Cold atmospheric plasma-enabled platelet vesicle incorporated iron oxide nano-propellers for thrombolysis.

A new approach to treating vascular blockages has been developed to overcome the limitations of current thrombolytic therapies. This approach involves biosafety and multimodal plasma-derived theranostic platelet vesicle incorporating iron oxide constructed nano-propellers platformed technology that possesses fluorescent and magnetic features and manifold thrombus targeting modes. The platform is capable of being guided and visualized remotely to specifically target thrombi, and it can be activated using near-infrared phototherapy along with an actuated magnet for magnetotherapy. In a murine model of thrombus lesion, this proposed multimodal approach showed an approximately 80 % reduction in thrombus residues. Moreover, the new strategy not only improves thrombolysis but also boosts the rate of lysis, making it a promising candidate for time-sensitive thrombolytic therapy.

P-Selectin mediates targeting of a self-assembling phototherapeutic nanovehicle enclosing dipyridamole for managing thromboses.

Thrombotic vascular disorders, specifically thromboembolisms, have a significant detrimental effect on public health. Despite the numerous thrombolytic and antithrombotic drugs available, their efficacy in penetrating thrombus formations is limited, and they carry a high risk of promoting bleeding. Consequently, the current medication dosage protocols are inadequate for preventing thrombus formation, and higher doses are necessary to achieve sufficient prevention. By integrating phototherapy with antithrombotic therapy, this study addresses difficulties related to thrombus-targeted drug delivery. We developed self-assembling nanoparticles (NPs) through the optimization of a co-assembly engineering process. These NPs, called DIP-FU-PPy NPs, consist of polypyrrole (PPy), dipyridamole (DIP), and P-selectin-targeted fucoidan (FU) and are designed to be delivered directly to thrombi. DIP-FU-PPy NPs are proposed to offer various potentials, encompassing drug-loading capability, targeted accumulation in thrombus sites, near-infrared (NIR) photothermal-enhanced thrombus management with therapeutic efficacy, and prevention of rethrombosis. As predicted, DIP-FU-PPy NPs prevented thrombus recurrence and emitted visible fluorescence signals during thrombus clot penetration with no adverse effects. Our co-delivery nano-platform is a simple and versatile solution for NIR-phototherapeutic multimodal thrombus control.

A Biomimicking and Multiarm Self-Indicating Nanoassembly for Site-Specific Photothermal-Potentiated Thrombolysis Assessed in Microfluidic and In Vivo Models.

Thrombolytic and antithrombotic therapies are limited by short circulation time and the risk of off-target hemorrhage. Integrating a thrombus-homing strategy with photothermal therapy are proposed to address these limitations. Using glycol chitosan, polypyrrole, iron oxide and heparin, biomimicking GCPIH nanoparticles are developed for targeted thrombus delivery and thrombolysis. The nanoassembly achieves precise delivery of polypyrrole, exhibiting biocompatibility, selective accumulation at multiple thrombus sites, and enhanced thrombolysis through photothermal activation. To simulate targeted thrombolysis, a microfluidic model predicting thrombolysis dynamics in realistic pathological scenarios is designed. Human blood assessments validate the precise homing of GCPIH nanoparticles to activated thrombus microenvironments. Efficient near-infrared phototherapeutic effects are demonstrated at thrombus lesions under physiological flow conditions ex vivo. The combined investigations provide compelling evidence supporting the potential of GCPIH nanoparticles for effective thrombus therapy. The microfluidic model also offers a platform for advanced thrombolytic nanomedicine development.

Metabolic adaptation supports enhanced macrophage efferocytosis in limited-oxygen environments.

Apoptotic cell (AC) clearance (efferocytosis) is performed by phagocytes, such as macrophages, that inhabit harsh physiological environments. Here, we find that macrophages display enhanced efferocytosis under prolonged (chronic) physiological hypoxia, characterized by increased internalization and accelerated degradation of ACs. Transcriptional and translational analyses revealed that chronic physiological hypoxia induces two distinct but complimentary states. The first, "primed" state, consists of concomitant transcription and translation of metabolic programs in AC-naive macrophages that persist during efferocytosis. The second, "poised" state, consists of transcription, but not translation, of phagocyte function programs in AC-naive macrophages that are translated during efferocytosis. Mechanistically, macrophages efficiently flux glucose into a noncanonical pentose phosphate pathway (PPP) loop to enhance NADPH production. PPP-derived NADPH directly supports enhanced efferocytosis under physiological hypoxia by ensuring phagolysosomal maturation and redox homeostasis. Thus, macrophages residing under physiological hypoxia adopt states that support cell fitness and ensure performance of essential homeostatic functions rapidly and safely.

Pentraxin 3 regulates tyrosine kinase inhibitor-associated cardiomyocyte contraction and mitochondrial dysfunction via ERK/JNK signalling pathways.

BACKGROUND: Hepatocellular carcinoma (HCC) patients suffer varying degrees of heart dysfunction after tyrosine kinase inhibitor (TKI) treatment. Interestingly, HCC patients often have higher levels of pentraxin 3 (PTX3), and PTX3 inhibition was found to improve left ventricular dysfunction in animal models. OBJECTIVES: We sought to assess the therapeutic potential of PTX3 inhibition on TKI-associated cardiotoxicity. METHODS: We used a human embryonic stem cell line, RUES2, to generate cardiomyocyte cultures (RUES2-CM) for functional testing. We also assessed heart function and PTX3 expression levels in 16 HCC patients who received TKI treatment, 3 HCC patients who did not receive TKIs, and 7 healthy volunteers. RESULTS: Significantly higher PTX3 expression was noted in HCC patients with TKI treatment versus those without, and 38% of male and 33% of female patients had QTc prolongation after TKI treatment. Treatment of cardiomyocyte cultures with sorafenib also increased PTX3 expression and induced cytoskeletal remodelling, contraction reduction, sodium current inhibition, and mitochondrial respiratory dysfunction. PTX3 colocalised with CD44 in cardiomyocytes, and cardiomyocyte contraction, mitochondrial respiratory function, and regular cytoskeletal and apoptotic protein expression were restored with PTX3 inhibition. CD44 knockdown confirmed PTX3/CD44 signalling. These results suggest a possible mechanism in which sorafenib treatment increases PTX3 expression, thereby resulting in reduced extracellular signal-regulated kinase (ERK) 1/2 expression that affects cardiomyocyte contraction, while also activating c-Jun N-terminal kinase (JNK) downstream pathways to disrupt mitochondrial respiration and trigger apoptosis. CONCLUSIONS: TKI-induced cardiotoxicity may be partly mediated by the upregulation of PTX3, and thus PTX3 inhibition has potential as a therapeutic strategy.

Genome-wide CRISPR screens of T cell exhaustion identify chromatin remodeling factors that limit T cell persistence.

T cell exhaustion limits antitumor immunity, but the molecular determinants of this process remain poorly understood. Using a chronic stimulation assay, we performed genome-wide CRISPR-Cas9 screens to systematically discover regulators of T cell exhaustion, which identified an enrichment of epigenetic factors. In vivo CRISPR screens in murine and human tumor models demonstrated that perturbation of the INO80 and BAF chromatin remodeling complexes improved T cell persistence in tumors. In vivo Perturb-seq revealed distinct transcriptional roles of each complex and that depletion of canonical BAF complex members, including Arid1a, resulted in the maintenance of an effector program and downregulation of exhaustion-related genes in tumor-infiltrating T cells. Finally, Arid1a depletion limited the acquisition of exhaustion-associated chromatin accessibility and led to improved antitumor immunity. In summary, we provide an atlas of the genetic regulators of T cell exhaustion and demonstrate that modulation of epigenetic state can improve T cell responses in cancer immunotherapy.

Prognostic gene expression analysis in a retrospective, multinational cohort of 155 multiple myeloma patients treated outside clinical trials.

OBJECTIVES: Typically, prognostic capability of gene expression profiling (GEP) is studied in the context of clinical trials, for which 50%-80% of patients are not eligible, possibly limiting the generalizability of findings to routine practice. Here, we evaluate GEP analysis outside clinical trials, aiming to improve clinical risk assessment of multiple myeloma (MM) patients. METHODS: A total of 155 bone marrow samples from MM patients were collected from which RNA was analyzed by microarray. Sixteen previously developed GEP-based markers were evaluated, combined with survival data, and studied using Cox proportional hazard regression. RESULTS: Gene expression profiling-based markers SKY92 and the PR-cluster were shown to be independent prognostic factors for survival, with hazard ratios and 95% confidence interval of 3.6 [2.0-6.8] (P < .001) and 5.8 [2.7-12.7] (P < .01) for overall survival (OS). A multivariate model proved only SKY92 and the PR-cluster to be independent prognostic factors compared to cytogenetic high-risk patients, the International Staging System (ISS), and revised ISS. A substantial number of high-risk individuals could be further identified when SKY92 was added to the cytogenetic, ISS, or R-ISS. In the cytogenetic standard-risk group, ISS I/II, and R-ISS I/II, 13%, 23%, and 23% of patients with adverse survivals were identified. CONCLUSIONS: For the first time, this study confirmed the prognostic value of GEP markers outside clinical trials. Conventional prognostic models to define high-risk MM are improved by the incorporation of GEP markers.

Embryonic exposure to hyper glucocorticoids suppresses brown fat development and thermogenesis via REDD1.

Maternal stress during pregnancy is prevailing worldwide, which exposes fetuses to intrauterine hyper glucocorticoids (GC), programming offspring to obesity and metabolic diseases. Despite the importance of brown adipose tissue (BAT) in maintaining long-term metabolic health, impacts of prenatal hyper GC on postnatal BAT thermogenesis and underlying regulations remain poorly defined. Pregnant mice were administrated with synthetic GC dexamethasone (DEX) at levels comparable to fetal GC exposure of stressed mothers. Prenatal GC exposure dose-dependently reduced BAT thermogenic activity, contributing to lower body temperature and higher mortality of neonates; such difference was abolished under thermoneutrality, underscoring BAT deficiency was the major contributor to adverse changes in postnatal thermogenesis due to excessive GC. Prenatal GC exposure highly activated Redd1 expression and reduced Ppargc1a transcription from the alternative promoter (Ppargc1a-AP) in neonatal BAT. During brown adipocyte differentiation, ectopic Redd1 expression reduced Ppargc1a-AP expression and mitochondrial biogenesis; and the inhibitory effects of GC on mitochondrial biogenesis and Ppargc1a-AP expression were blocked by Redd1 ablation. Redd1 reduced protein kinase A phosphorylation and suppressed cyclic adenosine monophosphate (cAMP) -responsive element-binding protein (CREB) binding to the cAMP regulatory element (CRE) in Ppargc1a-AP promoter, leading to Ppargc1a-AP inactivation. In summary, excessive maternal GC exposure during pregnancy dysregulates Redd1-Ppargc1a-AP axis, which impairs fetal BAT development, hampering postnatal thermogenic adaptation and metabolic health of offspring.

Comparison of 27-gauge and 25-gauge vitrectomy in the management of tractional retinal detachment secondary to proliferative diabetic retinopathy.

OBJECTIVE: To compare surgical outcomes between 27 and 25-gauge vitrectomy in proliferative diabetic retinopathy (PDR) with tractional retinal detachment (TRD). METHODS: This retrospective study was conducted to compare the intraoperative status, operation time, use of instruments, endotamponade substance, wound suture number, and iatrogenic break, between 27 and 25-gauge vitrectomy in 43 eyes afflicted by PDR with TRD. The post-surgical results, best-corrected visual acuity, intraocular pressure, recurrent vitreous haemorrhage, and re-operation rate were regularly followed up for 6 months. RESULTS: Patients in the 25 and the 27-gauge groups did not differ significantly in terms of pre-surgical conditions, such as age, gender, pre-existing glaucoma, best-corrected visual acuity (BCVA) and the severity of their TRD. The mean operation time was 56.7 minutes in the 27-gauge group and 63.7 minutes in the 25-gauge group (p = 0.94). There is significantly less use of micro forceps in the 27-gauge group (p = 0.004). No difference between micro scissors and chandelier usage were noted; neither was their difference in iatrogenic retinal breaks. Significantly fewer wound sutures were noted in the 27-gauge group (p < 0.001). The post-operative results revealed no significant difference in ocular hypertension, hypotony, BCVA improvement, recurrent vitreous haemorrhage and re-operation rate. CONCLUSIONS: The 27-gauge vitrectomy system offers comparable surgical outcomes in PDR with TRD. The 27-gauge vitrectomy system is suitable for complicated retinal surgery.

The HDAC3 inhibitor RGFP966 ameliorated ischemic brain damage by downregulating the AIM2 inflammasome.

Histone deacetylases 3 (HDAC3) modulates the acetylation state of histone and non-histone proteins and could be a powerful regulator of the inflammatory process in stroke. Inflammasome activation is a ubiquitous but poorly understood consequence of acute ischemic stroke. Here, we investigated the potential contributions of HDAC3 to inflammasome activation in primary cultured microglia and experimental stroke models. In this study, we documented that HDAC3 expression was increased in microglia of mouse experimental stroke model. Intraperitoneal injection of RGFP966 (a selective inhibitor of HDAC3) decreased infarct size and alleviated neurological deficits after the onset of middle cerebral artery occlusion (MCAO). In vitro data indicated that LPS stimulation evoked a time-dependent increase of HDAC3 and absent in melanoma 2 (AIM2) inflammasome in primary cultured microglia. Interestingly, AIM2 was subjected to spatiotemporal regulation by RGFP966. The ability of RGFP966 to inhibit the AIM2 inflammasome was confirmed in an experimental mouse model of stroke. As expected, AIM2 knockout mice also demonstrated significant resistance to ischemia injury compared with their wild-type littermates. RGFP966 failed to exhibit extra protective effects in AIM2-/- stroke mice. Furthermore, we found that RGFP966 enhanced STAT1 acetylation and subsequently attenuated STAT1 phosphorylation, which may at least partially contributed to the negative regulation of AIM2 by RGFP966. Together, we initially found that RGFP966 alleviated the inflammatory response and protected against ischemic stroke by regulating the AIM2 inflammasome.

Glycol chitin/PAA hydrogel composite incorporated bio-functionalized PLGA microspheres intended for sustained release of anticancer drug through intratumoral injection.

A novel anti-hepatoma drug release hybrid system is prepared by using poly(acrylic acid) (PAA) and glycol chitin as substrate in combination with Paclitaxel (PTX)-loaded bio-biofunctionalized poly(lactic-co-glycolic acid) (PLGA) micro-particles, which is intended for cancer therapy through intratumoral injection. The rheological behavior of glycol chitin (7 wt%)/PAA illustrates that it has low gelling temperature (i.e. 17 °C at pH 7.56) which ensures that the formulation turns to gel at physiological condition. The gelling time of glycol chitin/PAA is 16 minutes at 25 °C and 3 minutes at 37 °C, which is convenient for doctors to inject the in-situ gel formulations into the tumor location of patient. The drug release behavior reveals that the system can dramatically postpone the drug release. The cell viability test indicates that the micro-particles with drug still have 62% inhibitory effect on hepatoma cells in the fourteenth day after combing with hydrogel. This system is a promising approach for cancer therapy through intratumoral injection of in-situ gel formulations to extend retention time at tumor sites.

[Pollution Characteristics of Heavy Metals in PM2.5 and Their Human Health Risks Among the Coastal City Group Along Western Taiwan Straits Region, China].

PM2.5 samples were collected from 11 sampling sites in the coastal city group along western Taiwan Straits region, China, and these heavy metal elements (Zn, Cu, Pb, Ni, Cr, As) were detected using particle-induced X-ray emission (PIXE) method. The pollution characteristics, enrichment factors and source apportionment of heavy metals in PM2.5 were analyzed, and furthermore, their human health risks were determined. The result showed concentration distribution was obviously different between PM2.5 and heavy metals in the city group, for the main sources (e.g. construction dust and ground dust) for PM2.5 were not the main contribution to these heavy metals. The enrichment factors of Zn, Cu, Pb, Mn, Ni, Cr, As exceeded 10, which suggested these metals were enriched and significantly impacted by anthropogenic pollution. Three main groups of heavy metals in PM2.5 were identified by principal component analysis (PCA-MLR), such as coal combustion and traffic emissions (70.59%), multiple sources (coal and oil combustion, pyrometallurgical process, 17.55%) and other industry (11.86%). The risk levels for carcinogenic heavy metals (Ni, Cr, As) and non-carcinogenic heavy metals (Zn, Cu, Pb, Mn) were lower than the average level of risk acceptance (10-6), which suggested these heavy metals did not cause harm to human health in these cities.

[Pollution Assessment and Source Analysis of Metals in PM2.5 in Haicang District, Xiamen City, China].

To determine the spatial-temporal distributions and potential sources of metals in PM2.5 and assess health risks from heavy metals, 348 PM2.5 samples were collected in the Haicang District of Xiamen, China from April 2015 to January 2016. Metals (K, Ca, Na, Mg, Al, Zn, Cu, Fe, Ti, As, V, Mn, Ba, Co) in PM2.5 were detected using an X-ray fluorescence analyzer (XRF). Pollution assessment was performed via enrichment factor calculation and health risk assessment. Potential sources were explored using Pearson's correlation coefficient, principal component analysis, and the HYSPLIT Trajectory Model. Results showed that the total concentration of 14 metal elements contributed to 5.4%-10.6% of PM2.5 during the sampling period. The total concentration of metals was higher in spring and winter than those in summer and autumn. The concentrations were higher in the port and the industrial areas than in residential areas and background locations, in agreement with the seasonal and spatial distribution of PM2.5. The frequency of PM2.5 daily concentrations exceeding the Chinese Ambient Air Quality Standards was higher in the port and residential areas in the summer due to operations at the port and the wind direction. Zn concentration was the highest in the industrial area followed by the background location. Meanwhile, the highest concentration of V was observed in the port area; V concentration in the residential area was high in the summer. These variations in Zn and V indicated that the elements emitted in the polluted areas migrated easily to residential and background areas. K concentrations were the highest in winter and As showed a higher rate of exceeding the standard in winter and spring, indicating that activities, such as biomass burning and coal combustion in the winter severely impacted air quality. The enrichment factors of Cu, Zn, As, Co, Na, and Mn varied considerably, from 67 to 8,449. The total risk level for non-carcinogenic heavy metals (Zn, Cu, Mn) was lower than the average level of risk acceptance (1×10-6 a-1) and Mn contributed 74%-88% of the total risk level of Zn, Cu, and Mn. The combined results of the correlation analysis and the principal component analysis revealed that metals in PM2.5 were mainly came from re-suspension of ground dust, motor vehicle emissions, coal combustion, industrial emissions, and heavy oil combustion, with contributions of 34.5%, 12.5%, 10.6%, and 7.8% respectively. The HYSPLIT Trajectory Model showed that Xiamen was affected by the local air mass in spring, autumn, and winter, but not in summer. Moreover, the rise of PM2.5 in spring and winter was attributed to air masses traveling through the Yangtze River Delta.

Neuronal Soluble Fas Ligand Drives M1-Microglia Polarization after Cerebral Ischemia.

AIMS: This study explored sFasL expression in neurons and the potential role of neuronal sFasL in modulating the microglial phenotypes. METHODS: In vivo, middle cerebral artery occlusion (MCAO) was induced in both FasL-mutant (gld) and wild-type (wt) mice. In vitro, primary cortical neuron or microglia or coculture from wt/gld mice was subjected to oxygen glucose deprivation (OGD). sFasL level in the supernatant was evaluated by ELISA. Neuronal-conditioned medium (NCM) or exogenous sFasL was applied to primary microglia with or without FasL neutralizing antibody. Protein expression of JAK2/STAT3 and NF-κB pathways were determined by Western blot. The effect of microglia phenotype from wt/gld mice on the fate of ischemic neurons was further elucidated. RESULTS: In vivo, compared with wild-type mice, M1 markers (CD16, CD32 and iNOS) were attenuated in gld mice after MCAO. In vitro, post-OGD neuron released more sFasL. Both post-OGD NCM and exogenous sFasL could trigger M1-microglial polarization. However, this M1 phenotype shift was partially blocked by utilization of FasL neutralizing antibody or gld NCM. Consistently, JAK2/STAT3 and NF-κB signal pathways were both activated in microglia after exogenous sFasL treatment. Compared with wild-type mice, M1-conditioned medium prepared from gld mice protected neuron against OGD injury. CONCLUSIONS: Ischemic neurons release sFasL, which contributes to M1-microglial polarization. The underlying mechanisms may involve the activation of JAK2/STAT3 and NF-κB signaling pathways.

Gastroesophageal Reflux Disease Diagnosis Using Hierarchical Heterogeneous Descriptor Fusion Support Vector Machine.

A new computer-aided diagnosis method is proposed to diagnose the gastroesophageal reflux disease (GERD) from endoscopic images of the esophageal-gastric junction. To avoid the interferences of different endoscope devices and automatic camera white balance adjustment, heterogeneous descriptors computed from heterogeneous color models are used to represent endoscopic images. Instead of concatenating these descriptors to a super vector, a hierarchical heterogeneous descriptor fusion support vector machine (HHDF-SVM) framework is proposed to simultaneously apply heterogeneous descriptors for GERD diagnosis and overcome the curse of dimensionality problem. During validation, heterogeneous descriptors are extracted from test endoscopic images at first. The classification result is obtained by using HHDF-SVM with heterogeneous descriptors. As shown in the experiments, our method can automatically diagnose GERD without any manual selection of region of interest and achieve better accuracy compared to states-of-the-art methods.

Nanotechnology-based drug delivery treatments and specific targeting therapy for age-related macular degeneration.

Nanoparticles combined with cells, drugs, and specially designed genes provide improved therapeutic efficacy in studies and clinical setting, demonstrating a new era of treatment strategy, especially in retinal diseases. Nanotechnology-based drugs can provide an essential platform for sustaining, releasing and a specific targeting design to treat retinal diseases. Poly-lactic-co-glycolic acid is the most widely used biocompatible and biodegradable polymer approved by the Food and Drug Administration. Many studies have attempted to develop special devices for delivering small-molecule drugs, proteins, and other macromolecules consistently and slowly. In this article, we first review current progress in the treatment of age-related macular degeneration. Then, we discuss the function of vascular endothelial growth factor (VEGF) and the pharmacological effects of anti-VEGF-A antibodies and soluble or modified VEGF receptors. Lastly, we summarize the combination of antiangiogenic therapy and nanomedicines, and review current potential targeting therapy in age-related macular degeneration.

Corneal neovascularization and contemporary antiangiogenic therapeutics.

Corneal neovascularization (NV), the excessive ingrowth of blood vessels from conjunctiva into the cornea, is a common sequela of disease insult that can lead to visual impairment. Clinically, topical steroid, argon laser photocoagulation, and subconjunctival injection of bevacizumab have been used to treat corneal NV. Sometimes, the therapies are ineffective, especially when the vessels are large. Large vessels are difficult to occlude and easily recanalized. Scientists and physicians are now dedicated to overcoming this problem. In this article, we briefly introduce the pathogenesis of corneal NV, and then highlight the existing animal models used in corneal NV research-the alkali-induced model and the suture-induced model. Most of all, we review the potential therapeutic targets (i.e., vascular endothelial growth factor and platelet-derived growth factor) and their corresponding inhibitors, as well as the immunosuppressants that have been discovered in recent years by corneal NV studies.

Stem Cell Therapy for Corneal Regeneration Medicine and Contemporary Nanomedicine for Corneal Disorders.

The ocular surface is the outermost part of the visual system that faces many extrinsic or intrinsic threats, such as chemical burn, infectious pathogens, thermal injury, Stevens-Johnson syndrome, ocular pemphegoid, and other autoimmune diseases. The cornea plays an important role in conducting light into the eyes and protecting intraocular structures. Several ocular surface diseases will lead to the neovascularization or conjunctivalization of corneal epithelium, leaving opacified optical media. It is believed that some corneal limbal cells may present stem cell-like properties and are capable of regenerating corneal epithelium. Therefore, cultivation of limbal cells and reconstruction of the ocular surface with these limbal cell grafts have attracted tremendous interest in the past few years. Currently, stem cells are found to potentiate regenerative medicine by their capability of differentiation into multiple lineage cells. Among these, the most common cell sources for clinical use are embryonic, adult, and induced stem cells. Different stem cells have varied specific advantages and limitations for in vivo and in vitro expansion. Other than ocular surface diseases, culture and transplantation of corneal endothelial cells is another major issue for corneal decompensation and awaits further studies to find out comprehensive solutions dealing with nonregenerative corneal endothelium. Recently, studies of in vitro endothelium culture and ρ-associated kinase (ROCK) inhibitor have gained encouraging results. Some clinical trials have already been finished and achieved remarkable vision recovery. Finally, nanotechnology has shown great improvement in ocular drug delivery systems during the past two decades. Strategies to reconstruct the ocular surface could combine with nanoparticles to facilitate wound healing, drug delivery, and even neovascularization inhibition. In this review article, we summarized the major advances of corneal limbal stem cells, limbal stem cell deficiency, corneal endothelial cell culture/transplantation, and application of nanotechnology on ocular surface reconstruction. We also illustrated potential applications of current knowledge for the future treatment of ocular surface diseases.

Coats' disease and neovascular glaucoma in a child with neurofibromatosis.

This report describes an extremely rare case of Coats' disease and neovascular glaucoma in a child with neurofibromatosis 1. Intraocular pressure control and vision restoration were achieved with intravitreal injection with bevacizumab, hemiretinal laser photocoagulation, peripheral retinal cryotherapy, and trabeculectomy with mitomycin C.

[Study on reversion of malignant phenotype of glioma by siRNA targeting p75 neurotrophin receptor].

OBJECTIVE: To study the therapeutic efficacy of siRNA fragments silencing p75 neurotrophin receptor (p75(NTR)), which may be a key regulator of glioma cell apoptosis and invasion. METHODS: The siRNA sequence fragments targeting p75(NTR) were designed and transferred into human glioma cell line U251. RT-PCR and immunocytochemistry method were used to explore the expression of p75(NTR) mRNA and protein. Cell adhesion assay was employed to detect cellular adhesion ability, and soft agar clone formation assay was adopted to identify oncogenicity, and a U251 glioma model was established in nude mice. The intracranial tumor volume was detected by MRI. The expression of p75(NTR), NGF and cyclin D2 were identified using immunohistochemistry. Cell apoptosis was detected by apoptosis kit in situ. RESULTS: The siRNA fragments targeting p75(NTR) were capable of decreasing mRNA and protein expression of p75(NTR) in U251 glioma cell line. Both the cellular adhesion ability and oncogenicity were weakly relevant. The p75(NTR) expression level was negatively correlated with cyclin D2 and apoptosis, and positively correlated with NGF expression. The siRNA sequence fragments targeting p75(NTR) were effective in decreasing the gross volume of tumor; prolonged the survival time of mice, and the edge of tumor was much sharper than that of the control group. CONCLUSIONS: The gene silencing technique by siRNA targeting p75(NTR) is capable of decreasing tumor invasion and cell proliferation as well as inducing cell apoptosis. It is expected to be a new choice for glioma gene therapy.