2002 and 2006. All patients who had received previous therapy were excluded. HCC tissues were analyzed by immunohistochemistry using anti-HAb18G/CD147. RESULTS: HAb18G/CD147 was widely expressed in Hep-G2, SMCC-7721 and BEL7402 cell lines, but not expressed in L-02, a human normal hepatic cell line. HAb18G/CD147 was mainly localized to the membrane of tumor cells in 74.0% (37/50) HCC patients. We found that higher HAb18G/CD147 expression and poor tumor differentiation were correlated with patient survival (P = 0.026 and P = 0.014, respectively). Furthermore, the distribution of HAb18G/CD147 was similar to that of hepatitis B virus (HBV) infection, but negatively related to hepatic cirrhosis. CONCLUSION: HAb18G/CD147 has shown its potentials in HCC development and patient survival. Moreover, it may also cooperate with chronic HBV infection and cirrhosis during HCC development. Its functions in the two factors may be different. Therefore, HAb18G/CD147 may be a marker for poor prognosis in HCC patients and could be a useful therapeutic target for interfering with or reversing HCC progression.

13.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 34(4): 460-5, 2014 Apr.
Artículo en Zh | MEDLINE | ID: mdl-24812905

RESUMEN

OBJECTIVE: To explore the effect of Ginkgo biloba extract (GBE) on the function of alveolar polymorphonuclear neutrophils (PMN) in severe acute pancreatitis (SAP) rats complicated with lung injury (LI). METHODS: Forty-eight adult SD rats were randomly divided into three groups, i.e., the sham-operation group, the SAP group, and the GBE treatment group, 16 in each group. The SAP model was successfully induced by retrograde injection of 5% sodium taurocholate solution into the biliopancreatic duct. Rats in the sham-operation group only received flipping of the duodenum. Those in the GBE treatment group received GBE intervention based on SAP model. Equal volume of normal saline was given to rats in the sham-operation group and the SAP group. Rats were sacrificed at 6 and 12 h after operation respectively. The lung tissue was sampled to evaluate the LI score. The wet/dry ratio (W/D) of lung tissues was detected. The activity of myeloperoxidase (MPO) was measured. Alveolar PMN was harvested by bronchoalveolar lavage. The content of neutrophil elastase (NE) in bronchoalveolar lavage fluid (BALF) was measured by enzyme-linked immunoabsorbent assay (ELISA). The percentage of CD11b/CD18 double positive PMN was detected using flow cytometry. The expression of intercellular adhesion molecule-1 (ICAM-1) and NE protein in the lung tissue was detected by Western blot. RESULTS: Compared with the sham-operation group, significant pathologic lesion occurred in the lung tissue of rats in the SAP group; the pathologic LI score, lung tissue W/D ratio, MPO, and NE content in BALF significantly increased, the expression of ICAM-1 and NE in the lung tissue was obviously up-regulated, and the percentage of CD11b/CD18 double positive PMN significantly increased (P < 0.01). Compared with the SAP group, pathological lesion of the lung tissue was obviously attenuated, and the above indices were all significantly declined in the GBE treatment group (P < 0.01). CONCLUSIONS: Expression of ICAM-1 in the lung tissue and the percentage of D11b/ CD18 double positive PMN were up-regulated in SAP rats complicated with LI, resulting in the adherence of PMN to pulmonary vascular endothelial cells, and then activating PMN to release NE and aggravate LI. GBE could alleviate LI through down-regulating the expression ICAM-1 and CD11b/CD18, and hindering the adherence and activation of PMN to pulmonary vascular endothelial cells.


Asunto(s)
Ginkgo biloba/química , Lesión Pulmonar/metabolismo , Neutrófilos/metabolismo , Pancreatitis/metabolismo , Extractos Vegetales/farmacología , Animales , Líquido del Lavado Bronquioalveolar/citología , Molécula 1 de Adhesión Intercelular/metabolismo , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/etiología , Elastasa Pancreática/metabolismo , Pancreatitis/complicaciones , Pancreatitis/tratamiento farmacológico , Ratas , Ratas Sprague-Dawley
14.
Indian J Ophthalmol ; 72(Suppl 1): S53-S59, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38131543

RESUMEN

PURPOSE: We aimed to develop an artificial intelligence-based myopic maculopathy grading method using EfficientNet to overcome the delayed grading and diagnosis of different myopic maculopathy degrees. METHODS: The cooperative hospital provided 4642 healthy and myopic maculopathy color fundus photographs, comprising the four degrees of myopic maculopathy and healthy fundi. The myopic maculopathy grading models were trained using EfficientNet-B0 to EfficientNet-B7 models. The diagnostic results were compared with those of the VGG16 and ResNet50 classification models. The leading evaluation indicators were sensitivity, specificity, F1 score, area under the receiver operating characteristic (ROC) curve area under curve (AUC), 95% confidence interval, kappa value, and accuracy. The ROC curves of the ten grading models were also compared. RESULTS: We used 1199 color fundus photographs to evaluate the myopic maculopathy grading models. The size of the EfficientNet-B0 myopic maculopathy grading model was 15.6 MB, and it had the highest kappa value (88.32%) and accuracy (83.58%). The model's sensitivities to diagnose tessellated fundus (TF), diffuse chorioretinal atrophy (DCA), patchy chorioretinal atrophy (PCA), and macular atrophy (MA) were 96.86%, 75.98%, 64.67%, and 88.75%, respectively. The specificity was above 93%, and the AUCs were 0.992, 0.960, 0.964, and 0.989, respectively. CONCLUSION: The EfficientNet models were used to design grading diagnostic models for myopic maculopathy. Based on the collected fundus images, the models could diagnose a healthy fundus and four types of myopic maculopathy. The models might help ophthalmologists to make preliminary diagnoses of different degrees of myopic maculopathy.


Asunto(s)
Degeneración Macular , Miopía Degenerativa , Enfermedades de la Retina , Humanos , Miopía Degenerativa/diagnóstico , Agudeza Visual , Inteligencia Artificial , Factores de Riesgo , Enfermedades de la Retina/diagnóstico , Atrofia
15.
Front Neurosci ; 18: 1339075, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38808029

RESUMEN

Aim: Conventional approaches to diagnosing common eye diseases using B-mode ultrasonography are labor-intensive and time-consuming, must requiring expert intervention for accuracy. This study aims to address these challenges by proposing an intelligence-assisted analysis five-classification model for diagnosing common eye diseases using B-mode ultrasound images. Methods: This research utilizes 2064 B-mode ultrasound images of the eye to train a novel model integrating artificial intelligence technology. Results: The ConvNeXt-L model achieved outstanding performance with an accuracy rate of 84.3% and a Kappa value of 80.3%. Across five classifications (no obvious abnormality, vitreous opacity, posterior vitreous detachment, retinal detachment, and choroidal detachment), the model demonstrated sensitivity values of 93.2%, 67.6%, 86.1%, 89.4%, and 81.4%, respectively, and specificity values ranging from 94.6% to 98.1%. F1 scores ranged from 71% to 92%, while AUC values ranged from 89.7% to 97.8%. Conclusion: Among various models compared, the ConvNeXt-L model exhibited superior performance. It effectively categorizes and visualizes pathological changes, providing essential assisted information for ophthalmologists and enhancing diagnostic accuracy and efficiency.

16.
Med Phys ; 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38767532

RESUMEN

BACKGROUND: Bladder prolapse is a common clinical disorder of pelvic floor dysfunction in women, and early diagnosis and treatment can help them recover. Pelvic magnetic resonance imaging (MRI) is one of the most important methods used by physicians to diagnose bladder prolapse; however, it is highly subjective and largely dependent on the clinical experience of physicians. The application of computer-aided diagnostic techniques to achieve a graded diagnosis of bladder prolapse can help improve its accuracy and shorten the learning curve. PURPOSE: The purpose of this study is to combine convolutional neural network (CNN) and vision transformer (ViT) for grading bladder prolapse in place of traditional neural networks, and to incorporate attention mechanisms into mobile vision transformer (MobileViT) for assisting in the grading of bladder prolapse. METHODS: This study focuses on the grading of bladder prolapse in pelvic organs using a combination of a CNN and a ViT. First, this study used MobileNetV2 to extract the local features of the images. Next, a ViT was used to extract the global features by modeling the non-local dependencies at a distance. Finally, a channel attention module (i.e., squeeze-and-excitation network) was used to improve the feature extraction network and enhance its feature representation capability. The final grading of the degree of bladder prolapse was thus achieved. RESULTS: Using pelvic MRI images provided by a Huzhou Maternal and Child Health Care Hospital, this study used the proposed method to grade patients with bladder prolapse. The accuracy, Kappa value, sensitivity, specificity, precision, and area under the curve of our method were 86.34%, 78.27%, 83.75%, 95.43%, 85.70%, and 95.05%, respectively. In comparison with other CNN models, the proposed method performed better. CONCLUSIONS: Thus, the model based on attention mechanisms exhibits better classification performance than existing methods for grading bladder prolapse in pelvic organs, and it can effectively assist physicians in achieving a more accurate bladder prolapse diagnosis.

17.
Adv Mater ; : e2312566, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38630368

RESUMEN

Transition metal oxides (TMOs) are widely studied for loading of various catalysts due to their low cost and high structure flexibility. However, the prevailing close-packed nature of most TMOs crystals has restricted the available loading sites to surface only, while their internal bulk lattice remains unactuated due to the inaccessible narrow space that blocks out most key reactants and/or particulate catalysts. Herein, using tunnel-structured MnO2, this study demonstrates how TMO's internal lattice space can be activated as extra loading sites for atomic Ag in addition to the conventional surface-only loading, via which a dual-form Ag catalyst within MnO2 skeleton is established. In this design, not only faceted Ag nanoparticles are confined onto MnO2 surface by coherent lattice-sharing, Ag atomic strings are also seeded deep into the sub-nanoscale MnO2 tunnel lattice, enriching the catalytically active sites. Tested for electrochemical CO2 reduction reaction (eCO2RR), such dual-form catalyst exhibits a high Faradaic efficiency (94%), yield (67.3 mol g-1 h-1) and durability (≈48 h) for CO production, exceeding commercial Ag nanoparticles and most Ag-based electrocatalysts. Theoretical calculations further reveal the concurrent effect of such dual-form catalyst featuring facet-dependent eCO2RR for Ag nanoparticles and lattice-confined eCO2RR for Ag atomic strings, inspiring the future design of catalyst-substrate configuration.

18.
Carcinogenesis ; 34(3): 678-88, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23172665

RESUMEN

The transcription factor signal transducer and activator of transcription 3 (STAT3) contributes to cell proliferation, apoptosis and motility in human cancer cells. We aim to elucidate the function of STAT3 in esophageal carcinogenesis process and molecular mechanisms. We showed that hyperactivated STAT3 in esophageal carcinogenesis tissues correlated with the overexpression of octamer transcription factor-1 (Oct-1). High STAT3 phosphorylation correlated with shorter survival compared with low STAT3 phosphorylation. STAT3 and Oct-1 expression levels affected the proliferation and colony formation of Eca-109 esophageal squamous cell carcinoma cells by altering Erk and Akt activation. Nevertheless, STAT3 regulated the migration and invasion of esophageal squamous cell carcinoma cells independent of Oct-1. In conjunction with Oct-1, STAT3 inhibited apoptosis in esophageal squamous cell carcinoma cells. Constitutively activated STAT3 in normal human esophageal epithelium cells (HET-1A) elevated Oct-1 expression,and promoted proliferation and decreased apoptosis. STAT3 activated HET-1A cells to form tumors in vivo, suggesting that overactivated STAT3 is sufficient for carcinogenesis. We further confirmed the colocalization of STAT3 and Oct-1 in the nucleus and found that STAT3 regulates the transcription and expression of Oct-1 by directly targeting its promoter. Activated STAT3 also upregulated many genes associated with Oct-1. Together, our results indicate that STAT3 plays a crucial role in esophageal carcinogenesis by regulating the cell proliferation and apoptosis in conjunction with Oct-1.


Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Transformación Celular Neoplásica/metabolismo , Neoplasias Esofágicas/metabolismo , Transportador 1 de Catión Orgánico/genética , Factor de Transcripción STAT3/fisiología , Animales , Apoptosis , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Supervivencia Celular , Neoplasias Esofágicas/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Trasplante de Neoplasias , Transportador 1 de Catión Orgánico/metabolismo , Regiones Promotoras Genéticas , Factor de Transcripción STAT3/metabolismo , Activación Transcripcional , Carga Tumoral
19.
Exp Mol Pathol ; 95(3): 270-5, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23906871

RESUMEN

OBJECTIVES: PTPN13 is a new candidate tumor-suppressing gene. To investigate the PTPN13 expression and its potential function in the invasion and metastasis of lung squamous cell carcinoma (LSCC), we performed this study in 91 primary LSCC tissues and the adjacent non-cancerous tissues. METHODS: The mRNA expression of PTPN13 and FAK was quantitated by reverse transcription polymerase chain reaction. The protein expression of PTPN13, focal adhesion kinase (FAK) and phosphorylated FAK (P-FAK) was evaluated using immunohistochemical staining and western blotting. The association among PTPN13 expression, FAK expression and the clinicopathological parameters were analyzed. RESULTS: PTPN13 expression was down-regulated in LSCC, and was negatively correlated with the cancer grade and stage. FAK mRNA, as well as FAK protein level was elevated in LSCC tissues. P-FAK level, also found increased, had no association with FAK mRNA and FAK protein expression, but had a negative correlation with the PTPN13 expression. P-FAK level had a significant positive correlation with the TNM classification. CONCLUSION: The over-expression of FAK and increased FAK phosphorylation plays an important role in the invasion and metastasis of LSCC.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/secundario , Quinasa 1 de Adhesión Focal/metabolismo , Neoplasias Pulmonares/patología , Proteína Tirosina Fosfatasa no Receptora Tipo 13/metabolismo , Anciano , Biomarcadores de Tumor/genética , Western Blotting , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Femenino , Quinasa 1 de Adhesión Focal/genética , Humanos , Técnicas para Inmunoenzimas , Pulmón/metabolismo , Pulmón/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Metástasis Linfática , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Fosforilación , Pronóstico , Proteína Tirosina Fosfatasa no Receptora Tipo 13/genética , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
20.
Indian J Ophthalmol ; 71(5): 2115-2131, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37203092

RESUMEN

Purpose: Recently, the proportion of patients with high myopia has shown a continuous growing trend, more toward the younger age groups. This study aimed to predict the changes in spherical equivalent refraction (SER) and axial length (AL) in children using machine learning methods. Methods: This study is a retrospective study. The cooperative ophthalmology hospital of this study collected data on 179 sets of childhood myopia examinations. The data collected included AL and SER from grades 1 to 6. This study used the six machine learning models to predict AL and SER based on the data. Six evaluation indicators were used to evaluate the prediction results of the models. Results: For predicting SER in grade 6, grade 5, grade 4, grade 3, and grade 2, the best results were obtained through the multilayer perceptron (MLP) algorithm, MLP algorithm, orthogonal matching pursuit (OMP) algorithm, OMP algorithm, and OMP algorithm, respectively. The R2 of the five models were 0.8997, 0.7839, 0.7177, 0.5118, and 0.1758, respectively. For predicting AL in grade 6, grade 5, grade 4, grade 3, and grade 2, the best results were obtained through the Extra Tree (ET) algorithm, MLP algorithm, kernel ridge (KR) algorithm, KR algorithm, and MLP algorithm, respectively. The R2 of the five models were 0.7546, 0.5456, 0.8755, 0.9072, and 0.8534, respectively. Conclusion: Therefore, in predicting SER, the OMP model performed better than the other models in most experiments. In predicting AL, the KR and MLP models were better than the other models in most experiments.


Asunto(s)
Miopía , Refracción Ocular , Humanos , Niño , Estudios Retrospectivos , Pruebas de Visión , Miopía/diagnóstico , Miopía/epidemiología , Aprendizaje Automático , Longitud Axial del Ojo
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