Trends in molecular medicine最新文献

Dysbiotic intestinal flora and a disrupted circadian clock are intimately related to cancer biological behaviors, yet their interwoven regulatory mechanisms remain an explorative field. Studies by Ren et al. and Liu et al. provide deeper insights into the potential roles of intestinal flora and the circadian clock in colorectal tumorigenesis and lung metastasis.

Fibrodysplasia ossificans progressiva (FOP), a disorder of congenital skeletal malformations and progressive extraskeletal ossification, is the most severe form of heterotopic ossification (HO) in humans. Gain-of-function pathogenic variants in activin A receptor type I (ACVR1), a bone morphogenetic protein (BMP) type 1 receptor, cause FOP by dramatically altering the normal physiologic functions of ACVR1, impacting BMP signaling and other interacting pathways. These alterations affect various systems, including inflammation, innate immunity, hypoxia sensing, wound healing, aging, temperature and mechanical thresholds, pain sensitivity, skeletal growth, diarthrodial joint patterning, joint function and fate, and HO. This article examines the emergent properties of FOP’s diverse phenotypes, proposes a schema for targeting these phenotypes, and highlights outstanding questions and knowledge gaps.

Despite recent standardization of placental evaluation and establishment of criteria for diagnosis of major patterns of placental injury, placental pathological examination remains undervalued and under-utilized. The placenta can harbor a significant amount of information relevant to both the pregnant person and offspring. Placental pathology can also provide a significant context for pathophysiological study of adverse pregnancy outcomes, helping to optimally subcategorize the ‘great obstetric syndromes’ of pre-eclampsia (PE), spontaneous preterm birth (sPTB), and fetal growth restriction (FGR), and to identify causes of stillbirth. We hereby propose that placental evaluation should be incorporated into routine delivery of obstetric and neonatal care, and further suggest that its integration into clinical, translational, and basic research could significantly advance our understanding of pregnancy complications and adverse neonatal outcomes.

Ferroptosis, a novel cell death mode driven by iron-dependent phospholipid (PL) peroxidation, has emerged as a promising therapeutic strategy for the treatments of cancer, cardiovascular diseases, and ischemic-reperfusion injury (IRI). PL peroxidation, the key process of ferroptosis, requires polyunsaturated fatty acid (PUFA)-containing PLs (PL-PUFAs) as substrates, undergoing a chain reaction with iron and oxygen. Cells prevent ferroptosis by maintaining a homeostatic equilibrium among substrates, processes, and detoxification of PL peroxidation. Sterols, lipids abundant in cell membranes, directly participate in PL peroxidation and influence ferroptosis sensitivity. Sterol metabolism also plays a key role in ferroptosis, and targeting sterols presents significant potential for treating numerous ferroptosis-associated disorders. This review elucidates the fundamental mechanisms of ferroptosis, emphasizing how sterols modulate this process and their therapeutic potential.

Increasing evidence suggests that the gut microbiome plays a key role in a host of pathological conditions, including cancer. Indeed, the bidirectional communication that occurs between the gut and the brain, known as the ‘gut–brain axis,’ has recently been implicated in brain tumour pathology. Here, we focus on current research that supports a gut microbiome–brain tumour link with emphasis on high-grade gliomas, the most aggressive of all brain tumours, and the impact on the glioma tumour microenvironment. We discuss the potential use of gut–brain axis signals to improve responses to current and future therapeutic approaches. We highlight that the success of novel treatment strategies may rely on patient-specific microbiome profiles, and these should be considered for personalised treatment approaches.

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.