Serum amyloid P (PTX2) attenuates hepatic fibrosis in mice by inhibiting the activation of fibrocytes and HSCs.

Background: Liver fibrosis is caused by chronic toxic or cholestatic liver injury. Fibrosis results from the recruitment of myeloid cells into the injured liver, the release of inflammatory and fibrogenic cytokines, and the activation of myofibroblasts, which secrete extracellular matrix, mostly collagen type I. Hepatic myofibroblasts originate from liver-resident mesenchymal cells, including HSCs and bone marrow-derived CD45+ collagen type I+ expressing fibrocytes.

The association between dissociative symptoms and schizophrenia-related negative symptoms: A transdiagnostic approach.

Negative symptoms of schizophrenia remain clinically and theoretically understudied and represent an unmet psychiatric need. Negative symptoms are assumed to be related to other psychiatric disorders, but their association with dissociative symptoms is yet to be explored, particularly in light of depression and anxiety symptoms. We examined the five domains of negative symptoms (anhedonia, asociality, avolition, blunted affect and alogia) in an Israeli national sample of 1930 participants of whom 645 (33.

Traumatic brain injury induces TDP-43 mislocalization and neurodegenerative effects in tissue distal to the primary injury site in a non-transgenic mouse.

Traumatic brain injury (TBI) initiates tissue and cellular damage to the brain that is immediately followed by secondary injury sequalae with delayed and continual damage. This secondary damage includes pathological processes that may contribute to chronic neurodegeneration and permanent functional and cognitive deficits. TBI is also associated with an increased risk of developing neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS) as indicated by shared pathological features.

PINE-TREE enables highly efficient genetic modification of human cell lines.

Prime editing technologies enable precise genome editing without the caveats of CRISPR nuclease-based methods. Nonetheless, current approaches to identify and isolate prime-edited cell populations are inefficient. Here, we established a fluorescence-based system, prime-induced nucleotide engineering using a transient reporter for editing enrichment (PINE-TREE), for real-time enrichment of prime-edited cell populations.

The Multifaceted Role of WNT Signaling in Alzheimer's Disease Onset and Age-Related Progression.

The evolutionary conserved WNT signaling pathway orchestrates numerous complex biological processes during development and is critical to the maintenance of tissue integrity and homeostasis in the adult. As it relates to the central nervous system, WNT signaling plays several roles as it relates to neurogenesis, synaptic formation, memory, and learning. Thus, dysfunction of this pathway is associated with multiple diseases and disorders, including several neurodegenerative disorders.

Modeling long QT syndrome type 2 on-a-chip via in-depth assessment of isogenic gene-edited 3D cardiac tissues.

Long QT syndrome (LQTS) is a cardiovascular disease characterized by QT interval prolongation that can lead to sudden cardiac death. Many mutations with heterogeneous mechanisms have been identified in , the gene that encodes for hERG (Kv11.1), which lead to onset of LQTS type 2 (LQTS2).

Therapeutic horseback riding for at-risk adolescents in residential care.

Background: Over the past two decades, a large body of research has focused on the contribution of equine-assisted therapies to positive psychological changes in at-risk adolescents. The current study aimed to explore the subjective experiences of therapeutic horseback riding (THR, a type of equine-assisted therapy) among at-risk adolescents and examine how they describe the psychological benefits and the mechanisms of change of a THR intervention.

Methods: This qualitative study focused on at-risk adolescents living in residential care.

A microcarrier-based protocol for scalable generation and purification of human induced pluripotent stem cell-derived neurons and astrocytes.

Here, we describe a protocol for a microcarrier (MC)-based, large-scale generation and cryopreservation of human-induced pluripotent stem cell (hiPSC)-derived neurons and astrocytes. We also detail steps to isolate these populations with a high degree of purity. Finally, we describe how to cryopreserve these cell types while maintaining high levels of viability and preserving cellular function post-thaw.

A qualitative study of equine-assisted therapy for Israeli military and police veterans with PTSD-impact on self-regulation, bonding and hope.

Equine-assisted therapy (EAT) is an increasingly popular form of treatment for people suffering from post-traumatic stress disorder (PTSD) who, for one reason or another, find psychotherapy and other traditional treatment approaches unsuitable or unhelpful. However, the concomitant growth of research in the field is yet to engage with key factors relating to EAT; specifically, there are few studies considering the phenomenological perspective of patients, and the embodied knowledge deriving from the lived experience of PTSD patients who participated in EAT-based intervention programmes. Based on a qualitative-phenomenological study, interviews were conducted with 12 PTSD patients who had completed an EAT-based intervention programme.

The Emergence of Model Systems to Investigate the Link Between Traumatic Brain Injury and Alzheimer's Disease.

Numerous epidemiological studies have demonstrated that individuals who have sustained a traumatic brain injury (TBI) have an elevated risk for developing Alzheimer's disease and Alzheimer's-related dementias (AD/ADRD). Despite these connections, the underlying mechanisms by which TBI induces AD-related pathology, neuronal dysfunction, and cognitive decline have yet to be elucidated. In this review, we will discuss the various and models that are being employed to provide more definite mechanistic relationships between TBI-induced mechanical injury and AD-related phenotypes.

Weighing up the evidence used by direct-to-consumer stem cell businesses.

Hundreds of businesses across the United States offer direct-to-consumer stem-cell-based interventions that have not been approved by the Food and Drug Administration. Here, we characterize the types of evidence used on the websites of 59 stem cell businesses in the Southwest United States to market their services. We identify over a dozen forms of evidence, noting that businesses are less likely to rely on "gold-standard" scientific evidence, like randomized clinical trials, and instead draw substantially on forms of evidence that we identify as being "ambiguous.

Generation of 3X FLAG-tagged human embryonic stem cell (hESC) line to study WNT-induced β-catenin DNA interactions (HVRDe009-A-2).

In the canonical WNT signaling pathway, active WNT signaling results in the nuclear translocation of β-catenin where it regulates target gene expression. As a tool to understand these β-catenin DNA interactions, we used a CRISPR/Cas9 based approach to engineer a human embryonic stem cell line (hESC) harboring a 3X FLAG sequence fused to the C-terminus of β-catenin. Engineered cells displayed a characteristic hESC morphology, expressed pluripotency-associated markers, retained tri-lineage differentiation potential, and had a normal euploid karyotype.

Apolipoprotein E regulates lipid metabolism and α-synuclein pathology in human iPSC-derived cerebral organoids.

APOE4 is a strong genetic risk factor for Alzheimer's disease and Dementia with Lewy bodies; however, how its expression impacts pathogenic pathways in a human-relevant system is not clear. Here using human iPSC-derived cerebral organoid models, we find that APOE deletion increases α-synuclein (αSyn) accumulation accompanied with synaptic loss, reduction of GBA levels, lipid droplet accumulation and dysregulation of intracellular organelles. These phenotypes are partially rescued by exogenous apoE2 and apoE3, but not apoE4.

Cytosine and adenosine base editing in human pluripotent stem cells using transient reporters for editing enrichment.

Deaminase fused-Cas9 base editing technologies have enabled precise single-nucleotide genomic editing without the need for the introduction of damaging double-stranded breaks and inefficient homology-directed repair. However, current methods to isolate base-edited cell populations are ineffective, especially when utilized with human pluripotent stem cells, a cell type resistant to genome modification. Here, we outline a series of methods that employ transient reporters of editing enrichment (TREE) to facilitate the highly efficient single-base editing of human cells at precise genomic loci.

APOE2 mitigates disease-related phenotypes in an isogenic hiPSC-based model of Alzheimer's disease.

Genome-wide association studies (GWAS) have identified polymorphism in the Apolipoprotein E gene (APOE) to be the most prominent risk factor for Alzheimer's disease (AD). Compared to individuals homozygous for the APOE3 variant, individuals with the APOE4 variant have a significantly elevated risk of AD. On the other hand, longitudinal studies have shown that the presence of the APOE2 variant reduces the lifetime risk of developing AD by 40 percent.

Prime Editing Guide RNA Design Automation Using PINE-CONE.

CRISPR-based technologies are paramount in genome engineering and synthetic biology. Prime editing (PE) is a technology capable of installing genomic edits without double-stranded DNA breaks (DSBs) or donor DNA. Prime editing guide RNAs (pegRNAs) simultaneously encode both guide and edit template sequences.

A Cas9-mediated adenosine transient reporter enables enrichment of ABE-targeted cells.

Background: Adenine base editors (ABE) enable single nucleotide modifications without the need for double-stranded DNA breaks (DSBs) induced by conventional CRIPSR/Cas9-based approaches. However, most approaches that employ ABEs require inefficient downstream technologies to identify desired targeted mutations within large populations of manipulated cells. In this study, we developed a fluorescence-based method, named "Cas9-mediated adenosine transient reporter for editing enrichment" (CasMAs-TREE; herein abbreviated XMAS-TREE), to facilitate the real-time identification of base-edited cell populations.

Human Autopsy-Derived Scalp Fibroblast Biobanking for Age-Related Neurodegenerative Disease Research.

The Arizona Study of Aging and Neurodegenerative Disorders/Brain and Body Donation Program at Banner Sun Health Research Institute (BSHRI) is a longitudinal clinicopathological study with a current enrollment of more than 900 living subjects for aging and neurodegenerative disease research. Annual clinical assessments are done by cognitive and movement neurologists and neuropsychologists. Brain and body tissues are collected at a median postmortem interval of 3.

APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer's disease patient iPSC-derived cerebral organoids.

APOE4 is the strongest genetic risk factor associated with late-onset Alzheimer's disease (AD). To address the underlying mechanism, we develop cerebral organoid models using induced pluripotent stem cells (iPSCs) with APOE ε3/ε3 or ε4/ε4 genotype from individuals with either normal cognition or AD dementia. Cerebral organoids from AD patients carrying APOE ε4/ε4 show greater apoptosis and decreased synaptic integrity.

Guidelines for establishing a 3-D printing biofabrication laboratory.

Advanced manufacturing and 3D printing are transformative technologies currently undergoing rapid adoption in healthcare, a traditionally non-manufacturing sector. Recent development in this field, largely enabled by merging different disciplines, has led to important clinical applications from anatomical models to regenerative bioscaffolding and devices. Although much research to-date has focussed on materials, designs, processes, and products, little attention has been given to the design and requirements of facilities for enabling clinically relevant biofabrication solutions.

Engineering anisotropic human stem cell-derived three-dimensional cardiac tissue on-a-chip.

Despite significant efforts in the study of cardiovascular diseases (CVDs), they persist as the leading cause of mortality worldwide. Considerable research into human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) has highlighted their immense potential in the development of in vitro human cardiac tissues for broad mechanistic, therapeutic, and patient-specific disease modeling studies in the pursuit of CVD research. However, the relatively immature state of hPSC-CMs remains an obstacle in enhancing clinical relevance ofengineered cardiac tissue models.

A Defined and Scalable Peptide-Based Platform for the Generation of Human Pluripotent Stem Cell-Derived Astrocytes.

Astrocytes comprise the most abundant cell type in the central nervous system (CNS) and play critical roles in maintaining neural tissue homeostasis. In addition, astrocyte dysfunction and death has been implicated in numerous neurological disorders such as multiple sclerosis, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). As such, there is much interest in using human pluripotent stem cell (hPSC)-derived astrocytes for drug screening, disease modeling, and regenerative medicine applications.

Using human induced pluripotent stem cells (hiPSCs) to investigate the mechanisms by which Apolipoprotein E (APOE) contributes to Alzheimer's disease (AD) risk.

Although the biochemical and pathological hallmarks of Alzheimer's disease (AD), such as axonal transport defects, synaptic loss, and selective neuronal death, are well characterized, the underlying mechanisms that cause AD are largely unknown, thereby making it difficult to design effective therapeutic interventions. Genome-wide association studies (GWAS) studies have identified several factors associated with increased AD risk. Of these genetic factors, polymorphisms in the Apolipoprotein E (APOE) gene are the strongest and most prevalent.