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Cardiotoxicity (CDTX) is a critical side effect of many cancer therapies, leading to increased morbidity and mortality if not addressed. Early detection of CDTX is essential, and while echocardiographic measures like global longitudinal strain offer promise in identifying early myocardial dysfunction, the search for reliable biomarkers continues. MicroRNAs (miRNAs) are emerging as important non-coding RNA molecules that regulate gene expression post-transcriptionally, influencing key biological processes such as the cell cycle, apoptosis, and stress responses. In cardiovascular diseases, miRNAs have demonstrated potential as biomarkers due to their stability in circulation and specific expression patterns that reflect pathological changes. Certain miRNAs have been linked to CDTX and hold promise for early detection, prognosis, and therapeutic targeting. These miRNAs not only assist in identifying early cardiac injury, but also offer opportunities for personalized interventions by modulating their expression to influence disease progression. As research advances, integrating miRNA profiling with traditional diagnostic methods could enhance the management of CDTX in cancer patients, paving the way for improved patient outcomes and more tailored therapeutic strategies. Further clinical studies are essential to validate the clinical utility of miRNAs in managing CDTX. [ABSTRACT FROM AUTHOR]

Blau syndrome (BS) is a rare autoinflammatory granulomatosis characterized by granulomatous arthritis, uveitis, and dermatitis. Ocular complications are particularly severe in BS, significantly contributing to morbidity. This study aims to identify potential biomarkers for BS ocular degeneration through proteomic profiling of tear samples from affected patients. Seven subjects from the same family, including four carriers of the BS-associated NOD2 mutation (p.E383K), were recruited alongside healthy controls. Tear samples were collected using Schirmer strips and analyzed via mass spectrometry. A total of 387 proteins were identified, with significant differences in protein expression between BS patients, healthy familial subjects, and healthy controls. Key findings include the overexpression of alpha-2-macroglobulin (A2M) and immunoglobulin heavy constant gamma 4 (IGHG4) in BS patients. Bioinformatic analysis revealed that differentially expressed proteins are involved in acute-phase response, extracellular exosome formation, and protein binding. Notably, neutrophils' azurophilic granule components, as azurocidin (AZU1), myeloperoxidases (MPO), and defensins (DEFA3), were highly expressed in the most severely affected subject, suggesting a potential role of neutrophils in BS ocular severity. These proteins might be promising biomarkers for ocular involvement in BS, facilitating early detection and tailored treatment strategies. [ABSTRACT FROM AUTHOR]

As the prevalence of coronary artery disease continues to increase worldwide, understanding the nuances of complex calcific coronary lesions becomes paramount. Coronary artery calcium (CAC) is a well-established, widely available, and highly specific marker of subclinical and advanced atherosclerosis. It remains a vital adjudicator of atherosclerotic cardiovascular disease (ASCVD) and facilitates the up- or down-stratifying of asymptomatic, intermediate risk patients. Notably, the high prevalence of CAC in coronary heart disease (CHD) patients makes the percutaneous treatment of heavily calcified coronary lesions particularly challenging. These cases have a higher risk of immediate complications, late failures due to stent underexpansion or malapposition, and poor clinical outcomes. In this setting, understanding lesion pathophysiology and characterizing calcium deposition with multimodal imaging are crucial steps to improve the successful treatment of these lesions. Therefore, this review explores CAC in the context of complicated and severely calcified lesions. We seek to ameliorate clinical uncertainties and synthesize growing amounts of research to help encourage a homogenous approach to complex calcific coronary lesions. To that end, this comprehensive review paper will first cover epidemiology, pathophysiology, and the types of calcific lesions. Next, we will review acute and long-term complications, as well as lesion preparation and intervention. Last, this review will explore the role of imaging and the contemporary management of severely calcified lesions. [ABSTRACT FROM AUTHOR]

Given continued failure of BACE1 inhibitor programs at symptomatic and prodromal stages of Alzheimer's disease (AD), clinical trials need to target the earlier preclinical stage. However, trial design is complex in this population with negative diagnosis of classical hippocampal amnesia on standard memory tests. Besides recent advances in brain imaging, electroencephalogram, and fluid-based biomarkers, new cognitive markers should be established for earlier diagnosis that can optimize recruitment to BACE1 inhibitor trials in presymptomatic AD. Notably, accelerated long-term forgetting (ALF) is emerging as a sensitive cognitive measure that can discriminate between asymptomatic individuals with high risks for developing AD and healthy controls. ALF is a form of declarative memory impairment characterized by increased forgetting rates over longer delays (days to months) despite normal storage within the standard delays of testing (20–60 min). Therefore, ALF may represent a harbinger of preclinical dementia and the impairment of systems memory consolidation, during which memory traces temporarily stored in the hippocampus become gradually integrated into cortical networks. This review provides an overview of the utility of ALF in a rational design of next-generation BACE1 inhibitor trials in preclinical AD. I explore potential mechanisms underlying ALF and relevant early-stage biomarkers useful for BACE1 inhibitor evaluation, including synaptic protein alterations, astrocytic dysregulation and neuron hyperactivity in the hippocampal-cortical network. Furthermore, given the physiological role of the isoform BACE2 as an AD-suppressor gene, I also discuss the possible association between the poor selectivity of BACE1 inhibitors and their side effects (e.g., cognitive worsening) in prior clinical trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Molecular biomarkers in cancer are measurable genomic alterations that can indicate the risk of developing neoplasia, the presence of neoplastic cells, patient outcome, and/or a likely response to therapy. This review discusses the different uses of molecular biomarkers in the veterinary clinic and how their presence can be determined. In particular, we showcase which genomic alterations are currently used to date as molecular biomarkers in the clinic and for what purposes. We also look at biomarkers that are currently being developed and show promise for clinical use. Finally, we consider the important factors that allow a molecular biomarker to move from the research laboratory to the clinic. This review aims to enable veterinarians to understand the benefits of molecular biomarkers in delivering precision veterinary care to dogs and cats with cancer. Molecular biomarkers are central to personalised medicine for human cancer patients. It is gaining traction as part of standard veterinary clinical practice for dogs and cats with cancer. Molecular biomarkers can be somatic or germline genomic alterations and can be ascertained from tissues or body fluids using various techniques. This review discusses how these genomic alterations can be determined and the findings used in clinical settings as diagnostic, prognostic, predictive, and screening biomarkers. We showcase the somatic and germline genomic alterations currently available to date for testing dogs and cats in a clinical setting, discussing their utility in each biomarker class. We also look at some emerging molecular biomarkers that are promising for clinical use. Finally, we discuss the hurdles that need to be overcome in going 'bench to bedside', i.e., the translation from discovery of genomic alterations to adoption by veterinary clinicians. As we understand more of the genomics underlying canine and feline tumours, molecular biomarkers will undoubtedly become a mainstay in delivering precision veterinary care to dogs and cats with cancer. [ABSTRACT FROM AUTHOR]