Biology subjects

Abdelsalam, A.

Publications and source records attributed to Abdelsalam, A..

5 recordsLinked to original sources

bioRxiv2026

Gelatin coating enhances flow diverting stent endothelial cell coverage, parent vessel healing and aneurysm occlusion

BackgroundFlow diversion stent treatment of cerebral aneurysms has demonstrated high rates of aneurysm occlusion and long-term durability. However, complete endothelization of the flow diverting stent is required for parent vessel healing which closes the aneurysm and metal stent from the circulation. Therefore, stent coatings which enhance endothelial migration and attachment may increase the rate of aneurysm occlusion and reduce complications associated with flow diversion treatment. Here we investigate the use of gelatin as a stent surface coating to enhance the rate of stent endothelialization and coverage and increase aneurysm healing. MethodsNitinol- Neuroform stents (Stryker, Kalamazoo, MI) and cobalt-chromium-Pipeline Flex flow diverting stents (Medtronic, Minneapolis, MN) were used for this study. The stents were coated with gelatin and endothelial cell attachment, proliferation and stent coverage were determined in vitro and compared to uncoated stent controls. A rabbit elastase-aneurysm model was used to determine the effects of endothelial cell seeded-gelatin coated flow diverting stents on aneurysm obliteration and parent vessel healing. ResultsIn vitro, gelatin coating of nitinol stents did not significantly alter endothelial cell attachment, proliferation, or stent coverage. However, gelatin coating of cobalt-chromium stents significantly increased endothelial cell attachment, proliferation and migration. In fact, gelatin coating significantly (p< 0.001) increased the rate of complete stent endothelization by 33% compared to unmodified controls. In vivo, treating aneurysm with endothelial cell seeded-gelatin coated stents resulted in aneurysm occlusion in 8 of 8 (100%) rabbit aneurysms at 90 days compared to only 4 of 7 (57%) in unmodified controls (p< 0.001). Histologically, there were trends in increased neoarterial wall thickness across the aneurysm neck and neointimal formation in the parent artery. Angiographic assessment demonstrated strong parent and side branch patency. ConclusionsGelatin coating enhances EC attachment and stent coverage which is dependent upon the type of stent. Endothelial cell seeded-gelatin coated-flow diverting stents allowed 100% aneurysm obliteration and neoarterial formation without affecting side branch patency or parent artery perfusion. Gelatin coating therefore represents a valuable strategy to enhance stent cellularization and aneurysm occlusion rates.

neuroscience↗

bioRxiv2026

Regulation of Chlamydia trachomatis infection in the female genital tract by type I and type II interferons

Following an intravaginal inoculation with Chlamydia trachomatis, mice deficient in type I interferon receptor IFNR1 (IFNR1-/-) significantly increased the yield of live chlamydiae on days 3 & 5 but reduced it to the level of wild-type mice by day 7, while mice deficient in type II interferon receptor IFN{gamma}R1 (IFN{gamma}R1-/-) significantly increased the chlamydial yield by day 5 and the increase persisted throughout the remainder of the infection course. These observations reveal a temporal division of labor between type I & II interferons in regulating C. trachomatis infection in the female genital tract. Interestingly, mice deficient in both IFNR1 & IFN{gamma}R1 exhibited higher mortality and shed more chlamydial organisms than IFN{gamma}R1-/- mice by week 6, suggesting that IFNR1 remains critical for inhibiting C. trachomatis at late stages. An anti-IFNR1 antibody blockade significantly increased chlamydial yields in IFN{gamma}R1-/- mice, suggesting that the anti-chlamydial activities of type I & II interferon systems are both distinct and overlapping throughout the infection course. Furthermore, the anti-chlamydial activity of type I interferon signaling is localized to the lower vagina, while that of type II interferon signaling is localized to the upper vagina. Thus, we have demonstrated that type I & II interferons function complementarily and synergistically in time and space to control C. trachomatis infection, laying the foundation for further elucidating the mechanisms of IFN regulation of chlamydial infection and for developing interventional and preventive strategies against C. trachomatis in the female genital tract. ImportanceLack of information on the precise roles of type I and type II interferons during chlamydial infection has hindered the development of interferon-based strategies to prevent chlamydial infection and pathogenicity. The current study has revealed a temporal division of labor between type I & type II interferons in regulating chlamydial infection in the female genital tract, with type I acting earlier than type II during the innate phase. Nevertheless, type I remains critical for cooperating with type II to suppress chlamydia 6 weeks after infection. Finally, type I interferons seem to mainly target chlamydial infection in the lower vagina, while type II interferons target the infection in the upper vagina. These new findings on the distinct and overlapping roles of type I and type II interferons in regulating chlamydial infection may guide the development of interferon-based precision strategies to reduce chlamydial infection and pathogenicity in the female genital tract.

immunology↗

bioRxiv2025

Coil and flow diverting stents as drug delivery platforms for cerebral aneurysm treatment

Cerebral aneurysm occlusion with coils and flow diverting stents has become the first line treatment for both unruptured and ruptured cerebral aneurysms. As these technologies have advanced, there have been changes in device shape and surface coating to enhance aneurysm embolization while reducing stent thrombogenicity. Drug eluting stents have been used with great success in the targeted delivery of rapamycin, a mTOR complex 1 inhibitor to prevent restenosis in coronary and peripheral artery disease. However, few studies have investigated the use of coils and stents as delivery platforms for sustained drug release to cerebral aneurysm tissue. In this study, we used the bio-compatible and degradable polymers, gelatin and PLGA and a simple evaporative coating technique to investigate the release of rapamycin over time from coated platinum coils and Pipeline flow diverting stents. Rapamycin coated coils were incubated with human vascular endothelial cells in vitro to confirm therapeutic levels of rapamycin release. The rate of rapamycin release was similar in both gelatin and PLGA coated coils and was sustained for more than three weeks. Rapamycin was bioactive, at a therapeutic dose and inhibited mTOR complex 1 in human brain endothelial cells treated with a rapamycin coated coil. The relative degree of mTOR complex 1 inhibition was greater in PLGA compared to gelatin coated coils. Coating flow diverting stents with a rapamycin-PLGA coating demonstrated continuous rapamycin release over a 35 day period. Reducing the percent PLGA polymer concentration caused a robust and sustainable release of rapamycin. The PLGA coating was resilient enough to allow device recapturing without affecting rapamycin eluting rates or device deployment and expansion. This work provides a simple, feasible and tunable method to coat occlusion devices for preclinical studies investigating targeted drug delivery for improved parent vessel healing and aneurysm obliteration.

bioengineering↗

bioRxiv2025

Cerebral vascular tortuosity and aneurysm formation and rupture: a novel vessel tortuosity scale

Cerebral aneurysm (CA) rupture is the most common cause of nontraumatic subarachnoid hemorrhage. Recent data suggests that tortuosity is associated with aneurysm formation and rupture risk. We aimed to determine if tortuosity correlates with CA development and rupture in a mouse CA model and to develop a novel tortuosity scale to be used for in vivo CA studies. A highly validated, elastase-mouse CA model was used to assess cerebral vessel tortuosity with CA formation and rupture in sham and elastase groups. A 4-point ordinal scale was created to evaluate predictive capacity for vessel tortuosity level and CA formation and rupture. Nearly all sham animals (92%) had little to no vessel tortuosity on the visual scale (median, IQR: 1, [1-2]), compared to 24% in the elastase groups (2, [2-3]) (p=0.001). Sham cohorts had zero animals with highly tortuous vessels, while 3.5mU and 35mU cohorts had >35% of animals with significant visual tortuosity, p=0.003 and p<0.000, respectively. CA formation and rupture was higher in the elastase groups compared to the sham group (p=0.002). Both the visual scale and tortuosity index significantly predicted CA formation (p<0.001) and rupture (p<0.001). A novel tortuosity scale is highly predictive of CA formation and rupture in vivo. It may offer a new measurement to better understand vessel stress in the pathogenesis and progression of CAs.

neuroscience↗

bioRxiv2025

Hematopoietic proliferation is orchestrated by the sequential and lineage-specific activation of Cyclin D, Cyclin E and CDKN sub-modules within the G1/S network

Commitment to the cell division cycle constrains other fate choices at the single cell level. Hence the molecular network controlling the G1/S transition must be coordinated with developmental phases. Healthy hematopoiesis relies on shifts in cell cycle dynamics that balance proliferation and differentiation of hematopoietic stem cells (HSCs) and lineage progenitors, offering an ideal model system to study the coordination of cell division with development. The G1/S network orchestrates this process by regulating the activites of the master G1/S transcription factors (E2F), and cyclin dependent kinases whose activities drive the progression to S phase. By using single cell transcriptomics profiles of human bone marrow cells and mathematical modeling, we demonstrate that variations in the expression of cyclin D- and cyclin E-centered sub-modules of the G1/S network carve out distinct trajectories from G1 to S, explaining the distinct proliferation properties of hematopoietic cell types evolving in the same microenvironment, and biasing cell fate decisions towards certain lineages. We map 68 hematopoietic cell types to specific model parameters, and identify their individual route through G1/S, using our model. This improved mechanistic understanding of the G1/S transition across cell types could enhance the design of more nuanced pharmacological strategies, enabling more personalized treatment recommendations for current cell cycle-targeted cancer therapies.

systems biology↗