Expert Reviews in Molecular Medicine最新文献

Background: Perimenopausal women often experience physiological and psychological decline due to the effects of oestrogen fluctuations and the decline of ovarian function, leading to significantly increased depression rates, decreases in the quality of life and mental health issues. Studies have shown that the gut microbiota exerts anti-perimenopausal depression (PMD) effects via the microbiota-gut-brain (MGB) axis, the mechanisms of which may be related to inflammation. In this review, we discuss the effects and mechanisms of gut microbiota in PMD and provide new insights for future PMD treatment.

Methods: This review elaborates on the role of MGB axis in PMD from different aspects of inflammation, including gut microbiota metabolites, inflammatory signaling pathways, and clinical applications.

Results: Disorders of gut microbiota and decreased levels of gut microbiota metabolites (short-chain fatty acids, monoamine neurotransmitters) may cause PMD. The mechanism of intestinal microbiota-mediated inflammation may be related to TLR4/NF-κB pathway, NOD-like receptor protein 3 (NLRP3) inflammasome pathway and JAK-STAT pathway. At the same time, it was found that gut microbiota (probiotics, prebiotics, etc.) had good therapeutic potential in the treatment of PMD.

Conclusions: MGB axis mediated inflammation may play an important role in PMD. The application of gut microbiota in the treatment of PMD patients has profound clinical transformation value, but a lot of efforts are still needed.

Endothelial progenitor cells (EPCs) are key regulators of vascular homeostasis in both health and disease, playing a crucial role in regenerating the human vascular lining throughout life. These circulating cells can differentiate into mature endothelial cells and are increasingly recognized as important biological markers of vascular function and cumulative risk for various diseases, including cardiovascular conditions. In recent decades, the role of EPCs, particularly the endothelial colony-forming cells (ECFCs) subtype, in pregnancy-related disorders and maternal and neonatal endothelial health has garnered significant attention. Evidence suggests that ECFCs may serve as predictor of future endothelial health in women and their offspring following pregnancy complications, making them particular relevant for research and therapeutic applications in adulthood, as well as potential indicators of vascular health. This review summarizes the evidence on EPCs, specifically ECFCs, as biomarkers of endothelial health in pregnancy, pregnancy-related diseases and ageing, with a focus on maternal and foetal endothelial abnormalities that may serve as prognostic factors for the development of future diseases.

Background: Tumour immunotherapy holds great promise as a treatment for cancer, which ranks as the second highest cause of mortality worldwide. This therapeutic approach can be broadly categorized into two main types: active immunotherapy and passive or adoptive immunotherapy. Active immunotherapy, such as cancer vaccines, stimulates the patients' immune system to target tumour cells. On the other hand, adoptive immunotherapy involves supplying in vitro activated immune cells, such as T cells, natural killer cells and macrophages, to the patient to combat the tumour. Induced pluripotent stem cells are extensively utilized in both active and adoptive tumour immunotherapy due to their pluripotency and ease of gene editing. They can be differentiated into various types of immune cells for direct cancer treatment and can also function as tumour vaccines to elicit an immune response against the tumour. Importantly, iPSCs can be leveraged to develop off-the-shelf allogenic immunotherapy products.

Conclusion: This article provides a comprehensive review of the application of iPSCs in tumor immunotherapy, along with a discussion of the opportunities and challenges in this evolving field.

Background: In this short narrative review, we would like to discuss the immunomodulatory effects of South African geranium (Pelargonium sidoides) root extract EPs7630 in treating acute rhinosinusitis. The plant has been used for centuries to treat respiratory tract inflammation, such as sinusitis, pharyngitis and bronchitis. South African geranium is rich in polyphenols, flavonoids, tannins, diterpenes and proanthocyanidins, but the main constituent is a type of coumarin called 'umckalin' (6-hydroxy-5,5-dimethoxy-coumarin). The substance is standardised as an aqueous-ethanolic extract from the root of this plant under the code name EPs7630.

Methods: The article presents the results of in vitro and in vivo studies of administering this herbal drug in acute viral, post-viral and bacterial rhinosinusitis. The focus is on the immunomodulatory effects of EPs7630 during the therapy of this acute inflammation of the nasal mucosa.

Results: According to the results of some studies, EPs7630 stimulates monocyte-dependent activity and inhibits neutrophil-dependent chemokine activity. However, given the small number of studies, the level of evidence is low, implying the need for new research.

Conclusion: Particular attention should be paid to the effect of EPs7630 on bradykinin, the mediator that triggers most inflammatory processes in acute rhinosinusitis.

Introduction: Irisin is a glycosylated polypeptide hormone derived from muscles that plays a crucial role in learning and memory by promoting the growth of hippocampal neurons, thereby influencing cognitive function.

Objective: Despite increasing evidence, a comprehensive understanding of the exact role of irisin remains elusive, necessitating further research to unravel the complex mechanisms through which irisin influences cognitive function and to explore therapeutic approaches targeting irisin.

Method: A literature review was performed by searching PubMed for articles published between 2012 and 2024, using the keywords ‘fibronectin type III domain-containing 5 (FNDC5)’, ‘irisin’, ‘cognitive impairment’, ‘Alzheimer’s disease’, ‘Age-related cognitive dysfunction’ and ‘Diabetes-associated cognitive dysfunction’, combined with Boolean operators (AND/OR).

Results: This review highlighted the potential impact of irisin on cognitive function in the context of ageing, diabetes and Alzheimer’s disease. The anti-cognitive impairment effects of irisin are associated with the regulation of energy metabolism, insulin resistance, inflammation, oxidative stress, amyloid-beta deposition, synaptogenesis and plasticity. The signalling pathways through which irisin improves cognitive impairment are complex and highly regulated processes, involving multiple signalling pathways such as the adenosine monophosphate-activated protein kinase (AMPK) signalling pathway, mitogen-activated protein kinase (MAPK) signalling pathway, nuclear factor-κB (NF-κB) signalling pathway, ERK-STAT3 signalling pathway, cAMP/PKA/CREB signalling pathway and Nrf2/HO-1 signalling pathway.

Conclusion: This review delves into the positive effects of irisin on cognitive impairment, examines the signalling pathways related to fibronectin type III domain-containing 5 (FNDC5)/irisin and provides future perspectives for research on the anti-cognitive impairment effects of irisin.

SIGIRR, also known as the single immunoglobulin interleukin-1 receptor (IL-1R)-related molecule, is a member of the IL-1 receptor superfamily and is believed to play a pivotal role in inflammation and anti-inflammatory regulation within the body. Studies have shown that SIGIRR expression is associated with autoimmunity, inflammatory disorders, graft rejection, viral infection, thrombosis and tumour progression. Due to its unique structure and function, SIGIRR is commonly referred to as an 'orphan receptor', with IL-37 being the only confirmed ligand molecule for SIGIRR to date. The primary mechanism through which SIGIRR exerts its anti-inflammatory regulatory effect involves the negative modulation of the Toll-like receptor-IL-1R (TLR-IL-1R) signalling pathway. TLR-IL-1R signalling plays critical roles in immune responses triggered by microbial invasion and alterations in the tumour immune microenvironment. This article provides an overview of research findings on SIGIRR as an orphan receptor and its regulatory role in maintaining a delicate balance between natural immune activation and uncontrolled inflammatory processes under pathological conditions.

Search results: Reactive oxygen species (ROS) play a dual role in leishmaniasis by contributing to both host defence and parasite survival mechanisms. In the host, ROS promote parasite clearance through induction of apoptosis, activation of pro-inflammatory signalling pathways (e.g., MAPK, JNK), inflammasome assembly, and M1 macrophage polarisation. Conversely, Leishmania species have evolved multiple strategies to neutralize ROS, including the upregulation of host antioxidant enzymes like HO-1, inhibition of ROS-producing pathways, and expression of parasite-derived antioxidants such as SOD, GPx, and trypanothione reductase. The parasite alsoadapts through gene regulation and metabolic changes to counter oxidative stress. Importantly, ROS have emerged as key targets for antileishmanial therapies, with various drugs and natural compounds shown to induce ROS-mediated parasite death, highlighting their potential in future therapeutic development.

Conclusions: In summary, the survival of Leishmania hinges on its ability to counteract host-induced oxidative stress. Targeting its antioxidant defences and enhancing host ROS production can disrupt this balance, leading to parasite death. Exploring ROS-related signalling offers a promising path for developing effective therapies against leishmaniasis.

Background: Current breast cancer (BC) diagnostics include detailed pathological and genetic analysis for biological subtype identification; however, throughout the course of the disease, new alterations determining the progression of the disease or resistance to treatment appear. The tests based on liquid biopsy allow minimally invasive real-time monitoring of tumour-specific alteration during the entire disease treatment. Tumour-specific genetic material fragments occur in bodily fluids, and cell-free nucleic acids are a convenient tool for analysing genetic and epigenetic changes in tumours. Evidence for the diagnostic and prognostic value of epigenetic biomarkers is gradually increasing. Although, up to date, there is limited access to in vitro diagnostic (IVD) epigenetic liquid biopsy-based tests for BC management, the data on the clinical potential of such tests and biomarkers are accumulating rapidly.

Methods: In this review, we focused on research involving cell-free DNA methylation biomarkers in blood serum or plasma samples from BC patients.

Results: Our review systematises data from genome-wide and targeted studies of DNA methylation changes in liquid biopsies from BC patients, aiming to highlight the most critical biomarkers suitable for early BC diagnosis, treatment personalisation and prognosis.

Conclusion: In summary, cell-free DNA methylation biomarkers show strong potential to enhance breast cancer diagnosis, prognosis, and personalised treatment through integrated clinical profiling.