Cardiovascular models for personalised medicine: Where now and where next?

Three-dimensional printing (3DP) has a significant impact on organ transplant, cosmetic surgery, surgical planning, prosthetics and other medical fields. Recently, 3 DP attracted the attention as a promising method for the production of small-scale drug production. The knowledge expansion about the population differences in metabolism and genetics grows the need for personalised medicine substantially. In personalised medicine, the patient receives a tailored dose and the release profile is based on his pharmacokinetics data. 3 DP is expected to be one of the leading solutions for the personalisation of the drug dispensing. This technology can fabricate a drug-device with complicated geometries and fillings to obtain the needed drug release profile. The extrusionbased 3 DP is the most explored method for investigating the feasibility of the technology to produce a novel dosage form with properties that are difficult to achieve using the conventional industrial methods. Extrusionbased 3 DP is divided into two techniques, the semi-solid extrusion (SSE) and the fused deposition modeling (FDM). This review aims to explain the extrusion principles behind the two techniques and discuss their capabilities to fabricate novel dosage forms. The advantages and limitations observed through the application of SSE and FDM for fabrication of drug dosage forms were discussed in this review. Further exploration and development are required to implement this technology in the healthcare frontline for more effective and personalised treatment.

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COPD Phenotypes and Biomarkers: Introducing Personalised Medicine

Current Respiratory Medicine Reviews ◽

10.2174/1573398x10666140527000115 ◽

2014 ◽

Vol 9 (6) ◽

pp. 372-378 ◽

Cited By ~ 1

Author(s):

Alexandros G. Mathioudakis ◽

Victoria Chatzimavridou-Grigoriadou ◽

Alexandru Corlateanu ◽

Georgios A. Mathioudakis ◽

Peter M.A. Calverley

Keyword(s):

Personalised Medicine

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Deconvolution of monocyte responses in inflammatory bowel disease reveals an IL-1 cytokine network that regulates IL-23 in genetic and acquired IL-10 resistance

Gut ◽

10.1136/gutjnl-2020-321731 ◽

2020 ◽

pp. gutjnl-2020-321731

Author(s):

Dominik Aschenbrenner ◽

Maria Quaranta ◽

Soumya Banerjee ◽

Nicholas Ilott ◽

Joanneke Jansen ◽

...

Keyword(s):

Mononuclear Cells ◽

Personalised Medicine ◽

Mononuclear Phagocytes ◽

Cytokine Network ◽

Peripheral Blood Mononuclear ◽

Transcriptional Signature ◽

Inflammatory Monocytes ◽

Transcriptomic Signature ◽

Inflammatory Bowel

ObjectiveDysregulated immune responses are the cause of IBDs. Studies in mice and humans suggest a central role of interleukin (IL)-23-producing mononuclear phagocytes in disease pathogenesis. Mechanistic insights into the regulation of IL-23 are prerequisite for selective IL-23 targeting therapies as part of personalised medicine.DesignWe performed transcriptomic analysis to investigate IL-23 expression in human mononuclear phagocytes and peripheral blood mononuclear cells. We investigated the regulation of IL-23 expression and used single-cell RNA sequencing to derive a transcriptomic signature of hyperinflammatory monocytes. Using gene network correlation analysis, we deconvolved this signature into components associated with homeostasis and inflammation in patient biopsy samples.ResultsWe characterised monocyte subsets of healthy individuals and patients with IBD that express IL-23. We identified autosensing and paracrine sensing of IL-1α/IL-1β and IL-10 as key cytokines that control IL-23-producing monocytes. Whereas Mendelian genetic defects in IL-10 receptor signalling induced IL-23 secretion after lipopolysaccharide stimulation, whole bacteria exposure induced IL-23 production in controls via acquired IL-10 signalling resistance. We found a transcriptional signature of IL-23-producing inflammatory monocytes that predicted both disease and resistance to antitumour necrosis factor (TNF) therapy and differentiated that from an IL-23-associated lymphocyte differentiation signature that was present in homeostasis and in disease.ConclusionOur work identifies IL-10 and IL-1 as critical regulators of monocyte IL-23 production. We differentiate homeostatic IL-23 production from hyperinflammation-associated IL-23 production in patients with severe ulcerating active Crohn’s disease and anti-TNF treatment non-responsiveness. Altogether, we identify subgroups of patients with IBD that might benefit from IL-23p19 and/or IL-1α/IL-1β-targeting therapies upstream of IL-23.

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The effect of protein mutations on drug binding suggests ensuing personalised drug selection

Scientific Reports ◽

10.1038/s41598-021-92785-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shunzhou Wan ◽

Deepak Kumar ◽

Valentin Ilyin ◽

Ussama Al Homsi ◽

Gulab Sher ◽

...

Keyword(s):

Estrogen Receptor ◽

Ligand Binding ◽

Binding Free Energy ◽

Personalised Medicine ◽

Clinical Decision ◽

Drug Binding ◽

Dynamics Simulation ◽

Breast Cancer Patients ◽

Natural Ligand ◽

Affinity Interaction

AbstractThe advent of personalised medicine promises a deeper understanding of mechanisms and therefore therapies. However, the connection between genomic sequences and clinical treatments is often unclear. We studied 50 breast cancer patients belonging to a population-cohort in the state of Qatar. From Sanger sequencing, we identified several new deleterious mutations in the estrogen receptor 1 gene (ESR1). The effect of these mutations on drug treatment in the protein target encoded by ESR1, namely the estrogen receptor, was achieved via rapid and accurate protein–ligand binding affinity interaction studies which were performed for the selected drugs and the natural ligand estrogen. Four nonsynonymous mutations in the ligand-binding domain were subjected to molecular dynamics simulation using absolute and relative binding free energy methods, leading to the ranking of the efficacy of six selected drugs for patients with the mutations. Our study shows that a personalised clinical decision system can be created by integrating an individual patient’s genomic data at the molecular level within a computational pipeline which ranks the efficacy of binding of particular drugs to variant proteins.

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Ethical Issues in Consent for the Reuse of Data in Health Data Platforms

Science and Engineering Ethics ◽

10.1007/s11948-021-00282-0 ◽

2021 ◽

Vol 27 (1) ◽

Cited By ~ 1

Author(s):

Alex McKeown ◽

Miranda Mourby ◽

Paul Harrison ◽

Sophie Walker ◽

Mark Sheehan ◽

...

Keyword(s):

Social Contract ◽

Ethical Issues ◽

Personalised Medicine ◽

Data Reuse ◽

Remote Access ◽

Risk Indicators ◽

New Paradigm ◽

The Social ◽

New Thinking ◽

The Relationship

AbstractData platforms represent a new paradigm for carrying out health research. In the platform model, datasets are pooled for remote access and analysis, so novel insights for developing better stratified and/or personalised medicine approaches can be derived from their integration. If the integration of diverse datasets enables development of more accurate risk indicators, prognostic factors, or better treatments and interventions, this obviates the need for the sharing and reuse of data; and a platform-based approach is an appropriate model for facilitating this. Platform-based approaches thus require new thinking about consent. Here we defend an approach to meeting this challenge within the data platform model, grounded in: the notion of ‘reasonable expectations’ for the reuse of data; Waldron’s account of ‘integrity’ as a heuristic for managing disagreement about the ethical permissibility of the approach; and the element of the social contract that emphasises the importance of public engagement in embedding new norms of research consistent with changing technological realities. While a social contract approach may sound appealing, however, it is incoherent in the context at hand. We defend a way forward guided by that part of the social contract which requires public approval for the proposal and argue that we have moral reasons to endorse a wider presumption of data reuse. However, we show that the relationship in question is not recognisably contractual and that the social contract approach is therefore misleading in this context. We conclude stating four requirements on which the legitimacy of our proposal rests.

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Organoids of the female reproductive tract

Journal of Molecular Medicine ◽

10.1007/s00109-020-02028-0 ◽

2021 ◽

Vol 99 (4) ◽

pp. 531-553 ◽

Cited By ~ 1

Author(s):

Cindrilla Chumduri ◽

Margherita Y. Turco

Keyword(s):

Reproductive Tract ◽

Personalised Medicine ◽

Three Dimensional ◽

In Vitro Models ◽

Experimental Models ◽

Female Reproductive Tract ◽

Cellular Heterogeneity ◽

Dynamic Regulation ◽

Pregnancy And Childbirth

AbstractHealthy functioning of the female reproductive tract (FRT) depends on balanced and dynamic regulation by hormones during the menstrual cycle, pregnancy and childbirth. The mucosal epithelial lining of different regions of the FRT—ovaries, fallopian tubes, uterus, cervix and vagina—facilitates the selective transport of gametes and successful transfer of the zygote to the uterus where it implants and pregnancy takes place. It also prevents pathogen entry. Recent developments in three-dimensional (3D) organoid systems from the FRT now provide crucial experimental models that recapitulate the cellular heterogeneity and physiological, anatomical and functional properties of the organ in vitro. In this review, we summarise the state of the art on organoids generated from different regions of the FRT. We discuss the potential applications of these powerful in vitro models to study normal physiology, fertility, infections, diseases, drug discovery and personalised medicine.

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