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BACKGROUND: Cisplatin is integral to ovarian cancer treatment, yet resistance to this drug often results in adverse patient outcomes. The association of circular RNA (circRNA) with cisplatin resistance in ovarian cancer has been observed, but the mechanisms governing this relationship require further elucidation. METHODS: High-throughput sequencing was utilized to profile circRNA expression in cisplatin-resistant ovarian cancer cells. Gain-and-loss-of-function experiments assessed the impact on cisplatin sensitivity, both in vitro and in vivo. Fluorescence in situ hybridization was conducted to determine the cellular distribution of circRNAs, and RNA pulldown and immunoprecipitation experiments were performed to identify associated binding proteins. RESULTS: The study revealed that circ_ARHGEF28 is overexpressed in certain cisplatin-resistant ovarian cancer tissues and cell lines, and is associated with reduced progression-free survival in patients. It was observed that circ_ARHGEF28 contributes to cisplatin resistance in ovarian cancer models, both in vitro and in vivo. Importantly, circ_ARHGEF28 was found to interact directly with MST1/2, inhibiting the SARAH coiled-coil binding domains and consequently deactivating the Hippo pathway. CONCLUSION: This investigation identifies circ_ARHGEF28 as a novel circRNA that contributes to cisplatin resistance in ovarian cancer by suppressing the Hippo pathway. Therapeutic strategies targeting circ_ARHGEF28 may offer a potential avenue to mitigate cisplatin resistance in ovarian cancer treatment.
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Corneal neovascularization (CNV) is one of the common blinding factors worldwide, leading to reduced vision or even blindness. However, current treatments such as surgical intervention and anti-VEGF agent therapy still have some shortcomings or evoke some adverse effects. Recently, SU6668, an inhibitor targeting angiogenic tyrosine kinases, has demonstrated growth inhibition of neovascularization. But the hydrophobicity and low ocular bioavailability limit its application in cornea. Hereby, we proposed the preparation of SU6668 pure nanoparticles (NanoSU6668; size ~135 nm) using a super-stable pure-nanomedicine formulation technology (SPFT), which possessed uniform particle size and excellent aqueous dispersion at 1 mg/mL. Furthermore, mesenchymal stem cell membrane vesicle (MSCm) was coated on the surface of NanoSU6668, and then conjugated with TAT cell penetrating peptide, preparing multifunctional TAT-MSCm@NanoSU6668 (T-MNS). The T-MNS at a concentration of 200 µg/mL was treated for CNV via eye drops, and accumulated in blood vessels with a high targeting performance, resulting in elimination of blood vessels and recovery of cornea transparency after 4 days of treatment. Meanwhile, drug safety test confirmed that T-MNS did not cause any damage to cornea, retina and other eye tissues. In conclusion, the T-MNS eye drop had the potential to treat CNV effectively and safely in a low dosing frequency, which broke new ground for CNV theranostics.
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Córnea , Neovascularización de la Córnea , Nanopartículas , Soluciones Oftálmicas , Neovascularización de la Córnea/tratamiento farmacológico , Animales , Nanopartículas/química , Soluciones Oftálmicas/química , Córnea/metabolismo , Córnea/efectos de los fármacos , Ratones , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/farmacología , Tamaño de la Partícula , Humanos , Masculino , Ratones Endogámicos C57BL , ConejosRESUMEN
BACKGROUND: To investigate the effects of vitamin C on central retinal thickness and choroidal thickness. METHODS: A total of 69 patients diagnosed with vitamin C deficiency and 1:1 age- and gender-matched 69 healthy individuals with normal serum vitamin C were included in this study. Demographic characteristics of the individuals were collected. All patients underwent a comprehensive ophthalmic examination. Subfoveal choroidal thickness and retinal thickness were measured using a swept-source optical coherence tomography (SS-OCT). RESULTS: The average retinal thickness was 269.07 ± 13.51 µm in the vitamin C deficiency group and 276.92 ± 13.51 µm in the control group. The average choroidal thickness was 195.62 ± 66.40 µm in the in the vitamin C deficiency group and 238.86 ± 55.08 µm in the control group. There was a significant decrease in both average choroidal thickness and retinal thickness in vitamin C deficiency group compared with normal individuals (p < 0.001, and = 0.001 respectively). CONCLUSION: The central retinal and choroidal thickness were thinner in vitamin C deficiency group compared with normal individuals. These findings suggested that vitamin C deficiency might play an important role in retinal and choroidal diseases.
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Deficiencia de Ácido Ascórbico , Tomografía de Coherencia Óptica , Ácido Ascórbico , Deficiencia de Ácido Ascórbico/complicaciones , Coroides , Humanos , Retina , Tomografía de Coherencia Óptica/métodosRESUMEN
BACKGROUND: Mycobacterium houstonense is rapidly growing mycobacteria (RGM) that belongs to M. fortuitum group. So far, there have been few associated reports of human diseases induced by M. houstonense worldwide. CASE PRESENTATION: We present a delayed-onset postoperative endophthalmitis caused by M. houstonense after glaucoma drainage implant (GDI) surgery. The ocular infection lasted for 2 months without appropriate treatment that developed into endophthalmitis and the patient underwent an emergency enucleation. CONCLUSION: Implant erosion and a delay in diagnosis of ocular infection could lead to irreversible damage as observed in our case. Ophthalmologists should be alert for ocular RGM infection, and prompt laboratory diagnosis with initiation of effective multidrug therapy might prevent loss of vision.
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Endoftalmitis/diagnóstico , Endoftalmitis/etiología , Implantes de Drenaje de Glaucoma/efectos adversos , Mycobacteriaceae/genética , Complicaciones Posoperatorias/diagnóstico , Amicacina/uso terapéutico , Antibacterianos/uso terapéutico , Quimioterapia Combinada , Endoftalmitis/tratamiento farmacológico , Endoftalmitis/cirugía , Enucleación del Ojo , Estudios de Seguimiento , Humanos , Levofloxacino/uso terapéutico , Masculino , Persona de Mediana Edad , Mycobacteriaceae/aislamiento & purificación , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/microbiología , Complicaciones Posoperatorias/cirugía , ARN Ribosómico 16S/genética , ARN Ribosómico 23S/genética , Resultado del TratamientoRESUMEN
BACKGROUND: Posterior scleritis is an uncommon vision-threatening disorder that is often recurrent and difficult to cure due to its complex etiology. In HIV patients, posterior scleritis may develop several months after significant rise in CD4+ T-lymphocyte, even after several years, which may be diagnosed as late-onset immune recovery scleritis. CASE PRESENTATION: Here we report a case of posterior scleritis in a HIV positive patient who presented with severe periocular pain and decreased vision in the left eye, with exudative retinal detachment and optic nerve involvement. CONCLUSIONS: Early differential diagnosis of immune recovery posterior scleritis and intensive corticosteroids treatment, can prevent vision loss effectively in HIV patients.
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Infecciones por VIH , Desprendimiento de Retina , Escleritis , Corticoesteroides , Infecciones por VIH/complicaciones , Humanos , Escleritis/diagnóstico , Escleritis/tratamiento farmacológico , Escleritis/etiología , Trastornos de la VisiónRESUMEN
BACKGROUND: Intravitreal methotrexate has been proven to be an effective treatment method for vitreoretinal lymphoma. However, keratopathy occurs as the major side effect during treatment in most cases. The purpose of this study is to describe the characteristics of primary central nervous system lymphoma (PCNSL) with intraocular involvement and to attempt to reduce the incidence of keratopathy caused by intravitreal methotrexate. METHODS: The medical records of 22 PCNSL patients with intraocular involvement (33 eyes) were reviewed. Patients were divided into two groups. Group A (22 eyes) received the induction-consolidation-maintenance regimen, which consisted of intravitreal methotrexate injection at a dosage of 400 µg/0.1 ml twice a week for the first four weeks, weekly for the following eight weeks, and then monthly for the last nine months. Patients with a poor systemic condition were assigned to Group B (8 eyes), who were started on the treatment protocol described above and switched directly to monthly injection (9 months) when ocular remission was achieved. RESULTS: Blurred vision (31%) and floaters (25%) were common presenting symptoms. Vitritis was the most common clinical sign and was present in 29 eyes (90%) on B-ultrasound examination. Diagnosis was made by 25G-pars plana vitrectomy, and most diagnoses were diffuse large B-cell lymphoma. Ocular remission was achieved after 8.2 (SD = 4.6) injections of methotrexate. The mean VA (visual acuity) was improved from LogMAR 0.65 to 0.3 (P = 0.002). Keratopathy was observed in 21 eyes (66%) after an average of 8.2 (SD = 2.3) injections. With a reduced injection frequency, the incidence of keratopathy was lowered from 86.4% (Group A) to 25.0% (Group B) without ocular recurrence during follow-up. CONCLUSIONS: Intravitreal methotrexate is a safe, effective and flexible treatment for PCNSL patients with intraocular involvement. Keratopathy is the most common adverse effect and can be controlled by reducing the injection frequency.
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Enfermedades de la Córnea/tratamiento farmacológico , Linfoma/complicaciones , Metotrexato/administración & dosificación , Neoplasias de la Retina/complicaciones , Agudeza Visual , Adulto , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Enfermedades de la Córnea/diagnóstico , Enfermedades de la Córnea/etiología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Inyecciones Intravítreas , Linfoma/diagnóstico , Linfoma/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Neoplasias de la Retina/diagnóstico , Neoplasias de la Retina/tratamiento farmacológico , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Resultado del Tratamiento , UltrasonografíaRESUMEN
PURPOSE: To evaluate the safety of phacoemulsification cataract surgery in the patients undergoing dual antiplatelet therapy with aspirin and clopidogrel. METHODS: Consecutive patients undergoing phacoemulsification cataract surgery with a clear corneal incision under topical anesthesia were eligible for inclusion in the study. Thirty-eight eyes from 38 patients on combined aspirin and clopidogrel therapy who continued the treatment were classified into the maintenance group, a matched group of 38 eyes from 38 patients on no antiplatelet/anticoagulant therapy as the control group. The best-corrected visual acuity (BCVA) and incidences of complications were compared between the two groups. RESULTS: There was no significant difference in final BCVA between the maintenance group and the control group (p = 0.178). No significant difference existed in the incidences of hemorrhagic or non-hemorrhagic complications between the two groups (p = 0.529 and p = 0.589, respectively). Moreover, no surgery was postponed or cancelled due to hemorrhagic complications in either group, and no cardiovascular events occurred during the follow-up. There was no case of anterior chamber hemorrhage, vitreous hemorrhage, or suprachoroidal hemorrhage. CONCLUSIONS: Our outcomes indicated that phacoemulsification cataract surgery using a clear corneal incision with topical anesthesia could be safely done without stopping dual antiplatelet therapy with aspirin and clopidogrel.
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Catarata , Facoemulsificación , Aspirina/efectos adversos , Catarata/complicaciones , Clopidogrel , Humanos , Implantación de Lentes Intraoculares , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Factores de Riesgo , Agudeza VisualRESUMEN
OBJECTIVE: This study aims to investigate the functions and mechanistic pathways of Astrocyte Elevated Gene-1 (AEG-1) in the disruption of the blood-retinal barrier (BRB) caused by the HIV-1 envelope glycoprotein gp120. DESIGN: We utilized ARPE-19 cells challenged with gp120 as our model system. METHODS: Several analytical techniques were employed to decipher the intricate interactions at play. These included PCR, Western blot, and immunofluorescence assays for the molecular characterization, and transendothelial electrical resistance (TEER) measurements to evaluate barrier integrity. RESULTS: We observed that AEG-1 expression was elevated, whereas the expression levels of tight junction proteins ZO-1, Occludin, and Claudin5 were downregulated in gp120-challenged cells. TEER measurements corroborated these findings, indicating barrier dysfunction. Additional mechanistic studies revealed that the activation of NFκB and MMP2/9 pathways mediated the AEG-1-induced barrier destabilization. Through the use of lentiviral vectors, we engineered cell lines with modulated AEG-1 expression levels. Silencing AEG-1 alleviated gp120-induced downregulation of tight junction proteins and barrier impairment while concurrently inhibiting the NFκB and MMP2/9 pathways. Conversely, overexpression of AEG-1 exacerbated these pathological changes, further compromising the integrity of the BRB. CONCLUSION: Gp120 upregulates the expression of AEG-1 and activates the NFκB and MMP2/9 pathways. This in turn leads to the downregulation of tight junction proteins, resulting in the disruption of barrier function.
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Barrera Hematorretinal , Proteína gp120 de Envoltorio del VIH , Infecciones por VIH , VIH-1 , Proteínas de la Membrana , Proteínas de Unión al ARN , Humanos , Barrera Hematorretinal/metabolismo , Infecciones por VIH/metabolismo , VIH-1/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Proteínas de Uniones Estrechas/metabolismo , Proteína gp120 de Envoltorio del VIH/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de Unión al ARN/metabolismoRESUMEN
To present a modified technique for the reconstruction of a large cyclodialysis cleft with capsular tension ring (CTR) and continuous and cerclage sutures without scleral flaps in 12 cases. The mean visual acuity was 0.75 ± 0.47 logarithm of the minimal angle of resolution (logMAR), and the average intraocular pressure (IOP) was 3.35 ± 0.41 mmHg before surgery. Ultrasound biomicroscopy (UBM) revealed a ciliary cleft of 4.3 ± 3.5 clock hours. We performed the modified technique for the reconstruction of a large cyclodialysis cleft. Postoperative visual acuity improved to 0.48 ± 0.26 logMAR, and the IOP improved to 15.88 ± 3.81 mmHg. Postoperative UBM showed that cyclodialysis disappeared in the whole circumference of 12 eyes. The postoperative complications included 42% (5 eyes) with a temporary elevation of IOP and 16% (2 eyes) with a posterior shift of the ciliary body. No other complications were detected during the follow-up. Based on the results, our modified technique might be useful for most cyclodialysis clefts.
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Hendiduras de Ciclodiálisis , Lesiones Oculares , Humanos , Hendiduras de Ciclodiálisis/cirugía , Lesiones Oculares/diagnóstico , Lesiones Oculares/cirugía , Lesiones Oculares/complicaciones , Presión Intraocular , Tonometría Ocular , Cuerpo Ciliar/cirugía , SuturasRESUMEN
Background: Although gastric adenocarcinoma (GA) related ocular metastasis (OM) is rare, its occurrence indicates a more severe disease. We aimed to utilize machine learning (ML) to analyze the risk factors of GA-related OM and predict its risks. Methods: This is a retrospective cohort study. The clinical data of 3532 GA patients were collected and randomly classified into training and validation sets in a ratio of 7:3. Those with or without OM were classified into OM and non-OM (NOM) groups. Univariate and multivariate logistic regression analyses and least absolute shrinkage and selection operator were conducted. We integrated the variables identified through feature importance ranking and further refined the selection process using forward sequential feature selection based on random forest (RF) algorithm before incorporating them into the ML model. We applied six ML algorithms to construct the predictive GA model. The area under the receiver operating characteristic (ROC) curve indicated the model's predictive ability. Also, we established a network risk calculator based on the best performance model. We used Shapley additive interpretation (SHAP) to identify risk factors and to confirm the interpretability of the black box model. We have de-identified all patient details. Results: The ML model, consisting of 13 variables, achieved an optimal predictive performance using the gradient boosting machine (GBM) model, with an impressive area under the curve (AUC) of 0.997 in the test set. Utilizing the SHAP method, we identified crucial factors for OM in GA patients, including LDL, CA724, CEA, AFP, CA125, Hb, CA153, and Ca2+. Additionally, we validated the model's reliability through an analysis of two patient cases and developed a functional online web prediction calculator based on the GBM model. Conclusion: We used the ML method to establish a risk prediction model for GA-related OM and showed that GBM performed best among the six ML models. The model may identify patients with GA-related OM to provide early and timely treatment.
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Adenocarcinoma , Neoplasias del Ojo , Neoplasias Gástricas , Humanos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Algoritmos , Aprendizaje AutomáticoRESUMEN
AIM: To evaluate the relationship of overweight and obesity with retinal and choroidal thickness in adults without ocular symptoms by swept-source optical coherence tomography (SS-OCT). METHODS: According to the body mass index (BMI) results, the adults enrolled in the cross-sectional study were divided into the normal group (18.50≤BMI<25.00 kg/m2), the overweight group (25.00≤BMI<30.00 kg/m2), and the obesity group (BMI≥30.00 kg/m2). The one-way ANOVA and the Chi-square test were used for comparisons. Pearson's correlation analysis was used to evaluate the relationships between the measured variables. RESULTS: This research covered the left eyes of 3 groups of 434 age- and sex-matched subjects each: normal, overweight, and obesity. The mean BMI was 22.20±1.67, 26.82±1.38, and 32.21±2.35 kg/m2 in normal, overweight and obesity groups, respectively. The choroid was significantly thinner in both the overweight and obesity groups compared to the normal group (P<0.05 for all), while the retinal thickness of the three groups did not differ significantly. Pearson's correlation analysis showed that BMI was significantly negatively correlated with choroidal thickness, but no significant correlation was observed between BMI and retinal thickness. CONCLUSION: Choroidal thickness is decreased in people with overweight or obesity. Research on changes in choroidal thickness contributes to the understanding of the mechanisms of certain ocular disorders in overweight and obese adults.
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OBJECTIVE: To study the role of MLN4924 in corneal stem cell maintenance and corneal injury repair. METHODS: In cell experiments, the Sprague-Dawley (SD) rat corneal epithelial cells were co-cultured with mitomycin C-inactivated mouse feeder cells in a supplemental hormonal epithelial medium (SHEM) with or without MLN4924. Cells were photographed using an optical microscope. Furthermore, we performed crystal violet, polymerase chain reaction (PCR), and immunofluorescence staining on limbal stem cells (LSCs). In animal experiments, we scraped the corneal epithelium with a central corneal diameter of 4 mm in SD rats. The area of the corneal epithelial defect was calculated by fluorescein sodium staining. RESULTS: LSCs in the MLN4924 group had significantly proliferated. The MLN4924 treatment evidently enhanced the clone formation rate and clone area of LSCs. The expression levels of Ki67, p63, ABCG2, Bmi1, and C/EBPδ increased in LSCs after MLN4924 treatment, whereas the expression of K12 decreased. At 12 and 24 h after scraping, the corneal epithelium recovery rate in the eyes of the MLN4924-treated rats was accelerated. CONCLUSIONS: MLN4924 can maintain stemness, reduce differentiation, promote the proliferative capacity of rat LSCs, and accelerate corneal epithelial wound healing in SD rats.
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Purpose: To evaluate the efficacy and safety of idiopathic epiretinal membrane (ERM) surgery in patients aged over 80 years. Methods: Consecutive patients who underwent pars plana vitrectomy (PPV) combined with ERM and internal limiting membrane (ILM) peeling with retrobulbar anesthesia were recruited. Based on age, the patients were divided into the elderly group (≥ 80 years of age) and the control group (< 80 years of age). The best-corrected visual acuity (BCVA) and surgical complications were regarded as the main measurement indicators. Results: This study included 43 eyes from 43 patients aged 80 to 91 years and 86 eyes from 86 patients aged 54 to 79 years. Surgical intervention substantially improved BCVA both in the elderly and control groups (p = 0.005 and p < 0.001, respectively). Statistical analyses showed no significant difference in the incidence of surgical complications between the two groups (p = 0.631). The operations in either group were not delayed or canceled for the reason of complications of retrobulbar anesthesia, severe anxiety, or physical discomfort in the perioperative period. Moreover, no patient required a second operation. Also, no stroke, myocardial infarction, or death occurred during the follow-up period. All the surgical complications were treated satisfactorily. Conclusion: Our outcomes indicate that PPV combined with ERM and ILM peeling with retrobulbar anesthesia is effective and safe in elderly patients aged 80 years or older. Based on age alone, we believe that advancing age should not be the risk factor for idiopathic ERM surgery.
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Despite improvements in reducing hunger in recent years, undernutrition remains a global public health problem. This study utilizes the swept-source optical coherence tomography (SS-OCT) technique to assess changes in retinal and choroidal thickness in underweight subjects. Ophthalmic examinations were conducted on all adults participating in this cross-sectional research. Depending on their body mass index (BMI), the participants were divided into two groups: the underweight group and the normal group. The study included the right eyes of the underweight adults and an equal number of age- and gender-matched normal-weight subjects. The retinal thickness showed no significant difference between the underweight and normal groups (P > 0.05 for all). In males, the retina of the center and inner ring in the underweight group was significantly thinner than that in the normal group, while no such results were found in females. The choroid in the underweight group was significantly thinner compared to that in the normal group (all P < 0.05). Being underweight may affect choroidal thickness in both males and females. In comparison with underweight females, underweight males may experience more retinal damage. These findings contribute to a better understanding of the pathogenesis underlying specific ocular diseases in malnourished individuals.
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Delgadez , Tomografía de Coherencia Óptica , Adulto , Femenino , Masculino , Humanos , Estudios Transversales , Retina/diagnóstico por imagen , Coroides/diagnóstico por imagenRESUMEN
OBJECTIVE: To evaluate the effect of hydroxychloroquine on conjunctival and retinal microvascular density in rheumatoid arthritis (RA) patients. METHODS: Ten healthy controls, 10 RA patients who had not been treated with hydroxychloroquine, and 10 RA patients who had been treated with chloroquine for more than 5 years were recruited. Optical coherence tomography (OCTA) was used to examine the conjunctival and superficial and deep retinal microvascular density and compared the differences in microvascular density between the three groups. RESULTS: The vascular density in RA group in superficial microvascular was significantly lower than that in control group (p < 0.001). Compared with RA group, the chloroquine group showed statistically significantly lower microvascular (p < 0.001) and deep microvascular (p = 0.018). Superficial microvascular was positively correlated with conjunctival vessel density in RA patients (r = 0.868, p = 0.0048). CONCLUSIONS: The use of chloroquine could further reduce the vascular density in the absence of statistical difference in the course of the disease.
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Artritis Reumatoide , Hidroxicloroquina , Humanos , Hidroxicloroquina/uso terapéutico , Hidroxicloroquina/farmacología , Vasos Retinianos/diagnóstico por imagen , Cloroquina/uso terapéutico , Cloroquina/farmacología , Angiografía con Fluoresceína/métodos , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/tratamiento farmacológico , Tomografía de Coherencia Óptica/métodosRESUMEN
Although immune checkpoint inhibitors improved the clinical outcomes of advanced triple negative breast cancer (TBNC) patients, the response rate remains relatively low. Nigericin is an antibiotic derived from Streptomyces hydrophobicus. We found that nigericin caused cell death in TNBC cell lines MDA-MB-231 and 4T1 by inducing concurrent pyroptosis and apoptosis. As nigericin facilitated cellular potassium efflux, we discovered that it caused mitochondrial dysfunction, leading to mitochondrial ROS production, as well as activation of Caspase-1/GSDMD-mediated pyroptosis and Caspase-3-mediated apoptosis in TNBC cells. Notably, nigericin-induced pyroptosis could amplify the anti-tumor immune response by enhancing the infiltration and anti-tumor effect of CD4+ and CD8+ T cells. Moreover, nigericin showed a synergistic therapeutic effect when combined with anti-PD-1 antibody in TNBC treatment. Our study reveals that nigericin may be a promising anti-tumor agent, especially in combination with immune checkpoint inhibitors for advanced TNBC treatment.
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AIM: To assess the retinal thickness and fundus blood flow density changes in chest pain patients with dyslipidemia using optical coherence tomography angiography (OCTA). METHODS: All subjects with chest pain as the main symptom accepted a comprehensive ophthalmological examination. According to the serum lipid levels, the participants were divided into the control group and the dyslipidemia group. The retina thickness and fundus blood flow density were determined using OCTA. RESULTS: The study enrolled 87 left eyes from 87 adults with dyslipidemia and 87 left eyes from age- and sex-matched participants without dyslipidemia. The retina of dyslipidemia subjects was significantly thinner than that of the controls in the inferior (P=0.004 and P=0.014, respectively) and temporal (P=0.015 and P=0.019, respectively) regions, both inner and outer layers. In terms of blood flow density in the macula or optic disk, there was a decreasing trend in the dyslipidemia group compared with the control group, especially in the inferior and temporal regions. CONCLUSION: Dyslipidemia may contribute to the decrease in retinal thickness and fundus blood flow density. Further validation of the association between abnormal lipid metabolism and fundus microcirculation alterations needs to be carried out in chest pain patients.
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BACKGROUND: Ocular metastasis (OM) is a rare metastatic site of primary liver cancer (PLC). The purpose of this study was to establish a clinical predictive model of OM in PLC patients based on machine learning (ML). METHODS: We retrospectively collected the clinical data of 1540 PLC patients and divided it into a training set and an internal test set in a 7:3 proportion. PLC patients were divided into OM and non-ocular metastasis (NOM) groups, and univariate logistic regression analysis was performed between the two groups. The variables with univariate logistic analysis p < 0.05 were selected for the ML model. We constructed six ML models, which were internally verified by 10-fold cross-validation. The prediction performance of each ML model was evaluated by receiver operating characteristic curves (ROCs). We also constructed a web calculator based on the optimal performance ML model to personalize the risk probability for OM. RESULTS: Six variables were selected for the ML model. The extreme gradient boost (XGB) ML model achieved the optimal differential diagnosis ability, with an area under the curve (AUC) = 0.993, accuracy = 0.992, sensitivity = 0.998, and specificity = 0.984. Based on these results, an online web calculator was constructed by using the XGB ML model to help clinicians diagnose and treat the risk probability of OM in PLC patients. Finally, the Shapley additive explanations (SHAP) library was used to obtain the six most important risk factors for OM in PLC patients: CA125, ALP, AFP, TG, CA199, and CEA. CONCLUSION: We used the XGB model to establish a risk prediction model of OM in PLC patients. The predictive model can help identify PLC patients with a high risk of OM, provide early and personalized diagnosis and treatment, reduce the poor prognosis of OM patients, and improve the quality of life of PLC patients.
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Neoplasias del Ojo , Neoplasias Hepáticas , Humanos , Calidad de Vida , Estudios Retrospectivos , Aprendizaje Automático , Factores de Riesgo , Neoplasias Hepáticas/diagnósticoRESUMEN
Objective: The aim of the study is to develop and validate a deep learning model to predict the platinum sensitivity of patients with epithelial ovarian cancer (EOC) based on contrast-enhanced magnetic resonance imaging (MRI). Methods: In this retrospective study, 93 patients with EOC who received platinum-based chemotherapy (≥4 cycles) and debulking surgery at the Sun Yat-sen Memorial Hospital from January 2011 to January 2020 were enrolled and randomly assigned to the training and validation cohorts (2:1). Two different models were built based on either the primary tumor or whole volume of the abdomen as the volume of interest (VOI) within the same cohorts, and then a pre-trained convolutional neural network Med3D (Resnet 10 version) was transferred to automatically extract 1,024 features from two MRI sequences (CE-T1WI and T2WI) of each patient to predict platinum sensitivity. The performance of the two models was compared. Results: A total of 93 women (mean age, 50.5 years ± 10.5 [standard deviation]) were evaluated (62 in the training cohort and 31 in the validation cohort). The AUCs of the whole abdomen model were 0.97 and 0.98 for the training and validation cohorts, respectively, which was better than the primary tumor model (AUCs of 0.88 and 0.81 in the training and validation cohorts, respectively). In k-fold cross-validation and stratified analysis, the whole abdomen model maintained a stable performance, and the decision function value generated by the model was a prognostic indicator that successfully discriminates high- and low-risk recurrence patients. Conclusion: The non-manually segmented whole-abdomen deep learning model based on MRI exhibited satisfactory predictive performance for platinum sensitivity and may assist gynecologists in making optimal treatment decisions.
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Aberrant activation of NFκB orchestrates a critical role in tumor carcinogenesis; however, the regulatory mechanisms underlying this activation are not fully understood. Here we report that a novel long noncoding RNA (lncRNA) Uc003xsl.1 is highly expressed in triple-negative breast cancer (TNBC) and correlates with poor outcomes in patients with TNBC. Uc003xsl.1 directly bound nuclear transcriptional factor NFκB-repressing factor (NKRF), subsequently preventing NKRF from binding to a specific negative regulatory element in the promoter of the NFκB-responsive gene IL8 and abolishing the negative regulation of NKRF on NFκB-mediated transcription of IL8. Activation of the NFκB/IL8 axis promoted the progression of TNBC. Trop2-based antibody-drug conjugates have been applied in clinical trials in TNBC. In this study, a Trop2-targeting, redox-responsive nanoparticle was developed to systematically deliver Uc003xsl.1 siRNA to TNBC cells in vivo, which reduced Uc003xsl.1 expression and suppressed TNBC tumor growth and metastasis. Therefore, targeting Uc003xsl.1 to suppress the NFκB/IL8 axis represents a promising therapeutic strategy for TNBC treatment. SIGNIFICANCE: These findings identify an epigenetic-driven NFκB/IL8 cascade initiated by a lncRNA, whose aberrant activation contributes to tumor metastasis and poor survival in patients with triple-negative breast cancer.