Harnessing the Power of AI to Improve Detection, Monitoring, and Public Health Interventions for Japanese Encephalitis.

Unlabelled: Japanese Encephalitis (JE) is the leading cause of viral encephalitis in regions with endemic Japanese Encephalitis Virus (JEV) infections.

Background/objectives: The aim of this review is to consider the potential role of artificial intelligence (AI) to improve detection, monitoring and public health interventions for JE.

Discussion: As climate change continues to impact mosquito population growth patterns, more regions will be affected by mosquito-borne diseases, including JE.

Repairing muscle with broccoli-derived sulforaphane: A preclinical evaluation for the treatment of mitochondrial myopathies.

Skeletal muscle health relies on the production of adenosine triphosphate (ATP) in the mitochondria. ATP production is accompanied by oxidative phosphorylation, which generates reactive oxygen species (ROS). When there is an imbalance in ROS levels, oxidative stress and subsequent mitochondrial dysfunction, mitochondrial myopathies including sarcopenia, chronic progressive external ophthalmoplegia, and proximal myopathy can result.

Efficacy and challenges involving combination therapies in CLL.

Chronic lymphocytic leukemia (CLL), a malignant tumour, is characterized by expansion of mature monoclonal B lymphocytes expressing CD23 and CD5 in secondary lymphocytic organs, blood, and bone marrow. Here, we provide an in-depth review of CLL, emphasizing its pathophysiology, cytogenic changes, and treatment strategies, particularly the efficacy and challenges of treatments, such as Bruton tyrosine kinase (BTK) inhibitors, B cell lymphoma 2 (BCL2) inhibitors, and phosphatidylinositol 3-kinase (PI3K) inhibitors, as well as the need to understand their role in managing disease progression, chemoresistance, and intolerance. In addition, we explore efficacy based on patient response and comparison between monotherapy and combination therapy.

Precision medicine and Friedreich ataxia: promoting equity, beneficence, and informed consent for novel gene therapies.

Friedreich Ataxia (FA) is an incurable neurodegenerative disease with systemic consequences affecting vital organs including those of the central and peripheral nervous systems. This article will use FA as an example to explore some of the practical and ethical issues emerging in precision medicine for rare diseases. It will first describe the existing management strategies available for FA patients, before considering the potential impact of gene therapy trials on the prevention and treatment of disease symptoms.

Preclinical investigations on broccoli-derived sulforaphane for the treatment of ophthalmic disease.

Vision loss causes a significant burden on individuals and communities on a financial, emotional and social level. Common causes include age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma and retinitis pigmentosa (RP; also known as 'rod-cone dystrophy'). As the population continues to grow and age globally, an increasing number of people will experience vision loss.

A comparative analysis of the CP and CG using 2D and 3D visualisation approaches.

Investigations on the structural variations in the cribriform plate (CP), olfactory foramina and the Crista Galli showcase the benefits of using 3D imaging on smaller structures. These techniques reveal accurate details about bone morphology and density. Comparing different techniques, this project aims to examine the correlation between the CP, olfactory foramina, and Crista Galli.

Molecular approaches for the treatment and prevention of Friedreich's ataxia.

Friedreich's ataxia (FRDA) is caused by an intronic guanine-adenine-adenine (GAA) trinucleotide expansion in the gene encoding the frataxin protein (FXN). This triggers the transcriptional silencing of the fratxin gene (FXN) and subsequent FXN deficiency in affected cells, which accounts for the multisystemic symptoms of this condition. Current management strategies aim for symptomatic relief and no treatments can prevent disease onset or progression.

Midkine: The Who, What, Where, and When of a Promising Neurotrophic Therapy for Perinatal Brain Injury.

Midkine (MK) is a small secreted heparin-binding protein highly expressed during embryonic/fetal development which, through interactions with multiple cell surface receptors promotes growth through effects on cell proliferation, migration, and differentiation. MK is upregulated in the adult central nervous system (CNS) after multiple types of experimental injury and has neuroprotective and neuroregenerative properties. The potential for MK as a therapy for developmental brain injury is largely unknown.

New generation drugs for treatment of multiple myeloma.

Multiple myeloma (MM), a plasma cell malignancy, is characterised by lesions in multiple bones involving transformed, matured post-follicular B cells. The course of the disease involves an initial development of monoclonal gammopathy of undetermined significance (MGUS), followed by smouldering MM, before the full MM disease emerges. Despite novel therapies, MM remains incurable, managed by combination therapies, including proteasome inhibitors (PIs), immunomodulators (IMiDs) and anti-human CD38 (daratumumab).

Lipidomics reveal the protective effects of a vegetable-derived isothiocyanate against retinal degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness in the ageing population. Without effective treatment strategies that can prevent disease progression, there is an urgent need for novel therapeutic interventions to reduce the burden of vision loss and improve patients' quality of life. Dysfunctional innate immune responses to oxidative stress observed in AMD can be caused by the formation of oxidised lipids, whilst polyunsaturated fatty acids have shown to increase the risk of AMD and disease progression in affected individuals.

Ponatinib Tyrosine Kinase Inhibitor Induces a Thromboinflammatory Response.

Both nilotinib, a second-generation tyrosine kinase inhibitor (TKI) used in the treatment of chronic myeloid leukaemia (CML), and ponatinib, a third-generation TKI used in CML and Philadelphia positive acute lymphocytic leukaemia, have been associated with an increase in arterial occlusive events, in contrast to other TKIs such as imatinib and dasatinib. We have previously demonstrated evidence of a pro-thrombotic state associated with nilotinib, using microvascular and arterial thrombosis C57BL/6 mouse models. In this study, we examined ponatinib and determined if a calcium channel blocker could ameliorate the pro-thrombotic and pro-inflammatory phenotypes.

Recent advances in the management of diabetic retinopathy.

Diabetic retinopathy (DR) is a microvascular complication of diabetes and is the leading cause of vision loss in people with diabetes. The current treatments do not target early stages of disease or impede disease progression. Therefore, the identification of new therapeutic targets, the development of novel therapies targeting early stages of the disease and accurate models that simulate pathological characteristics of this disorder are crucial.

Combination Treatment of p53-Null HL-60 cells with Histone Deacetylase Inhibitors and Chlorambucil Augments Apoptosis and Increases BCL6 and p21 Gene Expression.

Background: Treatment of hematological malignancies with conventional DNA-damaging drugs, such as chlorambucil (CLB), commonly results in p53-dependent chemo-resistance. Chromatin modifying agents, such as histone deacetylase inhibitors (HDACIs), sodium butyrate (NaBu) and trichostatin A (TSA), may reverse chemo-resistance by modulating the activity of chromatin remodeling enzymes and/or genes that control cell proliferation, differentiation and survival.

Objective: This study examined the potential use of HDACIs and CLB combination therapies in an in vitro chemo-resistant leukemia model.

L-Sulforaphane Confers Protection Against Oxidative Stress in an In Vitro Model of Age-Related Macular Degeneration.

Background: In age-related macular degeneration, oxidative damage and abnormal neovascularization in the retina are caused by the upregulation of vascular endothelium growth factor and reduced expression of Glutathione-S-transferase genes. Current treatments are only palliative. Compounds from cruciferous vegetables (e.

Manipulating the epigenome for the treatment of disorders with thrombotic complications.

The haemostatic system is tightly regulated to maintain homeostasis to avoid unwanted bleeding or thrombotic complications. Recent research has highlighted the importance of epigenetic changes, such as DNA methylation, histone modifications, and miRNA-based mechanisms, that alter gene expression. This can give rise to dysregulated haemostatic or vascular expressed molecules contributing to the development of thrombotic complications.

Mimicking the ocular environment for the study of inflammatory posterior eye disorders.

The common inflammatory posterior eye disorders, age-related degeneration and glaucoma often lead to irreversible vision loss. Current treatments do not target early stages or prevent disease progression. Consequently, the identification of biomarkers or early disease models that can accurately mimic the pathological processes involved is essential.

The tyrosine kinase inhibitor, nilotinib potentiates a prothrombotic state.

Tyrosine kinase inhibitors (TKI) such as imatinib, nilotinib and dasatinib are now established as highly effective frontline therapies for chronic myeloid leukaemia (CML). Disease control is achieved in the majority of patients and survival is excellent such that recent focus has been on toxicities of these agents. Cumulative data have reported an excess of serious vascular complications, including arterial thrombosis and peripheral arterial occlusive disease, in patients receiving nilotinib in comparison with other TKIs, with resultant interest in delineating the pathophysiology and implications for rationale cardiovascular risk modification.

Epigenetic modifications as potential therapeutic targets in age-related macular degeneration and diabetic retinopathy.

Recently, aberrant epigenetic modifications have been identified in the pathogenesis of the posterior eye diseases, age-related macular degeneration (AMD) and diabetic retinopathy (DR). This has led to the development of alternative therapies that can alter aberrant chromatin-remodelling processes involved in AMD and DR. These novel therapeutic agents could help to ameliorate the challenges associated with current treatments that are limited by variable patient response and disease heterogeneity.

Investigation of the biological properties of Cinnulin PF in the context of diabetes: mechanistic insights by genome-wide mRNA-Seq analysis.

The accumulating evidence of the beneficial effects of cinnamon (Cinnamomum burmanni) in type-2 diabetes, a chronic age-associated disease, has prompted the commercialisation of various supplemental forms of the spice. One such supplement, Cinnulin PF(®), represents the water soluble fraction containing relatively high levels of the double-linked procyanidin type-A polymers of flavanoids. The overall aim of this study was to utilize genome-wide mRNA-Seq analysis to characterise the changes in gene expression caused by Cinnulin PF in immortalised human keratinocytes and microvascular endothelial cells, which are relevant with respect to diabetic complications.

Influence of natural and synthetic histone deacetylase inhibitors on chromatin.

Significance: Histone deacetylase inhibitors (HDACIs) have emerged as a new class of anticancer therapeutics. The hydroxamic acid, suberoylanilide hydroxamic acid (Vorinostat, Zolinza™), and the cyclic peptide, depsipeptide (Romidepsin, Istodax™), were approved by the U.S.

Chromatin modifying agents - the cutting edge of anticancer therapy.

Chromatin modifying compounds are emerging as the next generation of anticancer therapies. By altering gene expression they could be able to correct uncontrolled proliferation and, in certain cases, aberrant apoptotic pathways, which are hallmarks of malignant cells. The modulation of gene expression is regulated via chromatin remodelling processes that include DNA methylation and chromatin modifications.

Chlorambucil-sensitive and -resistant lymphoid cells display different responses to the histone deacetylase inhibitor, sodium butyrate.

Clinical chemoresistance is a frequent complication of alkylating agent treatment of malignant tumours. Chromatin remodelling using histone deacetylase inhibitors (e.g.