Cerebral ischemic injury after transcatheter aortic valve replacement in patients with pure aortic regurgitation

Considering the surgical risk stratification for patients with severe calcific aortic stenosis(AS),transcatheter aortic valve replacement(TAVR)is a reliable alternative to surgical aortic valve replacement(SAVR)(Fan et al.,2020,2021;Lee et al.,2021).Despite the favorable clinical benefits of TAVR,stroke remains a dreaded perioperative complication(Auffret et al.,2016;Kapadia et al.,2016;Kleiman et al.,2016;Huded et al.,2019).Ischemic overt stroke,identified in 1.4%to 4.3%of patients in TAVR clinical practice,has been associated with prolonged disability and increased mortality(Auffret et al.,2016;Kapadia et al.,2016;Levi et al.,2022).The prevalence of hyperintensity cerebral ischemic lesions detected by diffusion-weighted magnetic resonance imaging(DW-MRI)was reported to be about 80%,which is associated with impaired neurocognitive function and vascular dementia(Vermeer et al.,2003;Barber et al.,2008;Kahlert et al.,2010).

Immunity-and-matrix-regulatory cells enhance cartilage regeneration for meniscus injuries: a phase I dose-escalation trial

Immunity-and-matrix-regulatory cells(IMRCs)derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix,which could be mass-produced with stable biological properties.Despite resemblance to mesenchymal stem cells(MSCs)in terms of self-renew and tri-lineage differentiation,the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined.Here,we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury.Following injection into the knees of rabbits with meniscal injury,IMRCs enhanced endogenous fibrocartilage regeneration.In the dose-escalating phase I clinical trial(NCT03839238)with eighteen patients recruited,we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting.Furthermore,the effective results of magnetic resonance imaging(MRI)of meniscus repair and knee functional scores suggested that 5×107 cells are optimal for meniscus injury treatment.In summary,we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury.Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.

In situ construction of ligand nano-network to integrin αvβ3 for angiogenesis inhibition

Angiogenesis occurs during the process of tumor growth,invasion and metastasis,and is essential for the survival of solid tumors.As an integrin significantly ove rexpressed in human tumor vascular endothelial cells,αvβ3 is a suitable targeting site for anti-angiogenesis of tumor.We designed and prepared a selfassembling peptide(SAP)with the ability to targeting αvβ3 and self-assembly.SAP formed nanoparticles in solution and transformed into nanofibrous network once specifically binding to integrin αvβ3 on the surface of human umbilical vein endothelial cells(HUVECs).The SAP network stably anchored on HUVECs over 24h,which consequently resulted in high-efficient inhibition of vascularization.In vitro anti-angiogenesis experiment displayed that the inhibition rate of tube-formation reached 94.9%.In vivo anti-angiogenesis array based on chick chorioallantoic membrane(CAM)model exhibited that the SAP had an inhibition rate up to 63.1%.These results indicated the outstanding anti-angiogenic ability of SAP,potentially for tumor therapy.

Kidney function change after transcatheter aortic valve replacement in patients with diabetes and/or hypertension

Aortic stenosis(AS)is a progressive heart valve disease occurring predominantly in older patients.According to a survey in a western country,the prevalence of AS is nearly 6.4%in patients over 75 years old(Carabello and Paulus,2009).Transcatheter aortic valve replacement(TAVR)is an alternative method for AS patients.Previous studies have described how up to 66%of TAVR patients have concomitant baseline kidney dysfunction(Ferro et al.,2015;Gargiulo et al.,2015).The majority of patients can benefit from the TAVR procedure with the recovery of kidney function.

A self-assembling peptide targeting VEGF receptors to inhibit angiogenesis

Vascular endothelial growth factor(VEGF)-vascular endothelial growth factor receptor(VEGFR)pathways are essential in tumor angiogenesis,growth and metastasis.Studies on anti-angiogenic therapy have been mostly focused on the blockage of VEGF-VEGFR pathways.We report an extracellularly transformable peptide-based nanomaterial to develop artificial extracellular matrix(ECM)-like networks for high-efficient blockage of natural VEGF-VEGFR interactions.The transformable peptide-based nanomaterial transforms from nanoparticles into nanofibers upon binding to VEGFR in solution.In addition,the transformable peptide-based nanomate rial forms ECM-like fibrous netwo rks on VEGFR overexpressed cells,inhibiting the VEGF-VEGFR interactions and the subsequent angiogenesis.The tube formation is reduced by nearly 85.1% after treatment.This strategy shows excellent potential for anti-angiogenesis,and inhibition of tumor invasion and metastasis.

Transformable peptide nanoparticles inhibit the migration of N-cadherin overexpressed cancer cells

About 90%cancer-related mortality results from the cancer metastasis,which generally undergoes after epithelial-mesenchymal transition(EMT)process.N-Cadherin,overexpressed on cancer cell surface during EMT,can enhance the migration of cancer cells.He rein,we design and synthesize a transformable peptide BP-KLVFF-SWTLYTPSGQSK(BFS)that can block N-cadherin for inhibiting cancer migration and metastasis.The peptide BFS consists of three modules including(1)the hydrophobic bis-pyrene(BP)unit for forming and locating nanoparticles,(2)the KLVFF peptide sequence for forming and stabilizing fibrous structures and(3)the targeting peptide sequence SWTLYTPSGQSK that can specifically bind to Ncadherin.The peptide BFS can form nanoparticles in PBS,which can transform to nanofibers when targeting and binding to N-cadherin.The nanofibers inhibit the migration of N-cadherin overexpressed MDA-MB-436 cancer cells.The peptide BFS shows 83.6%inhibiting rate in cells wound healing assay.In addition,the inhibition rate is 67.9%when the BFS applied in transwell migration assay.These results indicate that the BFS has excellent ability to inhibit migration of cancer cells.This self-assembly strategy could be potentially utilized to regulate the key protein during EMT for inhibiting the tumor metastasis.

Novel apical-to-femoral rail technique for horizontal aorta in transcatheter aortic valve replacement

Transcatheter aortic valve replacement(TAVR)has emerged as a viable treatment option for patients with severe aortic stenosis regardless of its surgical risk stratification(Otto et al.,2021).Aortic angulation is usually measured as the angle between the horizon-tai and the aortic annulus planes based on preprocedural multidetector computed tomography(MDCT)(Al-Lamee et al.,2011).Extremely horizontal aorta,defined as an aortic angulation greater than 70°.