Research on in vitro skin models has advanced remarkably, driven by a better understanding of the skin and the search for more ethical and efficient methods. The development of these models was initially motivated by the need for reduced animal testing and a faster and more ethical approach for the safety evaluation of cosmetic and pharmaceutical products. Stricter regulations and growing ethical awareness have driven further evolution, resulting in more refined and reliable methods. Diversity of cell types is crucial to replicating the complexity of human skin, including epithelial, dendritic, endothelial, and adipose cells, providing environments that closely mimic the physiological skin environment. This allows for more precise studies on skin interactions with cosmetic, dermatological, and pharmaceutical products. In vitro skin models have applications in toxicity testing, dermatological product evaluation, skin ageing studies, and drug research, reducing dependence on animal testing. This review presents a look at the different types of in vitro skin models developed for various applications, with a brief look at their strengths and drawbacks. Models developed for disease-specific applications are also covered. Techniques such as bioprinting and organ-on-a-chip have revolutionised the manufacturing of these models. Challenges persist, such as the need to improve vascularisation and faithfully replicate skin architecture. The promising future of these models points to an exciting path forward for dermatological research and the cosmetic industry. This review addresses the history and regulations of skin models, explores various skin models, and highlights the most recent advances, outlining future perspectives and offering a comprehensive overview.

Patients that receive a T-cell depleted (TCD) hematopoietic stem cell transplantation (SCT) show higher risk of graft failure/rejection and of disease relapse than those that receive unmanipulated grafts. The purpose of the present investigation was to analyze the usefulness of chimaerism quantification in bone marrow (BM), peripheral blood (PB), and leukocyte lineages such as T lymphocytes (CD3+, both CD4+ and CD8+), B lymphocytes (CD19+) and myeloid cells (CD15+), for the early detection of graft failure/rejection episodes and disease relapse after TCD-PBSCT. Two of the ten (2/10) patients included in the study showed stable complete chimaerism (CC). The other 8/10 patients showed decreasing mixed chimaerism (MC) and 7 of them had either graft failure (n =1) /rejection (n =3) or disease relapse (n =3). In two patients relapsed from chronic myeloid leukemia, MC was observed in BM and PB, with higher percentages of autologous cells in BM, as well as in leukocyte lineages, with higher percentages of recipient cells in the myeloid lineage than in lymphocytes. Combined analysis of chimaerism and minimal residual disease allowed early diagnosis of relapse and successful rescue therapy with donor leukocyte infusions (DLI), before the onset of hematological relapse. Chimaerism analysis allowed early diagnosis of incipient graft rejection in 3 patients. These patients showed MC both in BM and PB, with greater percentages of recipient cells in PB. Analysis of leukocyte lineages showed higher percentages of autologous cells in T lymphocytes (mainly CD8+) than in B or myeloid cells. Two of these patients were successfully treated with DLI and recovered normal PB counts and BM cellularity, as well as CC. The graft versus recipient hemopoiesis effect harbored by the donor immunocompetent cells infused seems useful for the treatment of graft rejection, provided that an early diagnosis is made.

Spry2 is a molecular modulator of tyrosine kinase receptor signaling pathways that has cancer-type-specific effects. Mammalian Spry2 protein undergoes tyrosine and serine phosphorylation in response to growth factor stimulation. Spry2 expression is distinctly altered in various cancer types. Inhibition of the proteasome functionality results in reduced intracellular Spry2 degradation. Using in vitro and in vivo assays, we show that protein kinase D (PKD) phosphorylates Spry2 at serine 112 and interacts in vivo with the C-terminal half of this protein. Importantly, missense mutation of Ser112 decreases the rate of Spry2 intracellular protein degradation. Either knocking down the expression of all three mammalian PKD isoforms or blocking their kinase activity with a specific inhibitor contributes to the stabilization of Spry2 wild-type protein. Downregulation of CSN3, a component of the COP9/Signalosome that binds PKD, significantly increases the half-life of Spry2 wild-type protein but does not affect the stability of a Spry2 after mutating Ser112 to the non-phosphorylatable residue alanine. Our data demonstrate that both PKD and the COP9/Signalosome play a significant role in control of Spry2 intracellular stability and support the consideration of the PKD/COP9 complex as a potential therapeutic target in tumors where Spry2 expression is reduced.

Background and Aims: Chronic inflammation contributes to various chronic diseases, emphasizing the need for reliable biomarkers for early detection and understanding its causes. Measuring chronic inflammation poses challenges since most biomarkers are influenced by both acute and chronic states and recent exposures. Joint analysis of inflammatory biomarkers may help identify specific biological signatures linked to chronic inflammation. The scoping review whose protocol is described here, aims to map the existing literature identifying these signatures in adults using data reduction methods in epidemiological studies. Methods: The review will follow the Joanna Briggs Institute methodology and the extension for Scoping Reviews of the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis checklist (PRISMA‐ScR). An electronic search will be performed in Medline (via PubMed) and Embase (via Elsevier) for studies published until October 2023, using relevant terms related to inflammation biomarkers, and data reduction methods. Eligible studies include systematic reviews and primary experimental, quasi‐experimental, and observational research analyzing inflammation biomarkers in blood, urine, or saliva from adults. Studies focused on acute infectious diseases, transient inflammatory conditions, and those not published in English or Spanish will be excluded. Four independent reviewers will conduct a two‐phase screening of studies (title/abstract and full‐text), with a third reviewer resolving disagreements. Data extraction will be handled by one reviewer and verified by another using a predefined form. Results: Findings will be summarized in a PRISMA flowchart. Interactive visual maps will illustrate the identified inflammatory signatures, categorized by study design, data reduction method, population type, and clinical condition. All resources will be publicly available. Conclusion: This review will provide a comprehensive overview of inflammation biomarker signatures derived from data reduction methods while identifying existing knowledge gaps in the field. Scoping Review Registration: This protocol was registered on January 25, 2024, on Open Science Framework ( https://doi.org/10.17605/OSF.IO/85XUF ).