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1.
Acad Radiol ; 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38902111

ABSTRACT

RATIONALE AND OBJECTIVES: It is critical to predict early recurrence (ER) after percutaneous thermal ablation (PTA) for hepatocellular carcinoma (HCC). We aimed to develop and validate a delta-radiomics nomogram based on multi-phase contrast-enhanced magnetic resonance imaging (MRI) to preoperatively predict ER of HCC after PTA. MATERIALS AND METHODS: We retrospectively enrolled 164 patients with HCC and divided them into training, temporal validation, and other-scanner validation cohorts (n = 110, 29, and 25, respectively). The volumes of interest of the intratumoral and/or peritumoral regions were delineated on preoperative multi-phase MR images. Original radiomics features were extracted from each phase, and delta-radiomics features were calculated. Logistic regression was used to train the corresponding radiomics models. The clinical and radiological characteristics were evaluated and combined to establish a clinical-radiological model. A fusion model comprising the best radiomics scores and clinical-radiological risk factors was constructed and presented as a nomogram. The performance of each model was evaluated and recurrence-free survival (RFS) was assessed. RESULTS: Child-Pugh grade B, high-risk tumor location, and an incomplete/absent tumor capsule were independent predictors of ER. The optimal radiomics model comprised 12 delta-radiomics features with areas under the curve (AUCs) of 0.834, 0.795, and 0.769 in the training, temporal validation, and other-scanner validation cohorts, respectively. The nomogram showed the best predictive performance with AUCs as 0.893, 0.854, and 0.827 in the three datasets. There was a statistically significant difference in RFS between the risk groups calculated using the delta-radiomics model and nomogram. CONCLUSIONS: The nomogram combined with the delta-radiomic score and clinical-radiological risk factors could non-invasively predict ER of HCC after PTA.

2.
IEEE Trans Pattern Anal Mach Intell ; 45(10): 12321-12340, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37126624

ABSTRACT

Quantum computers are next-generation devices that hold promise to perform calculations beyond the reach of classical computers. A leading method towards achieving this goal is through quantum machine learning, especially quantum generative learning. Due to the intrinsic probabilistic nature of quantum mechanics, it is reasonable to postulate that quantum generative learning models (QGLMs) may surpass their classical counterparts. As such, QGLMs are receiving growing attention from the quantum physics and computer science communities, where various QGLMs that can be efficiently implemented on near-term quantum machines with potential computational advantages are proposed. In this paper, we review the current progress of QGLMs from the perspective of machine learning. Particularly, we interpret these QGLMs, covering quantum circuit Born machines, quantum generative adversarial networks, quantum Boltzmann machines, and quantum variational autoencoders, as the quantum extension of classical generative learning models. In this context, we explore their intrinsic relations and their fundamental differences. We further summarize the potential applications of QGLMs in both conventional machine learning tasks and quantum physics. Last, we discuss the challenges and further research directions for QGLMs.

3.
Neural Netw ; 163: 86-96, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37030278

ABSTRACT

Off-Policy Actor-Critic methods can effectively exploit past experiences and thus they have achieved great success in various reinforcement learning tasks. In many image-based and multi-agent tasks, attention mechanism has been employed in Actor-Critic methods to improve their sampling efficiency. In this paper, we propose a meta attention method for state-based reinforcement learning tasks, which combines attention mechanism and meta-learning based on the Off-Policy Actor-Critic framework. Unlike previous attention-based work, our meta attention method introduces attention in the Actor and the Critic of the typical Actor-Critic framework, rather than in multiple pixels of an image or multiple information sources in specific image-based control tasks or multi-agent systems. In contrast to existing meta-learning methods, the proposed meta-attention approach is able to function in both the gradient-based training phase and the agent's decision-making process. The experimental results demonstrate the superiority of our meta-attention method in various continuous control tasks, which are based on the Off-Policy Actor-Critic methods including DDPG and TD3.


Subject(s)
Algorithms , Reinforcement, Psychology , Learning
4.
iScience ; 26(4): 106281, 2023 Apr 21.
Article in English | MEDLINE | ID: mdl-36950123

ABSTRACT

The study of superatoms has attracted great interest since they apparently go beyond the traditional understanding of the periodic table of elements. In this work, we clearly show that superatoms can be extended from conventional structures to states under pressure condition. By studying the compression process of the CH4@C60 system formed via embedding methane molecules inside fullerene C60, it is found that the system maintains superatomic properties in both static states, and even dynamic rotation situations influenced by quantum tunneling. Remarkably, the simulations reveal the emergence of new superatomic molecular orbitals by decreasing the confined space to approach the van der Waals boundary between CH4 and C60. Our current results not only establish a complete picture of superatoms from ambient condition to high pressure, but also offer a perspective for the discovery and exploration of new properties in superatom systems under extreme conditions.

5.
J Phys Chem Lett ; 14(11): 2862-2868, 2023 Mar 23.
Article in English | MEDLINE | ID: mdl-36920152

ABSTRACT

This work reports a series of endohedral metallofullerene superatoms [Mg@C20]n, where n = 4, 2, 0, -2, and -4. It was found that Mg transfers virtually all of its 3s electrons to the C20 shell, resulting in the ionic states of Mg2+@[C20]n-2. Detailed calculations revealed that the superatomic electronic configuration of these clusters is 1S21P61D101F4-n. The first nine superatomic molecular orbitals (SAMOs), 1S21P61D10, housed with 18 electrons, are largely based on [C20]n-2 with small contributions from magnesium, while the outmost SAMOs, 1F4-n, with 4 - n extra electrons, reside solely on [C20]n-2. The interaction between the Mg2+ ion and [C20]n-2 was found to be predominately ionic in character. Furthermore, ultraviolet-visible spectra provide a theoretical basis for fingerprinting these clusters. It is hoped that this work will encourage the synthetic pursuit of these smallest superatomic systems.

6.
J Clin Med ; 12(2)2023 Jan 06.
Article in English | MEDLINE | ID: mdl-36675415

ABSTRACT

BACKGROUND: Hydroxychloroquine (HCQ) has been used in the treatment of systematic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), but its effect on lupus activity during pregnancy, preeclampsia and intrauterine growth restriction (IUGR) remains unclear. METHODS: PubMed, Embase and Cochrane databases were searched before 11 September 2022 for randomized clinical trials (RCT) or observational studies involving additional HCQ treatment and pregnant women diagnosed as having SLE and/or APS/positive antiphospholipid antibodies (aPLs). Risks of high lupus activity, preeclampsia and IUGR were explored. RESULTS: One RCT and 13 cohort studies were included. A total of 1764 pregnancies were included in the pooled meta-analysis (709 in the HCQ group vs. 1055 in the control group). After the additional use of HCQ, the risk of high lupus activity decreased (RR: 0.74, 95% CI: 0.57-0.97, p = 0.03). For preeclampsia, the total incidence decreased (RR: 0.54, 95% CI: 0.37-0.78, p = 0.001). The subgroup analysis showed statistical significance in the SLE subgroup (RR: 0.51, 95% CI: 0.34-0.78, p = 0.002) but not in the APS/aPLs subgroup (RR: 0.66, 95% CI: 0.29-1.54, p = 0.34). For IUGR, the decrease in incidence was not statistically significant (RR: 0.80, 95% CI: 0.47-1.35, p = 0.46), neither in the SLE subgroup (RR: 0.74, 95% CI: 0.40-1.36, p = 0.33) nor in the APS/aPLs subgroup (RR: 1.26, 95% CI: 0.34-4.61, p = 0.73). CONCLUSION: The additional use of HCQ may decrease the risk of high lupus activity during pregnancy and the incidence of preeclampsia for SLE patients, but the results do not support that using HCQ decreases the incidence of preeclampsia for APS/aPLs patients or reduces IUGR risk for SLE and/or APS/aPLs patients.

7.
Adv Sci (Weinh) ; 10(9): e2206899, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36698290

ABSTRACT

In this work, a novel discovery that the coinage-metal near-plane superatoms (CM-NPSs) formed by embedding actinide elements into the coinage metal rings can realize the "Z"-type tilted quasi-one-dimensional (1D) direct assembly is reported. This success can be attributed to the strong bonding between the overlapping parts of adjacent superatomic motifs. First-principles calculations reveal that the motifs maintain their geometric and electronic structures robustly during the assembly process. With the accumulation of motifs, the intensity of the absorption peak increases continuously in the ultraviolet-visible (UV-Vis) absorption spectra range of 300-450 nm, resulting in the hyperchromic effect, which is closely related to the degree of the participation of Th atoms. Furthermore, the absorption spectra show a continuously tunable feature in the 450-900 nm range, as the interlayer stacking pattern leads to a pronounced redshift. More importantly, the valence 5f-shells of Th atoms have an increased contribution to the final orbitals of electronic transition, which demonstrates the advantages of the active high angular momentum electrons of actinide elements in spectral properties. These findings provide a valuable reference for the direct artificial assembly of near-plane superatoms and optical properties of superatomic assemblies embedded with rare elements.

8.
J Phys Chem Lett ; 13(36): 8455-8461, 2022 Sep 15.
Article in English | MEDLINE | ID: mdl-36053267

ABSTRACT

A new type of excimer formation was reported, which stems from an unexpected discovery of a short-lived excited-state dimer of superatomic dimers. In theoretical investigation of the dimer formation, it was found that the physical adsorption states maintain the closed-shell properties of the dimeric units via van der Waals interaction, while the chemical adsorption excited state is a broken-symmetry (BS) state, having a higher energy of about 0.5 eV. Potential energy surface calculations indicate that the short-lived metastable chemical bonding state can transform into energetically lower physical adsorption states by crossing a shallow energy barrier and eventually disintegrate into two ground-state dimers. Since the basic unit is a superatomic cluster, the chemical adsorption state discovered may be called "super-excimer", which opens up a new avenue for the discovery of tailorable excimer materials.

9.
Int J Comput Assist Radiol Surg ; 17(10): 1923-1931, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35794409

ABSTRACT

PURPOSE: The gene mutation status of isocitrate dehydrogenase (IDH) in gliomas leads to a different prognosis. It is challenging to perform automated tumor segmentation and genotype prediction directly using label-deprived multimodal magnetic resonance (MR) images. We propose a novel framework that employs a domain adaptive mechanism to address this issue. METHODS: Multimodal domain adaptive segmentation (MDAS) framework was proposed to solve the gap issue in cross dataset model transfer. Image translation was used to adaptively align the multimodal data from two domains at the image level, and segmentation consistency loss was proposed to retain more pathological information through semantic constraints. The data distribution between the labeled public dataset and label-free target dataset was learned to achieve better unsupervised segmentation results on the target dataset. Then, the segmented tumor foci were used as a mask to extract the radiomics and deep features. And the subsequent prediction of IDH gene mutation status was conducted by training a random forest classifier. The prediction model does not need any expert segmented labels. RESULTS: We implemented our method on the public BraTS 2019 dataset and 110 astrocytoma cases of grade II-IV brain tumors from our hospital. We obtained a Dice score of 77.41% for unsupervised tumor segmentation, a genotype prediction accuracy (ACC) of 0.7639 and an area under curve (AUC) of 0.8600. Experimental results demonstrate that our domain adaptive approach outperforms the methods utilizing direct transfer learning. The model using hybrid features gives better results than the model using radiomics or deep features alone. CONCLUSIONS: Domain adaptation enables the segmentation network to achieve better performance, and the extraction of mixed features at multiple levels on the segmented region of interest ensures effective prediction of the IDH gene mutation status.


Subject(s)
Brain Neoplasms , Glioma , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/genetics , Genotype , Glioma/diagnostic imaging , Glioma/genetics , Humans , Image Processing, Computer-Assisted/methods , Isocitrate Dehydrogenase/genetics , Magnetic Resonance Imaging/methods
10.
Front Endocrinol (Lausanne) ; 13: 905263, 2022.
Article in English | MEDLINE | ID: mdl-35757417

ABSTRACT

Purpose: To explore another choice for a controlled ovarian stimulation (COS) protocol that does not increase severe ovarian hyperstimulation syndrome (OHSS) risk among polycystic ovarian syndrome (PCOS) patients with specific clinical features. Methods: A retrospective study was performed. Two hundred and fifty-nine participants were divided into two groups, group 1 (fixed GnRH antagonist protocol, n = 295) and group 2 (follicular-phase GnRH agonist protocol, n = 69) according to COS protocols. The basic characteristics and laboratory indicators between these two groups were compared. The severe OHSS rate and clinical pregnancy rate were selected as indicators to evaluate the risks and benefits of the two COS protocols. Subgroup analyses for the severe OHSS rate and clinical pregnancy rate were performed based on baseline luteinizing hormone/follicle-stimulating hormone (bLH/FSH) and anti-Mullerian hormone (AMH) levels. Results: The severe OHSS rate was statistically higher in group 2 than in group 1 (11.6% vs. 3.7%, p = 0.008), but the biochemical pregnancy rate and clinical pregnancy rate showed no statistical difference between the groups (71.9% vs. 60.3% and 62.5% vs. 54.3%). In the higher bLH/FSH subgroup (≥1.33) and the higher serum AMH level subgroup (>3.4 ng/ml), severe OHSS incidence was statistically higher in group 2 compared to group 1, but this incidence was lower in the bLH/FSH subgroup (<1.33) and the subgroup with lower serum AMH levels (≤3.4 ng/ml); a difference in severe OHSS risk was not observed. There was no statistical difference between the two groups regarding clinical pregnancy rate in any subgroup. Conclusion: The limited evidence from this study indicates that in PCOS patients with lower bLH/FSH levels (<1.33) and lower serum AMH levels (≤3.4 ng/ml), a follicular-phase GnRH agonist protocol may be another choice that does not increase the risk of severe OHSS.


Subject(s)
Ovarian Hyperstimulation Syndrome , Polycystic Ovary Syndrome , Anti-Mullerian Hormone , Female , Fertilization in Vitro/methods , Follicle Stimulating Hormone , Gonadotropin-Releasing Hormone , Humans , Luteinizing Hormone , Ovarian Hyperstimulation Syndrome/chemically induced , Ovarian Hyperstimulation Syndrome/epidemiology , Ovulation Induction/adverse effects , Ovulation Induction/methods , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/drug therapy , Pregnancy , Retrospective Studies
12.
Acta Radiol ; 63(12): 1661-1668, 2022 Dec.
Article in English | MEDLINE | ID: mdl-34709088

ABSTRACT

BACKGROUND: The differentiation of supratentorial pilocytic astrocytomas (STPAs) and supratentorial extraventricular ependymomas (STEEs) is clinically pivotal because of distinct therapeutic management and prognosis, which is sometimes challenging to both neuroradiologists and pathologists. PURPOSE: To explore and compare the conventional and advanced magnetic resonance imaging (MRI) features between STPA and STEE. MATERIAL AND METHODS: A total of 23 patients with STPAs and 23 patients with STEEs were reviewed in this study. All patients performed conventional MRI, susceptibility-weighted imaging (SWI), and diffusion-weighted imaging (DWI), and 34 patients (17 with STPAs and 17 with STEEs) examined dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI) in addition. Clinical data, conventional MRI features, minimum relative apparent diffusion coefficient ratio (rADCmin), and maximum relative cerebral blood volume ratio (rCBVmax) were compared between the two groups and subgroups. The optimal cutoff values of rADCmin and rCBVmax with sensitivity and specificity were calculated. RESULTS: STPA manifested similar to STEE as a solid-cystic mass but more frequently presented with a marked enhancing deep nodule (P = 0.02), no peritumoral edema (P = 0.036), higher rADCmin value (2.0 ± 0.5 vs. 0.9 ± 0.2; P < 0.001), and lower rCBVmax value (2.1 ± 0.4 vs. 14.4 ± 5.5; P < 0.001). The cutoff value of >1.39 for rADCmin and ≤ 2.81 for rCBVmax produced a high sensitivity of 95.65% and 100.0%, respectively, and all produced a specificity of 100.0% in differentiating STPAs from STEEs. CONCLUSION: Multiparametric MRI techniques including conventional MRI, DWI, and DSC-PWI contribute to the differential diagnosis of STPA and STEE.


Subject(s)
Astrocytoma , Brain Neoplasms , Ependymoma , Multiparametric Magnetic Resonance Imaging , Supratentorial Neoplasms , Humans , Brain Neoplasms/pathology , Retrospective Studies , Astrocytoma/diagnostic imaging , Astrocytoma/pathology , Ependymoma/diagnostic imaging , Diffusion Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging/methods , Supratentorial Neoplasms/diagnostic imaging , Diagnosis, Differential
13.
J Phys Chem Lett ; 12(36): 8713-8719, 2021 Sep 16.
Article in English | MEDLINE | ID: mdl-34473516

ABSTRACT

In this work, we investigate the relationship between the charge distribution and electron occupation by exploring neutral gold superatoms Aun and their anion structures [Aun]- (n = 13, 55, and 147). It is shown that there exists "skin behavior" of charge distribution for gold superatoms. For the neutral Aun, there are negative charges of -0.1 e, -0.54 e, and -1.16 e distributed in the surface area of 1D5 SAMOs of Au13, 1F12 1G15 SAMOs of Au55, and 2D6 1H22 2F14 1I6 3S2 1J6 1I8 1J4 3P1 SAMOs of Au147, respectively. For the anion [Aun]-, more negative charges of -1.08 e, -1.55 e, and -2.14 e are distributed in the surface area of 1D SAMO of [Au13]-, 1G SAMO of [Au55]-, and 3P SAMO of [Au147]-. In addition, adding an electron will cause the SAMOs rearrangement and enhance the geometric symmetry of superatoms, especially in [Au13]- and [Au55]-. Our findings provide a new perspective on microelectronic structure in understanding the skin effects.


Subject(s)
Gold/chemistry , Metal Nanoparticles/chemistry , Anions/chemistry , Computer Simulation , Electrochemical Techniques , Electrons , Surface Properties
14.
Arch Pharm (Weinheim) ; 353(6): e1900371, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32237167

ABSTRACT

In an effort to develop a new class of potent aldose reductase inhibitors against diabetic cataracts, a series of novel 2-thioxothiazolidine-4-one derivatives was synthesized in excellent yields via a facile synthetic route. These compounds were tested against aldehyde (ALR1) and aldose reductase (ALR2) enzymes, where they showed considerable inhibitory activity. Among the tested derivatives, compound 6e showed selective and excellent inhibition of ALR2 over ALR1. The experimental diabetes was induced by the intraperitoneal administration of streptozotocin in male Wistar rats. Compound 6e showed positive modulation of body weight, blood glucose, and blood insulin levels in diabetic rats. Compound 6e also showed ALR2 inhibition as evidenced by Western blot analysis in lens homogenates of Wistar rats having cataract. The docking study of 6e was also performed inside the active site of ALR2 to enumerate the key contacts for inhibitory activity.


Subject(s)
Aldehyde Reductase/antagonists & inhibitors , Diabetes Mellitus, Experimental/drug therapy , Enzyme Inhibitors/pharmacology , Hypoglycemic Agents/pharmacology , Thiazolidinediones/pharmacology , Aldehyde Reductase/metabolism , Animals , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/metabolism , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Hypoglycemic Agents/chemical synthesis , Hypoglycemic Agents/chemistry , Male , Molecular Docking Simulation , Molecular Structure , Rats , Rats, Wistar , Streptozocin , Structure-Activity Relationship , Thiazolidinediones/chemical synthesis , Thiazolidinediones/chemistry
15.
Diabetes Ther ; 10(5): 1801-1809, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31321746

ABSTRACT

INTRODUCTION: Vitrectomy is one of the main treatments for proliferative diabetic retinopathy (PDR). Postoperative neovascular glaucoma, in which it is difficult to obtain satisfactory results using conventional filtering surgery, is one of the most serious complications of vitrectomy. It often requires destructive surgery, such as ciliary body photocoagulation or freezing, and the outcome with regard to visual acuity (VA) is extremely poor. The purpose of this study was to evaluate the prevalence of neovascular glaucoma (NVG) after modern vitrectomy techniques and investigate how variables assessed before and after vitrectomy are associated with patients who develop NVG after PDR surgery. METHODS: This was an observational study including the medical records of patients who underwent vitrectomy for PDR at Tianjin Eye Hospital from June 2014 to July 2016, were followed for at least 24 months postoperatively, and NVG developed within 2 years after surgery was recorded. Each patient underwent complete preoperative ophthalmic examinations in both preoperative and follow-up appointments. Factors associated with survival were determined using the Kaplan-Meier (KM) survival analysis to calculate the incidence of NVG after vitrectomy for PDR. Multivariable analysis was performed with the Cox regression proportional hazards model to verify the results of the analysis and eliminate interference factors between variables. All statistical analyses were performed using R statistical software ( http://www.r-project.org ) for Windows. RESULTS: In all, 238 patients (238 eyes) fulfilled the study criteria. NVG occurred in 11 of 238 eyes (4.6%). The percentages of NVG development after vitrectomy at 6, 12, and 24 months were 0.42%, 3.3%, and 4.6%, respectively. After step analysis, multivariable regression identified preoperative high intraocular pressure (IOP) combined with retinal vein occlusion (RVO), severe PDR, no postoperative intravitreal injection of ranibizumab (IVR), and higher HbA1c levels as significant predictors of NVG. CONCLUSION: Preoperative high IOP combined with RVO, severe PDR, no postoperative intravitreal injection of ranibizumab (IVR), and higher HbA1c levels are significant predictors of NVG after vitrectomy.

16.
Medicine (Baltimore) ; 98(20): e15735, 2019 May.
Article in English | MEDLINE | ID: mdl-31096535

ABSTRACT

To evaluate the outcomes and complications of intravitreal injections of ranibizumab in patients during pars plana vitrectomy for treatment of diabetic vitreous hemorrhage. This retrospective, observational, comparative study included 103 patients (103 eyes) who underwent pars plana vitrectomy for treatment of diabetic vitreous hemorrhage. Sixty-six patients received an intravitreal injection of 0.05 mg (0.05 cc) of ranibizumab at the end of surgery. Main outcome measures were the occurrence of recurrent early vitreous hemorrhage, reoperation, intraocular pressure, best corrected visual acuity. Mean follow-up time was 6 months. The rate of rebleeding in the intravitreal ranibizumab (IVR) group was 6.1% (4 eyes), which is significantly lower than the control group (24.3%, 9 eyes, P < .01). The incidence of postoperative diabetic vitreous hemorrhage (PDVH) was significantly lower in the IVR group than the control group, OR=0.26, 95% CI= (0.06, 0.95). Visual acuity 6 months after operation was better in IVR group (P<.01) There was no difference in mean intraocular pressure between the 2 groups (P=.56). The present clinical study suggests that intravitreal injection of ranibizumab is effective in the prevention of postoperative diabetic vitreous hemorrhage in eyes undergoing pars plana vitrectomy for the treatment of diabetic vitreous hemorrhage.


Subject(s)
Diabetic Retinopathy/therapy , Ranibizumab/administration & dosage , Vitrectomy/methods , Vitreous Hemorrhage/therapy , Adult , Diabetic Retinopathy/complications , Female , Humans , Intravitreal Injections/statistics & numerical data , Male , Middle Aged , Reoperation , Retrospective Studies , Treatment Outcome , Visual Acuity , Vitreous Hemorrhage/etiology
17.
Mol Med Rep ; 19(5): 4449-4456, 2019 May.
Article in English | MEDLINE | ID: mdl-30942394

ABSTRACT

Posterior capsular opacification (PCO) remains a major complication of cataract surgery and is the most common reason for loss of vision. PCO is primarily associated with uncontrolled proliferation of residual human lens epithelial cells (HLEs). Sanguinarine is a type of benzophenanthridine alkaloid extracted from the herbaceous plant Sanguinaria canadensis, which is widely used for its anti­microbial, anti­inflammatory, anti­oxidative and anti­proliferative properties. However, studies examining the effect of sanguinarine on HLEs and the underlying mechanism are scarce. The present study aimed to investigate the effects of sanguinarine on HLEs. An MTT assay was used to determine the effect of sanguinarine on cell viability. Flow cytometry was used to evaluate cell apoptosis, and the mitochondrial membrane potential and reactive oxygen species (ROS) levels. A caspase 3/7 activity assay was also used to evaluate cell apoptosis, while western blotting was performed to determine protein levels. The results demonstrated that sanguinarine exerted an anti­proliferative effect by inducing ROS, and caused cell apoptosis via mitochondrial and caspase­dependent pathways. Treatment with sanguinarine led to the loss of mitochondrial membrane potential. Sanguinarine also significantly increased the phosphorylation levels of c­Jun N­terminal kinase and p38, which indicated the involvement of the mitogen­activated protein kinase signaling pathway. These results suggested that sanguinarine may have a noteworthy pro­apoptotic effect on HLEs, and may be used as a potential drug for PCO or even cataract prevention.


Subject(s)
Anti-Infective Agents/pharmacology , Apoptosis/drug effects , Benzophenanthridines/pharmacology , Isoquinolines/pharmacology , MAP Kinase Signaling System/drug effects , Reactive Oxygen Species/metabolism , Caspase 3/metabolism , Cell Line , Cell Survival/drug effects , Epithelial Cells/cytology , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Humans , Membrane Potential, Mitochondrial/drug effects
18.
Med Sci Monit ; 24: 7424-7430, 2018 Oct 17.
Article in English | MEDLINE | ID: mdl-30332398

ABSTRACT

BACKGROUND In view of the high incidence of posterior capsule opacification (PCO) and the effects of TGF-ß signaling on the epithelial-mesenchymal transition (EMT) of human lens epithelial cells (LECs), our study aimed to explore the mechanism of the function of TGF-ß signaling in LECs EMT. MATERIAL AND METHODS Human lens epithelial cells (HLEC-h3) were treated with TGF-ß, ILK siRNA, ILK inhibitor, and NF-κB inhibitor to study the effects of TGF-ß, ILK, and NF-κB on cell migration and EMT. Cell migration assay was used to measure cell migration ability. Western blot was performed to detect the expression of ILK, E-cadherin, and a-SMA at the protein level. QRT-PCR was used to detect the expression of ILK at the mRNA level. RESULTS Compared with control cells, TGF-ß treatment increased the expression level of ILK HLEC-h3, promoted migration of HLEC-h3 cells, increased the expression level of E-cadherin protein, and decreased the expression level of a-SMA protein. However, treatment with ILK siRNA, ILK inhibitor, and NF-κB inhibitor reversed the effects of TGF-ß on HLEC-h3 cells. CONCLUSIONS TGF-ß-stimulated ILK regulates the migration and EMT of human LECs via NF-κB.


Subject(s)
Capsule Opacification/metabolism , Lens, Crystalline/metabolism , NF-kappa B/metabolism , Protein Serine-Threonine Kinases/metabolism , Transforming Growth Factor beta1/pharmacology , Antigens, CD/metabolism , Cadherins/metabolism , Capsule Opacification/pathology , Cell Movement/drug effects , Cell Movement/physiology , Cells, Cultured , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Epithelial-Mesenchymal Transition/drug effects , Humans , Lens, Crystalline/cytology , Lens, Crystalline/drug effects , NF-kappa B/antagonists & inhibitors , Posterior Capsule of the Lens/metabolism , Posterior Capsule of the Lens/pathology , Protein Serine-Threonine Kinases/antagonists & inhibitors , Protein Serine-Threonine Kinases/biosynthesis , Signal Transduction , Transforming Growth Factor beta1/metabolism
19.
Molecules ; 19(6): 7785-97, 2014 Jun 11.
Article in English | MEDLINE | ID: mdl-24962386

ABSTRACT

Shikonin is a compound from the herbal plant Lithospermum erythrorhizon that has been proved to possess powerful anti-proliferative effect on many kinds of cancers and to be safe in in vivo study. Posterior capsular opacification (PCO), the most frequent complication of cataract surgery, is mainly caused by the uncontrolled proliferation of retained human lens epithelial cells (HLEs). In this study, we investigated the effect of shikonin on the proliferation of HLEs and explored its underlying mechanism of action. Shikonin significantly inhibited the proliferation of HLEs in a dose- and time-dependent manner. Its anti-proliferative effect was exerted through induction of apoptosis. Reactive oxygen species (ROS) generation played an essential role in this apoptotic process. Interestingly, scavenging of ROS completely blocked the apoptosis induced by shikonin. In addition, the treatment of shikonin in HLEs significantly increased the ratio of Bax/Bcl-2, disrupted mitochondria membrane potential (MMP) and activated caspases. The inhibition of caspase largely blocks the apoptosis. The changes of MAPK pathway were also demonstrated. Shikonin effectively inhibited the phosphorylation of ERK, while it activated the phosphorylation of JNK and p38. These results suggested that shikonin inhibited the proliferation of HLEs by inducing apoptosis through ROS generation and the caspase-dependent pathway and the MAPK pathway was also involved.


Subject(s)
Apoptosis/drug effects , Caspase Inhibitors/pharmacology , Cell Proliferation/drug effects , Lens, Crystalline/growth & development , Naphthoquinones/pharmacology , Reactive Oxygen Species/metabolism , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Caspase 3/metabolism , Caspase 7/metabolism , Caspase 9/metabolism , Cell Line , Drugs, Chinese Herbal/pharmacology , Epithelial Cells/cytology , Extracellular Signal-Regulated MAP Kinases/metabolism , Humans , JNK Mitogen-Activated Protein Kinases/metabolism , Lens, Crystalline/cytology , Membrane Potential, Mitochondrial/drug effects , Phosphorylation/drug effects , Proto-Oncogene Proteins c-bcl-2/biosynthesis , bcl-2-Associated X Protein/biosynthesis , p38 Mitogen-Activated Protein Kinases/metabolism
20.
Int J Ophthalmol ; 5(1): 74-5, 2012.
Article in English | MEDLINE | ID: mdl-22553759

ABSTRACT

AIM: To study the tear film stability after lamellar keratoplasty. METHODS: Five female and eight male patients with lamellar keratoconus, aged from 18 to 32, were involved. After lamellar keratoplasty, Schirmer I test(S I t), tear break-up time(BUT) test, fluorescein staining test were used to judge the effect of the surgery at different time point. RESULTS: The S I t were greatly increased in 7 days post operation (11.86±2.28 -25.14±1.97, 19.86±1.61) (P<0.05), there is no significant difference between 2(nd) month, 3(rd) month post-operative and pre-operation (11.86±2.28 - 14.57±1.48, 8.14±0.86) (P>0.05). The mean break-up time decreased in 7 days post operation (5.00±1.31 - 2.71±0.18, 2.57±0.20, 2.71±0.36, 2.43±0.20) (P<0.05). The mean scores of fluorescence increased post-operatively (0.14±0.14 - 8.00±0.00, 8.00±0.00, 8.00±0.00, 7.57±0.20) (P<0.01). CONCLUSION: Lamellar keratoplaty influence the tear film stability, artificial tears and improving corneal epithelium cured medicine should be used after surgery.

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