The receptor for advanced glycation end-products (RAGE) is a unique multi-ligand member of the immunoglobulin superfamily that exists in both membrane-bound and soluble forms. Under physiological conditions, RAGE expression is low in most tissues; however, it is markedly upregulated in response to tissue injury, inflammation or metabolic stress. Ligand-induced activation of RAGE initiates complex intracellular signalling cascades that regulate inflammation, extracellular matrix remodelling, cell proliferation, survival and migration.

While the contribution of RAGE to diabetes and chronic inflammatory diseases is well established, its role in gynaecological disorders remains insufficiently characterized.

This comprehensive review summarizes current evidence on the involvement of RAGE in the pathogenesis of benign gynaecological disorders, such as endometriosis and polycystic ovary syndrome (PCOS), pregnancy-related complications and malignant neoplasms of the female reproductive tract.

It also discusses emerging therapeutic strategies aimed at targeting the RAGE pathway, highlighting their potential translational relevance in gynaecological practice.

Prostate cancer (PCa) exhibits profound metabolic reprogramming, including dysregulation of the urea cycle (UC), an emerging driver of tumour growth, therapy resistance, and immune modulation. In normal physiology, the UC detoxifies ammonia via urea production. In PCa cells, however, altered expression of UC enzymes such as argininosuccinate synthase 1 (ASS1), arginase (ARG) and ornithine decarboxylase (ODC1) reroutes metabolites towards other pathways, including polyamine and nucleotide synthesis. These changes enhance proliferation, facilitate metabolic plasticity and influence the tumour microenvironment.

This review summarises mechanistic insights into UC dysregulation in PCa, with emphasis on its interplay with the tricarboxylic acid (TCA) cycle, choline metabolism, and polyamine synthesis.

We critically evaluate current therapeutic strategies such as arginine deprivation (PEGylated arginine deiminase, ADI-PEG 20, PEGylated recombinant human arginase 1, PEG-BCT-100), ODC1 inhibition (α-difluoromethylornithine, DFMO), and glutaminase blockade (CB-839) and discuss their integration with other therapies, including androgen deprivation. Furthermore, we explore the challenges and the usefulness of UC metabolites as diagnostic and prognostic biomarkers for early detection of PCa as well as for a follow-up of patients during therapy.

We conclude that UC dysregulation represents a targetable metabolic vulnerability in PCa. However, successful translation will require combinatorial therapeutic approaches and rigorous validation of UC-based biomarkers in prospective clinical trials.

Lactosylceramides (LacCers) are glycosphingolipids that play essential roles in physiological and pathological processes across immune, endocrine, and neurological systems, with mechanistic studies demonstrating that LacCers modulate inflammatory signalling, oxidative stress responses, membrane microdomain organisation, and control aspects of mitochondrial function. Historically, LacCers were quantified predominantly as a total lipid subclass, limiting the ability to discern how individual species contribute to biological processes in clinical contexts. Recent advances in mass spectrometry based lipidomics now enable LacCer species to be resolved by acyl-chain length and saturation, offering far greater biochemical and clinical insights.

In this narrative review, we examine evidence from population based lipidomic studies describing how LacCer composition varies across healthy and diseased states.

In metabolic and vascular disorders, multiple studies report elevations in specific short- and medium-chain LacCer species, whereas patterns involving longer-chain species appear more heterogeneous. Altered LacCer profiles have also been described in neurodegenerative disease, chronic kidney disease, and cancers, with species-level differences varying by disease-context, tissue type, and analytical platform.

Our findings describe disease- and tissue-specific variations in LacCer acyl-chain composition, underscoring the value of species-level resolution for mechanistic understanding and informing the application of LacCer profiles in future biomarker and therapeutic studies.

In 2025, transformative and transnational plans to phase out animal testing and reduce reliance on animal use in research settings were introduced.

Steps towards realising these plans can be addressed by using human tissues and metadata obtained from biobanks. Biobanks securely and ethically collect, process, store, manage and distribute human biological tissues donated by patients for biomedical research purposes.

Biobanks have developed at pace over the last decade, expanding their repertoires to meet increasingly complex demands from researchers.

This article outlines how the power of biobanks can be leveraged to drive innovative animal-free biomedical research, including the patient perspective.

Nerve growth factor (NGF), which acts on receptors tropomyosin receptor kinase A and p75 neurotrophic receptor, is a member of neurotrophin family and a kind of secretory polypeptides.

A comprehensive literature search was conducted in the following databases: PubMed and Web of Science. The following search terms were used in various combinations: “NGF,” “nerve growth factor,” “ovarian steroidogenesis,” “follicular development,” “oocyte maturation,” and “ovulation.” Boolean operators (AND, OR) were applied to combine search terms (e.g., “NGF AND PCOS,” “NGF AND follicular development”).

NGF plays important roles in multiple reproductive physiological activities. Its ovarian effects are crucial for oocyte maturation, follicular assembly, early follicle development, ovulation and steroidogenesis. While the ovary is a major target, NGF’s role extends to the broader regulation of the female reproductive system. In particular, the role of NGF in inducing ovulation by acting on the hypothalamus has garnered considerable scholarly attention. Although relatively few studies have examined the direct impact of NGF on hypothalamic gonadotrophin-releasing hormone neurons—the central regulators of the hypothalamic–pituitary–ovary (HPO) axis, extensive evidence demonstrates that NGF can cause an influence on the synthesis and release of follicle-stimulating hormone, luteinizing hormone and steroid hormones, which act downstream in the HPO axis.

Our review outlines the critical role of NGF in female reproductive physiology, with a particular focus on its modulatory influence on induced ovulation. Furthermore, in this review, we aim to provide a more comprehensive perspective on NGF’s role in reproductive disorders, such as polycystic ovary syndrome, diminished ovarian reserve and endometriosis.

CAR-T cell gene therapy has advanced from an experimental concept to a standard curative treatment for selected hematologic malignancies. Substantial clinical evidence has established CAR-T therapy as a cornerstone for relapsed/refractory B-cell malignancies and multiple myeloma, demonstrating durable, long-term remissions. In 2025, the U.S. Food and Drug Administration (FDA) eliminated the Risk Evaluation and Mitigation Strategy (REMS) requirement, reflecting improved clinical management of Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). Yet, the widespread adoption of these therapies has unveiled a new landscape of long-term and next-generation challenges.

This review critically analyzes CAR-T therapy’s clinical trajectory and the bioengineering strategies redefining its safety, scalability, and translational potential.

A major hurdle is therapeutic resistance driven by antigen escape, notably through alternative splicing and lineage switching. The emergence of long-term safety signals, specifically secondary T-cell malignancies, has necessitated rigorous surveillance, exemplified by the European Medicines Agency’s (EMA) mandate for lifelong patient monitoring. The therapeutic landscape is further complicated by histopathological and immunological barriers limiting the expansion and persistence of engineered cells. These include deficient T-cell trafficking, an immunosuppressive tumor microenvironment (TME), and antigen heterogeneity, which have historically constrained efficacy in solid tumors. To address these hurdles, the field is leveraging CRISPR-enhanced allogeneic platforms, cytokine-secreting armored CARs (TRUCKs), and logic-gated systems showing early clinical promise.

Building on these developments, we hypothesize that CAR-T therapy is undergoing a paradigm shift from single-target cytotoxicity toward a multi-functional, programmable framework capable of overcoming resistance, enhancing safety, and enabling effective penetration of solid tumors.

Acupuncture is increasingly used during in vitro fertilization and embryo transfer (IVF-ET), but its therapeutic benefits for women with polycystic ovary syndrome (PCOS) remain uncertain.

Eight databases were investigated from the inception until April 1, 2024. We screened randomized controlled trials (RCTs) using acupuncture undergoing IVF-ET, the population was patients with PCOS.

We analyzed 13 RCTs with 1,203 patients. Acupuncture significantly improved clinical pregnancy rate (P < 0.01), high-quality embryo rate (P < 0.01), and live birth rate (P < 0.01). It also reduced gonadotropin (Gn) dose (P = 0.0002), Gn duration (P = 0.005), and OHSS incidence (P < 0.01). No significant differences were seen in fertilization rate, oocyte yield, endometrial thickness, progesterone, LH, E2, miscarriage rate, or cycle cancellation rate.

Our results showed that acupuncture therapy could increase the high-quality embryo rate, live birth rate and also the clinical pregnancy rate in PCOS patients undergoing IVF. Acupuncture could reduce the dose and duration of Gn. It also decreased the incidence of OHSS. Based on the result of this meta-analysis, acupuncture therapy is suggested in the IVF process for PCOS patients.

Lifestyle changes and unhealthy eating habits have led to a sharp rise in obesity rates worldwide. Obesity is closely associated with a range of complications, including cognitive impairment and dementia. Accumulating evidence indicates that obesity negatively affects cognitive function and may increase the risk of neurodegenerative diseases. Conversely, cognitive dysfunction may further contribute to the development and progression of obesity. With growing attention in this field, obesity-related cognitive impairment has emerged as an important research focus at the intersection of metabolic and neurological disorders.

This article reviews the potential mechanisms underlying obesity-related cognitive impairment and summarizes emerging therapeutic strategies.

The development and progression of obesity-related cognitive impairment involve multiple mechanisms, including insulin resistance, systemic and central inflammation, immune dysregulation, microcirculatory alterations and changes in neurotransmitters and synaptic plasticity. Recent studies have focused on the adipose tissue-brain axis and the microbiota–gut–brain axis, in particular, the targeted effects of extracellular vesicles released from adipose tissue and microbiota on the brain.

This article systematically reviews the mechanisms underlying obesity-related cognitive impairment and presents novel therapeutic strategies.

Radiotherapy (RT) and immune checkpoint inhibitors (ICIs) have each transformed the treatment of malignant solid tumors (STs). Beyond direct tumor killing, RT remodels the tumor microenvironment (TME), promotes antigen release, and enhances immune activation. ICIs targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1) restore antitumor immunity by reversing T cell exhaustion. Increasing evidence indicates that RT can synergize with ICIs through mechanisms such as the abscopal effect, immunogenic cell death (ICD), and activation of the cyclic guanosine monophosphate–adenosine monophosphate (cGMP–AMP) synthase–stimulator of interferon genes (cGAS–STING) pathway.

This review summarizes current radiobiological, immunological, and clinical evidence regarding the synergistic effects of RT and ICIs in malignant STs, with a focus on underlying mechanisms, recent clinical advances, and translational challenges.

RT can enhance tumor immunogenicity, promote immune priming, and reshape the TME to improve the efficacy of ICIs. Synergy between RT and ICIs is associated with ICD induction, cGAS‒STING activation, enhanced systemic antitumor immunity, and modulation of immune cell infiltration and checkpoint signaling. Clinical studies across multiple STs have shown encouraging efficacy and manageable safety, although outcomes vary according to tumor type, disease stage, radiation schedule, and patient selection.

RT combined with ICIs is a promising therapeutic strategy for malignant STs. Further optimization of treatment regimens and biomarker-guided patient selection will be essential to maximize clinical benefit and enable more precise combination therapies.

High altitude cerebral edema (HACE), a fatal terminal stage of acute mountain sickness (AMS), is triggered by rapid exposure to hypoxia at high altitudes. The pathophysiology of HACE is complex, involving multiple key processes including energy metabolism disorders, oxidative stress, blood-brain barrier (BBB) injury, and neuroinflammation, all of which interact to drive disease progression. Lactylation, a novel epigenetic regulatory mechanism discovered in 2019, provides a fresh perspective for HACE research.

This study integrates the latest research findings on the pathophysiology of HACE, lactate metabolism, and the role of lactylation in hypoxia-related diseases (such as cancer and ischemic-hypoxic diseases). It focuses on analyzing the potential molecular mechanisms of lactylation in HACE, including its regulation of the HIF-1α/NF-κB axis, inflammation, and metabolism, and discusses existing lactylation regulation strategies.

In HACE, hypoxia-driven glycolysis elevates lactate, promoting protein lactylation (e.g., NuRD complex in microglia, which is correlated with proinflammatory cytokines). Lactylation may regulate HIF-1α/NF-κB axis, inflammation, and metabolism in HACE pathogenesis. Currently, methods such as the inhibition of lactate dehydrogenase (LDH) /monocarboxylate transporters and the use of histone deacetylase inhibitors have been proven effective in regulating lactylation.

Lactylation is a key link connecting metabolic disorders and neuroinflammation in HACE. However, the dual role of lactate in neuroprotection and neuroinjury under hypoxic conditions still requires further exploration. Future research should focus on deciphering the molecular networks related to HACE and developing precise intervention strategies to provide new directions for HACE treatment.