Kunzea Ericoides (Kanuka) Leaf Extracts Show Moisturisation, Antioxidant, and UV Protection Effects in HaCaT Cells and Anti-melanogenesis Effects in B16F10 Cells.

Kunzea ericoides (kanuka) products are well-known for their potent medicinal values in antioxidant and anti-inflammatory applications. The present study identified various compounds, such as chlorogenic acid, gallic acid, quercetin, and (E)-ferulic acid in the kanuka leaf extract, showing its potential use in maintaining skin health. The influence of kanuka leaf extract upon epidermal cells concerning cytotoxicity and in vitro activities of moisturisation, antioxidation, UV protection, and anti-melanogenesis effects were explored in the study. Kanuka leaf extract demonstrated significant promotion in the proliferation of HaCaT and B16F10 cells. After incubation with kanuka leaf extract, the content of ROS and DPPH in HaCaT was significantly decreased; at the same time, more SOD was produced. Furthermore, hyaluronidase-1 (HYAL-1) and HYAL-4 expressions were inhibited, while the aquaporin 3 (AQP-3) content was significantly increased in HaCaT. Kanuka leaf extract also inhibited the expressions of matrix metalloproteinases-1 (MMP-1) and MMP-14 in UV-induced HaCaT cells. In the B16F10 cell line, melanin and tyrosinase production were decreased under the presence of kanuka leaf extract, and the expressions of microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (TYRP-1), and TYRP-2 were also inhibited. The study validated kanuka leaf extract as an effective natural product against photoaging and melanogenesis.

Quantitative optical coherence tomography angiography assessments in the fellow eyes of those with central serous chorioretinopathy.

BACKGROUND: To analyze the vessel density (VD) of the retina and choriocapillaris (CC) layer and the structure of the foveal avascular zone (FAZ) in the fellow eyes of central serous chorioretinopathy (CSC) patients by using optical coherence tomography angiography (OCTA). METHODS: This was a case-control study. Unilateral CSC patients and age-matched healthy subjects were recruited from the Affiliated Eye Hospital of Wenzhou Medical University between July 2016 and July 2021. All eyes were divided into three groups: acute CSC (aCSC), chronic CSC (cCSC), and healthy controls. Both aCSC and cCSC were again divided into two subgroups: the affected eyes and the fellow eyes. In this study, all parameters of VD and FAZ were measured by self-software of OCTA. RESULTS: A total of 231 eyes of 137 subjects were included, with 47 aCSC patients, 47 cCSC patients, and 43 healthy controls. In the fellow eyes of CSC, the retinal VD was significantly lower (all P < 0.05), and the FAZ was significantly larger (all P < 0.05) in the cCSC group than in healthy controls, while no difference was detected in the CC layer. There was no significant difference between the aCSC group and healthy controls in all OCTA parameters. In the affected eyes of CSC, the superficial retinal vessel density (SRVD) was significantly higher (all P < 0.05) in healthy controls than in the aCSC and cCSC groups, while the deep retinal vessel density (DRVD) was significantly lower (all P < 0.05) and the FAZ was larger (all P < 0.05) in the cCSC group than in the aCSC group and healthy controls. A liner regression equation was established: Y (BCVA, best corrected visual acuity) = 3.692-0.036✱X1 (DRVD-Fovea)-0.031✱X2 (FD-300, vessel density around the 300 µm width of the FAZ), R2 = 0.427. CONCLUSION: Based on OCTA measurements, this study revealed that the retinal microvascular network was impaired even in the fellow eyes of those with cCSC, which should arouse attention to the observation of unilateral CSC.

ALKBH5 facilitates the progression of skin cutaneous melanoma via mediating ABCA1 demethylation and modulating autophagy in an m6A-dependent manner.

Background: N6-methyladenosine (m6A) is the most common and abundant mRNA modification, playing an essential role in biological processes and tumor development. However, the role of m6A methylation in skin cutaneous melanoma (SKCM) is not yet clear. This study analyzed the expression of m6A-related functional genes in SKCM and aimed to explore the key demethylase ALKBH5 mediated m6A modification and its potential mechanism in human SKCM. Methods: Based on public databases, the m6A-related gene expression landscape in SKCM was portrayed. MeRIP-Seq and RNA-Seq were used to recognize the downstream target of ALKBH5. In vivo and in vitro functional phenotype and rescue functional experiments were performed to explore the mechanism of the ALKBH5-m6A-ABCA1 axis in SKCM. Results: We found ALKBH5 upregulated in SKCM, associated with poor prognosis. ALKBH5 can promote melanoma cell proliferation, colony formation, migration, and invasion and inhibit autophagy in vitro, facilitating tumor growth and metastasis in vivo. We identified ABCA1, a membrane protein that assists cholesterol efflux, as a downstream target of ALKBH5-mediated m6A demethylation. Finally, our data demonstrated that ALKBH5 promoted SKCM via mediating ABCA1 downregulation by reducing ABCA1 mRNA stability in an m6A-dependent manner. Conclusion: Our findings exhibited the functional value of the key demethylase ALKBH5 mediated m6A modification in the progression of SKCM, suggesting the ALKBH5-m6A-ABCA1 axis as a potential therapeutic target in SKCM.

Inverted Internal Limiting Membrane Flap Coverage With Autologous Blood Technique After Air-Fluid Exchange and Silicone Oil Tamponade for Extensive Macular Hole Retinal Detachment in Highly Myopic Eyes.

PURPOSE: To report a technique consisting of inverted internal limiting membrane (ILM) flap coverage with autologous blood after air-fluid exchange and silicone oil tamponade in treating extensive retinal detachment secondary to a myopic macular hole (MH). METHODS: This was a retrospective case series. 18 eyes with MHRD extending beyond the equator were included in this study with a minimum follow-up of 6 months. The procedures for pars plan vitrectomy (PPV) included the following: 1) The ILM was peeled to the superior and inferior arcade margins and, except for the ILM in the temporal region, was hinged toward the edge of the MH. 2) Air-fluid exchange was then performed to drain the subretinal fluid through the MH with a flute needle, ensuring that a small amount of subretinal fluid remained to facilitate ILM flap inversion. 3) The ILM flap was used to cover the MH with the assistance of autologous blood. RESULTS: Six months after surgery, the MH was successfully anatomically closed, and retinal reattachment was observed in all 18 eyes of 18 patients. The mean best-corrected visual acuity logarithm of the minimum angle of resolution (logMAR) improved from 2.03 ± 0.61 (ranging from hand motion [2.6] to finger counting [2.3]) to 1.23 ± 0.63 (ranging from hand motion [2.6] to 20/28 [0.15]) ( P < 0.01) at 6 months. CONCLUSION: This surgical technique using an inverted ILM flap combined with autologous blood provides an option for the treatment of extensive MHRD.

Inhibition of phosphatidylinositol 3-kinase catalytic subunit alpha by miR-203a-3p reduces hypertrophic scar formation via phosphatidylinositol 3-kinase/AKT/mTOR signaling pathway.

Background: Hypertrophic scar (HS) is a common fibroproliferative skin disease that currently has no truly effective therapy. Given the importance of phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) in hypertrophic scar formation, the development of therapeutic strategies for endogenous inhibitors against PIK3CA is of great interest. Here, we explored the molecular mechanisms underlying the protective effects of miR-203a-3p (PIK3CA inhibitor) against excessive scar. Methods: Bioinformatic analysis, immunohistochemistry, immunofluorescence, miRNA screening and fluorescence in situ hybridization assays were used to identify the possible pathways and target molecules mediating HS formation. A series of in vitro and in vivo experiments were used to clarify the role of PIK3CA and miR-203a-3p in HS. Mechanistically, transcriptomic sequencing, immunoblotting, dual-luciferase assay and rescue experiments were executed. Results: Herein, we found that PIK3CA and the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway were upregulated in scar tissues and positively correlated with fibrosis. We then identified miR-203a-3p as the most suitable endogenous inhibitor of PIK3CA. miR-203a-3p suppressed the proliferation, migration, collagen synthesis and contractility as well as the transdifferentiation of fibroblasts into myofibroblasts in vitro, and improved the morphology and histology of scars in vivo. Mechanistically, miR-203a-3p attenuated fibrosis by inactivating the PI3K/AKT/mTOR pathway by directly targeting PIK3CA. Conclusions: PIK3CA and the PI3K/AKT/mTOR pathway are actively involved in scar fibrosis and miR-203a-3p might serve as a potential strategy for hypertrophic scar therapy through targeting PIK3CA and inactivating the PI3K/AKT/mTOR pathway.

Novel approach for enhancing skin allograft survival by bioadhesive nanoparticles loaded with rapamycin.

Skin graft rejection is a significant challenge in skin allografts for skin defects, particularly in extensive burn injury patients when autografts are insufficient. Enhancing the survival duration of allogeneic skin grafts can improve the success rate of subsequent autologous skin grafting, thereby promoting the therapeutic efficacy for wound healing. Rapamycin (Rapa), a potent immunosuppressant with favorable efficacy in organ transplantation, is limited by its systemic administration-associated toxicity and side effects. Therefore, addressing the short survival time of allogeneic skin grafts and minimizing the toxicity related to systemic application of immunosuppressive agents is an urgent requirement. Here, we present a topical formulation based on bioadhesive poly (lactic acid)-hyperbranched polyglycerol nanoparticles (BNPs) with surface-modified encapsulation of Rapamycin (Rapa/BNPs), applied for local immunosuppression in a murine model of allogeneic skin grafts. Our Rapa/BNPs significantly prolong nanoparticle retention, reduce infiltration of T lymphocytes and macrophages, decrease the level of pro-inflammatory cytokines and ultimately extend skin allograft survival with little systemic toxicity compared to free Rapa or Rapamycin-loaded non-bioadhesive nanoparticles (Rapa/NNPs) administration. In conclusion, Rapa/BNPs effectively deliver local immunosuppression and demonstrate potential for enhancing skin allograft survival while minimizing localized inflammation, thus potentially increasing patient survival rates for various types of skin defects.

Using Piezosurgery in Anterior Cervical Discectomy and Fusion to Treat Complex Cervical Spondylotic Myelopathy Is Safe and Effective.

Objective: To investigate the safety and efficacy of piezosurgery in anterior cervical discectomy and fusion (ACDF) for cervical spondylotic myelopathy (CSM). Methods: 47 patients with complex CSM (cCSM) underwent ACDF surgery from 2014 to 2017. Among these patients, 26 underwent ACDF using piezosurgery (group A) and 21 underwent ACDF by using traditional tools such as high-speed air drill, bone curette, and Kerrison bone punch (group B). Average surgical time, intraoperative blood loss, surgical complications, preoperative and postoperative Japanese Orthopaedic Association (JOA) scores, and improvement rate were measured. Results: Average surgical time and intraoperative blood loss were significantly lower in group A than those in group B (P < 0.01). The incidences of surgical complications were 3.8% and 23.8% in the A and B groups (P < 0.05), respectively. There were no significant differences in JOA scores and improvement rates between data collection periods at preoperative, 3-day postoperative, and 1-year postoperative follow-ups (P > 0.05). Conclusion: For treating cCSM, both the piezosurgery and traditional tools led to significant neurological improvement. However, the piezosurgery was superior to the traditional tools in terms of surgical time, blood loss, and complication rate. Hence, piezosurgery was a safe and effective adjunct for ACDF treating cCSM.

System analysis based on the pyroptosis-related genes identifes GSDMD as a novel therapy target for skin cutaneous melanoma.

BACKGROUND: Skin cutaneous melanoma (SKCM) is the most aggressive skin cancer, accounting for more than 75% mortality rate of skin-related cancers. As a newly identified programmed cell death, pyroptosis has been found to be closely associated with tumor progression. Nevertheless, the prognostic significance of pyroptosis in SKCM remains elusive. METHODS: A total of 469 SKCM samples and 812 normal samples were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Firstly, differentially expressed pyroptosis-related genes (PRGs) between normal samples and SKCM samples were identified. Secondly, we established a prognostic model based on univariate Cox and LASSO Cox regression analyses, which was validated in the test cohort from GSE65904. Thirdly, a nomogram was used to predict the survival probability of SKCM patients. The R package "pRRophetic" was utilized to identify the drug sensitivity between the low- and high-risk groups. Tumor immune infiltration was evaluated using "immuneeconv" R package. Finally, the function of GSDMD and SB525334 was explored in A375 and A2058 cells. RESULTS: Based on univariate Cox and LASSO regression analyses, we established a prognostic model with identified eight PRGs (AIM2, CASP3, GSDMA, GSDMC, GSDMD, IL18, NLRP3, and NOD2), which was validated in the test cohort. SKCM patients were divided into low- and high-risk groups based on the median of risk score. Kaplan-Meier survival analysis showed that high-risk patients had shorter overall survival than low-risk patients. Additionally, time-dependent ROC curves validated the accuracy of the risk model in predicting the prognosis of SKCM. More importantly, 4 small molecular compounds (SB525334, SR8278, Gemcitabine, AT13387) were identified, which might be potential drugs for patients in different risk groups. Finally, overexpression of GSDMD and SB525334 treatment inhibit the proliferation, migration, and invasion of SKCM cells. CONCLUSION: In this study, we constructed a prognostic model based on PRGs and identified GSDMD as a potential therapeutic target, which provide new insights into SKCM treatment.

Retained Intraocular Iron Foreign Body Leading to Late-Onset Siderotic Glaucoma: A Challenging Case Report.

BACKGROUND A retained ferrous intraocular foreign body (IOFB), introduced via penetrating ocular trauma, may result in ocular siderosis and visual loss that may occur after days or years. If diagnosis is delayed, therapy may also be delayed, resulting in a poor outcome. The present report presents the case of a 58-year-old man with a retained iron IOFB and late-onset siderotic glaucoma 1 month after the initial trauma. CASE REPORT A 58-year-old man presented with redness and eye pain in the right eye for 1 month after ocular trauma. His visual acuity was very good, with no sign of eye strain. High intraocular pressure had been detected for several weeks, but the B-scan ultrasound and fundus examination were normal and the reason for the high intraocular pressure was unknown. He was later transferred to our senior hospital. The diagnosis of IOFB was confirmed by computed tomography (CT) scan and ultrasound biomicroscopy (UBM). The patient was successfully managed by vitrectomy. CONCLUSIONS This report highlights that a retained IOFB can be challenging to diagnose and that cases associated with siderotic glaucoma require multiple investigations. Early detection of the IOFB using the right tools is vital to reduce the risk of siderotic glaucoma. Although the fundus examination was normal after ocular trauma, the use of CT scan and UBM assisted in finding the IFOB and the patient was successfully treated by vitrectomy.

Collagen scaffolds derived from bovine skin loaded with MSC optimized M1 macrophages remodeling and chronic diabetic wounds healing.

Owing to the persistent inflammatory microenvironment and unsubstantial dermal tissues, chronic diabetic wounds do not heal easily and their recurrence rate is high. Therefore, a dermal substitute that can induce rapid tissue regeneration and inhibit scar formation is urgently required to address this concern. In this study, we established biologically active dermal substitutes (BADS) by combining novel animal tissue-derived collagen dermal-replacement scaffolds (CDRS) and bone marrow mesenchymal stem cells (BMSCs) for the healing and recurrence treatments of chronic diabetic wounds. The collagen scaffolds derived from bovine skin (CBS) displayed good physicochemical properties and superior biocompatibility. CBS loaded with BMSCs (CBS-MCSs) could inhibit M1 macrophage polarization in vitro. Decreased MMP-9 and increased Col3 at the protein level were detected in CBS-MSCs-treated M1 macrophages, which may be attributed to the suppression of the TNF-α/NF-κB signaling pathway (downregulating phospho-IKKα/ß/total IKKα/ß, phospho-IκB/total IκB, and phospho-NFκB/total NFκB) in M1 macrophages. Moreover, CBS-MSCs could benefit the transformation of M1 (downregulating iNOS) to M2 (upregulating CD206) macrophages. Wound-healing evaluations demonstrated that CBS-MSCs regulated the polarization of macrophages and the balance of inflammatory factors (pro-inflammatory: IL-1ß, TNF-α, and MMP-9; anti-inflammatory: IL-10 and TGF-ß3) in db/db mice. Furthermore, CBS-MSCs facilitated the noncontractile and re-epithelialized processes, granulation tissue regeneration, and neovascularization of chronic diabetic wounds. Thus, CBS-MSCs have a potential value for clinical application in promoting the healing of chronic diabetic wounds and preventing the recurrence of ulcers.

Hypodense regions in the peripapillary region increased the risk of macular retinoschisis detected by optical coherence tomography.

Purpose: The purpose of the present study was to investigate the clinical features of peripapillary regions in patients with myopic macular retinoschisis (MRS) and its association with the development of retinoschisis (RS). Methods: In this cross-sectional study, high-myopic patients with or without MRS were recruited, and the hypodense regions were analyzed in the peripapillary regions. The vitreoretinal adhesions around both macular and paravascular arcades were compared between groups. The risk factors for the development of MRS were analyzed by logistic regression. Results: Of 88 myopic eyes, MRS was detected in 45 eyes (51%). The eyes with MRS showed a higher rate of peripapillary and paravascular retinoschisis (P < 0.001 and P = 0.006). Hypodense regions were detected in 25 eyes (20.35%). Higher rates of horizontal and vertical macular MRS were detected in the hypodense group (P = 0.012 and P = 0.002). Lower refractive error, longer axial length, and higher rates of outer retinoschisis both in horizontal and vertical macular regions were observed in the hypodense group (P = 0.012, P = 0.006, P = 0.038, and P = 0.034). Higher rates of inner and outer retinoschisis, vitreoschisis, and microfolds along superior vascular arcade were detected in the hypodense group (P = 0.005, P = 0.001, P = 0.014, and P = 0.014). Higher rates of internal limiting membrane (ILM) detachment, inner and outer RS were detected along the inferior vascular arcade in the hypodense group (P = 0.008, P = 0.001, and P = 0.028). Hypodense regions, the axial length and PICC (peripapillary intrachoroidal cavitation) were significantly correlated with the severity of MRS (Odds ratio = 0.207, P = 0.010; Odds ratio = 1.399, P = 0.016; Odds ratio = 0.142, P = 0.010). Conclusions: The hypodense regions were likely to affect outer retinoschisis both in macular and paravascular regions. It was a risk factor for the development of MRS.

Clinical characteristics and mutation spectrum in 33 Chinese families with familial exudative vitreoretinopathy.

OBJECTIVE: To explore the clinical manifestations and search for the variants of six related genes (LRP5, FZD4, TSPAN12, NDP, KIF11 and ZNF408) in Chinese patients with familial exudative vitreoretinopathy (FEVR), and investigate the correlation between the genetic variants and the clinical characteristics. PATIENTS AND METHODS: Clinical data, including the retinal artery angle, acquired from wide-field fundus imaging, structural and microvascular features of the retina obtained from optical coherence tomography (OCT) and OCT angiography (OCTA) were collected from 33 pedigrees. Furthermore, mutation screening was performed. Variants filtering, bioinformatics analysis and Sanger sequencing were conducted to verify the variants. RESULTS: Twenty-one variants were successfully detected in 16 of 33 families, of which 10 variants were newly identified. The proportion of variants in LRP5, FZD4, TSPAN12, NDP and KIF11 was 38.1% (8/21), 33.3% (7/21), 19.1% (4/21), 4.8% (1/21) and 4.8% (1/21), respectively. Three new variants were considered to be pathogenic or likely pathogenic. The FEVR group tended to exhibit a smaller retinal artery angle, higher incidence of foveal hypoplasia and lower vascular density compared to the control group. Patients who harboured variants of FZD4 exhibited greater severity of FEVR than those with LRP5 variants. However, those who harboured LRP5 variants tended to possess lower foveal vascular density. CONCLUSIONS: Six known pathogenic genes were screened in 33 pedigrees with FEVR in our study, which revealed 10 novel variants. These findings enrich the clinical features and mutation spectrum in Chinese patients with FEVR, revealing the genotype-phenotype relationship, and contributing to the diagnosis and treatment of the disease.Key messagesWe identified 21 variants in 5 genes (LRP5, FZD4, TSPAN12, NDP and KIF11) associated with FEVR, 10 of which are novel (three were pathogenic or likely pathogenic).The proportion of variants was the highest for the LRP5 gene.FZD4 variants may be responsible for greater FEVR severity than LRP5 variants.

High Expression of TIMELESS Predicts Poor Prognosis: A Potential Therapeutic Target for Skin Cutaneous Melanoma.

Background: Skin cutaneous melanoma (SKCM) is the most lethal skin cancer with an increasing incidence worldwide. The poor prognosis of SKCM urgently requires us to discover prognostic biomarkers for accurate therapy. As a regulator of DNA replication, TIMELESS (TIM) has been found to be highly expressed in various malignancies but rarely reported in SKCM. The objective of this study was to evaluate the relationship between TIM and SKCM tumorigenesis and prognosis. Methods: We obtained RNA sequencing data from TCGA and GTEx to analyze TIM expression and differentially expressed genes (DEGs). Subsequently, GO/KEGG, GSEA, immune cell infiltration analysis, and protein-protein interaction (PPI) network were used to perform the functional enrichment analysis of TIM-related DEGs. Moreover, the receiver operating characteristic (ROC) curves, Cox regression analysis, Kaplan-Meier (K-M) analysis, and nomograms were applied to figure out the clinical significance of TIM in SKCM. In addition, we investigated the relationship between TIM promoter methylation and SKCM prognosis through the UALCAN database. Finally, the immunohistochemical (IHC) results of normal skin and SKCM were analyzed to determine expression differences. Results: TIM was significantly elevated in various malignancies, including SKCM, and high expression of TIM was associated with poor prognosis. Moreover, a total of 402 DEGs were identified between the two distinct TIM expression groups, and functional annotation showed enrichment with positive regulation of cell cycle and classic oncogenic pathways in the high TIM expression phenotype, while keratinization pathways were negatively regulated and enriched. Further analysis showed that TIM was correlated with infiltration of multiple immune cells. Finally, IHC validated the differential expression of TIM in SKCM. Conclusion: TIM might play a pivotal role in tumorigenesis of SKCM and is closely related to its prognosis.

FTO knockdown alleviates hypoxia-induced PC12 cell injury by stabilizing GADD45B in an IGF2BP2-dependent manner.

RNA N6-methyladenosine (m6A) level is closely associated with neurodevelopment and central nervous system dysfunctions including spinal cord injury (SCI). M6A level can be dynamically regulated by m6A methyltransferases and demethylases. In this text, the roles of m6A demethylase FTO alpha-ketoglutarate dependent dioxygenase (FTO) in SCI development along with its m6A-dependent regulatory mechanisms were investigated in hypoxia-induced PC12 cell injury model. The results showed that FTO was low expressed in spinal cord tissues of rats after contusive SCI and hypoxia-treated PC12 cells. FTO knockdown alleviated hypoxia-induced PC12 cell injury. FTO loss increased GADD45B expression and m6A level in PC12 cells. GADD45B knockdown weakened the protective effects of FTO depletion on hypoxia-treated PC12 cells. FTO regulated GADD45B expression in an IGF2BP2-dependent manner. In conclusion, FTO knockdown mitigated the injury of hypoxia-induced PC12 cells by up-regulating GADD45B in an IGF2BP2-dependent manner.

Hyperosmolarity disrupts tight junction via TNF-α/MMP pathway in primary human corneal epithelial cells.

AIM: To investigate the mechanism of the tight junction (TJ) disruption and the association between tumor necrosis factor (TNF)-α and matrix metalloproteinase (MMPs) under hyperosmotic condition in primary human corneal epithelial cells (HCECs). METHODS: The cultured HCECs were exposed to media which adding sodium chloride (NaCl) for hyperosmolar stress or adding rh-TNF-α (10 ng/mL). NF-κB inhibitor (5 µmol/L) or GM-6001 (potent and broad spectrum MMP inhibitor, 20 µmol/L) was added 1h before that treatment. The integrity of TJ proteins was determined by immunofluorescent (IF) staining. The mRNA levels of TNF-α and MMPs were evaluated by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and the protein expression by enzyme-linked immunosorbent assay (ELISA). RESULTS: TJ proteins ZO-1 and Occludin were disrupted in primary HCECs exposed to hyperosmotic medium. The mRNA expression and protein production of TNF-α increased significantly in hyperosmotic media at 500 mOsM. TNF-α mediated the expression and production of MMP-1, MMP-13, MMP-9, and MMP-3 stimulated by hyperosmotic stress. The production of MMPs in hyperosmolar media were increased through the increase of TNF-α. GM-6001 prevent the destruction of ZO-1 and Occludin in hyperosmolar stress and rh-TNF-α treated medium. TNF-α induced activation of MMPs was involved in the TJ disruption by hyperosmolarity. CONCLUSION: TJ proteins ZO-1 and Occludin are disrupted by hyperosmolar stress and TNF-α, but protected by MMP inhibitor (GM-6001). It suggests that TNF-α/MMP pathway mediates the TJ disruption in primary HCECs exposed to hyperosmotic stress.

Prediction of anti-VEGF efficacy in diabetic macular oedema using intraocular cytokines and macular optical coherence tomography.

PURPOSE: In eyes with diabetic macular oedema (DME), aqueous humour (AH) cytokine levels before and after anti-vascular endothelial growth factor (VEGF) treatment were compared and correlated with optical coherence tomography structural parameters. METHODS: This prospective study included 56 control patients with cataracts and 83 patients with DME manifesting as diffuse retinal thickening (DRT), cystoid macular oedema and serous retinal detachment (SRD). AH samples were obtained before intravitreal injection of anti-VEGF or cataract surgery. VEGF, interleukin (IL)-6, IL-8, IL-10, interferon-inducible protein 10 (IP-10) and monocyte chemotactic protein 1 (MCP-1) levels were measured by multiplex bead assay. AH cytokine levels, central macular thickness (CMT), number of hyper-reflective foci (HF), continuity of external limiting membrane and ellipsoid zone (EZ) and best-corrected visual acuity were evaluated. RESULTS: In SRD, IL-6 and MCP-1 levels and HF were increased (all p < 0.05) compared to DRT. At baseline, the number of HF was correlated with VEGF, IL-6, IL-8, IP-10 and MCP-1 (all p < 0.05). Eyes sensitive to anti-VEGF treatment had high baseline levels of VEGF, MCP-1, HF and many EZ disruptions (all p < 0.05). DME patients with normal VEGF levels but with high levels of IL-8, IP-10 and MCP-1 (all p < 0.05) had little change in CMT after anti-VEGF treatment (p = 0.678). CONCLUSIONS: AH concentrations of some inflammatory cytokines in DME were differentially expressed among the three DME morphologies. HF was associated with VEGF and other inflammatory cytokine levels. Multiple HF at baseline predicted a significant decrease in CMT, and eyes with normal VEGF but increased inflammatory cytokines may be insensitive to anti-VEGF treatment.

Simultaneous reduction of microwave reflection and infrared emission enabled by a phase gradient metasurface.

Metasurfaces have shown promising applications in radar-infrared compatible stealth because of its superior electromagnetic wave control capabilities, but, to date, the majority of designs still suffer from the defects of large thickness, limited working bandwidth, relatively high infrared emissivity and so on. Here, an exotic phase gradient metasurface (PGM) is proposed to achieve low microwave reflection and low infrared emission concurrently, which has a small thickness of about 0.10λ0. The microwave reflection reduction larger than 10 dB in 14-20 GHz is attributed to the anomalous reflection for arbitrary LP incident waves, and the infrared emissivity less than 0.28 from 3 to 14 µm is due to the indium-tin-oxide (ITO) with low infrared emissivity and high filling ratio. Also, the designed PGM can also realize beam deflection for orthogonal CP waves because of the meta-atoms' isotropic characteristics. Our methodology is fully verified by numerous simulations and experiments and may open a new avenue for radar-infrared compatible stealth research.

Secondary choroidal neovascularization due to choroidal osteoma after 9 years follow-up.

BACKGROUND: Choroidal osteoma is a benign intraocular tumor that can increase risk of developing choroidal neovascularization. The visual prognosis is influenced by the tumor location, decalcification status, overlying RPE atrophy, presence of choroidal neovascularization, persistence of subretinal fluid and occurrence of subretinal hemorrhages. CASE PRESENTATION: The authors present a 40-year-old woman diagnosed with choroidal osteoma of the right eye. Her best corrected visual acuity was 12/20 but decreased to 5/20 due to secondary choroidal neovascularization after 8 years follow up. Fundus examination revealed an enlarged choroidal osteoma in most margins at posterior pole with schistose hemorrhage beside macula. Optical coherence tomography angiography revealed unique features in the vascular changes of choroidal neovascularization in choroidal osteoma in the outer retinal layer and choroid capillary layers, and subretinal neovascularization. Indocyanine green fluorescence angiography showed there was hypo-fluorescence at the peripapillary with faint hyper-fluorescence at the macular, corresponding to the location on the fundus photograph. The patient received 3 injections of intravitreal ranibizumab. After 1 year follow up, her visual acuity of the right eye was 18/20 and the CNV had regressed. CONCLUSIONS: We present the findings and treatment of a case of choroidal osteoma with secondary choroidal neovascularization. Optical coherence tomography angiography combined with FFA and ICGA is used to analysis the characteristics of secondary choroidal neovascularization. Optical coherence tomography angiography can reveal some unique characteristics in the vascular changes compared to fundus fluorescein angiography.

Comprehensive evaluation of intravitreal conbercept versus half-dose photodynamic therapy for chronic central serous chorioretinopathy.

AIM: To compare the safety and efficacy of conbercept intravitreal injection and half-dose photodynamic therapy (PDT) in treating chronic central serous chorioretinopathy (CSC). METHODS: This study was retrospective. Thirty-seven patients (37 eyes) with chronic CSC received conbercept injections while 57 patients (57 eyes) were treated with half-dose PDT. All subjects were followed in 6mo. Outcome measures included change in best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and resolution of subretinal fluid (SRF). RESULTS: There was no adverse event observed in either treatment group. At the 6-month follow-up, 26 eyes (70.3%) in the conbercept group and 54 eyes (94.7%) in the half-dose PDT group (P<0.05) reached full resolution of SRF. The mean logarithm of the minimum angle of resolution (logMAR) BCVA significantly improved (P<0.001) in both treatment groups with better outcome at early phase in the half-dose PDT group (2wk, 1, and 2mo, P<0.05). All subjects experienced significant CMT improvement (P<0.001) with no statistical difference between the two groups (P>0.05). The SFCT also improved in all subjects (P<0.001) with better outcome in the half-dose PDT group (P<0.05). CONCLUSION: Both intravitreal conbercept and half-dose PDT are safe to use in treating chronic CSC. By 6mo, both treatment groups are efficacious in improving BCVA, reducing CMT and SFCT, and resolving SRF in eyes with chronic CSC. Half-dose PDT may show better outcome at initial phase of treatment in chronic CSC. Longer follow-up period is necessary to study for long-term effect and safety.