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Metabolic reprogramming is crucial to respond to cancer cell requirements during tumor development. In the last decade, metabolic alterations have been shown to modulate cancer cells’ sensitivity to chemotherapeutic agents including conventional and targeted therapies. Recently, it became apparent that changes in lipid metabolism represent important mediators of resistance to anticancer agents. In this review, we highlight changes in lipid metabolism associated with therapy resistance, their significance and how dysregulated lipid metabolism could be exploited to overcome anticancer drug resistance.

Biological aging can be described as accumulative, prolonged metabolic stress and is the major risk factor for cognitive decline and Alzheimer's disease (AD). Recently, we identified and described a quinone reductase 2 (QR2) pathway in the brain, in which QR2 acts as a removable memory constraint and metabolic buffer within neurons. QR2 becomes overexpressed with age, and it is possibly a novel contributing factor to age-related metabolic stress and cognitive deficit. We found that, in human cells, genetic removal of QR2 produced a shift in the proteome opposing that found in AD brains while simultaneously reducing oxidative stress. We therefore created highly specific QR2 inhibitors (QR2is) to enable evaluation of chronic QR2 inhibition as a means to reduce biological age-related metabolic stress and cognitive decline. QR2is replicated results obtained by genetic removal of QR2, while local QR2i microinjection improved hippocampal and cortical-dependent learning in rats and mice. Continuous consumption of QR2is in drinking water improved cognition and reduced pathology in the brains of AD-model mice (5xFAD), with a noticeable between-sex effect on treatment duration. These results demonstrate the importance of QR2 activity and pathway function in the healthy and neurodegenerative brain and what we believe to be the great therapeutic potential of QR2is as first-in-class drugs.

To evaluate the impact of corneas from donors over 80 years of age on the activity of the North of France Tissue Bank and to determine the potential cost implications for banks using corneas from older donors. We analyzed data from a single-center retrospective cohort study of 6,023 corneas preserved at the Lille Tissue Bank between 2012 and 2023. Donors, unrestricted by age, were divided into two groups: younger (≤ 80 years) and older (> 80 years). Corneas were categorized based on endothelial cell density (ECD). Data were collected from patients who underwent corneal transplantation. A financial impact model was created to assess the effects of using corneas from different age groups on the overall benefits of corneal transplant procedures. The average donor age was 67.5 ± 14.5 years. The median age of donors gradually increased from 66 to 73 years over the 12-year study period, with donors over 80 years old representing more than 24% since 2021. Corneas from older donors had a higher discard rate (62.53% vs. 39.66%) due to poor endothelial quality and serological concerns (both  < 0.0001). Additionally, these corneas had lower ECD, with a larger proportion deemed unsuitable for grafting due to low ECD (30% vs. 8.2%). Corneas from younger donors were more often used for endothelial transplants, which require higher ECD. The mean economic benefit per cornea showed a moderate negative correlation with donor age. The net benefit of corneal transplants decreased as the proportion of donors aged over 80 years increased. It is predicted that a net benefit of zero would be attained when the proportion of donors over 80 years is 44.4%. Using corneas from donors over 80 years of age can help alleviate the shortage of donor tissue and be effective if certain quality standards are met. However, additional costs incurred by eye banks must be factored into this equation.

Background Soft-tissue reconstruction is crucial in fields such as plastic surgery and oncology to address the repair of damaged tissues. Knitted scaffolds from bioresorbable copolymers, specifically poly(D,L-lactide) (PLA) and polycaprolactone (PCL), offer mechanical and biological properties that are essential for tissue engineering. This study assessed three-dimensional knitted scaffolds fabricated from melt-spun PLA and PCL multifilaments for soft tissue engineering applications. It examined the impact of the PLA/PCL ratio on the knitted scaffold structure, mechanical properties, and biological responses to determine the optimal composition for adipose tissue reconstruction. Results Knitted scaffolds fabricated with the PLA/PCL blends (PLA 70 /PCL 30 and PLA 90 /PCL 10 ) exhibited distinct mechanical and biological profiles. PLA 70 /PCL 30 scaffolds with a higher PCL content showed enhanced elasticity and porosity, whereas PLA 90 /PCL 10 scaffolds maintained better structural integrity and stiffness. Biological assays confirmed the biocompatibility of all scaffolds in vitro, with no cytotoxic effects. The scaffolds supported adipogenic differentiation in vitro, although PLA 70 /PCL 30 exhibited slightly reduced efficacy. Vascularization was evident using chorioallantoic membrane assays, in which blood vessel formation and penetration were observed, regardless of the scaffold composition. In vivo implantation in rat models revealed effective adipocyte integration, structural stability, and minimal inflammatory response, with PLA 90 /PCL 10 scaffolds outperforming PLA 70 /PCL 30 in terms of vascularization and less macrophage infiltration of connective tissue. Conclusion PLA/PCL knitted scaffolds offer a promising solution for enhancing graft volume maintenance and improving long-term outcomes, with tunable mechanical properties and biodegradability. The PLA 90 /PCL 10 scaffold is a superior candidate for adipose tissue reconstruction, balancing the structural stability with biological compatibility. These findings underscore the potential of PLA/PCL scaffolds for reconstructive surgery. Future studies should focus on scalability and long-term biocompatibility to facilitate clinical translation.

Autologous fat grafting is the gold standard for treatment in patients with soft-tissue defects. However, the technique has a major limitation of unpredictable fat resorption due to insufficient blood supply in the initial phase after transplantation. To overcome this problem, we investigated the capability of a medical-grade poly L-lactide-co-poly ε-caprolactone (PLCL) scaffold to support adipose tissue and vascular regeneration. Deploying FDM 3D-printing, we produced a bioresorbable porous scaffold with interconnected pore networks to facilitate nutrient and oxygen diffusion. The compressive modulus of printed scaffold mimicked the mechanical properties of native adipose tissue. In vitro assays demonstrated that PLCL scaffolds or their degradation products supported differentiation of preadipocytes into viable mature adipocytes under appropriate induction. Interestingly, the chorioallantoic membrane assay revealed vascular invasion inside the porous scaffold, which represented a guiding structure for ingrowing blood vessels. Then, lipoaspirate-seeded scaffolds were transplanted subcutaneously into the dorsal region of immunocompetent rats (n = 16) for 1 or 2 months. The volume of adipose tissue was maintained inside the scaffold over time. Histomorphometric evaluation discovered small- and normal-sized perilipin+ adipocytes (no hypertrophy) classically organized into lobular structures inside the scaffold. Adipose tissue was surrounded by discrete layers of fibrous connective tissue associated with CD68+ macrophage patches around the scaffold filaments. Adipocyte viability, assessed via TUNEL staining, was sustained by the presence of a high number of CD31-positive vessels inside the scaffold, confirming the CAM results. Overall, our study provides proof that 3D-printed PLCL scaffolds can be used to improve fat graft volume preservation and vascularization, paving the way for new therapeutic options for soft-tissue defects.

Tumor cells evolve in a complex and heterogeneous environment composed of different cell types and an extracellular matrix. Current 2D culture methods are very limited in their ability to mimic the cancer cell environment. In recent years, various 3D models of cancer cells have been developed, notably in the form of spheroids/organoids, using scaffold or cancer-on-chip devices. However, these models have the disadvantage of not being able to precisely control the organization of multiple cell types in complex architecture and are sometimes not very reproducible in their production, and this is especially true for spheroids. Three-dimensional bioprinting can produce complex, multi-cellular, and reproducible constructs in which the matrix composition and rigidity can be adapted locally or globally to the tumor model studied. For these reasons, 3D bioprinting seems to be the technique of choice to mimic the tumor microenvironment in vivo as closely as possible. In this review, we discuss different 3D-bioprinting technologies, including bioinks and crosslinkers that can be used for in vitro cancer models and the techniques used to study cells grown in hydrogels; finally, we provide some applications of bioprinted cancer models.

As protein-losing enteropathy (PLE) can lead to hypogammaglobulinemia and lymphopenia, and since common variable immunodeficiency (CVID) is associated with digestive complications, we wondered if (1) PLE could occur during CVID and (2) specific features could help determine whether a patient with antibody deficiency has CVID, PLE, or both. Eligible patients were thus classified in 3 groups: CVID + PLE ( n  = 8), CVID-only (= 19), and PLE-only ( n  = 13). PLE was diagnosed using fecal clearance of α1-antitrypsin or 111In-labeled albumin. Immunoglobulin (Ig) A, G, and M, naive/memory B and T cell subsets were compared between each group. CVID + PLE patients had multiple causes of PLE: duodenal villous atrophy (5/8), nodular follicular hyperplasia (4/8), inflammatory bowel disease-like (4/8), portal hypertension (4/8), giardiasis (3/8), and pernicious anemia (1/8). Compared to the CVID-only group, CVID + PLE patients had similar serum Ig levels, B cell subset counts, but lower naive T cell proportion and IgG replacement efficiency index. Compared to the CVID-only group, PLE-only patients did not develop infections but had higher serum levels of IgG ( p  = 0.03), IgA ( p  < 0.0001), and switched memory B cells ( p  = 0.001); and decreased naive T cells (CD4 + : p  = 0.005; CD8 + : p  < 0.0001). Compared to the PLE-only group, CVID + PLE patients had higher infection rates ( p  = 0.0003), and lower serum Ig (especially IgA: p  < 0.001) and switched memory B cells levels. In conclusion, PLE can occur during CVID and requires higher IgG replacement therapy dosage. PLE can also mimic CVID and is associated with milder immunological abnormalities, notably mildly decreased to normal serum IgA and switched memory B cell levels.