Trends in molecular medicine最新文献

Beta-thalassemia is a severe, hereditary blood disorder characterized by anemia, transfusion dependence, reduced life expectancy, and poor quality of life. Allogeneic transplantation of hematopoietic stem cells (HSCs) is the only curative treatment for transfusion-dependent β-thalassemia, but a lack of compatible donors prevents the use of this approach for most patients. Over the past 20 years, the rise of gene therapy and the development of lentiviral vectors and genome-editing tools has extended curative options to a broader range of patients. Here, we review breakthroughs in gene addition- and genome-editing-based therapies for β-thalassemia, the clinical outcomes enabling approval by regulatory agencies, and perspectives for further development.

Spinal muscular atrophy (SMA) is a devastating, degenerative, paediatric neuromuscular disease which until recently was untreatable. Discovery of the responsible gene 30 years ago heralded a new age of pioneering therapeutic developments. Three disease-modifying therapies (DMTs) have received regulatory approval and have transformed the disease, reducing disability and prolonging patient survival. These therapies - with distinct mechanisms, routes of administration, dosing schedules, side effect profiles, and financial costs - have dramatically altered the clinical phenotypes of this condition and have presented fresh challenges for patient care. In this review article we discuss potential strategies to maximise clinical outcomes through early diagnosis and treatment, optimised dosing, use of therapeutic combinations and state-of-the-art physiotherapy techniques, and the development of innovative therapies targeting alternative mechanisms.

Bilirubin reductase (BilR), a gut microbiota-derived enzyme that reduces bilirubin to urobilinogen, was recently identified. Given the role of bilirubin in preventing modern diseases, understanding the link between the gut microbiota and health via modulation of bilirubin metabolism marks a major advance in medical research and potential treatments.

Disturbances in kidney tubular cell metabolism are increasingly recognized as a feature of acute kidney injury (AKI). In AKI, tubular epithelial cells undergo abnormal metabolic shifts that notably disrupt NAD⁺ metabolism. Recent advancements have highlighted the critical role of NAD⁺ metabolism in AKI, revealing that acute disruptions may lead to lasting cellular changes, thereby promoting the transition to chronic kidney disease (CKD). This review explores the molecular mechanisms underlying metabolic dysfunction in AKI, with a focus on NAD⁺ metabolism, and proposes several cellular processes through which acute aberrations in NAD⁺ may contribute to long-term changes in the kidney.

Seven primary familial brain calcification genes have been identified but their role in disease mechanisms has been less explored. Cheng et al. recently demonstrated that astrocyte-mediated regulation of brain phosphate (P_i) involves direct and functional interactions among three of these proteins, paving the way for new strategies to combat brain calcification.

Respiratory infections continue to pose a major global health challenge, leading to high morbidity and mortality. Effective vaccines are crucial for prevention of these, and nanotechnology offers a promising approach to enhance vaccine efficacy through nanocarrier systems. This review explores recent advances in nanocarrier-based vaccines for respiratory pathogens, focusing on their ability to promote mucosal immunity against viral infections. It examines various types of nanocarriers, their physicochemical properties, and their role in improving vaccine delivery and immune responses. Additionally, the review examines key findings from both preclinical and clinical studies, highlighting the progress and challenges in developing nanocarrier vaccines for respiratory infections. These insights underscore the potential of nanotechnology to transform vaccine strategies and address unmet needs in respiratory disease prevention.

Resident physicians face intense stressors that significantly heighten their depression risk. This article discusses research findings on critical factors contributing to depression among resident physicians. Understanding these factors is essential to developing targeted interventions, fostering healthy work environments, and ultimately improving physician wellbeing and patient care.

Never in mitosis A (NIMA)-related kinase 2 (NEK2) is a serine/threonine kinase found in the nucleus and cytoplasm throughout the cell cycle. NEK2 is overexpressed in many cancers and is a biomarker of poor prognosis. Factors contributing to NEK2 elevation in cancer cells include oncogenic transcription factors, decreased ubiquitination, DNA methylation, and the circular RNA (circRNA)/long noncoding RNA (lncRNA)-miRNA axis. NEK2 overexpression produces chromosomal instability and aneuploidy, thereby enhancing cancer progression and suppressing antitumor immunity, which highlights the prominence of NEK2 in tumorigenesis and tumor progression. Small-molecule inhibitors targeting NEK2 have demonstrated promising therapeutic potential in vitro and in vivo across various cancer types. This review outlines the regulatory mechanisms of NEK2 expression, emphasizes its functional roles in cancer initiation and progression, and highlights the anticancer properties of NEK2 inhibitors.

Exploring and exploiting the microenvironmental similarities between pulmonary tuberculosis (TB) granulomas and malignant tumors has revealed new strategies for more efficacious host-directed therapies (HDTs). This opinion article discusses a paradigm shift in TB therapeutic development, drawing on critical insights from oncology. We summarize recent efforts to characterize and overcome key shared features between tumors and granulomas, including excessive fibrosis, abnormal angiogenesis, hypoxia and necrosis, and immunosuppression. We provide specific examples of cancer therapy application to TB to overcome these microenvironmental abnormalities, including matrix-targeting therapies, antiangiogenic agents, and immune-stimulatory drugs. Finally, we propose a new framework for combining HDTs with anti-TB agents to maximize therapeutic delivery and efficacy while reducing treatment dosages, duration, and harmful side effects to benefit TB patients.

Although the field of psychiatry has made gains in biomarker discovery, our ability to change long-term outcomes remains inadequate. Matching individuals to the best treatment for them is a persistent clinical challenge. Moreover, the development of novel treatments has been hampered in part due to a limited understanding of the biological mechanisms underlying individual differences that contribute to clinical heterogeneity. The gut microbiome has become an area of intensive research in conditions ranging from metabolic disorders to cancer. Innovation in these spaces has led to translational breakthroughs, offering novel microbiome-informed approaches that may improve patient outcomes. In this review we examine how translational microbiome research is poised to advance biomarker discovery in mental health, with a focus on depression.