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.

Non-coding RNAs (ncRNAs) are transcribed RNA molecules that do not encode proteins but regulate diverse biological processes. Dysregulation of ncRNAs is implicated in cancer, where chemical modifications such as N6-methyladenosine (m6A), N4-acetylcytidine (ac4C), and glycosylation critically influence their function. However, these modifications, as precise regulators of ncRNA activity, have been less well-documented and understood in tumorigenesis and cancer progression.

This article systematically analyzes the roles of chemically modified ncRNAs – ribosomal RNA (rRNA), circular RNA (circRNA) and others – in cancer biology, synthesizingevidence from published studies on their mechanistic involvement in malignancy.

We reveal how specific chemical modifications drive oncogenesis, impact cancer diagnosis, and affect therapeutic responses, while also exploring their prognostic potential. Furthermore, we highlight emerging connections between ncRNA epitranscriptomics and cancer.

This review provides novel insights into ncRNA epitranscriptomics as emerging biomarkers and intervention targets for precision oncology.

Retinoic acid-induced 1 (RAI1) is a dosage-sensitive gene implicated in a range of rare neuropsychiatric diseases.

This review provides a comprehensive overview of RAI1’s role, integrating both clinical and basic research on Smith–Magenis syndrome (SMS) and Potocki–Lupski syndrome (PTLS) while also summarising research progress on its involvement in spinocerebellar ataxia (SCA), autism spectrum disorder (ASD), schizophrenia, bipolar disorder and major depression. A systematic review of the literature was conducted using PubMed and EMBASE, following the PRISMA guidelines, with the protocol registered in PROSPERO (CRD42023474165).

A total of 99 eligible studies on RAI1 were included. We presented detailed characterisations of SMS and PTLS patients, emphasising the crucial role of RAI1 haploinsufficiency and overexpression in their pathogenesis. Additionally, we summarised research progress on RAI1 in SCA, ASD, schizophrenia, bipolar disorder and major depression. Integrating findings from animal studies, particularly those examining the regulatory mechanisms of RAI1 in critical phenotypes, such as body weight, sleep and epilepsy, underscores the precise regulation of RAI1 expression in maintaining various nervous system functions.

Overall, this review contributes to the identification of RAI1-related neuropsychiatric diseases, with a particular emphasis on enhancing clinical diagnosis of SMS and PTLS in developing countries.

The global incidences of leishmaniasis are increasing due to changing environmental conditions and growing poverty. Leishmaniasis, caused by the Leishmania parasite, presents itself in six different clinical forms, the cutaneous and the visceral diseases being the most prevalent. While the cutaneous form causes disfigurement, the visceral form could be fatal if not treated. With no available vaccines combined with serious side effects of current medications and emerging drug resistance, it is crucial to discover new drugs whether as novel compounds or as repurposed existing pharmaceuticals. In the realm of drug development, mitochondria are recognized as important pharmacological targets due to their critical role in energy control, which, when disrupted, leads to irreversible cell damage. Certain plant-based compounds able to target the parasite mitochondrion, have been studied for their potential anti-leishmanial effects.

These compounds have shown promising effects in eliminating the Leishmania parasite. Artemisinin and chloroquine, two anti-malarial drugs that target mitochondria, exert strong anti-leishmanial effectiveness in both in vitro cultures and in vivo animal models. Quinolones, coumarins and quercetin are other compounds with leishmanicidal properties, which disrupt mitochondrial activity to effectively eliminate parasites in animal models of the disease and could be considered as potential drugs.

Therefore, plant-based compounds hold promise as potential candidates for anti-leishmanial drug development.

The recent emergence of three-dimensional organoids and their utilization as in vitro disease models confirmed the complexities behind organ-specific functions and unravelled the importance of establishing suitable human models for various applications. Also, in light of persistent challenges associated with their use, researchers have been striving to establish more advanced structures (i.e. assembloids) that can help address the limitations presented in the current organoids.

In this review, we discuss the distinct organoid types that are available to date, with a special focus on retinal and brain organoids, and highlight their importance in disease modelling.

We refer to published research to explore the extent to which retinal and brain organoids can serve as potential alternatives to organ/cell transplants and direct our attention to the topic of photostimulation in retinal organoids. Additionally, we discuss the advantages of incorporating microfluidics and organ-on-a-chip devices for boosting retinal organoid performance. The challenges of organoids leading to the subsequent development of assembloid fusion models are also presented.

In conclusion, organoid technology has laid the foundation for generating upgraded models that not only better replicate in vivo systems but also allow for a deeper comprehension of disease pathophysiology.

Lactylation, a new epigenetic modification, is an important way in which lactate exerts physiological functions. There is a close relationship between increased lactylations caused by lactate and glycolysis, which can interact and play a role in disease through lactate as an intermediate mediator. Current research on lactylations has focused on histone lactylation, but non-histone lactylation also has greater research potential. Due to the ubiquity of lactate modifications in mammalian cells, an increasing number of studies have found that lactate modifications play important roles in tumour cell metabolism, gene transcription and immunity.

A systematic literature search was carried out using search key terms and synonyms. Full-paper screening was performed based on specific inclusion and exclusion criteria.

Many literatures have reported that the lactylation of protein plays an important role in human diseases and is involved in the occurrence and development of human diseases.

This article summary the correlation between lactylation and glycolysis, histones and non-histone proteins; the relationship between lactonation modifications and tumour development; and the current existence of lactylation-related inhibitors, with a view to provide new basic research ideas and clinical therapeutic tools for lactylation-related diseases.

Fibrosis is a pathological condition that affects various organs by increasing fibrous connective tissue while reducing parenchymal cells. This imbalance can lead to compromised organ function and potential failure, posing significant health risks. The condition’s complexity necessitates the exploration of effective treatments to mitigate its progression and adverse outcomes.

This study aims to investigate the role of ghrelin, a peptide hormone known for its anti-inflammatory and anti-fibrotic properties, in modulating fibrosis across different organs. By binding to the growth hormone secretagogue receptor type 1a (GHSR-1a), ghrelin has shown potential in attenuating the fibrotic process, particularly through its interaction with the TGF-β signalling pathway.

An extensive review of clinical and animal model studies focusing on liver, kidney, lung, and myocardial fibrosis was conducted. The primary focus was on examining how ghrelin influences the TGF-β signalling pathway, with an emphasis on the regulation of TGF-β expression and the suppression of Smad signalling molecules. The methodology involved analysing data from various studies to understand ghrelin’s molecular mechanisms in combating fibrosis.

The findings from the reviewed studies indicate that ghrelin exerts significant anti-fibrotic effects across multiple organ systems. Specifically, ghrelin was found to downregulate TGF-β expression and suppress Smad signalling molecules, leading to a marked reduction in fibrous tissue accumulation and preservation of organ function. In liver fibrosis models, ghrelin reduced TGF-β1 levels and Smad3 phosphorylation, while in kidney and cardiac fibrosis, similar protective effects were observed. The data also suggest that ghrelin’s effects are mediated through both canonical and non-canonical TGF-β pathways.

Ghrelin presents a promising therapeutic agent in the management of fibrosis due to its potent anti-inflammatory and anti-fibrotic actions. Its ability to modulate the TGF-β signalling pathway underscores a vital molecular mechanism through which ghrelin can mitigate fibrotic progression in various organs. Future research should focus on further elucidating ghrelin’s molecular interactions and potential clinical applications in fibrosis treatment, offering new avenues for developing effective anti-fibrotic therapies.

Leishmaniasis, Chagas disease (CD), and Human African Trypanosomiasis (HAT) are neglected tropical diseases in humans caused by intracellular parasites from the class Kinetoplastida. Leishmaniasis is one infectious disease that exhibits sex-bias not explained solely by behavioral or cultural differences. However, HAT and CD have less well documented and understood sex-related differences, either due to a lack of differences or insufficient research and reporting.

This paper reviews the rate of disease and disease severity among male and females infected with CD, HAT, and leishmaniasis. We further review the specific immune response to each pathogen and potential sex-based mechanisms which could impact immune responses and disease outcomes.

These mechanisms include sex hormone modulation of the immune response, sex-related genetic differences, and socio-cultural factors impacting risky behaviors in men and women. The mechanistic differences in immune response among sexes and pathogens provide important insights and identification of areas for further research.

This information can aid in future development of inclusive, targeted, safe, and effective treatments and control measures for these neglected diseases and other infectious diseases.