Trends in molecular medicine最新文献

RNA modifications are crucial post-transcriptional processes that significantly influence gene expression, RNA stability, nuclear transport, and translational capacity. Angiogenesis, the formation of new blood vessels, is a physiological process that is dysregulated in many pathological conditions, including ocular diseases, immune disorders, and cancer. In this review, we compile the current understanding of the intricate relationship between various RNA modifications and angiogenic mechanisms, spotlighting emerging evidence that underscore their pivotal regulatory roles in both physiological and pathological angiogenesis. Furthermore, we delve into recent advances in innovative therapeutic approaches that target RNA modifications to modulate angiogenesis, offering insights into their potential as novel treatment modalities.

Primarily perceived as an anti-inflammatory and antimicrobial mediator in mucosa and skin, interleukin-22 (IL-22) has emerged as a pivotal metabolic regulator. Central to IL-22 signaling is its receptor, IL-22RA1. Through IL-22RA1, IL-22 orchestrates glucose homeostasis by modulating insulin secretion, reducing cellular stress in pancreatic islets, promoting beta-cell regeneration, and influencing hepatic glucose and lipid metabolism. These actions suggest its potential as a therapeutic for metabolic dysfunctions like diabetes, obesity, and steatohepatitis. However, clinical applications of IL-22 face challenges related to off-target effects and safety concerns. This review explores IL-22's physiological roles, regulatory mechanisms, and profound influence on metabolic tissues. It also underscores IL-22's dual role in metabolic health and disease, advocating further research to harness its therapeutic potential.

Tertiary lymphoid structures (TLSs) frequently occur at sites of chronic inflammation. A more advanced stage of multiple sclerosis (MS) has been associated with certain TLSs. However, tumor-associated TLSs have been shown to correlate with a greater treatment response rate and a better prognosis in glioma mouse models. In this review, we evaluate the clinical significances of TLSs in prognosis and treatment response, as well as the status of TLS-directed therapies targeting alternative biochemical pathways in various central nervous system (CNS) disorders. Potential molecular mechanisms underlying the development of TLSs are also discussed. Exploring these areas may provide an essential understanding of the processes behind disease advancement, uncover new therapeutic objectives, and detect biomarkers that forecast disease progression and treatment efficacy.

Functional precision medicine (FPM), combining ex vivo drug sensitivity testing with genomic profiling to identify treatment options for recurrent/refractory cancer, is feasible and poised to accelerate. This forum explores the history of FPM, recent clinical advancements, and barriers to expanding the clinical utility and accessibility for pediatric/adolescent and adult cancers.

Dry eye, a prevalent ocular surface disease, is significantly influenced by modern lifestyle factors such as night-shift work and extended screen time. Emerging evidence suggests a strong correlation between disturbances in circadian rhythm, sleep disorders, and dry eye. However, the precise underlying mechanisms remain unclear. Recent studies have underscored the crucial role of circadian rhythms and neuroendocrine regulation in maintaining ocular surface health. Advances in treatment strategies targeting neuroendocrine pathways have shown promising developments. This review explores the interplay between circadian rhythms, neuroendocrine regulation, and the ocular surface, examines the impact of circadian disruption on the pathophysiology of dry eye, and proposes intervention strategies to alleviate dry eye associated with disturbances in circadian rhythms.

Translational medicine is crucial for addressing health issues and translating research findings to improve population health. This Science and Society article highlights the potential of translational medicine in Mexico. It discusses the obstacles and challenges encountered in the translation process, instilling a sense of optimism for the future of healthcare in Mexico.

Multiciliated ependymal cells regulate cerebrospinal fluid (CSF) microcirculation and form a dynamic CSF-brain interface. Emerging evidence suggests that ependymal cells enter reactive states in response to pathology that are associated with ciliary and junctional protein alterations. The drivers of these alterations, likely from both acquired and inherited mechanisms, remain elusive.

Senescence is associated with multiple morbidities and therapeutic targeting of these cells is a key aim. In a recent study, Katsuumi et al. found that targeting sodium-glucose co-transporter 2 (SGLT2) promoted immune clearance of senescent cells via programmed cell death-1 ligand (PD-L1) suppression, thus promoting immunosurveillance. This could have profound implications for many age-related diseases, including cancer and frailty.

A healthy lifespan relies on independent living, in which active skeletal muscle is a critical element. The cost of not recognizing and acting earlier on unhealthy or aging muscle could be detrimental, since muscular weakness is inversely associated with all-cause mortality. Sarcopenia is characterized by a decline in skeletal muscle mass and strength and is associated with aging. Exercise is the only effective therapy to delay sarcopenia development and improve muscle health in older adults. Although numerous interventions have been proposed to reduce sarcopenia, none has yet succeeded in clinical trials. This review evaluates the biological gap between recent clinical trials targeting sarcopenia and the preclinical studies on which they are based, and suggests an alternative approach to bridge the discrepancy.

Although it is believed that ubiquitin (Ub) modification is required for protein degradation in the proteasome system (UPS), several proteins are subject to Ub-independent proteasome degradation, and in many cases ubiquitin-like (UBL) modifications, including neddylation, FAT10ylation, SUMOylation, ISGylation, and urmylation, are essential instead. In this Review, we focus on UBL-dependent proteasome degradation (UBLPD), on proteasome regulators especially shuttle factors and receptors, as well as potential competition and coordination with UPS. We propose that there is a distinct UBL-proteasome system (UBLPS) that might be underestimated in protein degradation. Finally, we investigate the association of UBLPD with muscle wasting and neurodegenerative diseases in which the proteasome is abnormally activated and impaired, respectively, and suggest strategies to modulate UBLPD for disease therapy.