Structural Prediction and Antigenic Analysis of ROP18, MIC4, and SAG1 Proteins to Improve Vaccine Design against Toxoplasma gondii: An In silico Approach.

BACKGROUND: Toxoplasmosis is a cosmopolitan infectious disease in warm-blooded mammals that poses a serious worldwide threat due to the lack of effective medications and vaccines. AIMS: The purpose of this study was to design a multi-epitope vaccine using several bioinfor-matics approaches against the antigens of Toxoplasma gondii (T. gondii). METHODS: Three proteins of T. gondii, including ROP18, MIC4, and SAG1, were analyzed to predict the most dominant B- and T-cell epitopes. Finally, we designed a chimeric immunogen RMS (ROP18, MIC4, and SAG1) using some domains of ROP18 (N377-E546), MIC4 (D302-G471), and SAG1 (T130-L299) linked by rigid linker A (EAAAK) A. Physicochemical prop-erties, secondary and tertiary structures, antigenicity, and allergenicity of RMS were predicted utilizing immunoinformatic tools and servers. RESULTS: RMS protein had 545 amino acids with a molecular weight (MW) of 58,833.46 Da and a theoretical isoelectric point (IP) of 6.47. The secondary structure of RMS protein con-tained 21.28% alpha-helix, 24.59% extended strand, and 54.13% random coil. In addition, eval-uation of antigenicity and allergenicity showed the protein to be an immunogen and non-aller-gen. The results of the Ramachandran plot indicated that 76.4%, 12.9%, and 10.7% of amino acid residues were incorporated in the favored, allowed, and outlier regions, respectively. ΔG of the best-predicted mRNA secondary structure was -593.80 kcal/mol, which indicated that a stable loop was not formed at the 5' end. CONCLUSION: Finally, the accuracy and precision of the in silico analysis must be confirmed by successful heterologous expression and experimental studies.

Clinicoepidemiological Profile of Retinopathy of Prematurity.

Purpose In previously performed studies, retinopathy of prematurity (ROP) has been shown to occur postpartum. As a result, mechanical ventilation and oxygen dependence were eventually connected to the development of ROP in these preterm children, and ROP prevalence is on the rise globally. Despite various improvements in childcare, ROP still tends to arise due to various risk factors associated with the disease. So, clinically the research was performed to determine the clinical and epidemiological profile of ROP. Materials and methods A total of 268 participants were to be enrolled in the study. It was an observational, cross-sectional study carried out at Department of Ophthalmology and Neonatal Intensive Care Unit in Veer Surendra Sai Institute of Medical Sciences and Research Centre, Burla, Sambalpur, Odisha, India. Ethical approval was provided on 30 November 2019. Results Overall 123 (46%) infants out of 268 infants developed retinopathy of prematurity. Majorly, the infants had stage 1 and stage 2 ROP. Most of the infants were male. Birth weight in ROP patients was 1000 g or less in 54% of infants, 1000-1500 g in 46% of infants and >1500 g in 33% of infants. Gestational age was found to be a predictor of retinopathy of prematurity. The adverse events that were found to be associated with retinopathy of prematurity were sepsis (53%), respiratory distress syndrome (RDS) (54.6%), intraventricular haemorrhage (IVH) (60%), anaemia (61.5%). Conclusion It has been observed that babies with higher birth weights and older gestations are also susceptible to developing ROP. Therefore, the greater birth weight newborns up to 1750 g and older gestational age babies >34 weeks should also be included in the screening criteria, especially if they have risk factors such as oxygen supplementation, sepsis, RDS, and anaemia.

Stereoselectivity Control Interplay in Racemic Lactide Polymerization by Achiral Al-Salen Complexes.

The origin of stereocontrol in ring opening polymerization (ROP) of racemic lactide (rac-LA) promoted by achiral aluminium-based catalysts has been explained through DFT calculations combined with a molecular descriptor (%VBur) and the activation strain model (ASM-NEDA) analysis. The proposed chain end control (CEC) model suggests that the ligand framework adopts a chiral configuration mimicking the enantiomorphic site control (ESC) while also incorporating control of the last inserted monomer unit. It is found that the ligand wrapping mode around the aluminium centre is dictated by the monomer configuration (R,R-LA and S,S-LA). A good correlation with experimental data is achieved only when accounting for the ligand dynamic features and its steric influences, as highlighted by %VBur steric maps and ASM-NEDA analysis. Understanding the ESC and CEC interplay is an important target for obtaining stereoselective ROP polymerization for the synthesis of biodegradable materials with tailored properties.

Plant Rho GTPase ROP6 Is Essential for Manganese Homeostasis in Arabidopsis.

Manganese (Mn) is an indispensable mineral for plant growth and development. However, plants cultivated in acidic and poorly drained soils are vulnerable to Mn2+ toxicity due to its heightened increased bioavailability. Despite the crucial roles of the Rho of plant (ROP) GTPases in various cellular processes, their precise function in regulating Mn homeostasis remains elusive. In this study, we unveil a novel ROP6 GTPase signalling pathway that profoundly influences Mn phytotoxicity tolerance in Arabidopsis. Remarkably, the rop6 and dominant-negative ROP6 (rop6DN) mutant plants displayed a dramatically sensitive phenotype to Mn toxicity, whereas ROP6-overexpression and constitutively activated ROP6 (rop6CA) lines exhibited enhanced Mn stress tolerance. Immunoblot analysis corroborated that the ROP6 protein, especially the active form of ROP6, increased in abundance in the presence of high Mn levels. Further, we identified that ROP6 physically interacted and colocalized with Metal Tolerance Protein 8 (MTP8) in vivo. Mn transport complementation assays in yeast, combined with biochemical analyses, emphasized the essentiality of ROP6 for MTP8's transport activity. In addition, genetic analyses indicated that ROP6 acted upstream of MTP8 in the regulatory cascade. Collectively, our findings elucidate that ROP6 GTPase signalling positively modulates and enhances Mn stress tolerance in plants.

Reduction of pathological retinal neovascularization, vessel obliteration, and artery tortuosity by PEDF protein in an oxygen-induced ischemic retinopathy rat model.

Retinopathy of prematurity (ROP) is a severe retinal disease in premature infants characterized by pathological neovascularization, obliteration of retinal vessels and increased vessel tortuosity. Currently, there are no completely satisfactory treatments for ROP. Pigment epithelium-derived factor (PEDF), a potent inhibitor of angiogenesis, appears late in gestation and its deficiency may be linked to development of ROP. This study investigates the preclinical efficacy of PEDF protein alone or in combination with VEGF antagonists for treating ROP. The safety of PEDF protein in the rat eye was assessed using functional in vivo measurements and histology. The efficacy of intravitreal injections (IVI) of various treatments was evaluated in a rat oxygen-induced retinopathy (OIR) model using in vivo imaging and flatmount analyses. No functional or histological side-effects were found in rat eyes after intravitreal PEDF protein injection. PEDF protein alone or combined with anti-VEGF drugs significantly reduced pathological neovascularization and vessel obliteration, comparable to the effects of anti-VEGF drugs alone. Regarding arterial tortuosity, treatment with a combination of PEDF, and VEGF antagonist was more effective than treatment with anti-VEGF alone. IVI of PEDF protein is safe. PEDF protein alone or combined with VEGF antagonists shows similar efficacy in reducing pathological neovascularization and vessel obliteration as anti-VEGF agents. Furthermore, only treatments involving PEDF protein, alone or with VEGF antagonists, significantly improved the quality of retinal vasculature. Thus, PEDF protein alone or combined with anti-VEGF agents presents a promising alternative to current anti-VEGF treatments for ROP.

Heterologous immunization targeting the CST1 antigen confers better protection than ROP18 in mice.

Aim: To evaluate the protective efficacy induced by heterologous immunization with recombinant baculoviruses or virus-like particles targeting the CST1 and ROP18 antigens of Toxoplasma gondii.Materials & methods: Recombinant baculovirus and virus-like particle vaccines expressing T. gondii CST1 or ROP18 antigens were developed to evaluate protective immunity in mice upon challenge infection with 450 Toxoplasma gondii (ME49).Results: Immunization with CST1 or ROP18 vaccines induced similar levels of T. gondii-specific IgG and IgA responses. Compared with ROP 18, CST1 vaccine showed better antibody-secreting cell response, germinal center B cell activation, and significantly reduced brain cyst burden and body weight loss.Conclusion: Our findings suggest that CST1 heterologous immunization elicited better protection than ROP18, providing important insight into improving the toxoplasmosis vaccine design strategy.

[Box: see text].

Red Blood Cell Transfusion for Incidence of Retinopathy of Prematurity: Prospective Multicenter Cohort Study.

Background: Retinopathy of prematurity (ROP) is a leading cause of visual impairment and blindness in preterm infants. Objective: This study sought to investigate the association between red blood cell (RBC) transfusion and ROP in very preterm infants (VPIs) to inform clinical strategies for ROP prevention and treatment. Methods: We designed a prospective multicenter cohort study that included VPIs and follow-up data from January 2017 to December 2022 at 3 neonatal clinical medicine centers. They were categorized into a transfusion group (infants who received an RBC transfusion within 4 wk) and a nontransfusion group. The relationship between RBC transfusion and ROP incidence was assessed using binary logistic regression, with subgroup analyses based on gestational age, birth weight, sex, and sepsis status. Inverse probability of treatment weighting and propensity score matching were applied to account for all potential confounding factors that could affect ROP development, followed by sensitivity analysis. Results: The study included 832 VPIs, including 327 in the nontransfusion group and 505 in the transfusion group. The transfusion group had a lower average birth weight and gestational age and a greater incidence of ROP, ≥stage 2 ROP, and severe ROP. Logistic regression analysis revealed that the transfusion group had a significantly greater risk of ROP (adjusted odds ratio [aOR] 1.70, 95% CI 1.14-2.53, P=.009) and ≥stage 2 ROP (aOR 1.68, 95% CI 1.02-2.78, P=.04) but not severe ROP (aOR 1.75, 95% CI 0.61-5.02, P=.30). The trend analysis also revealed an increased risk of ROP with an increasing number of transfusions and a larger volume of blood transfused (P for trend<.001). Subgroup analyses confirmed a consistent trend, with the transfusion group at a higher risk for ROP across all subgroups. Inverse probability of treatment weighting and propensity score matching analyses supported the initial findings. Conclusions: For VPIs, RBC transfusion significantly increases the risk of ROP, and the risk increases with an increasing number of transfusions and volume of blood transfused.

'All for the well-being of the infant': nurses' perceptions of preterm infants' eye examinations: a phenomenographic study.

BACKGROUND: Preterm infants are at risk of complications due to their prematurity and Retinopathy of Prematurity (ROP) is one of them. To discover and treat ROP the preterm infants regularly undergo eye examinations. Nurses are responsible for the infants' care during this painful and stressful procedure. AIM: The aim of this study was to explore nurses' perceptions of preterm infants' eye examinations. METHODS: Data were collected through semi-structured interviews with 10 nurses experienced in participating in preterm infants' eye examinations. Data were analysed using a phenomenographic approach. RESULTS: The results showed several perceptions of the eye examinations, and the analysis resulted in four descriptive categories: Infants are affected by the eye examination; Nurses have comprehensive overall responsibility for the infants; Parents are important to their infants, but they need support to fulfil their parental role, and Collaboration is important for the examination's favourable outcome. The category Nurses have comprehensive overall responsibility for the infants was regarded as the most comprehensive, covering all the other categories. CONCLUSIONS: Nurses felt a great responsibility during a painful and stressful procedure for preterm infants. Infants' well-being could be better protected by interprofessional collaboration, improved nursing care and involved parents.

Cord blood transfusions in extremely low gestational age neonates to reduce severe retinopathy of prematurity: results of a prespecified interim analysis of the randomized BORN trial.

BACKGROUND: Preterm infants are at high risk for retinopathy of prematurity (ROP), with potential life-long visual impairment. Low fetal hemoglobin (HbF) levels predict ROP. It is unknown if preventing the HbF decrease also reduces ROP. METHODS: BORN is an ongoing multicenter double-blinded randomized controlled trial investigating whether transfusing HbF-enriched cord blood-red blood cells (CB-RBCs) instead of adult donor-RBC units (A-RBCs) reduces the incidence of severe ROP (NCT05100212). Neonates born between 24 and 27 + 6 weeks of gestation are enrolled and randomized 1:1 to receive adult donor-RBCs (A-RBCs, arm A) or allogeneic CB-RBCs (arm B) from birth to the postmenstrual age (PMA) of 31 + 6 weeks. Primary outcome is the rate of severe ROP at 40 weeks of PMA or discharge, with a sample size of 146 patients. A prespecified interim analysis was scheduled after the first 58 patients were enrolled, with the main purpose to evaluate the safety of CB-RBC transfusions. RESULTS: Results in the intention-to-treat and per-protocol analysis are reported. Twenty-eight patients were in arm A and 30 in arm B. Overall, 104 A-RBC units and 49 CB-RBC units were transfused, with a high rate of protocol deviations. A total of 336 adverse events were recorded, with similar incidence and severity in the two arms. By per-protocol analysis, patients receiving A-RBCs or both RBC types experienced more adverse events than non-transfused patients or those transfused exclusively with CB-RBCs, and suffered from more severe forms of bradycardia, pulmonary hypertension, and hemodynamically significant patent ductus arteriosus. Serum potassium, lactate, and pH were similar after CB-RBCs or A-RBCs. Fourteen patients died and 44 were evaluated for ROP. Ten of them developed severe ROP, with no differences between arms. At per-protocol analysis each A-RBC transfusion carried a relative risk for severe ROP of 1.66 (95% CI 1.06-2.20) in comparison with CB-RBCs. The area under the curve of HbF suggested that HbF decrement before 30 weeks PMA is critical for severe ROP development. Subsequent CB-RBC transfusions do not lessen the ROP risk. CONCLUSIONS: The interim analysis shows that CB-RBC transfusion strategy in preterm neonates is safe and, if early adopted, might protect them from severe ROP. TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov on October 29, 2021. Identifier number NCT05100212.

In Silico Analysis of the ROP29 Protein as a Vaccine Candidate Against Toxoplasma gondii.

The progression of Toxoplasma gondii (T. gondii) invasion is aided by rhoptry proteins (ROPs), which are also crucial for the parasite's survival in host cells. In this study, in silico analysis was performed to examine the various aspects of the ROP29 protein, such as physicochemical properties, potential T- and B-cell epitopes, and other significant features. The research revealed that there were 55 possible sites for posttranslational modification in the ROP29 protein. The secondary structure of the ROP29 protein consists of a random coil, an alpha-helix, and an extended strand, which account for 49.69%, 36.81%, and 13.50%, respectively. Moreover, a number of putative T- and B-cell epitopes for ROP29 were found. The Ramachandran plot showed that 88.91% (crude model) and 97.54% (refine model) of the amino acid residues were located in the favored regions. Also, the testing of this protein's antigenicity and allergenicity showed that it was nonallergenic and immunogenic. Our results suggested that employing in silico tools to apply structural and functional predictions to the ROP29 protein can lower the likelihood that laboratory investigations will fail. This research served as a crucial foundation for further research. More research is required in the future in suitable animal model employing ROP29 alone or in combination with other antigens.

Vascular development analysis: a study for tertiary anti-vascular endothelial growth factor therapy after second reactivation of retinopathy of prematurity.

Purpose: To observe the vascular development results of tertiary anti-vascular endothelial growth factor (anti-VEGF) therapy following spontaneous second reactivation of retinopathy of prematurity (ROP). Methods: This retrospective study included 22 infants (42 eyes) with Type 1 or aggressive ROP (A-ROP) who received three anti-VEGF drug treatments for ROP from January 2018 to December 2022. The vascular growth, possible associated risk factors, and the retinal vascularization (DB/DF ratio) were assessed. Results: The mean follow-up was 17.6 months. After the 3rd intravitreal injection, seven eyes showed complete vascularization (Group 1), while the remaining 35 eyes demonstrated persistent avascular retina (PAR) (Group 2). In Group 2, 17 eyes maintained a stable state and were classified in the regression subgroup. The other 18 eyes developed a 3rd reactivation (reactivation subgroup) and were treated with laser photocoagulation (LPC).Birth weight (BW) was significantly lower in Group 2 than in Group 1 (p < 0.001). The decision tree analysis shows that only infants weighing more than 1,250 g (17.50%) had a chance to achieve complete retinal vascularization. The possibility of PAR was higher in patients with BW <1,250 g than ≥1,250 g (70.00% vs. 12.50%). In addition, most infants with BW ≥ 1,290 g and initial ROP disease in Zone I or posterior Zone II developed PAR. Conclusion: Tertiary IVR can successfully treat a second ROP reactivation and improve peripheral retinal vascularization. BW is the most significant factor related to complete retinal vascularization. Our decision tree model may be helpful in predicting the prognosis of anti-VEGF drugs in the event of a second ROP reactivation.

An Interpretable System for Screening the Severity Level of Retinopathy in Premature Infants Using Deep Learning.

Accurate evaluation of retinopathy of prematurity (ROP) severity is vital for screening and proper treatment. Current deep-learning-based automated AI systems for assessing ROP severity do not follow clinical guidelines and are opaque. The aim of this study is to develop an interpretable AI system by mimicking the clinical screening process to determine ROP severity level. A total of 6100 RetCam Ⅲ wide-field digital retinal images were collected from Guangdong Women and Children Hospital at Panyu (PY) and Zhongshan Ophthalmic Center (ZOC). A total of 3330 images of 520 pediatric patients from PY were annotated to train an object detection model to detect lesion type and location. A total of 2770 images of 81 pediatric patients from ZOC were annotated for stage, zone, and the presence of plus disease. Integrating stage, zone, and the presence of plus disease according to clinical guidelines yields ROP severity such that an interpretable AI system was developed to provide the stage from the lesion type, the zone from the lesion location, and the presence of plus disease from a plus disease classification model. The ROP severity was calculated accordingly and compared with the assessment of a human expert. Our method achieved an area under the curve (AUC) of 0.95 (95% confidence interval [CI] 0.90-0.98) in assessing the severity level of ROP. Compared with clinical doctors, our method achieved the highest F1 score value of 0.76 in assessing the severity level of ROP. In conclusion, we developed an interpretable AI system for assessing the severity level of ROP that shows significant potential for use in clinical practice for ROP severity level screening.

Risk factors for the time to development of retinopathy of prematurity in premature infants in Iran: a machine learning approach.

BACKGROUND: Retinopathy of prematurity (ROP), is a preventable leading cause of blindness in infants and is a condition in which the immature retina experiences abnormal blood vessel growth. The development of ROP is multifactorial; nevertheless, the risk factors are controversial. This study aimed to identify risk factors of time to development of ROP in Iran. METHODS: This historical cohort study utilized data from the hospital records of all newborns referred to the ROP department of Farabi Hospital (from 2017 to 2021) and the NICU records of infants referred from Mahdieh Hospital to Farabi Hospital. Preterm infants with birth weight (BW) ≤ 2000 g or gestational age (GA) < 34 wk, as well as selected infants with an unstable clinical course, as determined by their pediatricians or neonatologists, with BW > 2000 g or GA ≥ 34 wk. The outcome variable was the time to development of ROP (in weeks). Random survival forest was used to analyze the data. RESULTS: A total of 338 cases, including 676 eyes, were evaluated. The mean GA and BW of the study group were 31.59 ± 2.39 weeks and 1656.72 ± 453.80 g, respectively. According to the criteria of minimal depth and variable importance, the most significant predictors of the time to development of ROP were duration of ventilation, GA, duration of oxygen supplementation, bilirubin levels, duration of antibiotic administration, duration of Total Parenteral Nutrition (TPN), mother age, birth order, number of surfactant administration, and on time screening. The concordance index for predicting survival of the fitted model was 0.878. CONCLUSION: Our findings indicated that the duration of ventilation, GA, duration of oxygen supplementation, bilirubin levels, duration of antibiotic administration, duration of TPN, mother age, birth order, number of surfactant administrations, and on time screening are potential risk factors of prognosis of ROP. The associations between identified risk factors were mostly nonlinear. Therefore, it is recommended to consider the nature of these relationships in managing treatment and designing early interventions.

Surgical Outcomes of Rhegmatogenous Retinal Detachment Associated with Regressed Retinopathy of Prematurity.

Objectives: To evaluate the characteristics and surgical outcomes of late-onset rhegmatogenous retinal detachment (RRD) associated with regressed retinopathy of prematurity (ROP) and the status of fellow eyes. Materials and Methods: Retrospective review of consecutive cases undergoing surgery for regressed ROP-related RRD and the fellow eyes between 2012-2022. Demographic data, fundus findings, retinal detachment characteristics, surgical procedures, and anatomic and functional outcomes were analyzed. Anatomic success was defined as retinal attachment after silicone oil removal at final follow-up. Results: Fifteen eyes of 14 patients with a history of regressed ROP underwent surgical repair for RRD at a mean age of 12 (range, 3-26) years. Primary surgical intervention yielded a 53% failure rate overall. This rate was 33% for scleral buckling (SB), 100% for pars plana vitrectomy (PPV), and 40% for combined SB-PPV surgery. Eyes with posterior cicatricial changes and/or proliferative vitreoretinopathy (PVR) demonstrated a higher tendency for recurrence. The final anatomic success rate was 73% after a mean number of 2.3 (range, 1-5) surgeries. The chances of restoring useful vision diminished with repeated surgery despite the improvement in anatomic success. In the fellow eyes, peripheral retinal pathologies were universally observed, with posterior cicatricial changes noted in 33%. Conclusion: The study reveals a significant initial failure rate in surgical treatment of cases with late-onset RRD associated with regressed ROP, particularly in eyes with posterior cicatricial changes or PVR, suggesting the need for a combined surgical approach as an initial strategy in such high-risk cases. The consistent presence of retinal abnormalities in fellow eyes calls for proactive monitoring and potential prophylactic intervention.

Circulating VEGF-A Levels in Relation to Retinopathy of Prematurity and Treatment Effects: A Systematic Review and Meta-Analysis.

Topic: Retinopathy of prematurity (ROP) is a severe retinal vascular disorder affecting preterm infants, potentially leading to retinal detachment and blindness. This review aims to elucidate the relationship between systemic VEGF levels and ROP. Clinical Relevance: This systematic review aims to consolidate evidence from available studies to guide future research and inform clinical practice. In particular, the role of circulating VEGF-A levels in predicting ROP onset and progression, and evaluating the impact of anti-VEGF therapy on these levels, is crucial in ensuring efficacy and safety in patient care. Methods: Scopus and PubMed were searched to identify studies investigating circulating VEGF-gene products in ROP patients using immunologic assays. Two authors independently screened the literature and extracted data, employing a random-effects meta-analysis to compare VEGF levels as the ratio of means between ROP patients and controls before and after treatment, heterogeneity was reported by I2-statistics. Risks of bias and publication bias were assessed using Quality Assessment of Diagnostic Accuracy Studies-2 and funnel plots/Egger's tests, respectively. Results: Out of 941 papers, 54 were included, with 26 providing posttreatment data and 31 providing biomarker data. Findings show a significant decrease in VEGF-A levels in the first week after ROP treatment (ratio of means [95% confidence interval] 0.34 [0.25-0.45], I2 = 97%, 17 publications). Anti-VEGF therapy showed a significantly more pronounced decrease (0.31 [0.25-0.38], I2 = 40%, 7 publications) than laser treatment in the first week after treatment (0.77 [0.61-0.97], I2 = 42%, 2 publications, subgroup difference, P < 0.01), among studies with a low risk of bias. Serum samples demonstrated a more marked decrease in VEGF-A than plasma (subgroup difference P < 0.01). However, the use of blood VEGF-A concentration as a biomarker for ROP prediction has shown inconsistent trends. The risk of bias mainly stems from unclear patient selection and lack of sample timing or analytical method details. Conclusion: While anti-VEGF treatment significantly reduced blood VEGF-A levels in the first week post-ROP treatment, blood VEGF-A levels did not consistently predict ROP development. Heterogeneity in the results underscores the need for optimized analytical methods and emphasizes the importance of considering individual variation in VEGF-A concentrations independent of ROP diagnosis. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The anticancer mechanisms of Toxoplasma gondii rhoptry protein 16 on lung adenocarcinoma cells.

Lung adenocarcinoma is the most prevalent subtype of lung cancer, which is the leading cause of cancer-related mortality worldwide. Toxoplasma gondii (T.gondii) Rhoptry protein 16 (ROP16) has been shown to quickly enter the nucleus, and through activate host cell signaling pathways by phosphorylation STAT3 and may affect the survival of tumor cells. This study constructed recombinant lentiviral expression vector of T. gondii ROP16 I/II/III and stably transfected them into A549 cells, and the effects of ROP16 on cell proliferation, cell cycle, apoptosis, invasion, and migration of A549 cells were explored by utilizing CCK-8, flow cytometry, qPCR, Western blotting, TUNEL, Transwell assay, and cell scratch assay, and these effects were confirmed in the primary human lung adenocarcinoma cells from postoperative cancer tissues of patients. The type I and III ROP16 activate STAT3 and inhibited A549 cell proliferation, regulated the expression of p21, CDK6, CyclinD1, and induced cell cycle arrest at the G1 phase. ROP16 also regulated the Bax, Bcl-2, p53, cleaved-Caspase3, and Caspase9, inducing cell apoptosis, and reduced the invasion and migration of A549 cells, while type II ROP16 protein had no such effect. Furthermore, in the regulation of ROP16 on primary lung adenocarcinoma cells, type I and III ROP16 showed the same anticancer potential. These findings confirmed the anti-lung adenocarcinoma effect of type I and III ROP16, offering fresh perspectives on the possible application of ROP16 as a target with adjuvant therapy for lung adenocarcinoma and propelling the field of precision therapy research toward parasite treatment of tumors.

Predictive Role of Fluorescein Angiography in Retinopathy of Prematurity.

BACKGROUND: Fluorescein angiography (FA) has been a pivotal tool for studying the pathophysiology of retinopathy of prematurity (ROP) in vivo. We examined the course of ROP using FA to assess the predictive value of angiographic features. METHODS: This is an observational retrospective cohort study of eyes screened for ROP with a binocular indirect ophthalmoscope and FA. RetCam fundus imaging and video digital fluorescein angiography were performed in the neonatal intensive care unit of Santa Maria Hospital of Perugia. The masked grading of the FA images was retrospectively conducted by two ROP expert ophthalmologists. RESULTS: A total of 80 eyes of 40 patients were included for this study. Among the angiographic features evaluated, leakage, shunts, and tangles were predictive of the development of treatment-requiring ROP (p < 0.05). CONCLUSIONS: FA can add to our understanding of the evolution of vascular abnormalities in the course of ROP and can help predict which eyes will go on to treatment.

Myopia dominance in preterm infants without and with retinopathy of prematurity: Indian Twin Cities ROP study (ITCROPS) report number 15.

PURPOSE: To investigate the refractive error profile and progression in infants with different stages of ROP, without ROP, and those who received laser treatment for ROP. METHODS: This retrospective study included the data from 838 infants (baseline mean age 3.7 ± 5.4 months) who had premature birth. Among these, 433 infants had one of the stages of ROP and 405 had no ROP. Infants with ROP were sub-divided into stage 1 (n = 76), stage 2 (n = 142), and stage 3 (n = 136) and aggressive posterior ROP, (APROP, n = 79). They were further categorized into those who received treatment (n = 213) and with no treatment for ROP (n = 220). Data from a subset of 117 infants was used to assess the 1-year change in the refractive error. Myopia was defined as spherical equivalent refraction (SER) <-0.50 diopters (D). Eyes with retinal detachment were excluded. RESULTS: Higher percentage of myopia was found in infants with ROP (39.7%) than no-ROP (19.8%), and it increased with severity of ROP: stage 1: 19.7%, stage 2: 33.8%, stage 3: 45.6%, and 59.5% in APROP. Percentage of myopia doubled in those who underwent treatment for ROP (54.5%) compared to no-treatment group (25.5%). Mean (± SEM) change in SER after 1 year was significantly greater in infants with APROP -4.55 ± 1.38 D and stage 3 ROP -2.28 ± 0.57 D compared to other stages and no-ROP. CONCLUSION: Myopia was found to be more prevalent in preterm infants in general, and more in the presence of ROP. Preterm infants without or with any form of ROP, particularly those with severe form of ROP and those who received treatment require meticulous periodic refractive error assessment.

Comparison of Intravitreal Ranibizumab and Laser Photocoagulation in the Treatment of Type I Retinopathy of Prematurity in Malaysia: A One-Year Follow-Up Study.

PURPOSE: This study aimed to evaluate the treatment efficacy, anatomical outcomes, and refractive outcomes of laser photocoagulation (LPC) and intravitreal ranibizumab (IVR) in the treatment of type I retinopathy of prematurity (ROP) at one-year follow-up. METHODS: This is a retrospective study on the treatment of type I ROP and aggressive ROP (A-ROP) using LPC or IVR in three Malaysian hospitals providing pediatric ophthalmology services from January 2019 to December 2021. Information on gestational age, birth weight, ROP zone and stage, and underlying comorbidities was collected. Parameters for evaluating treatment efficacy include the time taken to achieve complete regression, the regression rate, and the reactivation rate. The anatomical and refractive outcomes were evaluated at one year of adjusted age. RESULTS: This study included 92 eyes from 46 infants. Of these, 42 eyes received LPC as the initial treatment, while 50 eyes underwent IVR. A higher percentage of infants with cardiovascular disease were treated with IVR (66.7%) compared to LPC (40%) (p<0.05). However, there were no significant differences in gestational age, birth weight, respiratory distress syndrome, sepsis, or intraventricular hemorrhage between the two treatment groups (p>0.05). Infants treated with LPC had a higher regression rate than those treated with IVR, but they were also significantly more myopic and had worse best-corrected visual acuity (BCVA). Conversely, infants treated with IVR experienced a significantly higher reactivation rate compared to those treated with LPC. Logistic regression analysis showed no significant associations between gestational age, birth weight, plus disease, zone 1 ROP, and the choice of initial treatment with the reactivation of ROP. CONCLUSIONS: Both LPC and IVR effectively treat type I ROP in infants, with IVR yielding superior anatomical and refractive outcomes and LPC offering a lower reactivation rate. Understanding individual patient characteristics is crucial for treatment selection.

The Role of HIF-1α in Retinopathy of Prematurity: A Review of Current Literature.

Hypoxia-inducible factor (HIF) plays a crucial role in regulating oxygen sensing and adaptation at the cellular level, overseeing cellular oxygen homeostasis, erythrocyte production, angiogenesis, and mitochondrial metabolism. The hypoxia-sensitive HIF-1α subunit facilitates tissue adaptation to hypoxic conditions, including the stimulation of proangiogenic factors. Retinopathy of prematurity (ROP) is a proliferative vascular disease of the retina that poses a significant risk to prematurely born children. If untreated, ROP can lead to retinal detachment, severe visual impairment, and even blindness. The pathogenesis of ROP is not fully understood; however, reports suggest that premature birth leads to the exposure of immature ocular tissues to high levels of exogenous oxygen and hyperoxia, which increase the synthesis of reactive oxygen species and inhibit HIF expression. During the ischemic phase, HIF-1α expression is stimulated in the hypoxia-sensitive retina, causing an overproduction of proangiogenic factors and the development of pathological neovascularization. Given the significant role of HIF-1α in the development of ROP, considering it as a potential molecular target for therapeutic strategies appears justified. This review synthesizes information from the last six years (2018-2024) using databases such as PubMed, Google Scholar, and BASE, focusing on the role of HIF-1α in the pathogenesis of ROP and its potential as a target for new therapies.