Identification of a choroid plexus vascular barrier closing during int... Science, 2021

Abstract Up to 40% of patients with inflammatory bowel disease present with psychosocial disturbances. We previously identified a gut vascular barrier that controls the dissemination of bacteria from the intestine to the liver. Here, we describe a vascular barrier in the brain choroid plexus (PVB) that is modulated in response to intestinal inflammation through bacteria-derived lipopolysaccharide. The inflammatory response induces PVB closure after gut vascular barrier opening by the up-regulation of the wingless-type, cat...



Cathepsin C promotes breast cancer lung metastasis by modulating neutr... Cancer Cell, 2021

Abstract Lung metastasis is the major cause of breast cancer-related mortality. The neutrophil-associated inflammatory microenvironment aids tumor cells in metastatic colonization in lungs. Here, we show that tumor-secreted protease cathepsin C (CTSC) promotes breast-to-lung metastasis by regulating recruitment of neutrophils and formation of neutrophil extracellular traps (NETs). CTSC enzymatically activates neutrophil membrane-bound proteinase 3 (PR3) to facilitate interleukin-1β (IL-1β) processing and nuclear factor κB a...



Patient-derived iPSC-cerebral organoid modeling of the 17q11.2 microde... Patient-derived iPSC-cerebral organoid modeling of the 17q11.2 microde...

Abstract Neurodevelopmental disorders are often caused by chromosomal microdeletions comprising numerous contiguous genes. A subset of neurofibromatosis type 1 (NF1) patients with severe developmental delays and intellectual disability harbors such a microdeletion event on chromosome 17q11.2, involving the NF1 gene and flanking regions (NF1 total gene deletion [NF1-TGD]). Using patient-derived human induced pluripotent stem cell (hiPSC)-forebrain cerebral organoids (hCOs), we identify both neural stem cell (NSC) proliferation and neuronal...



In vitro comparison of major memory-support dietary supplements for th...

Abstract Memory loss is primarily caused by the accumulation of both brain plaques [(consisting of beta-amyloid protein (Aβ) 1–42)] and neurofibrillary tangles (consisting of paired helical and straight filaments containing tau protein). Neuroinflammation is the third key and important factor that leads to accelerated memory loss and eventual dementia. Brain plaques, tangles and inflammation is the trilogy mainly responsible for causing memory loss that has now been documented for over 20 years in the scientific literature....



Biofunctionalization of Dental Abutment Surfaces by Crosslinked ECM Pr... Advanced Healthcare Material, 2021

Abstract To ensure the long-term success of dental implants, a functional attachment of the soft tissue to the surface of the implant abutment is decisively important in order to prevent the penetration of bacteria into the implant-bone interface, which can trigger peri-implant disease. Here a surface modification approach is described that includes the covalent immobilization of the extracellular matrix (ECM) proteins fibronectin and laminin via a crosslinker to silanized Ti6Al4V and Y-TZP surfaces. The surface properties are evaluated us...



Die IHC-Analyse von TIGIT für die Entwicklung eines neuen Scoring Syst... Nature, scientific reports, 2021

Die Immun-Checkpoint Blockade des PD1/PD-L1 Signalweges hat die Krebstherapie revolutioniert. Aktuelle Studien zeigen, dass die Kombination mit Therapieansätzen gegen neue Immun-Checkpoints wie TIGIT deutlich effektiver sein kann als klassische PD1/PD-L1 Monotherapien. In den letzten beiden Jahren ist TIGIT in den weltweiten Fokus der Pharmaindustrie gerückt und hat sich zum attraktivsten Target in der sogenannten „zweiten Welle von Checkpoint-Modulatoren“ entwickelt. Für neue Immuntherapien müssen jene Patienten diagno...



Development of a nano-drug delivery system based on mesoporous silica... Applied Nanoscience, 2020

Abstract Although current treatment strategies including systemic chemotherapy, local radiotherapy, biological immunology, and surgical resection have improved the remission rate of non-Hodgkin’s lymphoma (NHL) patients, the recurrence rate of the disease remains high, and the remission rate of retreatment after recurrence is low. Exploring and discovering new strategies for treating NHL has become a critical problem to be solved. Harmine (HM) has demonstrated anti-tumor activity; however, like most traditional Chinese medicines, it...



An interplay between UCP2 and ROS protects cells from high-salt-induce... Cell Death and Disease, 2021

Abstract The mitochondrial uncoupling protein 2 (UCP2) plays a protective function in the vascular disease of both animal models and humans. UCP2 downregulation upon high-salt feeding favors vascular dysfunction in knock-out mice, and accelerates cerebrovascular and renal damage in the stroke-prone spontaneously hypertensive rat. Overexpression of UCP2 counteracts the negative effects of high-salt feeding in both animal models. We tested in vitro the ability of UCP2 to stimulate autophagy and mitophagy as a mechanism mediating its protecti...



The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-re... PNAS, 2021

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic and has claimed over 2 million lives worldwide. Although the genetic sequences of SARS-CoV and SARS-CoV-2 have high homology, the clinical and pathological characteristics of COVID-19 differ significantly from those of SARS. How and whether SARS-CoV-2 evades (cellular) immune surveillance requires further elucidation. In this study, we show that SARS-CoV-2 infection leads to major histocompability complex class Ι (MHC-Ι) down-regula...



Catalytically potent and selective clusterzymes for modulation of neur... Nature Communications, 2021

Abstract Emerging artificial enzymes with reprogrammed and augmented catalytic activity and substrate selectivity have long been pursued with sustained efforts. The majority of current candidates have rather poor catalytic activity compared with natural molecules. To tackle this limitation, we design artificial enzymes based on a structurally well-defined Au25 cluster, namely clusterzymes, which are endowed with intrinsic high catalytic activity and selectivity driven by single-atom substitutions with modulated bond lengths. Au24Cu1 and Au...