Expert Reviews in Molecular Medicine最新文献

Polyamines putrescine, spermidine and spermine are small, positively charged metabolites indispensable for DNA stabilization, chromatin remodelling, RNA translation and redox balance, with dynamic distribution across the nucleus, mitochondria and endoplasmic reticulum. In cancer, polyamine homeostasis becomes profoundly dysregulated through altered biosynthesis, degradation and transport, driving malignant phenotypes and therapy resistance. Therefore, there is an urgent need to develop precision techniques that combine polyamine metabolism with immunotherapeutic and redox-based therapies, identify biomarkers to predict therapy response and create logical combination regimens to overcome resistance. The existing literature lacks in providing a holistic view of how polyamine dynamics intersect with diverse cancer hallmarks. Thus, this review consolidates emerging evidence on the multifaceted roles of polyamines in cancer hallmarks, with a particular focus on their impact on efferocytosis, ferroptosis and the dynamics of polyploid giant cancer cells (PGCCs). Furthermore, a comprehensive evaluation of contemporary treatment approaches that focus on polyamine metabolism, including transport blockers, biosynthesis inhibitors and various polyamine analogues, was discussed. While addressing context-dependent effects of polyamines that impede therapeutic progress, our discussion also incorporates important findings from pre-clinical and clinical investigations. Going forward, this review aims to enlighten and direct future translational research by situating polyamine biology within the broader context of cancer evolution and treatment adaptation.

Background: Respiratory diseases are increasing global health burden with persistently high morbidity and mortality. Extracellular vesicles (EVs), which are virtually released by all cell types and carry a variety of molecules like miRNAs, have emerged as crucial mediators of intercellular communication. They play a key role in maintaining lung homeostasis and are involved in the pathogenesis of various respiratory conditions. Furthermore, mesenchymal stromal cell-derived EVs (MSC-EVs) have shown significant therapeutic potential due to their anti-inflammatory, antimicrobial, and reparative properties.

Methods: This narrative review critically assesses the current body of literature on the roles of EVs in respiratory diseases. We examine evidence from pre-clinical and clinical studies that investigate EVs as biomarkers and therapeutics for conditions including asthma, bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), lung cancer, and pulmonary arterial hypertension (PAH).

Results: EVs reflect the physiological or pathological state of their parental cells, making them promising multimodal biomarkers for the early diagnosis and monitoring of disease progression. Additionally, MSC-EVs function as effective, cell-free therapeutic agents. In a variety of disease models, they demonstrate efficacy by modulating immune responses, enhancing alveolar fluid clearance, and restoring epithelial and endothelial barrier integrity, leading to improved survival and outcomes.

Conclusions: EVs hold a dual and transformative potential in respiratory medicine. They may serve as valuable diagnostic and prognostic tools, and their application as cell-free therapeutics represents a novel and promising strategy for treating a wide spectrum of debilitating respiratory diseases.

Background: As a highly aggressive tumour of the digestive tract, pancreatic cancer has a high mortality rate and poor treatment outcomes. The five-year survival rate for patients with pancreatic cancer is distressingly low, and the recurrence chance remains unacceptably high even with successful treatment. Surgical procedures and chemotherapy are the main treatments of pancreatic cancer, and surgical procedures are the only effective treatment at present. However, these cancer cells can easily develop resistance to chemotherapy agents, which leads to low treatment efficacy and high mortality in pancreatic cancer. Additionally, early diagnosis of pancreatic cancer is challenging due to the absence of obvious symptoms, making surgical intervention unattainable in early stages. However, pancreatic cancer cells show unique changes at genetic and cellular levels, which makes them sensitive to metalrelated cell death or exhibit some characteristics related to metalrelated cell death. These changes and characteristics could be utilized for treatment and diagnosis in pancreatic cancer.

Method: Therefore, our motivation is to explain the potential of metalrelated cell death in treating this aggressive cancer. This review begins by analysing the types of metal-related cell death: ferroptosis, cuproptosis and lysozincrosis. Each form is evaluated based on its unique features and related metabolic pathways.

Results: By examining the key characteristics of metal-related cell death modalities, their primary metabolic patterns and their interactions with pancreatic cancer, our aim is to point the direction to identify potential therapies and treatments.

Conclusions: Our review expands the possibilities for utilizing metal-related cell death and instils hope for its future potential in pancreatic cancer treatment.

Background: Kidneys are crucial for systemic lactate homeostasis, and a proper lactate balance subsequently supports normal kidney structure and function. The physiological lactate production-clearance axis along the proximal-distal tubular network may represent an important mechanism for maintaining tubulointerstitial microenvironmental balance. In the context of kidney diseases, the dynamic changes in lactate levels reveal the process of renal metabolic remodelling and even participate in the regulation of disease occurrence and progression.

Methods: This review systematically combs the maintenance of renal lactate homeostasis under physiological conditions and integrates current research findings on the roles of lactate in the initiation and progression of various kidney diseases, as well as the underlying core molecular mechanisms.

Results: Existing studies confirm that, in a variety of kidney diseases, abnormal lactate levels are closely associated with the occurrence of renal metabolic remodelling, and lactate itself can further regulate the progression of kidney diseases. Targeted regulation of lactate metabolism or lactate-related mechanisms of action is expected to provide a new perspective for the treatment of kidney diseases.

Conclusion: The exploration of lactate-related mechanisms offers potential insights for developing novel strategies for early diagnosis and therapeutic intervention of kidney diseases; however, more in-depth studies are still required to translate these findings into clinical practice.

Background: Opioid use disorder (OUD) is a major global-scale social issue affecting public health. The high potential for addiction and dependence makes opioid use a significant concern, contributing to substance-related disorders. Both genetic and environmental factors contribute to the predisposition to OUD, with the opioidergic, dopaminergic, and GABAergic systems playing primary roles in itsonset.

Methods: This narrative review documents the association between genes and their variants related to these three systems, along with current evidence on epigenetic interventions in OUD. Relevant studies investigating candidate-gene associations and molecular mechanisms were synthesized to highlight genetic variants and epigenetic processes linked to OUD.

Results: Genetic associations play a prominent role in OUD, with several single-nucleotide variants identified in affected populations. Key genes implicated include OPRM1, OPRD1, OPRK1, PDYN, OPRL1, and POMC from the opioidergic system; DRD1, DRD2, DRD3, DRD4, ANKK1, and COMT from the dopaminergic system; and GABRA2, GABRB3, GABRG2, GAD1, and GAD2 from the GABAergic system. Evidence also indicates that chronic opioid use is associated with epigenetic changes through posttranslational histone modifications and DNA methylation. However, limitations in existing studies include small sample sizes, limited replication, and potential stratification biases.

Conclusions: Although many candidate-gene associations have been proposed for OUD, robust evidence remains limited. Large, ancestrally diverse genome-wide association studies (GWAS) and systematic replication studies are urgently needed. A deeper understanding of the genetic, epigenetic, and neurobiological bases of addiction will be essential for the development of precisely targeted medications to improve prevention and treatment outcomes for OUD.

Colorectal cancer (CRC) is the second deadliest cancer worldwide, posing a great threat to human health and a social burden. Various genetic and epigenetic alterations can activate tumourigenesis-related signalling pathways, leading to CRC development and progression. Over the past two decades, the understanding of the role of S100 family proteins in different types of cancer has received great attention. S100 proteins, as intracellular and extracellular, play important roles in regulating various cellular processes, such as calcium homeostasis, apoptosis, tumour cell proliferation, invasion and motility. It is well documented that alteration in expression of S100 proteins can be associated with tumourigenesis and cancer progression. These proteins play important roles in CRC carcinogenesis by activating different signalling pathways, especially the nuclear factor kappa B (NF-κB) signalling pathway, which is involved in cell proliferation, invasion and migration. In this review, we describe the functions of S100 proteins in the context of inflammation, tumourigenesis, cancer progression, metastasis, and drug resistance in CRC. We also discuss the potential of targeting different S100 proteins as prognostic factors and therapeutic agents for CRC treatment. This narrative review will increase our understanding of the role of S100 proteins in the progression of CRC and provide insights into the use of S100 proteins as new biomarkers and therapeutic targets for CRC therapy.

Background: Dengue is one of the neglected tropical diseases endemic to tropical and subtropical regions worldwide. Due to its substantial disease burden, this arthropod-borne viral disease is a significant public health concern. Infection involving any one of the five distinct serotypes causes a wide range of disease manifestations, from self-limiting to mild to life-threatening outcomes.

Methods: The current review comprehensively provides an overview of dengue virus-mediated immunopathogenesis with special emphasis on innate immune cells, their pathogen recognition sensors and their association with pathogenesis. Additionally we have also briefly discussed recent advancements in vaccine studies and the development of therapeutics over the last decade.

Results: The immunological response to dengue virus involves an amalgamation of a variety of innate cells and inflammatory mediators, resulting in the favouring or dampening of the antiviral response. Viral components activating innate cells through pattern recognition receptors, such as Toll-like receptors, retinoic-acid-inducible gene I and melanoma differentiation-associated gene 5, are vital in eliciting a downstream signalling cascade, which culminates in the secretion of inflammatory proteins.

Conclusion: Understanding the specific mechanisms involved in the acute phase of infection is indispensable for detecting differential biomarkers against flavivirus infections as well as designing more efficient therapeutic agents and vaccines.

Aging is a process preserved in all living beings, progressive over time and inexorable. Despite the existence of several theories that attempt to explain changes associated with aging, scientists have not managed to satisfactorily explain the causes of aging. However, during the last decade, several cellular processes involved in the aging process have been shown to be involved, allowing scientists to identify new biomolecules as aging biomarkers and control the progression of aging. Currently, there is no single biomarker sensitive and specific enough to predict aging, so it is necessary to find a set of specific biomarkers of cellular processes involved in aging. These biomarkers must be accessible for quantification in biological samples in a noninvasive way to implement them in clinical practice. By 2050, it is estimated that approximately one in six people in the world will be over 65 years old, doubling the percentage of population over 60 years old. Therefore, the research of new biomarkers represents a novel strategy to counteract against aging and improve quality of life. In this review we summarize the potential biomarkers of aging that could be used in a noninvasive manner.

Background: The rapid advancement of 3D bioprinting is transforming possibilities in tissue engineering and personalised medicine, offering innovative solutions to critical biomedical challenges such as organ shortages and the need for precise 3D cellular models. To fully unlock the potential of this technology, anoptimised and comprehensive workflow is essential.

Methods: This review provides a systematic examination of the bioprinting process, covering key steps from medical image acquisition to the validation of bioprinted structures. The analysis includes biomaterial and cell type selection, conversion of DICOM images into 3D-printable models, and slicing techniques.

Results: Key factors influencing the precision, viability, and clinical relevance of bioprinted tissues are identified. Comparisons between planar and non-planar slicing algorithms highlight their impact on scaffold integrity. The review also discusses advancements in algorithm development, bioprinter technology, and biomaterial optimisation, emphasising their role in enhancing reproducibility and functionality.

Conclusions: This structured review offers actionable insights for researchers and practitioners aiming to refine bioprinting workflows. By integrating improvements across imaging, modelling, and material selection, 3D bioprinting can more effectively support the development of clinically relevant constructs, advancing regenerative medicine and personalisedhealthcare.

Human babesiosis is a disease transmitted by the bite of an infected tick or via blood transfusions involving contaminated blood products; in humans, it can lead to severe complications and even death, depending on the clinical history, age and health status of the affected patient. Babesiosis is caused by members of the Babesia spp., protozoan parasites whose life cycle includes sexual reproduction in the arthropod vector and asexual reproduction in the mainly mammalian host. Cases of human babesiosis have been rare, but there are increasing reports of human babesiosis associated with climatic changes affecting the geographical distribution of the parasite and tick vector, enhanced vector-human interactions and improved awareness of the disease in humans. Diagnostics and treatment options for humans are based around discoveries in veterinary research, such as point-of-care testing in cases of bovine babesiosis, and include direct diagnosis by blood smears, polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) technologies, and indirect diagnosis by ELISA, immunofluorescence tests (IFAT) and fluorescent in situ hybridisation. Treatment involves a combination of drugs such as azithromycin and atovaquone, or clindamycin and quinine, but more effective options are being investigated, including, but not limited to, trans-chalcones and tafenoquine. Improved surveillance, awareness and diagnosis, as well as advanced technologies to interrupt vector-host interactions, are crucial in managing the increased threat posed by this once-neglected disease in humans.