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A major goal in regenerative medicine is restoring damaged tissues through cell replacement or by activating endogenous repair pathways. Immune modulation is increasingly recognized as essential for creating a permissive environment for regeneration. Bioactive factors secreted by stem and stromal cells -either as soluble molecules or within extracellular vesicles (EVs)- can reshape immune responses, not just by reducing inflammation but by actively promoting pro-resolving, regenerative profiles. For nearly two decades, our research has focused on the therapeutic potential of human term placenta-derived cells, particularly mesenchymal stromal cells from the amniotic membrane (hAMSC). We have shown that hAMSC and their secretome (CM-hAMSC) exert potent immunomodulatory effects in vitro: suppressing T- and B-cell proliferation, downregulating proinflammatory Th1/Th17 phenotypes, enhancing regulatory T cells, and inhibiting naïve CD8 T cell polarization into memory subsets. They also reduce B-cell differentiation into antibody-secreting cells and steer monocytes away from dendritic cells and M1 macrophages toward anti-inflammatory M2 phenotypes. These effects have translated into therapeutic benefits in numerous preclinical models of inflammation-driven disease (including lung/liver fibrosis, sepsis, IBD, cardiac ischemia, autoimmune encephalomyelitis, rheumatoid arthritis, and traumatic brain injury) by tempering inflammation and promoting resolution. Ongoing studies aim to dissect the mechanisms driving these effects, especially whether they are mediated by soluble molecules, EVs, or both. A key area of interest is their ability to modulate the inflammasome pathway, a central driver of innate immunity linked to aging and degeneration. By regulating this pathway, placental factors may redirect chronic inflammation toward regeneration. Given inflammation’s dual role as trigger and barrier in many degenerative conditions, placental cells -especially those from the amniotic membrane- emerge as a powerful paradigm. This lecture will explore how their unique immunological properties can inspire innovative regenerative strategies.

Developing cellular therapies is not straightforward. This presentation summarizes the experience of academic stem cell investigators working in different clinical applications and aiming to share insight into what could be useful to consider, in light of the current situation regarding advanced therapies. These include 1) choosing the stem cell type and assessing a platform of technologies possibly common to multiple products, 2) familiarity with GMP manufacturing, reagent validation, and supply chain management, 3) product delivery issues and the additional regulatory challenges, 4) the relationship between clinical trial design and preclinical studies, and 5) the market approval requirements, scalability, pathways, and partnerships needed.

Monoclonal antibody-based therapies have become standard treatments for both hematological and solid malignancies. Trastuzumab (TZM), a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2), is a key therapy for HER2+ breast cancer. However, therapeutic efficacy is often compromised by tumor microenvironment (TME) features, such as dense extracellular matrix and poor vascularization, that limit antibody access and binding. Thus, there is a critical need for imaging approaches that can measure whether an antibody drug actually reaches and binds its target within heterogeneous tumors. We have developed a near-infrared (NIR) fluorescence lifetime (FLI) Förster Resonance Energy Transfer (FRET) optical imaging platform to address this challenge. This method directly reports drug-target engagement by measuring the fraction of donor labeled antibodies undergoing FRET when in proximity to acceptor-labeled antibodies upon receptor binding, using in vitro microscopy and in vivo macroscopy. We applied NIR-FLI-FRET to quantify HER2 binding in HER2+ breast cancer cells, tumor spheroids, and xenografts. To assess the influence of TME, we examined tumors with differing levels of collagen and vascularity. NIR-FLI-FRET imaging revealed that tumors with elevated collagen content and reduced vascularity showed decreased TZM- HER2 binding, despite robust HER2 expression, suggesting physical barriers to antibody penetration and reduced therapeutic efficacy. We further integrated site-specific labeling and antibody engineering via meditope- enabled TZM (MDT-TZM) to improve imaging precision and antibody performance. MDT-TZM exhibited deeper tumor penetration and more uniform binding in vivo compared to traditional NHS-labeled TZM. FRET signal maps correlated strongly with immunohistochemistry for HER2 and TZM, validating imaging results. Together, this antibody-to-imaging pipeline offers a powerful, non-invasive method to quantify drug-target engagement and understand how TME impacts antibody therapy. It represents a critical step toward precision imaging to guide antibody design and optimize treatment strategies in breast cancer.

The so-called global land rush has drawn new attention to land, its uses and value. But land is a strange object. Although it is often treated as a thing and sometimes as a commodity, it is not like a mat: you cannot roll it up and take it away. To turn it to productive use requires regimes of exclusion that distinguish legitimate from illegitimate uses and users, and the inscribing of boundaries through devices such as fences, title deeds, laws, zones, regulations, landmarks and story-lines. Its very 'resourceness' is not an intrinsic or natural quality. It is an assemblage of materialities, relations, technologies and discourses that have to be pulled together and made to align. To render it investible, more work is needed. This Transactions of the Institute of British Geographers Plenary Lecture uses an analytic of assemblage to examine the practices that make up land as a resource. It focuses especially on the 'statistical picturing' devices and other graphic forms that make large-scale investments in land thinkable, and the practices through which relevant actors (experts, investors, villagers, governments) are enrolled. It also considers some of the risks that follow when these large-scale investments land in particular places, as land they must.

EPA and DHA appear to be the most important n-3 fatty acids, but roles for n-3 docosapentaenoic acid are now also emerging. Intakes of EPA and DHA are usually low, typically below those recommended. Increased intakes result in higher concentrations of EPA and DHA in blood lipids, cells and tissues. Increased content of EPA and DHA modifies the structure of cell membranes and the function of membrane proteins. EPA and DHA modulate the production of lipid mediators and through effects on cell signalling can alter the patterns of gene expression. Through these mechanisms, EPA and DHA alter cell and tissue responsiveness in a way that often results in more optimal conditions for growth, development and maintenance of health. DHA has vital roles in brain and eye development and function. EPA and DHA have a wide range of physiological roles, which are linked to certain health or clinical benefits, particularly related to CVD, cancer, inflammation and neurocognitive function. The benefits of EPA and DHA are evident throughout the life course. Future research will include better identification of the determinants of variation of responses to increased intake of EPA and DHA; more in-depth dose–response studies of the effects of EPA and DHA; clearer identification of the specific roles of EPA, docosapentaenoic acid and DHA; testing strategies to enhance delivery of n-3 fatty acids to the bloodstream; and exploration of sustainable alternatives to fish-derived very long-chain n-3 fatty acids.

Mental illness, including depression, anxiety and bipolar disorder, accounts for a significant proportion of global disability and poses a substantial social, economic and heath burden. Treatment is presently dominated by pharmacotherapy, such as antidepressants, and psychotherapy, such as cognitive behavioural therapy; however, such treatments avert less than half of the disease burden, suggesting that additional strategies are needed to prevent and treat mental disorders. There are now consistent mechanistic, observational and interventional data to suggest diet quality may be a modifiable risk factor for mental illness. This review provides an overview of the nutritional psychiatry field. It includes a discussion of the neurobiological mechanisms likely modulated by diet, the use of dietary and nutraceutical interventions in mental disorders, and recommendations for further research. Potential biological pathways related to mental disorders include inflammation, oxidative stress, the gut microbiome, epigenetic modifications and neuroplasticity. Consistent epidemiological evidence, particularly for depression, suggests an association between measures of diet quality and mental health, across multiple populations and age groups; these do not appear to be explained by other demographic, lifestyle factors or reverse causality. Our recently published intervention trial provides preliminary clinical evidence that dietary interventions in clinically diagnosed populations are feasible and can provide significant clinical benefit. Furthermore, nutraceuticals including n-3 fatty acids, folate, S-adenosylmethionine, N-acetyl cysteine and probiotics, among others, are promising avenues for future research. Continued research is now required to investigate the efficacy of intervention studies in large cohorts and within clinically relevant populations, particularly in patients with schizophrenia, bipolar and anxiety disorders.

Consumption of sugar and alternative low- or no-energy sweeteners has increased in recent decades. However, it is still uncertain how consumption of sugar and alternative sweeteners during pregnancy affects pregnancy outcomes and long-term offspring health. This review aims to collate the available evidence surrounding the consequences of sugar and alternative sweetener consumption during pregnancy, a so-called secondhand sugar effect. We found evidence that sugar consumption during pregnancy may contribute to increased gestational weight gain and the development of pregnancy complications, including gestational diabetes, preeclampsia and preterm birth. Further, we found a growing body of the animal and human evidence that maternal sugar intake during pregnancy may impact neonatal and childhood metabolism, taste perception and obesity risk. Emerging evidence also suggests that both maternal and paternal preconception sugar intakes are linked to offspring metabolic outcomes, perhaps via epigenetic alterations to the germline. While there have been fewer studies of the impacts of alternative sweetener consumption before and during pregnancy, there is some evidence to suggest effects on infant outcomes including preterm birth risk, increased infant body composition and offspring preference for sweet foods, although mechanisms are unclear. We conclude that preconception and gestational sugar and alternative sweetener consumption may negatively impact pregnancy outcomes and offspring health and that there is a need for further observational, mechanistic and intervention research in this area.

My essay1 focuses on the marginalised people whose livelihoods depend on gathering, sorting, transporting and selling garbage in India's huge informal economy, livelihoods now challenged as municipal governments contract the recycling of waste to corporations. The evolving, bumpy geography of the waste economy creates permanent border areas of primitive accumulation and both devalorised and valorised people and places. I make a case for understanding informal sector activities, such as the work of transforming the city's detritus, as part of a vast infraeconomy and the varied forms of labour performed within heterogeneous value chains of waste transformation as infrastructural labour that produces what Marx called capital's 'general' and 'external' conditions of production. Through close examination of the spatiotemporal lattice of informal municipal solid waste recycling, I demonstrate how these economies are at once highly organised and brittle, with each node in their value chains subject to disruption by state and market forces. While relative opacity, labour intensity of tasks and dependence on embodied knowledge (metis), indeed a 'bodily' feel for space, give informal economies the capacity to resist external efforts to transform, subsume or eradicate them; lack of social security and employment protections also means that workers and micro-enterprise owners within them inhabit the thin line between survival and failure, rendering them vulnerable to economic and political fluctuations. The upshot is that the labour of waste and other informal sector workers is critical for maintaining the quality of life desired by the well off in cities of the global South, but fails to get the recognition it deserves. Waste workers are poorly compensated, regularly stigmatised and frequently invisible in policy decisions. This is an enduring inequity that demands urgent correction.