Causal effect of vascular endothelial growth factor on the risk of atrial fibrillation: a two-sample Mendelian randomization study.

Background: Observational studies have found that vascular endothelial growth factor (VEGF) levels are associated with the risk of cardiovascular disease. However, it remains unclear whether VEGF levels have a causal effect on the risk of atrial fibrillation. Methods: A two-sample Mendelian randomization (MR) study was conducted to explore the causal relationship between VEGF levels and the risk of atrial fibrillation. Genetic variants associated with VEGF [VEGF-A, VEGF-C, VEGF-D, VEGF receptor-2 (VEGFR-2), VEGFR-3] and atrial fibrillation (atrial fibrillation, atrial fibrillation and flutter) were used as instrumental variables. Data on genetic variants were obtained from published genome-wide association studies (GWAS) or the IEU Open GWAS project. Inverse-variance weighted (IVW) analysis was used as the primary basis for the results, and sensitivity analyses were used to reduce bias. Causal relationships were expressed as odds ratio (OR) with 95% confidence interval (CI), and a P-value of <0.1 corrected for False Discovery Rate (FDR) (PFDR < 0.1) was considered to have a significant causal relationship. Results: Genetically predicted high levels of VEGF-A [OR = 1.025 (95%CI: 1.004-1.047), PFDR = 0.060] and VEGF-D [OR = 1.080 (95%CI: 1.039-1.123), PFDR = 0.001]] were associated with an increased risk of atrial fibrillation, while no causal relationship was observed between VEGF-C (PFDR = 0.419), VEGFR-2 (PFDR = 0.784), and VEGFR-3 (PFDR = 0.899) and atrial fibrillation risk. Moreover, only genetically predicted high levels of VEGF-D [OR = 1.071 (95%CI: 1.014-1.132), PFDR = 0.087] increased the risk of atrial fibrillation and flutter. Sensitivity analysis demonstrated that the relationship between VEGF-D levels and the risk of atrial fibrillation was robust. Conclusion: This study supports a causal association between high VEGF-D levels and increased risk of atrial fibrillation.

The effect of VEGF and KDR gene variants on Crimean-Congo hemorrhagic fever.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF), an acute viral hemorrhagic fever disease, has a high mortality rate among humans. Hemorrhagic propensity is caused by coagulation malfunction and increased capillary permeability brought on by the resultant vascular injury. Vascular endothelial growth factor (VEGF) and VEGF receptor-2, or KDR (kinase insert domain containing receptor), are effective in vasculogenesis and angiogenesis. CCHF was stated to have endothelial dysfunction. This study aimed to evaluate whether the VEGF and KDR gene variants contribute to the development of CCHF in the Turkish population. METHODS: A total of 101 subjects, including 51 CCHF patients and 50 healthy controls, were included in the study. The polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method was used to genotype VEGF 936 C > T (rs3025039) and KDR - 604 T > C (rs2071559) variants. The results were statistically analyzed. RESULTS: The VEGF 936 C > T genotype and allele distributions did differ significantly between the patients and the controls. The subjects carrying the C/C genotype and C allele had a higher risk of developing CCHF than the control group (p˂0.05). There was a statistically significant association between the controls and the patients in terms of VEGF 936 C > T C/C versus C/T + T/T (p˂0.05, OR:3.273, 95%Cl: 1.44-7.63). The KDR - 604 T > C variant's allele and genotype distribution were not significantly different between the patients and controls. CONCLUSION: This study suggests the VEGF 936 C > T variant is a genetic marker of sensitivity to CCHF among the Turkish population and may help protect against the disease.

Hypoxic Responses in Periodontal Tissues: Influence of Smoking and Periodontitis.

AIM: This study aimed to investigate the hypoxic changes in periodontal tissues resulting from smoking and periodontitis by assessing levels of hypoxia-inducible factors (HIF-1α, HIF-2α, HIF-3α) and vascular endothelial growth factor (VEGF) in gingival crevicular fluid (GCF). MATERIALS AND METHODS: The study comprised 22 periodontally healthy non-smokers (Group H), 22 periodontally healthy smokers (Group HS), 22 non-smokers with periodontitis (Group P) and 22 smokers with periodontitis (Group PS). Clinical periodontal parameters were documented, and GCF samples were collected and analysed using enzyme-linked immunosorbent assay (ELISA). RESULTS: Significantly elevated levels of HIF-1α, HIF-3α and VEGF were observed in Groups HS, P and PS compared to Group H (p < 0.05). Moreover, higher HIF-2α levels were detected in the Groups HS and P compared to Group H (p < 0.05). Significant correlations were detected between all evaluated hypoxia biomarkers in the Group P (p < 0.05) except HIF-2α and HIF-3α. However, in the PS group, significant correlation appeared only between HIF-1α and HIF-2α (p < 0.05). CONCLUSION: Our findings indicate that smoking and periodontitis induce comparable hypoxic effects in periodontal tissues, as evidenced by the evaluated biomarkers. Further research is warranted to gain a deeper understanding of the mechanisms underlying hypoxia in periodontal tissues.

Bioprinting of Aptamer-Based Programmable Bioinks to Modulate Multiscale Microvascular Morphogenesis in 4D.

Dynamic growth factor presentation influences how individual endothelial cells assemble into complex vascular networks. Here, programmable bioinks are developed that facilitate dynamic vascular endothelial growth factor (VEGF) presentation to guide vascular morphogenesis within 3D-bioprinted constructs. Aptamer's high affinity is leveraged for rapid VEGF sequestration in spatially confined regions and utilized aptamer-complementary sequence (CS) hybridization to tune VEGF release kinetics temporally, days after bioprinting. It is shown that spatial resolution of programmable bioink, combined with CS-triggered VEGF release, significantly influences the alignment, organization, and morphogenesis of microvascular networks in bioprinted constructs. The presence of aptamer-tethered VEGF and the generation of instantaneous VEGF gradients upon CS-triggering restricted hierarchical network formation to the printed aptamer regions at all spatial resolutions. Network properties improved as the spatial resolution decreased, with low-resolution designs yielding the highest network properties. Specifically, CS-treated low-resolution designs exhibited significant vascular network remodeling, with an increase in vessel density(1.35-fold), branching density(1.54-fold), and average vessel length(2.19-fold) compared to non-treated samples. The results suggest that CS acts as an external trigger capable of inducing time-controlled changes in network organization and alignment on-demand within spatially localized regions of a bioprinted construct. It is envisioned that these programmable bioinks will open new opportunities for bioengineering functional, hierarchically self-organized vascular networks within engineered tissues.

VEGF-loaded ROS-responsive nanodots improve the structure and function of sciatic nerve lesions in type II diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) is a prevalent complication of diabetes mellitus (DM), significantly contributing to the risk of amputation and mortality. Reactive oxygen species (ROS) can induce both neurological and structural harm through direct impact and pyroptosis, underscoring the critical role of ROS regulation in mitigating DPN. In this research endeavor, we propose harnessing the inherent antioxidant properties of sulfhydryl groups by grafting them onto gold nanodots through an amidation reaction, resulting in the creation of ROS-responsive AuNDs. Additionally, we aim to synthesize AuNDs-VEGF, wherein VEGF is attached to AuNDs via electrostatic interactions, as a therapeutic strategy for addressing DPN in rat models. The results of in vivo experiments showed that AuNDs and AuNDs-VEGF nanoparticles could increase the nerve conduction velocity, shorten the latency of nerve conduction in the sciatic nerve, promote the regeneration of nerve trophectodermal vessels, improve the structure and function of the sciatic nerve, reduce the apoptosis of neural cells, and alleviate the atrophy of the gastrocnemius muscle. Thus, VEGF-loaded ROS-responsive nanodots present a promising avenue for ameliorating diabetic peripheral neuropathy. This innovative approach not only extends the application possibilities of nanodots but also introduces a novel avenue for the treatment of diabetic neuropathy.

Structural and dynamical insights revealed the anti-glioblastoma potential of withanolides from Withania coagulans against vascular endothelial growth factor receptor (VEGFR).

CONTEXT: Glioblastoma (GBM), well known as grade 4 tumors due to its progressive malignant features such as vascular proliferation and necrosis, is the most aggressive form of primary brain tumor found in adults. Mutations and amplifications in the vascular endothelial growth factor receptor (VEGFR) contribute to almost 25% of GBM tumors. And thus, VEGFR has been declared the primary target in glioblastoma therapeutic strategies. However, many studies have been previously reported that include GBM as global therapeutics challenge, but they lack the molecular level insights that could help in understanding the biological function of a therapeutically important protein playing a major role in the disease and design the best strategies to develop the potential drugs. METHODS: Therefore, to the best of our knowledge, the present study is the first time of kind, which involves multi-in silico approaches to predict the inhibition potential of withanolides from Withania coagulan against VEGFR. The study is actually based on determining the mode of action of five isolates: withanolide J, withaperuvin, 27-hydroxywithanolide I, coagule E, and coagule E, along with their respective binding energies. Molecular docking simulations revealed primarily four ligands, withanolide J (- 7.33 kJ/mol), 27-withanolide (- 7.01 kJ/mol), ajugine, withaperuvin (- 6.89 kJ/mol), and ajugine E (- 6.39 kJ/mol), to have significant binding potencies against the protein. Ligand binding was found to enhance the confirmational stability of the protein revealed through RMSD analysis, and RMSF assessment revealed the protein residues especially from 900-1000 surrounding the binding of the protein. Structural and dynamics of the protein via dynamics cross-correlation movement (DCCM) and principal component analysis (PCA) in both the unbound form and complexed with most potent ligand, withanolide J, reveal the ligand binding affecting the entire conformational integrity of the protein stabilized by hydrogen bonds and electrostatic attractions. Free energy of binding estimations by means of molecular mechanics Poisson-Boltzmann surface area (MMPBSA) method further revealed the withanolide J to have maximum binding potency of the all ligands. Withanolide J in final was also found to have suitable molecular characterizations to cross the blood-brain barrier (BBB +) and reasonable human intestinal absorption ability determined by ADMET profiling via admetSAR tools.

Microsecond Pulsing Laser for Choroidal Neovascularization Associated with Central Serous Chorioretinopathy.

PURPOSE: To analyze the efficacy and safety of microsecond pulsing laser therapy (MLT) in the management of central serous chorioretinopathy (CSCR) complicated by choroidal neovascularization (CNV). METHODS: Patients with CSCR complicated by CNV defined as the presence of characteristic OCT angiography features were randomly assigned to either study or control group. All patients of the study group underwent MLT targeting CNV area using navigated laser system followed by at least 6-month follow-up. Sham treatment was performed in the control group. No other treatment or anti-VEGF therapy was used during the follow-up. Main outcome measure was complete resolution of subretinal fluid at the end of follow-up. RESULTS: Twenty-three eyes (13 males and 10 females, mean age 58.2 ± 8.0 years) with a mean CNV area 0.62 ± 0.77 mm2 were included in the study group. Fourteen (60.9%) patients achieved complete resolution of SRF, five (21.7%) patients demonstrated some reduction of SRF, and four (17.4%) patients demonstrated no improvement after MLT in the study group. Twelve eyes (8 males and 4 females, mean age 59.8 ± 4.6 years) were included in the control group where none of them demonstrated resolution of SRF at the end of the follow-up (p = 0.0018 compared to the study group). No adverse effects, such as changes of CNV size, deterioration of exudation, or decline in visual acuity were observed in the study group. CONCLUSION: Microsecond pulsing laser is an effective and safe option for the treatment of CSCR complicated by relatively small CNV and achieves complete resolution of SRF in 61% of cases.

Ileal perforation at the site of peritoneal metastasis with intestinal infiltration by dual EGFR-VEGF pathway inhibition in an EGFR-mutant non-small cell lung cancer patient.

Gastrointestinal (GI) perforation including ileal perforation is a rare complication of antivascular endothelial growth factor (anti-VEGF) therapy. Risk factors of GI perforation have not been fully understood. This report highlights the case of a patient who experienced GI perforation at the site of peritoneal metastasis with intestinal infiltration immediately after treatment with dual epidermal growth factor receptor (EGFR)-VEGF pathway inhibition agents for EGFR-mutant non-small cell lung cancer (NSCLC). The administration of dual EGFR-VEGF pathway inhibition agents in EGFR mutant NSCLC patients appears to elevate the risk of GI perforation. This report provides insights into the association between EGFR mutant NSCLC and the susceptibility to GI perforation following treatment with dual EGFR-VEGF pathway inhibition agents.

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OBJECTIVES: To observe the effect of electroacupuncture(EA) on adenosine 5'-monophosphate-activated protein kinase (AMPK)/Kruppel-like factor 2 (KLF2) signaling pathway in ischemic myocardial tissues of rats, so as to explore the underlying mechanism of EA in attenuating myocardial ischemia-reperfusion injury (MIRI) through mediating angiogenesis. METHODS: Male SD rats were randomly divided into sham operation group, model group and EA group, with 10 rats in each group. The MIRI model was established by ligation of the anterior descending branch of the left coronary artery. Twenty-four hours after modeling, the rats in the EA group were given EA (2 Hz/100 Hz, 2 mA) at "Neiguan" (PC6) for 20 min each time, once a day for 5 consecutive days. Echocardiography was used to detect cardiac ejection fraction (EF) to evaluate cardiac function. HE staining was used to observe the morphological changes in rat myocardial tissue. Immunohistochemistry was used to detect the density of neovascularization in rat ischemic myocardium. Western blot and ELISA were used to detect the phosphorylated(p)-AMPK, AMPK, KLF2, vascular endothelial growth factor (VEGF) protein expression levels, and VEGF receptor 2 (VEGFR2) content in rat ischemic myocardial tissue, respectively. RESULTS: After modeling, compared with the sham operation group, rats in the model group had decreased EF(P<0.01), significant myocardial fiber damage with inflammatory cell infiltration, increased neovascular density (P<0.05), increased p-AMPK, AMPK, VEGF protein expression levels and VEGFR2 content in myocardial ischemic tissues(P<0.05, P<0.01), and decreased protein expression level of KLF2 (P<0.05). After EA intervention, compared with the model group, rats in the EA group had elevated EF(P<0.01), significantly reduced myocardial fiber damage, reduced inflammatory cell infiltration, increased neovascular density(P<0.01), and elevated p-AMPK, AMPK, KLF2, and VEGF protein expression levels and VEGFR2 content in the myocardial ischemic tissue (P<0.01). CONCLUSIONS: EA may promote angiogenesis, attenuate myocardial injury, and achieve cardioprotective effects in MIRI rats by regulating the expression of AMPK/KLF2 signaling pathway in myocardial tissues.

A biphasic drug-releasing microneedle with ROS scavenging and angiogenesis for the treatment of diabetic ulcers.

Diabetic ulcers are one of the common complications in diabetic patients. Delayed wound healing is associated with persistent pro-inflammatory M1 polarization, reduced angiogenesis and increased reactive oxygen species (ROS) in the microenvironment. Wound healing consists of multiple phases and therefore requires treatment tailored to each phase. In this study, a biphasic drug-releasing microneedle (MN) was fabricated to achieve early ROS scavenging and late accelerated angiogenesis to promote wound healing. Vascular endothelial growth factor (VEGF) was first encapsulated in methacryloylated sulfonated chitosan (SCSMA) microspheres (V@MP), and then V@MP was loaded into hyaluronic acid (HA) microneedles along with cerium dioxide nanoparticles (CONPs). Rapid dissolution of HA rapidly releases the CONPs to clear ROS, whereas the V@MP stays in the wound. SCSMA slow degradation prolongs the release of VEGF, thereby promoting angiogenesis. In vitro and in vivo studies have shown that this biphasic drug-releasing smart microneedle improves cell proliferation and migration, effectively scavenges ROS, promotes angiogenesis and tissue regeneration, and synergistically promotes M2 macrophage polarization. It provides a new delivery mode for nano-enzymes and growth factors that could be multifunctional and synergistic in the treatment of diabetic ulcers. STATEMENT OF SIGNIFICANCE: In our study, we present a microneedle (V@MP/C@MN) that can release drugs biphasically, which showed good repair ability in diabetic ulcer model. Large amounts of CONPs were rapidly released to alleviate oxidative stress during the inflammation of the wound, and V@MP stayed in the wound for a long period of time to release VEGF and promote angiogenesis in the late stage of wound healing. The results indicated that V@MP/C@MN could promote cell proliferation and migration, effectively scavenge ROS, promote angiogenesis and tissue regeneration, and synergistically promote M2 macrophage polarization, which could play a multifunctional and synergistic role in the treatment of diabetic ulcers.

Choroidal thickness after anti-vascular endothelial growth factor in typical neovascular age-related macular degeneration - A systematic review and meta-analysis.

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the world and anti-vascular endothelial growth factor (VEGF) injections have been the standard of care for the wet/neovascular variant since 2004. Currently, there are conflicting reports regarding its effect on the choroid, which supplies outer retina with oxygen and other nutrients. We synthesize available information of anti-VEGF on choroidal thickness (CT) in treatment-naïve typical neovascular AMD patients during the initial 12-week loading phase. We found 43 studies involving 1901 eyes from 1878 patients were included. Meta-analysis of 35 studies reporting CT at baseline and after 12 weeks suggested a significant decrease in CT with anti-VEGF treatment. A greater mean change with aflibercept compared to ranibizumab was found in subgroup analyses of sub-foveal CT in types 1 and 2 macular neovascularization. The long-term consequences of reduced CT in neovascular AMD remain unclear and require further targeted studies.

Demographic, Clinical, and Surgical Risk Factors of Pars Plana Vitrectomy (PPV) for Neovascular Glaucoma (NVG) Development in Type 2 Diabetes Mellitus Patients.

INTRODUCTION: Neovascular glaucoma (NVG) is a severe type characterized by forming new blood vessels on the iris and the anterior chamber angle, often resulting from ischemic retinal diseases. Pars plana vitrectomy (PPV) is a standard surgical procedure for treating various retinal and vitreous conditions. Understanding the risk factors associated with NVG development following PPV is crucial for improving patient outcomes. OBJECTIVE: To identify and evaluate demographic, clinical, and surgical risk factors associated with developing NVG following PPV. PATIENTS AND METHODS: A prospective cohort study was conducted over two years, involving 60 type 2 diabetes mellitus (T2DM) patients (31 males and 29 females; mean age 60.48±9.63 years) who underwent PPV at the Eye Clinic and Department of Clinical Immunology, University Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina. Patients were thoroughly informed about the study, and written informed consent was obtained. Comprehensive data collection included demographic information, medical history, preoperative and postoperative eye examinations, and intraoperative details. Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 21 (Released 2012; IBM Corp., Armonk, New York, United States). RESULTS:  Within 12 months postoperatively, 17 patients (28.3%) developed NVG. Significant preoperative risk factors for NVG included prolonged duration of T2DM (p=0.037), elevated preoperative intraocular pressure (IOP) (p=0.024), and higher levels of vascular endothelial growth factor (VEGF) (p=0.011). Intraoperative factors, such as sharp dissection (p=0.000) and operative complications (p=0.004), were also significantly associated with NVG development. Multivariate logistic regression analysis identified prolonged T2DM duration (OR 1.132, p=0.023), increased preoperative IOP (OR 1.192, p=0.029), elevated VEGF levels (OR 1.002, p=0.016), and intraoperative sharp dissection (OR 0.114, p=0.006) as independent risk factors. CONCLUSIONS: Multiple preoperative and intraoperative factors influence the development of NVG post-PPV. Prolonged T2DM duration, elevated preoperative IOP, high VEGF levels, and specific intraoperative techniques significantly increase the risk of NVG. These findings underscore the importance of careful preoperative assessment and tailored intraoperative strategies to mitigate NVG risk in PPV patients.

Longitudinal Changes in Diabetic Retinopathy Severity: Learnings from PANORAMA (78/80 characters including spaces).

We report changes in DR severity over time from the PANORAMA study of aflibercept versus sham in patients with moderately severe/severe NPDR that can help physicians and patients make informed management decisions for optimal outcomes.

Near-Infrared II Fluorescence Imaging Highlights Tumor Angiogenesis in Hepatocellular Carcinoma with a VEGFR-Targeted Probe.

Hepatocellular carcinoma (HCC) is typically characterized by rich vascularity, with angiogenesis playing a crucial role in its growth and invasion. Molecular imaging of specific receptors in blood vessels is crucial in HCC diagnosis. In particular, in vivo imaging utilizing the second near-infrared (NIR-II) window offers improved tissue penetration, reduced light scattering, and lower autofluorescence. Despite the great potential of the NIR-II window, developing safe and effective probes to provide better imaging performance for HCC is urgently needed. In this study, NIR-II imaging integrated with a vascular endothelial growth factor receptor (VEGFR)-targeted probe generated by combining a VEGFR-targeted peptide with indocyanine green (ICG) is used to characterize HCC-related angiogenesis at a resolution of 56.0 µm. For the first time, liver metabolic curves and parameters of liver function reserve (LFR) are obtained by fitting NIR-II fluorescence signals with high spatiotemporal resolution, showing significant differences between HCC mice and controls. Moreover, unlike ICG, the targeting probe has a targeted effect on blood vessels in vivo. The tumor-to-normal (T/N) ratio in NIR-II imaging reaches up to 3.30 after post-injection of the targeting probe. The results indicate that the VEGFR-targeted probe is a powerful tool for NIR-II fluorescence imaging to enhance early diagnosis of HCC.

Role of Plasma Angiopoietin-1 and VEGF Levels as Potential Biomarkers in Chronic Central Serous Chorioretinopathy with Macular Neovascularization.

To evaluate the plasma levels of angiopoietin-1 and vascular endothelial growth factor (VEGF) and their association with macular neovascularization (MNV) in patients with chronic central serous chorioretinopathy (cCSC). Correlations between plasma cytokine levels, CSC duration, and mean choroidal thickness (CT) were also investigated. Of the 59 patients with cCSC, 10 patients with MNV secondary to cCSC and 10 patients with cCSC without MNV were enrolled in the study. The control group included 15 healthy volunteers matched for age, sex, smoking status, and comorbidities. Chronic CSC was diagnosed based on typical findings on swept-source optical coherence tomography (OCT), fundus fluorescein angiography, and indocyanine green angiography. Additionally, all patients underwent OCT angiography to help detect MNV. Plasma angiopoietin-1 and VEGF levels were assessed using multiplex immunoassay. The plasma angiopoietin-1 levels differed between the 3 groups (p = 0.005). The angiopoietin-1 levels were lower in patients with cCSC with MNV than in controls (p = 0.006). There were no differences in the plasma VEGF levels between all the 3 groups (p = 0.329). The VEGF levels were negatively correlated with mean CT in cCSC patients with MNV (rho = -0.683, p = 0.042) but correlated positively with disease duration in patients with cCSC without MNV (rho = 0.886, p = 0.003). Our study confirms that MNV is a common complication of cCSC and provides new insights into the role of angiopoietin-1 in cCSC and MNV. Reduced angiopoietin-1 levels in cCSC patients, regardless of MNV status, highlight the importance of the Ang-Tie2 pathway in disease pathogenesis and may point to new therapeutic targets and future novel treatments to improve the management of these patients.

Baseline optical coherence tomography angiography biomarkers predict visual outcomes in treatment-naïve neovascular age-related macular degeneration patients.

This retrospective study aimed to assess different macular neovascular network characteristics in relation to changes in best corrected visual acuity (BCVA) over 3 and 12 months following treatment. Using optical coherence tomography angiography, we reviewed the medical records of 46 treatment-naïve patients with neovascular age-related macular degeneration (nAMD) who received intravitreal aflibercept injections. The change in BCVA from baseline to 3 months and 12 months after treatment was recorded. The mean vessels percentage area, junctions density, lacunarity, and fractal dimension were significantly correlated with the change of BCVA from baseline to month 3 (P = 0.003, 0.046, 0.007, and 0.005 respectively). Fractal dimension and vessels percentage area were correlated with the change of BCVA from baseline to month 12 (P = 0.023 and 0.023 respectively). The findings suggest that baseline characteristics of macular neovascular complexes may serve as predictors for BCVA changes following treatment with aflibercept in nAMD patients.

Vascular endothelial growth factor/connective tissue growth factor and proteomic analysis of aqueous humor after intravitreal conbercept for proliferative diabetes retinopathy.

AIM: To investigate the role of connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF) in the protein profile of the aqueous humor in patients with proliferative diabetic retinopathy (PDR) following intravitreal injection of conbercept. METHODS: This study included 72 PDR patients and 8 cataract patients as controls. PDR patients were divided into 3 groups according to the intervals of 3, 5, and 7d between intravitreal conbercept (IVC, 0.5 mg/0.05 mL) injection and pars plana vitrectomy (PPV) performed. Aqueous humor samples were collected before and after IVC and PPV for VEGF and CTGF levels detected with enzyme-linked immunosorbent assay (ELISA). The differential proteomics of 10 patients who underwent PPV surgery 5d after IVC and 8 normal controls was studied, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on the data, and the protein interaction network of 23 differential proteins was studied. RESULTS: Post-IVC, VEGF levels decreased and CTGF levels increased significantly in aqueous humor, with the CTGF/VEGF ratio rising significantly at all intervals. Liquid chromatography tandem mass spectrometry (LC-MS/MS) identified differentially expressed proteins between pre- and post-IVC samples. GO and KEGG analyses revealed involvement in immune response, stress response, complement and coagulation cascades, ferroptosis, and PPAR signaling pathways. PPI analysis highlighted key proteins like APOA1, C3, and transferrin (TF). ELISA assay confirmed the differential expression of proteins such as HBA1, SERPINA1, COL1A1, and ACTB, with significant changes in the IVC groups. CONCLUSION: The study demonstrates that IVC effectively reduces VEGF levels while increasing CTGF levels, thereby modifying the CTGF/VEGF ratio, and IVC significantly alters the protein profile in the aqueous humor of patients with PDR. Proteomic analysis reveals that these changes are associated with critical biological pathways and protein interactions involved in immune response, stress response, and cellular metabolism.

Inhibition of viability of human retinal microvascular endothelial cells by vialinin A under high glucose condition.

AIM: To investigate the effects of vialinin A on viability of human retinal endothelial cells (HRECs) under high glucose condition and its potential mechanism. METHODS: The HRECs were divided into four groups: normal glucose control group (NG, 5 mmol/L D-glucose), high glucose group (HG, 30 mmol/L D-glucose), HG+1 µmol/L vialinin A group, and HG+5 µmol/L vialinin A group. The cell viabilities were measured with cell counting kit-8 (CCK-8) assay for proliferation, with scratch assay for migration, and tube formation, for evaluation of the impact of vialinin A on cellular behaviour. Real-time PCR and Western blotting were used to determine the expression level of vascular endothelial growth factor (VEGF). RESULTS: The proliferative capacity and migration of HRECs was reduced by 5 µmol/L vialinin A in high glucose environment (both P<0.05). Vialinin A also inhibited high-glucose-induced tube formation of HRECs. The expression level of VEGF and PI3K in HRECs was also significantly decreased by vialinin A (P<0.05). CONCLUSION: Vialinin A inhibits the cell viability of HRECs. It may serve as a potential target for anti-angiogenic therapy.

Dexamethasone implant for refractory macular edema secondary to diabetic retinopathy and retinal vein occlusion.

AIM: To evaluate the efficacy, timing of retreatment and safety of dexamethasone (DEX) implant on macular edema (ME) secondary to diabetic retinopathy (DME) and retinal vein occlusion (RVO-ME) patients who were refractory to anti-vascular endothelial growth factor (VEGF) treatment. METHODS: This retrospective study included 37 eyes received at least one DEX implant treatment for DME or RVO-ME between January 1, 2019, and January 1, 2023. These refractory DME and RVO-ME cases received at least 5 anti-VEGF injections and failure to gain more than 5 letters or a significant reduction in central retinal thickness (CRT). The best corrected visual acuity (BCVA) and CRT were measured at baseline, and at 1, 3, 4 and 6mo post-DEX implant injection. Adverse events such as elevated intraocular pressure (IOP) and cataract were recorded. RESULTS: For RVO cases (n=22), there was a significant increase in BCVA from 0.27±0.19 to 0.35±0.20 at 6mo post-DEX injection (P<0.05) and CRT decreased from 472.1±90.6 to 240.5±39.0 µm at 6mo (P<0.0001). DME cases (n=15) experienced an improvement in BCVA from 0.26±0.15 to 0.43±0.20 at 6mo post-DEX implant injection (P=0.0098), with CRT reducing from 445.7±55.7 to 271.7±34.1 µm at 6mo (P<0.0001). Elevated IOP occurred in 45.9% of patients but was well-controlled with topical medications. No cases of cataract or other adverse events were reported. CONCLUSION: DEX implants effectively improve BCVA and reduce CRT in refractory DME and RVO-ME. Further research with larger cohorts and longer follow-up periods is needed to confirm these findings and assess long-term outcomes.

Utility of atezolizumab plus bevacizumab, carboplatin, and paclitaxel combination for the treatment of advanced non-squamous non-small cell lung cancer patients with malignant pleural effusion.

Background: Malignant pleural effusion (MPE) remains a negative prognostic factor in non-small cell lung cancer (NSCLC), even after the emergence of immune checkpoint inhibitors. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of MPE. Bevacizumab, a humanized monoclonal antibody against VEGF, is a key agent for patients who develop MPE. However, it is unclear whether MPE is a poor prognostic factor in patients with advanced non-squamous NSCLC receiving treatment with the atezolizumab plus bevacizumab, carboplatin, and paclitaxel (ABCP) regimen. Moreover, the effect of ABCP on MPE control is unknown. This study aimed to elucidate the efficacy and safety of ABCP for non-squamous NSCLC patients with MPE. Methods: We retrospectively analyzed consecutive patients with advanced non-squamous NSCLC who received treatment with ABCP (January 2019-September 2023). Patients were divided into two groups (non-MPE and MPE), and treatment outcomes were compared. In the MPE group, treatment efficacy for MPE control and toxicity were evaluated. Results: Of the 46 patients enrolled, 17 and 29 were included in the non-MPE and MPE groups, respectively. The objective response and disease control rates were not significantly different between the non-MPE and MPE groups (76.5% vs. 51.7%, P=0.13; 88.2% vs. 82.8%, P>0.99; respectively). Similarly, the median progression-free survival and median overall survival were not significantly different (9.9 vs. 10.1 months, P=0.87; 16.0 vs. 19.9 months, P=0.87, respectively). In the MPE group, 25 patients (86.2%) achieved MPE control lasting >8 weeks from the initiation of treatment with ABCP; the median progression-free survival without an unequivocal increase in MPE was 15.0 months. The incidence rates of grade ≥3 non-immune- and immune-related adverse events were 83% and 17%, respectively. There was no treatment-related death. Conclusions: The ABCP regimen may be a promising treatment option for non-squamous NSCLC patients with MPE.