IL-22/IL-22RA1 Promotes Human Tenon's Capsule Fibroblasts Proliferation and Regulates Fibrosis Through STAT3 Signaling Pathway.

Purpose: Although it is now understood that most antiglaucoma surgeries fail because of scarring of the filtering tract, the underlying mechanism remains to be elucidated. The present study investigated the mechanism by which the interleukin (IL)-22/IL-22 receptor alpha 1 (IL-22RA1) signaling pathway regulates scar formation in glaucoma patients. Method: A total of 31 glaucoma patients who underwent trabeculectomy surgery with uncontrollable intraocular pressure because of scarring and 19 strabismus patients as the control patient group were included in the present study. ELISA was performed to measure the content of IL-22 in peripheral blood. Serum from patients was used to incubate human Tenon's capsule fibroblasts (HTFs) cells and IL-22 antibody rescued the effect of IL-22 on the biological functions. qPCR and Western blot were performed to determine IL-22RA1 mRNA and protein expression levels. Flow cytometry was performed to assess the cell cycle distribution and the Cell Counting Kit-8 assay was used to analyze cell proliferation. Results: The ELISA assay revealed that the serum IL-22 level of glaucoma patients was significantly higher than the healthy group (29.80 ± 5.1 ng/µL vs. 5.21 ± 0.9 ng/µL). After incubation with patient serum, the proliferation and activation of human Tenon fibroblasts (HTFs) were promoted. IL-22 mediated the biological function of HTFs via directly binding IL-22RA1. Moreover, transfection of the siR-IL-22RA1 or IL-22RA1 gene resulted in significant antifibrosis or profibrosis in HTFs. When a signal transducer and activator of transcription (STAT) 3 inhibitor (BAY) was introduced to the IL-22RA1 overexpression group, IL-22-induced proliferation was reduced in HTFs. Additionally, glaucoma patients had increased levels of IL-22 expression following surgery. Conclusions: The IL-22/IL-22RA1/STAT3 signaling pathway promoted fibroblast cell proliferation and alpha-smooth muscle actin, potentially regulating fibrosis in glaucoma filtration tracts. Our results provide hitherto undocumented insights into the pathophysiology of postoperative scarring.

Understanding the variability of ground-level ozone and fine particulate matter over the Tibetan plateau with data-driven approach.

The Tibetan Plateau, known as the "Third Pole", is susceptible to ground-level ozone (O3) and fine particulate matter (PM2.5) pollution due to its unique high-altitude environment. This study constructed random forest regression models using multi-source data from ground measurements and meteorological satellites to predict variations in ground-level O3 and PM2.5 concentrations and their influencing factors across seven major cities in the Tibetan Plateau over two-year periods. The models successfully reproduced O3 and PM2.5 levels with satisfactory R-squared values of 0.71 and 0.73, respectively. Results reveal combustion-related carbon monoxide (CO) and nitrogen dioxide (NO2) as the most substantial influences on O3 and PM2.5 concentrations. Solar radiation, geographical factors, and meteorological variables also played crucial roles in driving pollutant variations. Conversely, transport-related and human activity factors exhibited relatively lower significance. High O3 and PM2.5 pollution occurred during pre-monsoon and post-monsoon/winter seasons, driven by solar radiation and emissions, respectively. While CO consistently contributed across cities and seasons, key influencing factors varied locally. This study unveils the key driving forces governing air pollutant variations across the Tibetan Plateau, shedding light on complex atmospheric processes in this unique high-altitude region.

Research progress of nano delivery systems for intraocular pressure lowering drugs.

Glaucoma is a chronic ocular disease characterized by optic atrophy and visual field defect. The main risk factor for glaucoma onset and progression is elevated intraocular pressure, which is caused by increased aqueous humor outflow resistance. Currently, the primary method for glaucoma therapy is the use of intraocular pressure lowering drugs. However, these drugs, when administered through eye drops, have low bioavailability, require frequent administration, and often result in adverse effects. To overcome these challenges, the application of nanotechnology for drug delivery has emerged as a promising approach. Nanoparticles can physically adsorb, encapsulate, or chemically graft drugs, thereby improving their efficacy, retention time, and reducing adverse reactions. Moreover, nanotechnology has opened up new avenues for ocular administration. This article provides a comprehensive review of nano systems for intraocular pressure lowering drugs, encompassing cholinergic agonists, ß-adrenergic antagonists, α-adrenergic agonists, prostaglandin analogs, carbonic anhydrase inhibitors, Rho kinase inhibitors, and complex preparations. The aim is to offer novel insights for the development of nanotechnology in the field of intraocular pressure lowering drugs.

Uneven Corneal Epithelial Redistribution After Femtosecond Laser-Assisted Lenticule Intrastromal Keratoplasty in Correcting Moderate-to-High Hyperopia.

PURPOSE: To evaluate the characteristic of corrective epithelial thickness after femtosecond laser-assisted lenticule intrastromal keratoplasty (LIKE) to correct moderate-to-high hyperopia. METHODS: The prospective case series study of the LIKE procedure was performed to correct moderate-to-high hyperopia. The epithelial thickness map was generated by anterior segment optical coherence tomography (AS-OCT) in the corneal central 9-mm zone. Keratometry and corneal higher order aberrations were analyzed by Pentacam (Oculus Optikgeräte GmbH) preoperatively and postoperatively. RESULTS: In the 26 eyes of 13 participants who underwent the LIKE procedure for moderate-to-high hyperopia, the attempted spherical equivalence (SEQ) was +6.50 ± 1.09 diopters (D). Compared to the preoperative epithelial thickness maps, the postoperative epithelial thickness had become significantly thinner in the central 5-mm zone; the difference was 6 to 7 µm. The paracentral epithelium performed nonuniform remodeling; the thinnest epithelial thickness was located in the inferotemporal section, which has the greatest difference from the superonasal; the difference between these two was approximately 3 µm. Through correlation analysis, it was found that the sections with thinner epithelium were significantly related to corneal curvature and corneal vertical coma. CONCLUSIONS: The LIKE procedure can be used to correct moderate-to-high hyperopia. This study further indicated the epithelial remodeling characteristic after the LIKE procedure: the central and paracentral corneal epithelial thickness becomes thinner, and the epithelial thickness distributes non-uniformly, which may be the important factor of the postoperative curvature asymmetric distribution and induction of corneal vertical coma. [J Refract Surg. 2024;40(5):e321-e327.].

Understanding the spatial and seasonal variation of the ground-level ozone in Southeast China with an interpretable machine learning and multi-source remote sensing.

Ground-level ozone (O3) pollution poses significant threats to both human health and air quality. This study uses ground observations and satellite retrievals to explore the spatiotemporal characteristics of ground-level O3 in Zhejiang Province, China. We created data-driven machine learning models that include meteorological, geographical and atmospheric parameters from multi-source remote sensing products, achieving good performance (Pearson's r of 0.81) in explaining regional O3 dynamics. Analyses revealed the crucial roles of temperature, relative humidity, total column O3, and the distributions and interactions of precursor (volatile organic compounds and nitrogen oxides) in driving the varied O3 patterns observed in Zhejiang. Furthermore, the interpretable modeling quantified multifactor interactions that sustain high O3 levels in spring and autumn, suppress O3 levels in summer, and inhibit O3 formation in winter. This work demonstrates the value of a combined approach using satellite and machine learning as an effective novel tool for regional air quality assessment and control.

Construction of miRNA-mRNA regulatory network indicates potential biomarkers for primary open-angle glaucoma.

BACKGROUND: Trabecular meshwork (TM) dysfunction-induced elevation of intraocular pressure has been identified as the main risk factor of irreversible optic nerve injury in Primary open­angle glaucoma (POAG). Increasing evidences suggest that microRNA (miRNA) plays a vital role in the pathogenesis of POAG. This study aims to construct a miRNA-mRNA regulatory network and identify biomarkers for POAG. METHODS: miRNAs and mRNAs expression profiling of TM samples from controls and POAG patients were assessed through microarray analysis. Target genes of differentially expressed miRNAs (DEmiRNAs) were predicted by miEAA and miRNet. Then GO and KEGG pathway analysis of differentially expressed mRNAs (DEmRNAs) were performed. PPI of top 30 hub genes was identified and miRNA-mRNA network was established by STRING database and Cytoscape software. GSE27276 and GSE105269 datasets were used to verify the expression of hub genes and to predict potential biomarkers in TM and aqueous humor (AH) for POAG, respectively. Finally, GSEA analysis was conducted to estimate the main signaling pathway of POAG pathogenesis. RESULTS: A total of 29 up-regulated and 7 down-regulated miRNAs, 923 up-regulated and 887 down-regulated mRNAs were identified in TM of POAG compared with controls. Target genes and DEmRNAs were mainly enriched in nitric oxide biosynthetic process, vasopressin-regulated water reabsorption, and so on. Through miRNA-mRNA network construction, top 30 hub genes were regulated by 24 DEmiRNAs. 8 genes were aberrantly expressed in dataset GSE27276. 3 genes (CREB1, CAPZA2, SLC2A3) and 2 miRNAs (miR-106b-5p, miR-15a-5p) were identified as potential biomarkers for POAG in TM and AH, respectively. GSEA analysis revealed that these 3 genes modulated POAG through different pathways. CONCLUSION: In this study, construction of miRNA-mRNA network and identification of biomarkers provide a novel insight into the pathogenesis, early diagnosis and treatment for POAG.

Human mesenchymal stem cells derived from adipose tissue showed a more robust effect than those from the umbilical cord in promoting corneal graft survival by suppressing lymphangiogenesis.

BACKGROUND: Mesenchymal stem cells (MSCs) have shown promising potential in allograft survival. However, few reports have focused on comparing the immunosuppressive capacity of MSCs from different sources and administered via different routes in inhibiting transplant rejection. Moreover, virtually nothing is known about the role of MSCs in the regulation of graft neovascularization and lymphangiogenesis. In this study, we compared the efficacy of human adipose MSCs (hAD-MSCs) and human umbilical cord MSCs (hUC-MSCs) in vitro and in corneal transplantation models to explore the underlying molecular mechanisms and provide a powerful strategy for future clinical applications. METHODS: hAD-MSCs and hUC-MSCs were generated, and their self-renewal and multi-differentiation abilities were evaluated. The inhibitory effect of human MSCs (hMSCs) was examined by T-cell proliferation assays with or without transwell in vitro. Two MSCs from different sources were separately adoptively transferred in mice corneal transplantation (5 × 105 or 1 × 106/mouse) via topical subconjunctival or intravenous (IV) routes. Allograft survival was evaluated every other day, and angiogenesis and lymphomagenesis were quantitatively analyzed by immunofluorescence staining. The RNA expression profiles of hMSCs were revealed by RNA sequencing (RNA-seq) and verified by quantitative real-time PCR (qRT‒PCR), western blotting or ELISA. The function of the differentially expressed gene FAS was verified by a T-cell apoptosis assay. RESULTS: hAD-MSCs induced stronger immunosuppression in vitro than hUC-MSCs. The inhibitory effect of hUC-MSCs but not hAD-MSCs was mediated by cell-cell contact-dependent mechanisms. Systemic administration of a lower dose of hAD-MSCs showed better performance in prolonging corneal allograft survival than hUC-MSCs, while subconjunctival administration of hMSCs was safer and further prolonged corneal allograft survival. Both types of hMSCs could inhibit corneal neovascularization, while hAD-MSCs showed greater superiority in suppressing graft lymphangiogenesis. RNA-seq analysis and confirmation experiments revealed the superior performance of hAD-MSCs in allografts based on the lower expression of vascular endothelial growth factor C (VEGF-C) and higher expression of FAS. CONCLUSIONS: The remarkable inhibitory effects on angiogenesis/lymphangiogenesis and immunological transplantation effects support the development of hAD-MSCs as a cell therapy against corneal transplant rejection. Topical administration of hMSCs was a safer and more effective route for application than systemic administration.

3% diquafosol sodium eye drops in Chinese patients with dry eye: a phase IV study.

Introduction: The efficacy and safety of 3% diquafosol sodium eye drops in Chinese patients with dry eye in the real-world setting remains unclear. Methods: 3099 patients with dry eye symptoms were screened according to Asia Dry Eye Society latest recommendation. Among them, 3000 patients were enrolled for a phase IV study. We followed up with multiple clinical characteristics including corneal fluorescein staining, tear break up time, Schirmer's tests, visual acuity, intraocular pressure, and others. The follow ups were performed at baseline, 2 weeks and 4 weeks after treatment. Results: Based on the results of corneal fluorescein staining and tear break up time, all age and gender subgroups exhibited obvious alleviation of the symptoms among the patients with dry eye, and the data in elderly group showed the most significant alleviation. All the adverse drug reactions (ADRs, 6.17%) were recorded, among which 6% local ocular ADRs were included. Meanwhile, mild ADRs (91.8%) accounted for the most. Most of the ADRs (89.75%) got a quick and full recovery, with an average time at 15.6 days. 1.37% of patients dropped out of the study due to ADRs. Discussion: The use of 3% diquafosol sodium eye drop is effective and safe in the treatment of dry eye, with a low incidence of ADRs showing mild symptoms. This trial was registered at Chinese Clinical Trial Registry ID: ChiCTR1900021999 (Registration Date: 19/03/2019).

A novel water-soluble Cu(II) gluconate complex inhibits cancer cell growth by triggering apoptosis and ferroptosis related mechanisms.

Metal copper complexes have attracted extensive attention as potential alternatives to platinum-based anticancer drugs due to their possible different modes of action. Herein, a new copper(II) gluconate complex, namely [Cu(DPQ)(Gluc)]·2H2O (CuGluc, DPQ = pyrazino[2,3-f][1,10]phenanthroline), with good water-solubility and high anticancer activity was synthesized by using D-gluconic acid (Gluc-2H) as an auxiliary ligand. The complex was well characterized by single-crystal X-ray diffraction analysis, elemental analysis, molar conductivity, and Fourier transform infrared spectroscopy (FTIR). The DNA-binding experiments revealed that CuGluc was bound to DNA by intercalation with end-stacking binding. CuGluc could oxidatively cleave DNA, in which 1O2 and H2O2 were involved. In addition, CuGluc was bound to the IIA subdomain of human serum albumin (HSA) through hydrophobic interaction and hydrogen bonding, showing a good affinity for HSA. The complex showed superior anticancer activity toward several cancer cells than cisplatin in vitro. Further studies indicated that CuGluc caused apoptotic cell death in human liver cancer (HepG2) cells through elevated intracellular reactive oxygen species (ROS) levels, mitochondrial dysfunction, cell cycle arrest, and caspase activation. Interestingly, CuGluc also triggered the ferroptosis mechanism through lipid peroxide accumulation and inhibition of glutathione peroxidase 4 (GPX4) activity. More importantly, CuGluc significantly inhibited tumor growth in vivo, which may benefit from the combined effects of apoptosis and ferroptosis. This work provides a promising strategy to develop highly effective antitumor copper complexes by coordinating with the glucose metabolite D-gluconic acid and exploiting the synergistic effects of apoptosis and ferroptosis mechanisms.

Synthesis, characterization and biological activity of novel copper complexes containing a ß-carboline derivative and amino acids.

Copper complexes have long been considered as a promising class of anticancer or antibacterial therapeutics. In this paper, two novel copper(II) complexes containing a ß-carboline derivative and amino acids, namely [Cu(1-Im-ßc)(L-Val)]ClO4·0.5H2O (Cu1) and [Cu(1-Im-ßc)(L-Phe)]ClO4·0.5H2O (Cu2), where 1-Im-ßc = 1-(2-imidazolyl)-ß-carboline, L-Val = L-valine, and L-Phe = L-phenylalanine, were designed and synthesized. The complexes were characterized by elemental analysis, infrared spectroscopy, molar conductivity measurements, and mass spectrometry to determine their spatial structures and compositions. Both complexes bind to DNA by insertion. The complexes also show a good affinity for human serum albumin (HSA). In addition, the antitumor activity of the two complexes against lung cancer cells (A549), cervical cancer cells (HeLa), and breast cancer cells (MBA-MD-231) is significantly superior to that of the traditional antitumor drug, cisplatin. Finally, the anticancer mechanism results show that the complexes can induce apoptosis in HeLa cells, which is associated with mitochondrial damage, oxidative stress caused by reactive oxygen species (ROS) production, and activation of the caspase protein family. This study demonstrates that the introduction of aromatic heterocyclic alkaloid ligands with a broad spectrum of biological activities and water-soluble amino acid ligands into copper complexes can regulate their amphiphilic properties and biological activity, so as to obtain highly efficient copper-based therapeutics.

Evaluation and correlation analysis of ocular surface disorders and quality of life in autoimmune rheumatic diseases: a cross-sectional study.

OBJECTIVE: This cross-sectional study aimed to reveal the association between ocular surface disorders and psychological, physiological situations among autoimmune rheumatic patients. METHODS: Ninety autoimmune rheumatic patients (180 eyes) hospitalized in the Department of Rheumatology, The Second Xiangya Hospital, Central South University and 30 controls (60 eyes) were enrolled in the study. All participants were assessed for ocular surface disorders including dry eye disease (DED) by the Ocular Surface Disease Index (OSDI) for symptoms evaluation, and slim lamp examinations for tear break-up time (TBUT), meibomian gland secretion, symblepharon and corneal clarity, Schirmer I test, corneal fluorescein staining (CFS), lid-parallel conjunctival folds (LIPCOF). Systematic conditions were evaluated using the Short Form 36-Health Survey (SF-36) for health-related quality of life, Hospital Anxiety and Depression Scale (HADS) for anxiety and depression, Health Assessment Questionnaire-Disability Index (HAQ-DI) for difficulties in activities of daily living, and Pittsburgh Sleep Quality Index (PSQI) for sleep quality. Pearson and spearman's analysis were conducted to examine the relationship between systematic conditions and ocular surface conditions. RESULTS: The analyses were controlled for age and sex. 52.22% of eyes (94 in 180) of autoimmune rheumatic patients and 21.67% of eyes (13 in 60) of controls were diagnosed with DED. The autoimmune rheumatic patients showed significant higher OSDI score, fewer basal tear secretion, more severe CFS and conjunctivochalasis than controls. There were no statistically significant differences in TBUT, meibomian gland secretion, symblepharon, and corneal clarity between the two groups. For systematic conditions, autoimmune rheumatic patients had significantly lower SF-36 scores, higher anxiety scores, and HAQ-DI scores than controls. No statistically significant differences were detected in depression scores and PSQI between the two groups. Among autoimmune rheumatic patients, OSDI scores were moderately correlated with quality of life, anxiety, depression and sleep quality. CONCLUSION: Factors including quality of life, anxiety, depression, and sleep quality are associated with ocular surface conditions, especially DED symptoms. Management of systemic conditions and psychotherapy should also be considered as part of the treatment among autoimmune rheumatic patients.

Rapamycin antagonizes angiogenesis and lymphangiogenesis through myeloid-derived suppressor cells in corneal transplantation.

Rapamycin is an immunosuppressive drug that is widely used in the postsurgery management of transplantation. To date, the mechanism by which rapamycin reduces posttransplant neovascularization has not been fully understood. Given the original avascularity and immune privilege of the cornea, corneal transplantation is considered as an ideal model to investigate neovascularization and its effects on allograft rejection. Previously, we found that myeloid-derived suppressor cells (MDSC) prolong corneal allograft survival through suppression of angiogenesis and lymphangiogenesis. Here, we show that depletion of MDSC abolished rapamycin-mediated suppression of neovascularization and elongation of corneal allograft survival. RNA-sequencing analysis revealed that rapamycin dramatically enhanced the expression of arginase 1 (Arg1). Furthermore, an Arg1 inhibitor also completely abolished the rapamycin-mediated beneficial effects after corneal transplantation. Taken together, these findings indicate that MDSC and elevated Arg1 activity are essential for the immunosuppressive and antiangiogenic functions of rapamycin.

A Comparison of the Outcomes of Open Trigger Release versus Ultrasound-Guided Modified Small Needle-Knife Percutaneous Release for Treatment of Trigger Digits.

Background: The aim of this randomised prospective study is to compare the outcomes of traditional open trigger digit release versus ultrasound-guided modified small needle-knife (SNK) percutaneous release in the treatment of trigger digits. Methods: Patients with grade 2 and above trigger digits were enrolled into the study and randomly assigned to traditional open surgery (OS) or ultrasound-guided modified SNK percutaneous release group. The patients were followed up for 7, 30 and 180 days after treatment and data with regard to visual analogue scale (VAS) score and Quinnell grading (QG) was collected and compared between the two groups. Results: A total of 72 patients were enrolled in the study with 30 in the OS group and 42 in the SNK group. VAS scores and QG of the two groups significantly decreased at 7 days and 30 days after treatment compared to before treatment, but there was no significant difference between the two groups. There was also no differences between the two groups at 180 days and between the values at 30 days and 180 days. Conclusions: The outcomes of ultrasound-guided SNK percutaneous release is similar to traditional OS. Level of Evidence: Level II (Therapeutic).

Continuous voriconazole lavage in managing moderate and severe fungal keratitis: a randomized controlled trial.

PURPOSE: To assess the effectiveness and safety of continuous lavage with 1% voriconazole (CL) for moderate and severe fungal keratitis. METHODS: Thirty-one patients were randomized to receive topical eye drops either alone (T) or combined with continuous 1% voriconazole lavage (CL-T). The primary outcome was the cure rate at 3 months. The secondary outcomes were the 6-day efficacy, 3-day infiltration size and depth, hypopyon height, central corneal thickness (CCT), epithelial defect size, and subject feelings and clinical signs assessment scores. RESULTS: At 3 months, the cure rate was comparable between the groups in patients with moderate fungal keratitis (66.7% vs. 62.5%, P = 0.60). However, among severe cases, 4 cases (44.4%) in the CL-T group healed successfully, while none in the T group; this difference was not significant (P = 0.08), although it was very close to 0.05. This may be related to the small sample size. After 6 days, the percentage of patients with "worsened" ulcers in the CL-T group was lower than that in the T group (0% vs. 31%, P = 0.043). The infiltration size, infiltration depth, and hypopyon height in the CL-T group were smaller than those in the T group after 3 days (all P < 0.05). There was no difference in CCT, epithelial defect size, subject feelings scores, or clinical signs scores between groups. CONCLUSION: These outcomes suggest that CL is an effective and safe adjuvant method for controlling the progression of moderate and severe fungal keratitis. TRIAL REGISTRATION NUMBER: ChiCTR2100050565.

Combined Phacovitrectomy with Metallic Intraocular Foreign Body Removal through Corneal Incision Using A Novel "Magnetic Conduction" Technique.

PURPOSE: To describe a "magnetic conduction" technique for the removal of metallic intraocular foreign bodies (IOFBs) in the posterior segment combined with cataract extraction and pars plana vitrectomy and to report its outcomes. METHODS: We retrospectively analyzed the data of 42 eyes of 42 patients with posterior metallic IOFBs between April 2020 and February 2022. In all patients, cataract extraction was combined with pars plana vitrectomy. With an external magnet, the IOFBs were captured by a magnetized vitrectomy cutter, delivered to the anterior chamber, and then extracted through a corneal phacoemulsification incision. RESULTS: All patients were men, with a mean age of 45.6 ± 10.7 years. The mean size of the IOFBs was 3.5 ± 1.7 mm (range, 1.5-8.9 mm) in their longest dimension. A final best-corrected visual acuity of 20/200 or better was noted in 24 of 42 patients (57.1%). Postoperatively, recurrent retinal detachment was seen in three eyes. There were no other intraoperative or postoperative complications. CONCLUSION: The "magnetic conduction" technique combined with phacovitrectomy is a safe and feasible approach to removing IOFBs in the posterior segment.

Insights into the spontaneous multi-scale supramolecular assembly in an ionic liquid-based extraction system.

Herein, we report a four-step mechanism for the spontaneous multi-scale supramolecular assembly (MSSA) process in a two-phase system concerning an ionic liquid (IL). The complex ions, elementary building blocks (EBBs), [EBB]n clusters and macroscopic assembly (MA) sphere are formed step by step. The porous large-sized [EBB]n clusters in the glassy state can hardly stay in the IL phase and they transfer to the IL-water interface due to both electroneutrality and amphiphilicity. Then, the clusters undergo random collision in the interface driven by the Marangoni effect and capillary force thereafter. Finally, a single MA sphere can be formed owing to supramolecular interactions. To our knowledge, this is the first example realizing spontaneous whole-process supramolecular assembly covering microscopic, mesoscopic and macroscopic scales in extraction systems. The concept of multi-scale selectivity (MSS) is therefore suggested and its mechanism is revealed. The selective separation and solidification of metal ions can be realized in a MSSA-based extraction system depending on MSS. In addition, insights into the physicochemical characteristics of ILs from microscopic, mesoscopic to macroscopic scales are provided, and especially, the solvation effect of ILs on the large-sized clusters leading to the phase-splitting is examined. It is quite important that the polarization of uranyl in its complex, the growing of uranyl clusters in an IL as well as the glassy material of uranyl are investigated systematically on the basis of both experiment and theoretical calculations in this work.

Synthesis, structural studies, interaction with DNA/HSA and antitumor evaluation of new Cu(II) complexes containing 2-(1H-imidazol-2-yl)pyridine and amino acids.

Copper complexes are considered as potential candidates for anticancer therapy and medical applications. In this paper, three new Cu(II) complexes, [Cu(IPY)2](ClO4)2·H2O (CuI1), [Cu(IPY)(L-Phe)H2O]ClO4·0.5H2O (CuI2) and [Cu(IPY)(L-Val)H2O]ClO4 (CuI3) (where IPY = 2-(1H-imidazol-2-yl)pyridine, L-Phe = L-phenylalanine, and L-Val = L-valine), with good amphipathic properties were synthesized and characterized. Their single crystal X-ray diffraction results revealed that CuI1 was four-coordinated, while CuI2 and CuI3 both adopted a five-coordinated tetragonal pyramidal configuration. Multi-spectral methods, viscosity experiment and molecular docking technique showed that the three complexes interacted with DNA through insertion. The results of the gel electrophoresis experiments indicated that DNA was oxidatively cleaved by all the complexes in a concentration-dependent manner. Moreover, singlet oxygen (1O2), hydrogen peroxide (H2O2) and superoxide anion radicals (˙O2-) were associated with the oxidative cleavage of DNA. All the complexes also had good binding affinity with human serum albumin (HSA). The MB degradation assay revealed that all complexes could react with H2O2 to form ˙OH through Fenton-like processes. The complexes displayed good antiproliferative activity against the tested human cancer cells in vitro, including cervical carcinoma cells (HeLa), liver cancer cells (HepG2 and BEL-7402) and gastric adenocarcinoma cells (SGC-7901), but showed lower toxicity to normal liver cells (LO2). The anticancer mechanism research revealed that CuI1, CuI2 and CuI3 arrested the cell cycle at the S phase, elevated intracellular reactive oxygen species (ROS) levels and induced loss of mitochondrial membrane potential (MMP). The results indicated that these Cu(II) complexes could induce DNA damage and ROS-mediated mitochondrial dysfunction, leading to cancer cell apoptosis. Our work provides a theoretical basis for the design of new low-toxicity and highly efficient anticancer Cu(II) complexes by incorporating biological metabolites and aromatic heterocyclic ligands.

Effects of Tafluprost on Ocular Blood Flow.

Increasing evidence indicates that improving ocular blood flow (OBF) can be a therapeutic direction for glaucoma therapy. Tafluprost, a prostaglandin analogue which lowers the intraocular pressure (IOP), has been shown to improve OBF in animals and humans. Several animal experiments showed that topical tafluprost significantly increased optic nerve head and retinal blood flow. Clinical trials also showed a beneficial effect of tafluprost on optic nerve head and macula blood flow, and a good ocular pulse amplitude-lowering effect. But, there are still a few conflicting results. Overall, tafluprost seems to have a beneficial effect on OBF, and the positive effect is probably independent from its IOP-lowering effect, which also is expected to improve OBF. Moreover, reducing the intracellular free Ca2+ concentration may be a possible mechanism of tafluprost's effect on OBF. More well-designed studies are required to reveal the truth.

Research Progress and Potential Applications of Spermidine in Ocular Diseases.

Spermidine, a natural polyamine, exists in almost all human tissues, exhibiting broad properties like anti-aging, autophagy induction, anti-inflammation, anti-oxidation, cell proliferation activation, and ion channel regulation. Considering that spermidine is already present in human nutrition, recent studies targeting supplementing exogenous sources of this polyamine appear feasible. The protective role of spermidine in various systems has been illuminated in the literature, while recent progress of spermidine administration in ocular diseases remains to be clarified. This study shows the current landscape of studies on spermidine and its potential to become a promising therapeutic agent to treat ocular diseases: glaucoma, optic nerve injury, age-related macular degeneration (AMD), cataracts, dry eye syndrome, and bacterial keratitis. It also has the potential to become a potent biomarker to predict keratoconus (KC), cataracts, uveitis, glaucoma, proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and retinopathy of prematurity (ROP). We also summarize the routes of administration and the effects of spermidine at different doses.

Protective activity of tert-butylhydroquinone against oxidative stress and apoptosis induced by glutamate agonizts in R28 cells and mice retina.

Glutamate excitotoxicity can cause cell damage and apoptosis and play an important role in a variety of retinal diseases. Tertiary-butylhydroquinone (tBHQ) is an approved food-grade phenolic antioxidant with antioxidant activity in a variety of cells and tissues. We observed the protective effect of tBHQ on glutamatergic agonist-induced retina and explored its possible mechanism of action through in vitro cell experiments. The results showed that tBHQ had protective effects on NMDA-induced mouse retinal excitotoxicity and glutamate-induced excitotoxicity in rat retinal precursor cells (R28 cells). tBHQ reversed glutamate-induced apoptosis, production of intracellular reactive oxygen species, and reduction of mitochondrial membrane potential. Western blot analysis showed that tBHQ could increase the expression of procaspase-3, Bcl-2, AIF precursor, CAT, SOD2, Nrf2, NQO1, HO-1 and NF-κB in glutamate-treated cells, and decrease the expression of AIF cleavage products. Furthermore, we discovered that tBHQ activated müller glial cells. Based on these results, tBHQ may have antioxidant and anti-apoptotic properties, thus serving as a potential retinal protective agent. Its anti-oxidative stress effect was attributed to up-regulation of Nrf2, and its anti-apoptotic effect was related to its up-regulation of Bcl-2 expression and inhibition of mitochondria-dependent apoptosis.