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Bioengineering the innate vasculature of complex organs: what have we learned so far

Wijesekara P, Ng WH, Feng M, Ren X

Curr Opin Organ Transplant, 2018 12;23(6):657-663.
PMID: 30234735 DOI: 10.1097/MOT.0000000000000577

PURPOSE OF REVIEW: Engineering vasculature that meets an organ's specific physiology and function is a fundamental step in organ bioengineering. In this article, we review approaches for engineering functional vasculature for organ bioengineering, with an emphasis on the engineering of organ-specific endothelium and vasculature.
RECENT FINDINGS: Recent advances in hydrogel-based engineering of vascularized organ bud enable vascular regeneration in self-assembled cellular niche containing parenchymal and stromal cells. The emerging technology of whole-organ decellularization provides scaffold materials that serve as extracellular niche guiding vascular regeneration to recapitulate native organ's vascular anatomy. Increasing morphological and molecular evidences suggest endothelial heterogeneity across different organs and across different vascular compartments within an organ. Deriving organ-specific endothelium from pluripotent stem cells has been shown to be possible by combining endothelial induction with parenchymal differentiation.
SUMMARY: Engineering organ-specific vasculature requires the combination of organ-specific endothelium with its unique cellular and extracellular niches. Future investigations are required to further delineate the mechanisms for induction and maintenance of organ-specific vascular phenotypes, and how to incorporate these mechanisms to engineering organ-specific vasculature.
Fulltext Finite Element Analysis of Cushioned Diabetic Footwear Using Ethylene Vinyl Acetate Polymer

Ghazali MJ, Ren X, Rajabi A, Zamri WFHW, Mohd Mustafah N, Ni J

Polymers (Basel), 2021 Jul 09;13(14).
PMID: 34301018 DOI: 10.3390/polym13142261

With the development of societies, diabetic foot ulcers have become one of the most common diseases requiring lower extremity amputation. The early treatment and prevention of diabetic foot ulcers can considerably reduce the possibility of amputation. Using footwear to redistribute and relieve plantar pressure is one of the important measures for the treatment and prevention of diabetic foot ulcers. Thus, the evaluation and prediction of the distribution of plantar pressure play an important role in designing footwears. Herein, the finite element method was used to study plantar pressure under two kinds of foot models, namely, the skeletal structure foot model and the whole foot model, to explore the influence of human bones on the pressure of the soles of the feet and obtain accurate foot pressure. Simulation results showed that under the two models, the plantar pressure and the pressure from the footwear with ethylene vinyl acetate were all reduced. The total deformation demonstrated a slight increase. These stresses are very useful as they enable the design of suitable orthotic footwear that reduces the amount of stress in individuals with diabetic foot ulcers.
68Ga-prostate specific membrane antigen-11 PET/CT versus multiparametric MRI in the detection of primary prostate cancer: A systematic review and head-to-head comparative meta-analysis

Ren X, Nur Salihin Yusoff M, Hartini Mohd Taib N, Zhang L, Wang K

Eur J Radiol, 2024 Jan;170:111274.
PMID: 38147764 DOI: 10.1016/j.ejrad.2023.111274

PURPOSE: The goal of this study was to evaluate the effectiveness of two diagnostic methods, 68Ga-PSMA-11 PET/CT and mpMRI, in detecting primary prostate cancer without limitations on the Gleason score.
METHODS: We conducted a comprehensive literature review, searching databases such as PubMed, Embase, and Web of Science until June 2023. Our objective was to identify studies that compared the efficacy of 68Ga-PSMA-11 PET/CT and mpMRI in detecting primary prostate cancer. To determine heterogeneity, the I2 statistic was used. Meta-regression analysis and leave-one-out sensitivity analysis were conducted to identify potential sources of heterogeneity.
RESULTS: Initially, 1286 publications were found, but after careful evaluation, only 16 studies involving 1227 patients were analyzed thoroughly. The results showed that the 68Ga-PSMA-11 PET/CT method had a pooled sensitivity and specificity of 0.87 (95 % CI: 0.80-0.92) and 0.80 (95 % CI: 0.69-0.89), respectively, for diagnosing prostatic cancer. Similarly, the values for mpMRI were determined as 0.84 (95 % CI: 0.75-0.92) and 0.74 (95 % CI: 0.61-0.86), respectively. There were no significant differences in diagnostic effectiveness observed when comparing two primary prostate cancer methodologies (pooled sensitivity P = 0.62, pooled specificity P = 0.50). Despite this, the funnel plots showed symmetry and the Egger test results (P values > 0.05) suggested there was no publication bias.
CONCLUSIONS: After an extensive meta-analysis, it was found that both 68Ga-PSMA-11 PET/CT and mpMRI demonstrate similar diagnostic effectiveness in detecting primary prostate cancer. Future larger prospective studies are warranted to investigate this issue further.
Fulltext Exosomal miR-224 contributes to hemolymph microbiota homeostasis during bacterial infection in crustacean

Gong Y, Wei X, Sun W, Ren X, Chen J, Aweya JJ, et al.

PLoS Pathog, 2021 08;17(8):e1009837.
PMID: 34379706 DOI: 10.1371/journal.ppat.1009837

It is well known that exosomes could serve as anti-microbial immune factors in animals. However, despite growing evidences have shown that the homeostasis of the hemolymph microbiota was vital for immune regulation in crustaceans, the relationship between exosomes and hemolymph microbiota homeostasis during pathogenic bacteria infection has not been addressed. Here, we reported that exosomes released from Vibrio parahaemolyticus-infected mud crabs (Scylla paramamosain) could help to maintain the homeostasis of hemolymph microbiota and have a protective effect on the mortality of the host during the infection process. We further confirmed that miR-224 was densely packaged in these exosomes, resulting in the suppression of HSP70 and disruption of the HSP70-TRAF6 complex, then the released TRAF6 further interacted with Ecsit to regulate the production of mitochondrial ROS (mROS) and the expression of Anti-lipopolysaccharide factors (ALFs) in recipient hemocytes, which eventually affected hemolymph microbiota homeostasis in response to the pathogenic bacteria infection in mud crab. To the best of our knowledge, this is the first document that reports the role of exosome in the hemolymph microbiota homeostasis modulation during pathogen infection, which reveals the crosstalk between exosomal miRNAs and innate immune response in crustaceans.
Fulltext Recapitulating human cardio-pulmonary co-development using simultaneous multilineage differentiation of pluripotent stem cells

Ng WH, Johnston EK, Tan JJ, Bliley JM, Feinberg AW, Stolz DB, et al.

Elife, 2022 01 12;11.
PMID: 35018887 DOI: 10.7554/eLife.67872

The extensive crosstalk between the developing heart and lung is critical to their proper morphogenesis and maturation. However, there remains a lack of models that investigate the critical cardio-pulmonary mutual interaction during human embryogenesis. Here, we reported a novel stepwise strategy for directing the simultaneous induction of both mesoderm-derived cardiac and endoderm-derived lung epithelial lineages within a single differentiation of human-induced pluripotent stem cells (hiPSCs) via temporal specific tuning of WNT and nodal signaling in the absence of exogenous growth factors. Using 3D suspension culture, we established concentric cardio-pulmonary micro-Tissues (μTs), and expedited alveolar maturation in the presence of cardiac accompaniment. Upon withdrawal of WNT agonist, the cardiac and pulmonary components within each dual-lineage μT effectively segregated from each other with concurrent initiation of cardiac contraction. We expect that our multilineage differentiation model will offer an experimentally tractable system for investigating human cardio-pulmonary interaction and tissue boundary formation during embryogenesis.
Fulltext A Complete Cross Section Data Set for Electron Scattering by Pyridine: Modelling Electron Transport in the Energy Range 0-100 eV

Costa F, Traoré-Dubuis A, Álvarez L, Lozano AI, Ren X, Dorn A, et al.

Int J Mol Sci, 2020 Sep 22;21(18).
PMID: 32971806 DOI: 10.3390/ijms21186947

Electron scattering cross sections for pyridine in the energy range 0-100 eV, which we previously measured or calculated, have been critically compiled and complemented here with new measurements of electron energy loss spectra and double differential ionization cross sections. Experimental techniques employed in this study include a linear transmission apparatus and a reaction microscope system. To fulfill the transport model requirements, theoretical data have been recalculated within our independent atom model with screening corrected additivity rule and interference effects (IAM-SCAR) method for energies above 10 eV. In addition, results from the R-matrix and Schwinger multichannel with pseudopotential methods, for energies below 15 eV and 20 eV, respectively, are presented here. The reliability of this complete data set has been evaluated by comparing the simulated energy distribution of electrons transmitted through pyridine, with that observed in an electron-gas transmission experiment under magnetic confinement conditions. In addition, our representation of the angular distribution of the inelastically scattered electrons is discussed on the basis of the present double differential cross section experimental results.
Metabolic glycan labeling and chemoselective functionalization of native biomaterials

Ren X, Evangelista-Leite D, Wu T, Rajab TK, Moser PT, Kitano K, et al.

Biomaterials, 2018 11;182:127-134.
PMID: 30118980 DOI: 10.1016/j.biomaterials.2018.08.012

Decellularized native extracellular matrix (ECM) biomaterials are widely used in tissue engineering and have reached clinical application as biomesh implants. To enhance their regenerative properties and postimplantation performance, ECM biomaterials could be functionalized via immobilization of bioactive molecules. To facilitate ECM functionalization, we developed a metabolic glycan labeling approach using physiologic pathways to covalently incorporate click-reactive azide ligands into the native ECM of a wide variety of rodent tissues and organs in vivo, and into the ECM of isolated rodent and porcine lungs cultured ex vivo. The incorporated azides within the ECM were preserved after decellularization and served as chemoselective ligands for subsequent bioconjugation via click chemistry. As proof of principle, we generated alkyne-modified heparin, immobilized it onto azide-incorporated acellular lungs, and demonstrated its bioactivity by Antithrombin III immobilization and Factor Xa inhibition. The herein reported metabolic glycan labeling approach represents a novel platform technology for manufacturing click-reactive native ECM biomaterials, thereby enabling efficient and chemoselective functionalization of these materials to facilitate tissue regeneration and repair.
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.

Autophagy, 2016;12(1):1-222.
PMID: 26799652 DOI: 10.1080/15548627.2015.1100356