Trends in molecular medicine最新文献

This article examines the contributions of disabled scientists and the barriers they face, including systemic ableism and lack of inclusivity. It offers recommendations to foster an inclusive STEM environment, underscoring the importance of supporting disabled scientists to boost innovation and equity.

Neurodegenerative diseases strongly impact our aging society, with treatments providing only symptomatic relief. Recent advancements in active immunotherapy offer solutions by stimulating the immune system to produce antibodies against misfolded and toxic amyloid proteins. We discuss vaccines under clinical evaluation for Alzheimer’s and Parkinson’s diseases, highlighting successes and ongoing trials.

Small cell lung cancer (SCLC) is highly aggressive with poor prognosis. Despite a relative prevalence of circulating tumour DNA (ctDNA) in SCLC, liquid biopsies are not currently implemented, unlike non-SCLC where cell-free DNA (cfDNA) mutation profiling in the blood has utility for guiding targeted therapies and assessing minimal residual disease. cfDNA methylation profiling is highly sensitive for SCLC detection and holds promise for disease monitoring and molecular subtyping; cfDNA fragmentation profiling has also demonstrated clinical potential. Extrachromosomal DNA (ecDNA), that is often observed in SCLC, promotes tumour heterogeneity and chemotherapy resistance and can be detected in blood. We discuss how these cfDNA profiling modalities can be harnessed to expand the clinical applications of liquid biopsy in SCLC.

Protoporphyrias are caused by pathogenic variants in genes encoding enzymes involved in heme biosynthesis. They induce the accumulation of a hydrophobic phototoxic compound, protoporphyrin (PPIX), in red blood cells (RBCs). PPIX is responsible for painful cutaneous photosensitivity, which severely impairs quality of life. Hepatic elimination of PPIX increases the risk of cholestatic liver disease, requiring lifelong monitoring. Treatment options are scarce and mainly limited to supportive care such as protection from visible light. Here, we review the pathophysiology of protoporphyrias, their diagnosis, and current recommendations for medical care. We discuss new therapeutic strategies, some of which are currently undergoing clinical trials and are likely to radically alter the severity of the disease in the years to come.

Endometriosis is a common disorder associated with pain, gastrointestinal and urinary symptoms, infertility, and fatigue. It is defined by the presence of endometrial-like lesions found predominantly in the pelvis. Mechanisms that contribute to disease aetiology include changes in hormonal, inflammatory, and pain pathways. In this article, we focus on recent developments in imaging technologies, on our improved understanding of mechanisms contributing to infertility, on drug therapies that are in clinical trials, and on insights from studies on the gut that offer potential to support self-management strategies. We postulate that improvements in the quality of life of patients will be accelerated by reframing endometriosis as a multi-system disorder and learning from treatments targeting symptoms shared between endometriosis, neuroinflammatory, and gastrointestinal disorders.

Polyglutamine (polyQ) disorders are monogenic neurodegenerative disorders. Currently, no therapies are available for this complex group of disorders. Here, we aim to provide an overview of recent promising preclinical studies and the ongoing clinical trials focusing on molecular therapies for polyQ disorders.

Innovative therapeutic strategies are urgently needed for Parkinson's disease due to limited efficacy of current treatments and a weak therapeutic pipeline. In this forum article, we propose targeting tyrosine hydroxylase phosphorylation as a novel mechanism of action to address this critical need.

Countless efforts have been made to eradicate cervical cancer worldwide, including improving disease screening and human papillomavirus (HPV) vaccination programs. Nevertheless, cervical cancer still claims the lives of more than 300 000 women every year. Persistent infections with high-risk HPV genotypes 16 and 18 are the main cause of cancer and may result in HPV integration into the host genome. The central dogma is that HPV integration is an important step in oncogenesis, but in fact, it impedes the virus from replicating and spreading. HPV causing cervical cancer can therefore be perceived as a failed evolutionary viral trait. Here we outline the occurrence and mechanisms of HPV integration and how this process results in oncogenic transformation.