An In Silico Investigation of the Pathogenic G151R G Protein-Gated Inwardly Rectifying K Channel 4 Variant to Identify Small Molecule Modulators.

Primary aldosteronism is characterised by the excessive production of aldosterone, which is a key regulator of salt metabolism, and is the most common cause of secondary hypertension. Studies have investigated the association between primary aldosteronism and genetic alterations, with pathogenic mutations being identified. This includes a glycine-to-arginine substitution at position 151 (G151R) of the G protein-activated inward rectifier potassium (K) channel 4 (GIRK4), which is encoded by the gene.

Respiratory Viral Infection Patterns in Hospitalised Children Before and After COVID-19 in Hong Kong.

Unlabelled: The study highlights the significant changes in respiratory virus epidemiology following the lifting of COVID-19 restrictions.

Method: In this single-centre retrospective study, the virological readouts of adenovirus (AdV), influenza virus A (IAV), influenza virus B (IBV), parainfluenza viruses (PIV) 1, 2, 3, 4, respiratory syncytial virus (RSV), and coupled enterovirus and rhinovirus (EV/RV) were extracted from the respiratory specimens of paediatric patients in Hong Kong from January 2015 to February 2024. The subjects were stratified into five age groups.

Investigation of the Anti-Inflammatory Properties of Bioactive Compounds from : In Silico Evaluation of Cyclooxygenase Enzyme Inhibition and Pharmacokinetic Profiling.

In a landmark study, oleocanthal (OLC), a major phenolic in extra virgin olive oil (EVOO), was found to possess anti-inflammatory activity similar to ibuprofen, involving inhibition of cyclooxygenase (COX) enzymes. EVOO is a rich source of bioactive compounds including fatty acids and phenolics; however, the biological activities of only a small subset of compounds associated with have been explored. Here, the OliveNet library (consisting of over 600 compounds) was utilized to investigate olive-derived compounds as potential modulators of the arachidonic acid pathway.

Identification and Evaluation of Olive Phenolics in the Context of Amine Oxidase Enzyme Inhibition and Depression: In Silico Modelling and In Vitro Validation.

The Mediterranean diet well known for its beneficial health effects, including mood enhancement, is characterised by the relatively high consumption of extra virgin olive oil (EVOO), which is rich in bioactive phenolic compounds. Over 200 phenolic compounds have been associated with , and of these, only a relatively small fraction have been characterised. Utilising the OliveNet library, phenolic compounds were investigated as potential inhibitors of the epigenetic modifier lysine-specific demethylase 1 (LSD1).

Factors influencing risk perception during Public Health Emergencies of International Concern (PHEIC): a scoping review.

The unknownness and dread potential of a risk event shapes its perceived risk. A public health emergency of international concern (PHEIC) declaration by the World Health Organisation (WHO) is a signal for such an event. Understanding perceived risk then shapes risk-avoiding behaviours, important for health prevention.

Bacterial infections in patients with COVID-19: the impact of procalcitonin testing on antibiotics prescription in the real world.

Background: Bacterial infections are not prevalent among patients hospitalized with COVID-19, while unnecessary prescription of antibiotics was commonly observed. This study aimed to determine the impact of procalcitonin testing on antibiotics prescription in the real-world setting.

Methods: We performed a territory-wide retrospective cohort study involving all laboratory-confirmed patients hospitalized in public hospitals in Hong Kong in 2020 with COVID-19.

EZH2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes donors.

β-cells are a type of endocrine cell found in pancreatic islets that synthesize, store and release insulin. In type 1 diabetes (T1D), T-cells of the immune system selectively destroy the insulin-producing β-cells. Destruction of these cells leads to a lifelong dependence on exogenous insulin administration for survival.

Identification of Potential Modulators of a Pathogenic G Protein-Gated Inwardly Rectifying K Channel 4 Mutant: Investigation in the Context of Drug Discovery for Hypertension.

Genetic abnormalities have been associated with primary aldosteronism, a major cause of secondary hypertension. This includes mutations in the gene, which encodes G protein-gated inwardly rectifying K channel 4 (GIRK4). For example, the substitution of glycine with glutamic acid gives rise to the pathogenic GIRK4 mutation, which alters channel selectivity, making it more permeable to Na and Ca.

γH2AX in mouse embryonic stem cells: Distribution during differentiation and following γ-irradiation.

Phosphorylated histone H2AX (γH2AX) represents a sensitive molecular marker of DNA double-strand breaks (DSBs) and is implicated in stem cell biology. We established a model of mouse embryonic stem cell (mESC) differentiation and examined the dynamics of γH2AX foci during the process. Our results revealed high numbers of γH2AX foci in undifferentiated mESCs, decreasing as the cells differentiated towards the endothelial cell lineage.

Characterization of K562 cells: uncovering novel chromosomes, assessing transferrin receptor expression, and probing pharmacological therapies.

Human erythroleukemic K562 cells represent the prototypical cell culture model of chronic myeloid leukemia (CML). The cells are pseudo-triploid and positive for the Philadelphia chromosome. Therefore, K562 cells have been widely used for investigating the BCR/ABL1 oncogene and the tyrosine kinase inhibitor, imatinib-mesylate.

Pharmacological inhibition of human EZH2 can influence a regenerative β-like cell capacity with in vitro insulin release in pancreatic ductal cells.

Background: Therapeutic replacement of pancreatic endocrine β-cells is key to improving hyperglycaemia caused by insulin-dependent diabetes . Whilst the pool of ductal progenitors, which give rise to the endocrine cells, are active during development, neogenesis of islets is repressed in the human adult. Recent human donor studies have demonstrated the role of EZH2 inhibition in surgically isolated exocrine cells showing reactivation of insulin expression and the influence on the H3K27me3 barrier to β-cell regeneration.

Modulation of lncRNA links endothelial glycocalyx to vascular dysfunction of tyrosine kinase inhibitor.

Aims: Novel cancer therapies leading to increased survivorship of cancer patients have been negated by a concomitant rise in cancer therapies-related cardiovascular toxicities. Sunitinib, a first line multi-receptor tyrosine kinase inhibitor, has been reported to cause vascular dysfunction although the initiating mechanisms contributing to this side effect remain unknown. Long non-coding RNAs (lncRNAs) are emerging regulators of biological processes in endothelial cells (ECs); however, their roles in cancer therapies-related vascular toxicities remain underexplored.

Pulmonary function in patients with transfusion-dependent thalassemia and its associations with iron overload.

In patients with transfusion-dependent thalassemia (TDT), pulmonary function impairment has been reported but data are conflicting. Moreover, it remains unclear whether pulmonary dysfunction is associated with iron overload. This study aimed to evaluate the pulmonary function in patients with TDT and to investigate the associations between pulmonary dysfunction and iron overload.

Gestational age-specific neonatal mortality in Hong Kong: a population-based retrospective study.

Background: The neonatal period is the most vulnerable period during childhood, with the risk of death being the highest even in developed countries/regions. Hong Kong's neonatal mortality (1‰) is among the world's lowest and has remained similar for 15 years. This study aimed to explore neonatal deaths in Hong Kong in detail and determine whether neonatal mortality is reducible at such a low level.

Teleconsultation adoption since COVID-19: Comparison of barriers and facilitators in primary care settings in Hong Kong and the Netherlands.

The COVID-19 pandemic has boosted the adoption of digital health technologies such as teleconsultation. This research aimed to assess and compare barriers and facilitators for teleconsultation uptake for primary care practitioners in Hong Kong and the Netherlands and evaluate the role of their different healthcare funding models in this adoption process within the context of the COVID-19 pandemic. A qualitative research following a social constructivist paradigm was performed.

Inhibition of pancreatic EZH2 restores progenitor insulin in T1D donor.

Type 1 diabetes (T1D) is an autoimmune disease that selectively destroys insulin-producing β-cells in the pancreas. An unmet need in diabetes management, current therapy is focussed on transplantation. While the reprogramming of progenitor cells into functional insulin-producing β-cells has also been proposed this remains controversial and poorly understood.

Immunogenicity and safety of inactivated and mRNA COVID-19 vaccines in patients with systemic lupus erythematosus.

Objective: To evaluate the effects and side effects of both inactivated and mRNA COVID-19 vaccines in patients with systemic lupus erythematosus (SLE).

Methods: This was a prospective, single-center, observational study. Patients with SLE planning to receive COVID-19 vaccines were recruited and matched 1:1 with healthy controls.

Metaboloepigenetics in cancer, immunity, and cardiovascular disease.

The influence of cellular metabolism on epigenetic pathways is well documented but misunderstood. Scientists have long known of the metabolic impact on epigenetic determinants. More often than not, that title role for DNA methylation was portrayed by the metabolite S-adenosylmethionine.

Establishment and characterization of meningioma patient-derived organoid.

Meningioma is a central nervous system tumor originated from arachnoid cells. 2D cell culture is widely used as a platform for tumor research as it enables us to culture cells in in vitro and a controlled environment. However, in 2D culture condition, 3D architecture of in vivo tumor mass is lost and phenotypic change may occur.

The Journal Club: Highlights on Recent Papers-9.

We are delighted to share with you our ninth Journal Club and highlight some of the most interesting papers published recently [...

Effects of selenium on coronary artery disease, type 2 diabetes and their risk factors: a Mendelian randomization study.

Background: The impact of selenium on coronary artery disease (CAD) and type 2 diabetes (T2D) remains unclear with inconsistent results from observational studies and randomized controlled trials. We used Mendelian randomization to obtain unconfounded estimates of the effect of selenium on CAD, T2D, lipids and glycemic traits.

Methods: We applied genetic variants strongly (P < 5 × 10) associated with blood and toenail selenium to publicly available summary statistics from large consortia genome-wide association studies of CAD (76,014 cases and 264,785 non-cases), T2D (74,124 cases and 824,006 controls), lipids and glycemic traits.