Biology subjects

Faisal, S.

Publications and source records attributed to Faisal, S..

5 recordsLinked to original sources

bioRxiv2024

Immunomodulatory Porous Regenerative Scaffolds for in situ Vascular Engineering

The 70-year quest for synthetic vascular graft (sVG) endothelialization has not led to completely healed endothelium in clinically used sVGs. In humans, healing is limited to the vicinity of anastomotic regions (pannus ingrowth) and does not reach the middle regions of sVGs. Here, we conducted proof-of-concept implantation of immunomodulatory porous regenerative scaffolds for in situ vascular engineering (IMPRESSIVE) as interposition grafts in sheep carotid arteries. These scaffolds are based on a new polyurethane (PU) material featuring a 40 {micro}m precision porous structure optimized for angiogenesis. The modulus of the PU was adjusted to match that of natural arteries. The implantation study revealed rapid healing in IMPRESSIVE sVGs. In side-by-side comparison with standard polytetrafluoroethylene (PTFE) grafts, the luminal surfaces of PU grafts were almost completely covered with nucleated cells, while healing in PTFE grafts was limited to several millimeters within anastomotic regions. Endothelialization was observed in the middle regions of PU grafts and overall endothelialization increased significantly compared to PTFE grafts. Densities of mononuclear cells, foreign body giant cells (FBGCs), and endothelial cells within graft walls of PU grafts were also significantly higher than those in PTFE grafts, suggesting transmural cellular infiltration may play a key role in overall improved healing. High percentages of macrophages in pores of PU grafts show Type 1 (CCR7+) and Type 2 (mannose receptor, MR+) characteristics. We also discovered that FBGCs exist in a diverse spectrum of phenotypes. Dually activated FBGCs (CCR7+MR+, G1/2) dominate the population of FBGCs associated with pro-healing PU grafts. These observations suggest a complex, balanced pro-healing response from macrophages and FBGCs. The IMPRESSIVE approach may enable complete endothelialization in pro-healing sVGs and have wide applications in implantable devices and tissue engineering.

bioengineering↗

bioRxiv2022

Residence time analysis on cerebral aneurysms treated with coils using planar-laser-induced fluorescence and computational fluid dynamics

Biofidelic numerical models have been developed such as the coil-resolved model to study hemodynamics in the treated aneurysm. In this model, the geometry of the coils is recreated from high-resolution tomography scans of a phantom aneurysm treated with coils. However, this model hasnt been validated. The purpose of this work is to validate the coil-resolved model. To achieve this, we used the planar-laser induced fluorescence technique on phantom aneurysm treated with coils and measured the residence time and the evolution of rhodamine concentration during the washout. We run passive scalar simulations with the coil-resolved model and measured the evolution of concentration over time. The comparison of the numerical and the experimental results shows that the coil-resolved model reproduces the hemodynamics of the experimental setup. Therefore it can be used as a reference to study hemodynamics in the treated aneurysm or to validate porous media models developed for treatment outcomes prediction.

neuroscience↗

bioRxiv2022

Chronic hyperglycemia drives alterations in macrophage effector function in pulmonary tuberculosis

BackgroundThe rising prevalence of Diabetes mellitus (DM) in high TB endemic countries has the potential to adversely affect sustainability of TB control since DM can lead to alterations in both innate and adaptive immune response constituting as a risk factor for development of active tuberculosis (TB). The impact of hyperglycemia on TB specific innate immune response in terms of macrophage functions remains poorly addressed. Material and methodsMacrophage effector functions in diabetic and non-diabetic individuals with and without PTB infection as well as non-diabetic-uninfected controls (fifty individuals in each group) were assessed. Phagocytic capacity against BCG and surface expression of PRRs (CD11b, CD14, CD206, MARCO and TLR2) were measured via flow cytometry. Effector molecules (ROS and NO) were assessed via DCFDA and Griess reaction respectively. ResultsA systematic dysregulation in phagocytic capacity with concurrent alterations in expression pattern of key PRRs (CD11b, MARCO and CD206) and effector molecules (ROS and NO) was observed in diabetic individuals with PTB. These altered macrophage functions were positively correlated with increase in disease severity in diabetic individuals. ConclusionOur results highlight several key patterns of immune dysregulation against M.Tb under hyperglycemic conditions. A significant reduction in macrophage effector functions in infected diabetic individuals which further correlated with increase in disease severity reveals a negative impact of hyperglycemia with aetiology and pathological progression of TB.

immunology↗

bioRxiv2020

G-CSF SECRETED BY EPIGENETICALLY REPROGRAMMED MUTANT IDH1 GLIOMA STEM CELLS REVERSES THE MYELOID CELLS'-MEDIATED IMMUNOSUPPRESSIVE TUMOR MICROENVIRONMENT

Mutation in isocitrate dehydrogenase (mIDH) is a gain of function mutation resulting in the production of the oncometabolite, R-2-hydroxyglutarate, that inhibits DNA and histone demethylases. The resultant hypermethylation phenotype reprograms the glioma cells transcriptome and elicits profound effects on glioma immunity. We report that in mouse models and human gliomas, mIDH1 in the context of ATRX and TP53 inactivation results in global expansion of the granulocytic myeloid cells compartment. Single-cell RNA-sequencing coupled with mass cytometry analysis revealed that these granulocytes are mainly non-immunosuppressive neutrophils and pre-neutrophils; with a small fraction of polymorphonuclear myeloid-derived suppressor cells. The mechanism of mIDH1 mediated pre-neutrophils expansion involves epigenetic reprogramming which leads to enhanced expression of the granulocyte colony-stimulating factor (G-CSF). Blocking G-CSF restored the inhibitory potential of PMN-MDSCs and enhanced tumor progression. Thus, G-CSF induces remodeling of the inhibitory PMN-MDSCs in mIDH1 glioma rendering them non-immunosuppressive; and having significant therapeutic implications. SIGNIFICANCEmIDH1 is the most common mutation in gliomas associated with improved prognosis. Gliomas harboring mIDH1, together with ATRX and TP53 inactivation, exhibit higher circulating levels of G-CSF, ensuing the recruitment and expansion of non-suppressive neutrophils, pre-neutrophils and small fraction of PMN-MDSCs to the TME leading to an immune permissive phenotype.

cancer biology↗

bioRxiv2018

Recurrent AIPL1 c.487C>T truncating variant in Leber Congenital Amaurosis: Support of pathogenicity and regional implications

BackgroundLeber Congenital Amaurosis (LCA) is a clinically and genetically heterogeneous inherited retinal dystrophy characterized by early onset visual impairment caused by mutations in not less than 17 genes. AIPL1 mutations cause LCA type 4, comprising approximately 7% of LCA worldwide. The importance of establishing a genetic diagnosis lies in the promise of gene therapy demonstrated in mouse models.\n\nResultswe genetically investigated a consanguineous Sudanese family with Leber Congenital Amaurosis. Eight members of the family were affected. Using whole exome sequencing in two siblings and their healthy mother, both inheritance-based and phenotype-based prioritization strategies converged to identify a truncating variant (rs62637009) in AIPL1, consistent with a diagnosis of LCA type 4. AIPL1 c.487C>T is an ultra-rare cause of LCA4 that was seen previously in homozygous state in a single Palestinian family. This recurrent variant seems to have a regional importance with a likely founder effect.\n\nConclusionsThis report adds evidence to the pathogenicity of AIPL1 c.487C>T meriting its conclusive annotation as a recurrent pathogenic variant. This variant is particularly relevant to the middle-eastern and northeast African regions.

genomics↗