GCN2-SLC7A11 axis coordinates autophagy, cell cycle and apoptosis and regulates cell growth in retinoblastoma upon arginine deprivation.

Background: Arginine deprivation was previously shown to inhibit retinoblastoma cell proliferation and induce cell death in vitro. However, the mechanisms by which retinoblastoma cells respond to arginine deprivation remain to be elucidated.

Methods: The human-derived retinoblastoma cell lines Y79 and WERI-Rb-1 were subjected to arginine depletion, and the effects on inhibiting cell growth and survival were evaluated.

Association of moderate alcohol intake with the risks of cirrhosis and steatotic liver disease: Results from a large population-based cohort study.

Background&aims: There is uncertainty about the associations between moderate alcohol consumption and liver-related outcomes. We aimed to explore the associations of moderate drinking with cirrhosis, steatotic liver disease (SLD), and liver cancer in a large cohort study.

Methods: A total of 215,559 non-drinkers and moderate drinkers (<20 g/day alcohol for females or < 30 g/day for males) were enrolled between 2006 and 2010 and followed up to 2022.

Roles of Thermosensitive Transient Receptor Channels TRPV1 and TRPM8 in Paclitaxel-Induced Peripheral Neuropathic Pain.

Paclitaxel, a microtubule-stabilizing chemotherapy drug, can cause severe paclitaxel-induced peripheral neuropathic pain (PIPNP). The roles of transient receptor potential (TRP) ion channel vanilloid 1 (TRPV1, a nociceptor and heat sensor) and melastatin 8 (TRPM8, a cold sensor) in PIPNP remain controversial. In this study, Western blotting, immunofluorescence staining, and calcium imaging revealed that the expression and functional activity of TRPV1 were upregulated in rat dorsal root ganglion (DRG) neurons in PIPNP.

Growth hormone releasing hormone signaling promotes Th17 cell differentiation and autoimmune inflammation.

Dysregulation of Th17 cell differentiation and pathogenicity contributes to multiple autoimmune and inflammatory diseases. Previously growth hormone releasing hormone receptor (GHRH-R) deficient mice have been reported to be less susceptible to the induction of experimental autoimmune encephalomyelitis. Here, we show GHRH-R is an important regulator of Th17 cell differentiation in Th17 cell-mediated ocular and neural inflammation.

rTMS ameliorates depression/anxiety-like behaviors in experimental autoimmune encephalitis by inhibiting neurotoxic reactive astrocytes.

One third of patients with multiple sclerosis (MS) suffered from depressive symptoms. The pathogenesis of depression in MS patients has been related to innate immune activation in certain regions of the brain such as hippocampus. However, pharmacotherapy lacks sufficient evidence for beneficial effects on depression in MS patients, urging for a novel treatment modality for this mental disorder.

ELEVATED LEVEL OF URIC ACID, BUT NOT GLUCOSE, IN AQUEOUS HUMOR AS A RISK FACTOR FOR DIABETIC MACULAR EDEMA IN PATIENTS WITH TYPE 2 DIABETES.

Purpose: To determine the association of uric acid (UA) and glucose in aqueous humor with diabetic macular edema (DME) in patients with Type 2 diabetes.

Methods: Patients with DME or diabetes mellitus without retinopathy were enrolled from August 2016 to December 2020. Nondiabetic patients with age-related cataract or age-related macular degeneration were included as controls.

Nogo-A Induced Polymerization of Microtubule Is Involved in the Inflammatory Heat Hyperalgesia in Rat Dorsal Root Ganglion Neurons.

The microtubule, a major constituent of cytoskeletons, was shown to bind and interact with transient receptor potential vanilloid subfamily member 1 (TRPV1), and serves a pivotal role to produce thermal hyperalgesia in inflammatory pain. Nogo-A is a modulator of microtubule assembly and plays a key role in maintaining the function of TRPV1 in inflammatory heat pain. However, whether the microtubule dynamics modulated by Nogo-A in dorsal root ganglion (DRG) neurons participate in the inflammatory pain is not elucidated.

Ruxolitinib Alleviates Uveitis Caused by Endotoxin.

Uveitis is characterized by inflammatory lesions of intraocular structures. It is one of the important manifestations in patients with Reiter's syndrome, an inflammatory arthritis, which is caused by enteric infection with bacteria, including Salmonella typhimurium. Corticosteroids remain the most frequently used therapies against uveitis associating with inflammatory arthritis.

Agonist of growth hormone-releasing hormone enhances retinal ganglion cell protection induced by macrophages after optic nerve injury.

Optic neuropathies are leading causes of irreversible visual impairment and blindness, currently affecting more than 100 million people worldwide. Glaucoma is a group of optic neuropathies attributed to progressive degeneration of retinal ganglion cells (RGCs). We have previously demonstrated an increase in survival of RGCs by the activation of macrophages, whereas the inhibition of macrophages was involved in the alleviation on endotoxin-induced inflammation by antagonist of growth hormone-releasing hormone (GHRH).

Is Involved in Corneal Stroma Development by Regulating Neural Crest Migration.

Previously, we identified RAD21 from a peripheral sclerocornea pedigree. Injection of this variant mRNA into embryos disrupted the organization of corneal stroma fibrils. To understand the mechanisms of RAD21-mediated corneal stroma defects, gene expression and chromosome conformation analysis were performed using cells from family members affected by peripheral sclerocornea.

Identification of a new functional domain of Nogo-A that promotes inflammatory pain and inhibits neurite growth through binding to NgR1.

Nogo-A is a key inhibitory molecule to axon regeneration, and plays diverse roles in other pathological conditions, such as stroke, schizophrenia, and neurodegenerative diseases. Nogo-66 and Nogo-Δ20 fragments are two known functional domains of Nogo-A, which act through the Nogo-66 receptor (NgR1) and sphingosine-1-phosphate receptor 2 (S1PR2), respectively. Here, we reported a new functional domain of Nogo-A, Nogo-A aa 846-861, was identified in the Nogo-A-specific segment that promotes complete Freund's adjuvant (CFA)-induced inflammatory pain.

Analysis of axon divergence at the optic chiasm in nogo-a knockout mice.

Our earlier studies have shown that the axon growth inhibitory molecule Nogo affects axon routing at the optic chiasm likely through a differential regulation of Nogo receptor on the optic axons. Using isoform specific antibodies, we further showed that Nogo-A was predominantly expressed by retinal ganglion cells and their axons, while Nogo-B was highly localized on the radial glia at the midline of the chiasm, suggesting a role of Nogo-B in regulating turning of uncrossed axons. To further investigate the roles of Nogo-A in axon divergence, we analyzed the routing of axons in the chiasm of Nogo-A knockout mice during the growth of axons across the midline.

Communication with family concerning body donation in Hong Kong: what do we know?

This study aimed to examine three major issues: (a) The extent to which registered donors have communicated with family about body donation; (b) The differences in demographics, life and death attitudes, and quality of relationship with family members between those who communicated their body donation decision and those who did not; (c) The factors associated with the act of communicating with family about body donation. A survey was conducted of people who registered in a body donation programme in Hong Kong. A total of 1,070 registered donors completed an online questionnaire between August and September 2016.

Signaling mechanisms of growth hormone-releasing hormone receptor in LPS-induced acute ocular inflammation.

Ocular inflammation is a major cause of visual impairment attributed to dysregulation of the immune system. Previously, we have shown that the receptor for growth-hormone-releasing hormone (GHRH-R) affects multiple inflammatory processes. To clarify the pathological roles of GHRH-R in acute ocular inflammation, we investigated the inflammatory cascades mediated by this receptor.

Increased Expression of Growth Hormone-Releasing Hormone in Fibrinous Inflammation of Proliferative Diabetic Retinopathy.

Purpose: To investigate the involvement of growth hormone-releasing hormone (GHRH) - growth hormone (GH) signaling in pathogenesis of proliferative diabetic retinopathy (PDR).

Design: Experimental laboratory study.

Methods: Vitreous humor, aqueous humor, and serum were obtained from 36 eyes of 36 patients with or without type 2 diabetes from 2017 to 2019.

Understanding family involvement in body donation in Hong Kong: A qualitative study of registered donors and bereaved family members.

Encouraging the public to donate their bodies after death is crucial for anatomy teaching in medical education. In Hong Kong, success may be affected if family members override the registered donors' wish after death, and thus the role of family in body donation is worth more attention. This study aims to examine how family is involved in the process of body donation.

Growth hormone-releasing hormone receptor mediates cytokine production in ciliary and iris epithelial cells during LPS-induced ocular inflammation.

The receptor for growth hormone-releasing hormone (GHRH-R) has been shown to upregulate specifically in the ciliary and iris epithelial cells and infiltrating cells in the aqueous humor in a rat model of acute anterior uveitis. Treatment with GHRHR-R antagonist alleviates significantly these inflammatory responses. Herein we investigated whether the ciliary and iris epithelial cells can respond directly to lipopolysaccharide (LPS) without the influences of circulating leukocytes to produce inflammatory mediators through a GHRH-R mediated mechanism.

Green tea catechins alleviate autoimmune symptoms and visual impairment in a murine model for human chronic intraocular inflammation by inhibiting Th17-associated pro-inflammatory gene expression.

Autoimmune uveitis is a sight-threatening disease mainly caused by dysregulation of immunity. We investigated the therapeutic effects of green tea extract (GTE) and its major component, epigallocatechin-3-gallate (EGCG), on a murine model of experimental autoimmune uveoretinitis (EAU). Oral administration of GTE, EGCG, dexamethasone, or water, which started 5 days before the induction, was fed every two days to each group.

Metabolomics of Green-Tea Catechins on Vascular-Endothelial-Growth-Factor-Stimulated Human-Endothelial-Cell Survival.

Neovascularization causes serious oculopathy related to upregulation of vascular-endothelial-growth factor (VEGF) causing new capillary growth via endothelial cells. Green-tea-extract (GTE) constituents possess antiangiogenesis properties. We used VEGF to induce human umbilical-vein endothelial cells (HUVECs) and applied GTE, epigallocatechin gallate (EGCG), and mixtures of different compositions of purified catechins (M1 and M2) to evaluate their efficacies of inhibition and their underlying mechanisms using cell-cycle analysis and untargeted metabolomics techniques.

Induction of Apoptosis in Pterygium Cells by Antagonists of Growth Hormone-Releasing Hormone Receptors.

Purpose: The aim of the study was to investigate the signaling of growth hormone-releasing hormone receptor (GHRH-R) in the pathogenesis of pterygium and determine the apoptotic effect of GHRH-R antagonist on pterygium epithelial cells (PECs).

Methods: Fourteen samples of primary pterygium of grade T3 with size of corneal invasion ≥ 4 mm were obtained for investigation by histology, immunofluorescence, electron microscopy, explant culture, and flow cytometry.

Results: We found that PECs were localized in the basal layer of the epithelium in advancing regions of the head of pterygium.

Association of glycated hemoglobin with the risk of advanced fibrosis in non-alcoholic fatty liver disease patients without diabetes.

Background: Association of diabetes with non-alcoholic steatohepatitis has been well documented. However, it remains unclear whether there is an association between levels of glycated hemoglobin (HbA) with severity of non-alcoholic fatty liver disease (NAFLD). This study was aimed to explore the relationship between levels of HbA and the risk of advanced fibrosis in patients with NAFLD.

Dynamic expression of p75 and Lingo-1 during development of mouse retinofugal pathway.

Our previous studies showed interaction of Nogo at the midline with its receptor (NgR) on optic axons plays a role in axon divergence at the mouse optic chiasm. Since NgR lacks a cytoplasmic domain, it needs transmembrane receptor partners for signal transduction. In this study, we examined whether the co-receptors of NgR, low-affinity neurotrophic receptor (p75) and Lingo-1, are localized on axons in the mouse optic pathway.

Nogo-A promotes inflammatory heat hyperalgesia by maintaining TRPV-1 function in the rat dorsal root ganglion neuron.

Nogo-A is a key inhibitory molecule of axon regeneration in oligodendrocytes. However, little is known about its role in adult neurons. In this study, we showed an important function of Nogo-A on regulation of inflammatory pain in dorsal root ganglion (DRG) neurons.

Bruton's tyrosine kinase potentiates ALK signaling and serves as a potential therapeutic target of neuroblastoma.

Aberrant activation of anaplastic lymphoma kinase (ALK) can cause sporadic and familial neuroblastoma. Using a proteomics approach, we identified Bruton's tyrosine kinase (BTK) as a novel ALK interaction partner, and the physical interaction was confirmed by co-immunoprecipitation. BTK is expressed in neuroblastoma cell lines and tumor tissues.