Biofabricated 3D Intestinal Models as an Alternative to Animal-Based Approaches for Drug Toxicity Assays.

Background: The main challenge in new drug development is accurately predicting the human response in preclinical models.

Methods: In this study, we developed three different intestinal barrier models using advanced biofabrication techniques: (i) a manual model containing Caco-2 and HT-29 cells on a collagen bed, (ii) a manual model with a Caco-2/HT-29 layer on a HDFn-laden collagen layer, and (iii) a 3D bioprinted model incorporating both cellular layers. Each model was rigorously tested for its ability to simulate a functional intestinal membrane.

Thalamic deep brain stimulation for central poststroke pain syndrome: an international multicenter study.

Objective: The effectiveness and optimal stimulation site of deep brain stimulation (DBS) for central poststroke pain (CPSP) remain elusive. The objective of this retrospective international multicenter study was to assess clinical as well as neuroimaging-based predictors of long-term outcomes after DBS for CPSP.

Methods: The authors analyzed patient-based clinical and neuroimaging data of previously published and unpublished cohorts from 6 international DBS centers.

Longevity of antibody responses is associated with distinct antigen-specific B cell subsets early after infection.

Introduction: Upon infection, T cell-driven B cell responses in GC reactions induce memory B cells and antibody-secreting cells that secrete protective antibodies. How formation of specifically long-lived plasma cells is regulated via the interplay between specific B and CD4+ T cells is not well understood. Generally, antibody levels decline over time after clearance of the primary infection.

MMP-9 expression in rat pup incisor teeth is not altered by maternal hypertension or maternal atenolol treatment during pregnancy and lactation.

Hypertension alters tooth formation and Atenolol reduces the blood pressure of spontaneously hypertensive rats (SHR) during pregnancy and lactation, and as demonstrated before, increases the microhardness of the SHR offspring's teeth. MMP-9 is overexpressed in different tissues of hypertensive animals and treatment of hypertension substances can reverse this alteration. We hypothesize hypertension alters the expression of MMP-9 in dental structures of SHR offspring and that treating female SHR with atenolol prevents this alteration.

SPLICER: a highly efficient base editing toolbox that enables in vivo therapeutic exon skipping.

Exon skipping technologies enable exclusion of targeted exons from mature mRNA transcripts, which have broad applications in medicine and biotechnology. Existing techniques including antisense oligonucleotides, targetable nucleases, and base editors, while effective for specific applications, remain hindered by transient effects, genotoxicity, and inconsistent exon skipping. To overcome these limitations, here we develop SPLICER, a toolbox of next-generation base editors containing near-PAMless Cas9 nickase variants fused to adenosine or cytosine deaminases for the simultaneous editing of splice acceptor (SA) and splice donor (SD) sequences.