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.

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).

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

The development of oxidative stress depends on the deregulation of the fine balance between the proportion of reactive oxygen species (ROS) generation and the activity of antioxidants. As oxidative stress is deleterious for Leishmania sp., their host cell generates ROS as one of the foremost defence strategies. The parasites have also raised a variety of counteracting tricks in order to conquer this challenge. Upon infection, the host’s own antioxidant system is activated by the parasite to neutralise the oxidative stress-mediated protection. In addition to using the host’s antioxidant mechanisms, some genes within the parasite also make them more tolerant against oxidative stress. Therefore, the present review focuses on some major regulators intimately related to the equilibrium between oxidation and antioxidation following infection with Leishmania sp., which may be helpful in developing a comprehensive knowledge of this specific wing of infection biology associated with oxidative stress.

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.

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.

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.

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

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.

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