Safety and Tolerability of Anti-microRNA-328 Ophthalmic Solution, SHJ002, in Pediatric Subjects: First-in-Human Clinical Study.

Purpose: microRNA-328 has been reported as a risk factor for myopia development. SHJ002 is an antisense for microRNA-328, and SHJ002 was formulated as ophthalmic solution for a novel microRNA therapy. We aimed to investigate the safety and tolerability of SHJ002 ophthalmic solution in children.

Thrombospondin-1 associated with carotid intima-media thickness among individuals with hypertension.

In vivo and in vitro studies have demonstrated that thrombospondin-1 (TSP-1) is involved in atherosclerotic pathogenesis. However, the role of TSP-1 in clinical atherosclerosis remains unknown. This cross-sectional study investigated the relationship between TSP-1 and carotid intima-media thickness (IMT) and examined whether it interacts with conventional cardiovascular risk factors.

Cerebral Semaphorin3D is a novel risk factor for age-associated cognitive impairment.

Background: We previously reported that miR-195 exerts neuroprotection by inhibiting Sema3A and cerebral miR-195 levels decreased with age, both of which urged us to explore the role of miR-195 and miR-195-regulated Sema3 family members in age-associated dementia.

Methods: miR-195a KO mice were used to assess the effect of miR-195 on aging and cognitive functions. Sema3D was predicted as a miR-195 target by TargetScan and then verified by luciferase reporter assay, while effects of Sema3D and miR-195 on neural senescence were assessed by beta-galactosidase and dendritic spine density.

Inhibition of microRNA-328 Increases Ocular Mucin Expression and Conjunctival Goblet Cells.

We previously reported anti-miR-328 therapy for dry eye disease (DED). Since decreased mucin secretion is a risk factor for DED, we aimed to explore whether anti-miR-328 affects mucin expression and goblet cells. MiR-328 was increased in goblet cells when they were under desiccating stress or treated with benzalkonium chloride (BAC), both of which are risk factors for DED.

miR-328-3p Affects Axial Length Via Multiple Routes and Anti-miR-328-3p Possesses a Potential to Control Myopia Progression.

Purpose: We previously reported miR-328-3p as a novel risk factor for myopia through a genetic association study of the PAX6 gene. In the present study, we first explored the effects of miR-328-3p on other myopia-related genes, and then tested whether anti-miR-328-3p may be used for myopia control.

Methods: The luciferase report assay and transient transfection were used to confirm miR-328-3p target genes.

Proposed as a High Myopia Susceptibility Gene in Chinese Population.

Myopia is the most common cause of refractive error worldwide. High myopia is a severe type of myopia, which usually accompanies pathological changes in the fundus. To identify high myopia susceptibility genes, DNA-pooling based genome-wide association analysis was used to search for a correlation between single nucleotide polymorphisms and high myopia in a Han Chinese cohort (cases vs.

MicroRNA Therapy for Dry Eye Disease.

We tested the role of microRNA-328 in dry eye disease (DED). Benzalkonium chloride (BAC) has been used to induce DED in animal models. We first demonstrated that both BAC and hyperosmotic stress induced overexpression of miR-328 in corneal cells and then tested whether anti-miR-328 could be a new therapy.

Carotid atherosclerosis among middle-aged individuals predicts cognition: A 10-year follow-up study.

Background And Aims: There is a lack of studies simultaneously evaluating the impact of structural and functional atherosclerosis on cognition. We investigated the long-term predictive and interaction effects of structural and functional carotid atherosclerosis markers on future cognitive decline.

Methods: Five hundred and twenty-eight middle-aged participants enrolled in the carotid atherosclerosis examination in Kaohsiung Atherosclerosis Longitudinal Study (KALS) between 2006 and 2009 were tested for cognition between 2016 and 2019.

miR-195 reduces age-related blood-brain barrier leakage caused by thrombospondin-1-mediated selective autophagy.

Blood-brain barrier (BBB) disruption contributes to neurodegenerative diseases. Loss of tight junction (TJ) proteins in cerebral endothelial cells (ECs) is a leading cause of BBB breakdown. We recently reported that miR-195 provides vasoprotection, which urges us to explore the role of miR-195 in BBB integrity.

Predictive Value of FOLFOX-Based Regimen, Long Interval, Hemoglobin Levels and Clinical Negative Nodal Status, and Postchemoradiotherapy CEA Levels for Pathological Complete Response in Patients with Locally Advanced Rectal Cancer after Neoadjuvant Chemoradiotherapy.

We aimed to identify predictors of a pathological complete response (pCR) in patients with locally advanced rectal cancer (LARC) following a multimodality therapy. We retrospectively reviewed 236 patients with LARC treated with neoadjuvant chemoradiotherapy (CRT) followed by radical resection from January 2011 to December 2017. Patients were administered CRT, which comprised radiotherapy and chemotherapy with an oxaliplatin plus 5-fluorouracil- or fluoropyrimidine-based regimen.

Traffic-related air pollutants increase the risk for age-related macular degeneration.

The aim of this study was to investigate whether ambient nitrogen dioxide (NO) and carbon monoxide (CO) increase the risk for age-related macular degeneration (AMD). This is a longitudinal population-based study using the data on Taiwan National Health Insurance Program between year 2000 and 2010. From the nationwide dataset, we enrolled subjects aged 50 or older and the annually total NO and CO exposure was calculated from 1998 to 2010 for each subject.

In-utero epigenetic factors are associated with early-onset myopia in young children.

Objectives: To assess whether epigenetic mechanisms affecting gene expression may be involved in the pathogenesis of early-onset myopia, we performed genome-wide DNA methylation analyses of umbilical cord tissues, and assessed any associations between CpG site-specific methylation and the development of the disorder when the children were 3 years old.

Methods: Genome-wide DNA methylation profiling of umbilical cord samples from 519 Singaporean infants involved in a prospective birth cohort 'Growing Up in Singapore Towards healthy Outcomes' (GUSTO) was performed using the Illumina Infinium HumanMethylation450K chip microarray. Multivariable logistic regression models were used to assess any associations between site-specific CpG methylation of umbilical cord tissue at birth and myopia risk in 3 year old children, adjusting for potential confounders.

miR-195 Has a Potential to Treat Ischemic and Hemorrhagic Stroke through Neurovascular Protection and Neurogenesis.

Tissue plasminogen activator is the only U.S. FDA-approved therapy for ischemic stroke, while there is no specific medication for hemorrhagic stroke.

HOXA9 is a novel myopia risk gene.

Purpose: A recent meta-analysis revealed PAX6 as a risk gene for myopia. There is a link between PAX6 and HOXA9. Furthermore, HOXA9 has been reported to activate TGF-β that is a risk factor for myopia.

Genome-wide DNA hypermethylation and homocysteine increase a risk for myopia.

Aim: To test for the association between genome-wide methylation and myopia in human and mice.

Methods: methylation levels were used to surrogate genome-wide methylation level. We first tested for the association between high myopia (<-6 D) and methylation in leukocytes in 220 cases and 220 control subjects.

Early functional improvement after stroke correlates with cardiovascular fitness.

Cardiovascular fitness exerts directly beneficial effects on functional and cognitive outcomes in patients of chronic stroke. However, the effect of early rehabilitation on cardiovascular function has not yet been thoroughly examined. We tested whether complementary rehabilitation program could influence cardiovascular fitness in an early stage of stroke patients.

MicroRNA let-7g inhibits angiotensin II-induced endothelial senescence via the LOX-1-independent mechanism.

Endothelial senescence leads to cell dysfunction, which in turn eventually results in cardiovascular disease. Identifying factors that regulate endothelial senescence may provide insight into the pathogenesis of aging. Insulin-like growth factor (IGF) signaling has a significant role in the physiology of endothelial cells (ECs).

Let-7g suppresses both canonical and non-canonical NF-κB pathways in macrophages leading to anti-atherosclerosis.

Transformation of macrophages to foam cells contributes to atherosclerosis. Here, we report that let-7g reduces macrophage transformation and alleviates foam cell apoptosis by suppressing both canonical and non-canonical NF-κB pathways. In the canonical pathway, let-7g inhibits phosphorylation of IKKβ and IκB, down-regulates SREBF2 and miR-33a, and up-regulates ABCA1.

microRNA let-7g suppresses PDGF-induced conversion of vascular smooth muscle cell into the synthetic phenotype.

Platelet-derived growth factor (PDGF) can promote vascular smooth muscle cells (VSMCs) to switch from the quiescent contractile phenotype to synthetic phenotype, which contributes to atherosclerosis. We aimed to investigate the role of microRNA let-7g in phenotypic switching. Bioinformatics prediction was used to find let-7g target genes in the PDGF/mitogen-activated protein kinase kinase kinase 1 (MEKK1)/extracellular signal-regulated kinase (ERK)/Krüppel-like factor-4 (KLF4) signalling pathway that affects VSMC phenotypic switching.

Methylation in the matrix metalloproteinase-2 gene is associated with cerebral ischemic stroke.

Matrix metalloproteinase-2 (MMP-2) is involved in the pathophysiology of stroke. Previous studies have shown that MMP-2 activity is increased in stroke; however, evidence of epigenetic regulation of the MMP-2 in stroke is still limited. We examined methylation of the MMP-2 promoter in patients with ischemic stroke.

MicroRNA let-7g possesses a therapeutic potential for peripheral artery disease.

Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis and conveys a significant health burden globally. Critical limb ischaemia encompasses the most severe consequence of PAD. Our previous studies indicate that microRNA let-7g prevents atherosclerosis and improves endothelial functions.

An observational study of extending FOLFOX chemotherapy, lengthening the interval between radiotherapy and surgery, and enhancing pathological complete response rates in rectal cancer patients following preoperative chemoradiotherapy.

Introduction: Patients with rectal cancer who exhibit a pathologic complete response to preoperative concurrent chemoradiotherapy have excellent oncologic outcomes. In this study, we evaluated the potential advantages of adding oxaliplatin to preoperative fluoropyrimidine-based chemoradiotherapy administered in rectal cancer patients.

Methods: A total of 78 patients with rectal cancer were enrolled.

Development of a deregulating microRNA panel for the detection of early relapse in postoperative colorectal cancer patients.

Background: Colorectal cancer (CRC) is the third leading cause of cancer mortality worldwide and is associated with high recurrence and mortality, despite recent advancements in therapeutic strategies. MicroRNA (miR) deregulation is associated with CRC development and recurrence; therefore, miRs may be reliable biomarkers for detecting early relapse postoperatively.

Methods: In this study ten candidates were identified using miR arrays: miR-7, miR-31, miR-93, miR-141, miR-195, miR-375, miR-429, miR-494, miR-650, and let-7b.