Role of APOE in glaucoma.

Glaucoma is a chronic blinding eye disease caused by the progressive loss of retinal ganglion cells (RGCs). Currently, no clinically approved treatment can directly improve the survival rate of RGCs. The Apolipoprotein E (APOE) gene is closely related to the genetic risk of numerous neurodegenerative diseases and has become a hot topic in the field of neurodegenerative disease research in recent years. The optic nerve and retina are extensions of the brain's nervous system. The pathogenesis of retinal degenerative diseases is closely related to the degenerative diseases of the nerves in the brain. APOE consists of three alleles, ε4, ε3, and ε2, in a single locus. They have varying degrees of risk for glaucoma. APOE4 and the APOE gene deletion (APOE-/-) can reduce RGC loss. By contrast, APOE3 and the overall presence of APOE genes (APOE+/+) result in significant loss of RGC bodies and axons, increasing the risk of glaucoma RGCs death. Currently, there is no clear literature indicating that APOE2 is beneficial or harmful to glaucoma. This study summarises the mechanism of different APOE genes in glaucoma and speculates that APOE targeted intervention may be a promising method for protecting against RGCs loss in glaucoma.

Correlation between refractive errors and ocular biometric parameters in children and adolescents: a systematic review and meta-analysis.

BACKGROUND: Refractive errors are one of the most common ocular conditions among children and adolescents, with myopia showing an increasing prevalence and early onset in this population. Recent studies have identified a correlation between refractive errors and ocular biometric parameters. METHODS: A systematic search was conducted in electronic databases including PubMed, EMBASE, Cochrane Library, Web of Science, and Medline from January 1, 2012, to May 1, 2023. Various ocular biometric parameters were summarized under different refractive states, including axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), corneal curvature (CC), Corneal curvature radius (CR),axial length-to-corneal radius ratio (AL/CR ratio), choroidal thickness (ChT), retinal thickness (RT), retinal nerve fiber layer thickness (RNFL), and retinal blood density (VD). The differences in these parameters among different refractive states were analyzed using Stata software with fixed or random-effects models, taking into account the assessed heterogeneity level. RESULTS: This meta-analysis included a total of 69 studies involving 128,178 eyes, including 48,795 emmetropic eyes, 60,691 myopic eyes, 13,983 hyperopic eyes, 2,040 low myopic eyes, 1,201 moderate myopic eyes, and 1,468 high myopic eyes. The results of our study demonstrated that, compared to the control group (emmetropic group), the myopic group and low, moderate, and high myopic groups showed significant increases in AL, AL/CR ratio, and ACD, while the hyperopic group exhibited significant decreases. Compared to the control group, the myopic group had a significantly increase for CC, while CR, CCT, perifoveal RT, subfoveal ChT, foveal ChT, parafoveal ChT, perifoveal (except nasal) ChT, and pRNFL (except temporal) significantly decreased. Compared to the control group, the hyperopic group had a significantly increase for subfoveal ChT, foveal ChT, parafoveal ChT, perifoveal ChT, and nasal pRNFL. Compared to the control group, the low and moderate myopic groups had a significantly decreases for the CCT, parafoveal RT (except nasal), perifoveal RT (except nasal), and pRNFL (except superior and temporal). Compared to the control group, the high myopic group had a significantly increase for CR, while LT, perifoveal ChT (except nasal), parafoveal RT, perifoveal RT, and pRNFL (except temporal) had significant decreased. CONCLUSION: The changes of ocular biometric parameters in children and adolescents are closely related to refractive errors. Ocular biometric parameters devices, as effective non-invasive techniques, provide objective biological markers for monitoring refractive errors such as myopia.

Ultra-thin silica shell-guarded nanoflares for high-fidelity live cell miRNA-21 imaging by fully avoiding the interference of biothiols.

We successfully constructed a new class of nanoflares based on ultra-thin silica-coated gold nanoparticles (Au@SiO2) with the covalent binding of nucleic acids, which demonstrated more resistance to biothiols than that exhibited in the traditional Au-S binding strategy, for imaging the target miRNA-21 with high fidelity in living cells.

Wide-field swept-source optical coherence tomography angiography (SS-OCTA) in the assessment of retinal vessel density and thickness in 4-to 16-year-old myopic children.

PURPOSE: To analyze the characteristics of macular retinal vessel density and thickness in children with myopia. METHODS: A cross-sectional study was conducted. A total of 228 children aged 4-16 years who visited the Ineye Hospital of Chengdu University of Traditional Chinese Medicine from September 2022 to November 2023 were included. Those with -0.5D < spherical equivalent (SE) < +2.0D were included in the non-myopia group (150 eyes), those with -3.0D < SE ≤ -0.5D were included in the low myopia group (246 eyes), and those with SE ≤ -3.0D were included in the moderate-to-high myopia group (60 eyes). All subjects underwent cycloplegic refraction, IOLmaster500, and Wide-field SS-OCTA (to exclude some peripheral retinal degeneration). Multiple linear regression analysis was used to analyze the correlation between macular ETDRS subfield of full retinal thickness (FRT), outer, inner retinal thickness (ORT, IRT), retinal vessel density (VD), deep and superficial retinal vessel density (DVD, SVD), and SE, axial length (AL). RESULTS: There were statistically significant differences (P < 0.05) in FRT in the central fovea (1 mm diameter)and perifovea (Diameter 3 to 6 mm) among the non-myopia group, low myopia group, and moderate-to-high myopia group. The three groups also showed statistically significant differences (P < 0.05) in VD in the central fovea and parafovea with a diameter of 1 to 3 mm (except the lower part). In multiple linear regression analysis adjusted for gender and age, SE and AL were found to be correlated with FRT in all ETDRS regions (except the central fovea) (P < 0.01), and SE and AL were correlated with IRT in the central fovea and perifovea, respectively (ß range -2.302 to 1.652; P < 0.05). SE and AL were also correlated with ORT in the parafovea and perifovea, respectively (ß range -4.371 to -2.344; P < 0.05). AL was negatively correlated with VD in the central fovea and parafovea (except the inferior region) (P < 0.05), as well as with DVD in all ETDRS regions (ß range -1.314 to -1.031; P < 0.05). AL was only negatively correlated with SVD in the parafoveal nasal region (ß = -0.633, P < 0.05). Additionally, the correlation between AL and DVD, ORT was higher than that with SVD, IRT. CONCLUSION: The more severe the myopia, the longer the AL, the thinner the FRT in the perifovea, and the lower the VD in both the fovea and parafovea in children. In addition, DVD and ORT were more significantly correlated with AL, suggesting that they may be more closely related to the growth of AL.

[Therapeutic effects of Fuzhenghuayu decoction in a CCl4-induced liver cirrhosis rat model and on hepatic stellate cell activation].

OBJECTIVE: To evaluate the influence of Fuzhenghuayu decoction on fibrotic liver tissue and activated hepatic stellate cells (HSCs) using a carbon tetrachloride (CCl4)-induced liver cirrhosis rat model system. METHODS: Sixty-four Sprague-Dawley rats were randomly divided into the following groups: normal (non-model, non-drug intervention), CCl4 liver fibrosis model, and CCl4 liver fibrosis model Fuzhenghuayu drug intervention at low dose (0.75 g/kg/d) and high dose (1.5 g/kg/d). The drug intervention was administered via oral-gastric irrigation once daily for 6 times per week over a 6-week period. Four rats from each group were sacrificed at the end of week 2, 4, and 6 for serum and liver tissue collection. Liver fibrosis was evaluated by histology, and expression of a-smooth muscle actin (a-SMA) was determined by immunohistochemistry. Liver function was assessed by measuring levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil). Between-group comparisons were made by completely random design and ANOVA with Bonferroni correction. RESULTS: At the end of weeks 2, 4 and 6, all four groups showed significantly different levels of ALT, AST, and TBil; in addition, the model group and drug intervention groups had significantly higher levels of ALT, AST, and TBil than the control group, the drug intervention groups showed significantly lower levels of ALT, AST, and TBil than the model group (P less than 0.01 or less than 0.05), and the differences between the low dose and high dose groups reached statistical significance (P less than 0.01 or less than 0.05). At the end of weeks 2, 4 and 6, the model group and drug intervention groups had significantly higher area ratio of liver fibrosis than the normal group (F = model: 18.68, low dose: 49.95, high dose: 82.44, P less than 0.01), but the two drug intervention groups had significantly less area ratio of liver fibrosis than the model group (P less than 0.05) and the high dose group showed the most robust decrease. In addition, the model group and drug intervention groups showed higher expression of a-SMA than the normal group (F = model: 18.68, low dose: 49.95, high dose: 82.44, P less than 0.01), but two drug intervention groups had significantly less a-SMA than the model group (F = model: 46.32, low dose: 40.30, high dose: 58.42, P less than 0.05) and the high dose group showed the most robust decrease. CONCLUSION: The Fuzhenghuayu decoction reduces the numbers of activated HSCs, thereby leading to down-regulated a-SMA expression and reduced degree of liver fibrosis; these effects may represent the mechanism by which this drug suppresses hepatic fibrosis.

GSH-depleting and H2O2-self-supplying hybrid nanozymes for intensive catalytic antibacterial therapy by photothermal-augmented co-catalysis.

Nanozyme-based chemodynamic therapy (CDT) has shown tremendous potential in the treatment of bacterial infections. However, the CDT antibacterial efficacy is severely limited by the catalytic activity of nanozymes or the infection microenvironments such as insufficient hydrogen peroxide (H2O2) and overexpressed glutathione (GSH). Herein, a versatile hybrid nanozyme (MoS2/CuO2) is rationally constructed by simply decorating ultrasmall CuO2 nanodots onto lamellar MoS2 platelets of hydrangea-like MoS2 nanocarrier via a covalent Cu-S bond. The MoS2/CuO2 nanozyme exhibits the peroxidase-mimic activity for catalytically converting H2O2 produced by acid-triggered decomposition of the decorated CuO2 into hydroxyl radical (•OH). Meanwhile, the MoS2/CuO2 can consume GSH overexpressed in the infection sites via redox reaction mediated by polyvalent transition metal ions (Cu2+ and Mo6+) for enhanced CDT. More importantly, MoS2 support can promote the conversion of Cu2+ to Cu+ by a co-catalytic reaction based on the Mo4+/Mo6+ redox couples, and provide photonic hyperthermia (PTT) to augment the peroxidase-mimic activity. The developed MoS2/CuO2 nanozymes possesses a desirable catalytic property, as well as a remarkably improved antibacterial efficiency both in vitro and in vivo. Taken together, this study proposes a synergetic multiple enhancement strategy to successfully construct the versatile hybrid nanozymes for intensive in vivo PTT/CDT dual-mode anti-infective therapy. STATEMENT OF SIGNIFICANCE: Chemodynamic therapy (CDT) has shown great potentialities in the treatment of bacterial infections, while its therapeutic efficiency is severely limited by the infection microenvironments such as insufficient hydrogen peroxide (H2O2) and overexpressed glutathione (GSH). Here, we rationally construct a hybrid nanozyme (MoS2/CuO2) with peroxidase-like activity that can enhance CDT by regulating local microenvironments, that is, simultaneously self-supplying H2O2 and consuming GSH. Importantly, MoS2 support can promote the conversion of Cu2+ to Cu+ by the Mo4+/Mo6+ redox couples, and provide photonic hyperthermia (PTT) to augment the peroxidase-mimic activity. The developed MoS2/CuO2 shows desirable PTT/CDT dual-mode antibacterial efficacy both in vitro and in vivo. This study proposes a versatile hybrid nanozyme with multiple enhancement effects for intensive in vivo anti-infective therapy.

A biofilm microenvironment-responsive one-for-all bactericidal nanoplatform for photothermal-augmented multimodal synergistic therapy of pathogenic bacterial biofilm infection.

Multimodal synergistic bactericidal agents display great potential for fighting biofilm infections. However, the rational design of biofilm microenvironment (BME)-activatable therapeutic agents with excellent specificities, effective eradications and minimal side effects remains a great challenge. Herein, we show a BME-responsive one-for-all bactericidal nanoplatform consisting of Fe3+-doped polydopamine (Fe/PDA)-capped ZnO nanoparticles with a successive assembly of methylene blue (MB) and poly(ethylene glycol) (PEG). In an acidic BME (pH 5.5), the constructed nanoagent (ZnPMp) can realize the co-delivery of dual metal ions (Zn2+ and Fe3+) and MB, and the latter shows an activated photodynamic antibacterial activity when irradiated with 635 nm laser. Zn2+ produced from acid-sensitive dissolution of ZnO is an effective chemical antibacterial agent. Additionally, the released Fe3+ is reduced to Fe2+ by glutathione (GSH) overexpressed in the BME to generate Fe2+/Fe3+ redox couples, which exhibit Fenton catalytic activity to convert endogenous H2O2 to hydroxyl radicals (˙OH) for chemodynamic sterilization and GSH depletion ability to improve ˙OH-induced oxidative damage. Interestingly, the hyperthermia caused by the Fe/PDA layer assisted with 808 nm laser can damage directly bacterial cells, accelerate the release of Zn2+, Fe3+and MB, and promote the catalytic activity of Fe2+/Fe3+ redox couples for photothermal-augmented multimodal antibiofilm therapy. With the help of dual lasers, ZnPMp displays the broad-spectrum antibacterial effect, inhibits effectively the formation of biofilms, and more importantly eliminates bacteria deep in mature biofilms. In addition, ZnPMp can be used to treat biofilm-related infections in vivo with excellent therapeutic performance and minimal toxicity. Overall, the developed ZnPMp may serve as a potential nano-antibacterial agent for intensive anti-infective therapy.

Rapid In Situ Deposition of Iron-Chelated Polydopamine Coating on the Polyacrylamide Hydrogel Dressings for Combined Photothermal and Chemodynamic Therapy of Skin Wound Infection.

Pathogenic bacterial infections of skin wounds have caused a significant threat to clinical treatment and human life safety. Here, we develop a bactericidal hydrogel dressing consisting of a polyacrylamide (PAM) hydrogel framework with in situ surface-deposition of iron-dopped polydopamine (FePDA). The prepared hydrogel dressing (FePDA-PAM) has a compact surface, good tensile strength, and excellent elastic recovery ability. The introduction of Fe3+ ions improve the photothermal therapy (PTT) efficiency of the PDA and endow the hydrogel dressing with chemodynamic therapy (CDT) properties. In vitro experiments show that the antibacterial effect of FePDA-PAM hydrogel on Staphylococcus aureus reach nearly 100% under the combined action of H2O2 and 808 nm near-infrared (NIR) laser, indicating an excellent combined antibacterial property of PTT and CDT. Furthermore, the FePDA-PAM + H2O2 + NIR treatment group in the in vivo antibacterial experiments displays lowest relative wound area and optimal wound healing within 5 days of treatment, thereby indicating the intensive skin wound disinfection. To summarize, the FePDA-PAM hydrogel has simple preparation and good biosafety. It may serve as a potential wound dressing for the combined PTT/CDT dual-mode antibacterial therapy.