The role of EZH2 in ocular diseases: a narrative review.

EZH2, acting as a catalytic subunit of PRC2 to catalyze lysine 27 in histone H3, induces the suppression of gene expression. EZH2 can regulate cell proliferation and differentiation of retinal progenitors, which are required for physiological retinal development. Meanwhile, an abnormal level of EZH2 has been observed in ocular tumors and other pathological tissues. This review summarizes the current knowledge on EZH2 in retinal development and ocular diseases, including inherited retinal diseases, ocular tumors, corneal injury, cataract, glaucoma, diabetic retinopathy and age-related retinal degeneration. We highlight the potential of targeting EZH2 as a precision therapeutic target in ocular diseases.

EZH2 is a protein that helps to regulate the activity of genes in cells. It works as a part of a complex called PRC2 to control a chemical group called lysine 27 in histone H3 and then inhibit the expression of genes. EZH2 is important for the normal development of the retina. Abnormal levels of EZH2 are associated with various eye diseases. This review summarizes the role of EZH2 in different ocular diseases and the potential mechanisms. Targeting EZH2 may be a novel way to treat or prevent ocular diseases.

Application of Mono- and Disaccharides in Drug Targeting and Efficacy.

Carbohydrates and their conjugates play important roles in many biological processes including fertilization, differentiation, development, immune response, and infection. Their activities are largely dependent on the properties of terminal mono- or disaccharides. Galactose, mannose, fucose, glucose, sialic acid, etc., are commonly used as powerful scaffolds installed on drug molecules for targeting specific tissues including brain, liver, and cancers, and as epitopes for enhancing the targeting of various vaccines. This review focuses on the influence of their structural variations, including changes in sugar type, substituent groups and their positions, as well as length of linker portion, on the targeting of drugs or their efficacy. Particular attention is paid to the targeting properties of mono- and disaccharides applied in drug design and discovery.

Interaction of maternal smoking and preterm birth on future risk of maternal cardiovascular disease: A population-based record linkage study.

BACKGROUND: While associations of smoking and preterm birth (PTB) with maternal cardiovascular disease (CVD) risks have been established, it is unknown whether the coexistence of these two conditions could synergistically increase the risks. METHODS: We linked birth records of 902,008 mothers with singleton infants during 1994-2011 in New South Wales, Australia to the mothers' subsequent CVD hospitalisation or death. Multiplicative interaction was tested through an interaction term in a multivariate Cox-proportional hazard regression model, while additive interaction was assessed by calculating the synergy index. RESULTS: Relative to never-smokers with term babies, the CVD risk in ever-smokers with PTBs (hazard ratio (HR) 3.35, 95% confidence interval (CI) 2.96-3.80) was significantly greater than the sum of risks in ever-smokers with term babies (HR 2.10, 95% CI 1.96-2.24) and in never-smokers with PTBs (HR 1.73, 95% CI 1.55-1.93), indicating an additive interaction (synergy index = 1.29, 95% CI 1.05-1.58). In ever-smokers, the association was stronger for extremely PTB (HR 3.83, 95% CI 3.23-4.69) than moderately PTB (HR 3.18, 95% CI 2.76-3.66), and for ≥2 PTB (HR 4.47, 95% CI 3.39-5.88) than one PTB (HR 3.20, 95% CI 2.81-3.64). CONCLUSION: Maternal smoking and PTB interact on the additive scale to synergistically increase maternal CVD risks. The interaction was dose-dependent according to both the severity and number of PTBs.

Pregnancy Outcomes in Women With Rare Autoimmune Diseases.

OBJECTIVE: To examine pregnancy outcomes and pregnancy-related health service utilization among women with rare autoimmune diseases. METHODS: This population-based cohort study of an Australian obstetric population (2001-2011) used birth records linked to hospital records for identification of rare autoimmune diseases including systemic vasculitis, vasculitis limited to the skin, Sjögren's syndrome, systemic sclerosis, Behçet's disease, polymyositis/dermatomyositis, and other systemic involvement of connective tissue. We excluded births in women with systemic lupus erythematosus or rheumatoid arthritis as well as births occurring ≥6 months before the diagnosis of the rare autoimmune disease. Modified Poisson regression was used to compare study outcomes between women with autoimmune diseases and the general obstetric population. RESULTS: There were 991,701 births, including 409 births (0.04%) in 293 women with rare autoimmune diseases. Of the 409 births, 202 (49%) were delivered by cesarean section and 72 (18%) were preterm; these rates were significantly higher than those in the general obstetric population (28% and 7%, respectively). Compared to the general population, women with autoimmune diseases had higher rates of hypertensive disorders, antepartum hemorrhage, and severe maternal morbidity and required longer hospitalization at delivery, more hospital admissions, and tertiary obstetric care. Compared to other infants, those whose mothers had a rare autoimmune disease were at increased risk of admission to a neonatal intensive care unit, severe neonatal morbidity, and perinatal death. CONCLUSION: While the majority of women with rare autoimmune diseases delivered healthy infants, they were at increased risk of having both maternal complications and adverse neonatal outcomes, suggesting that their pregnancies should be closely monitored.

Atypical antipsychotic medications and risk of falls in residents of aged care facilities.

OBJECTIVES: To determine whether use of atypical antipsychotics (olanzapine and risperidone) is associated with lower risk of falls than use of typical antipsychotics. DESIGN: Prospective cohort study with 1-month follow-up. SETTING: Residential aged care facilities in Sydney, Australia. PARTICIPANTS: Two thousand five people aged 65 to 104 (mean age 86). MEASUREMENTS: Medication use at baseline was collected from medical records. Data on potential confounders were collected at interview and physical examination and from medical records. The outcome was accidental falls (one or more). RESULTS: One thousand one hundred seven subjects (55%) used at least one type of psychotropic medication, with 289 (14%) using an antipsychotic. There were 82 olanzapine users, 38 risperidone users, and 181 users of typical antipsychotics. Eleven percent of subjects (n=226) had at least one fall during follow-up. After adjusting for a comprehensive range of falls risk factors, hazard ratios (HRs) for falls were 1.35 (95% confidence interval (CI)=0.87-2.09) for typical antipsychotics, 1.32 (95% CI=0.57-3.06) for risperidone, and 1.74 (95% CI=1.04-2.90) for olanzapine. Antidepressants were also associated with falls (adjusted HR=1.45, 95% CI=1.09-1.93). CONCLUSION: Despite fewer extrapyramidal side effects, atypical antipsychotic medications are not associated with fewer falls than the older, more-established antipsychotics.