Complement System and Adhesion Molecule Skirmishes in Fabry Disease: Insights into Pathogenesis and Disease Mechanisms.

Fabry disease is a rare X-linked lysosomal storage disorder caused by mutations in the galactosidase alpha () gene, resulting in the accumulation of globotriaosylceramide (Gb3) and its deacetylated form, globotriaosylsphingosine (Lyso-Gb3) in various tissues and fluids throughout the body. This pathological accumulation triggers a cascade of processes involving immune dysregulation and complement system activation. Elevated levels of complement 3a (C3a), C5a, and their precursor C3 are observed in the plasma, serum, and tissues of patients with Fabry disease, correlating with significant endothelial cell abnormalities and vascular dysfunction.

Humanin-G Ameliorates Hemorrhage-Induced Acute Lung Injury in Mice Through AMPKα1-Dependent and -Independent Mechanisms.

: The severity of acute lung injury is significantly impacted by age and sex in patients with hemorrhagic shock. AMP-activated protein kinase (AMPK) is a crucial regulator of energy metabolism but its activity declines with aging. Humanin is a mitochondrial peptide that exerts cytoprotective effects in response to oxidative stressors and is associated with longevity.

Patterns, Barriers, and Preferences of Treating Migraine Within the School Setting: A Survey Study of Students.

Migraine affects 10% of adolescents and children. Typical school protocols in the USA require pharmacological medications to be administered by school nurses, often resulting in treatment delays or omissions when migraine attacks occur during school hours. The Remote Electrical Neuromodulation (REN) wearable is an FDA-cleared smartphone-controlled device delivering acute and preventive treatment of migraine attacks in patients aged 8 and above, allowing safe, effective, discreet, and independent usage.

Fundamentals and Applications of Fluid Mechanics and Acoustics in Biomedical Engineering.

The field of biomedical engineering has experienced important recent advances in experimental, computational, and analytical research in fluid mechanics and acoustics [...

Gucy1α1 specifically marks kidney, heart, lung and liver fibroblasts.

Fibrosis is a common outcome of numerous pathologies, including chronic kidney disease (CKD), a progressive renal function deterioration. Current approaches to target activated fibroblasts, key effector contributors to fibrotic tissue remodeling, lack specificity. Here, we report Gucy1α1 as a specific kidney fibroblast marker.

The sclerotome is the source of the dorsal and anal fin skeleton and its expansion is required for median fin development.

Paired locomotion appendages are hypothesized to have redeployed the developmental program of median appendages, such as the dorsal and anal fins. Compared with paired fins, and limbs, median appendages remain surprisingly understudied. Here, we report that a dominant zebrafish mutant, smoothback (smb), fails to develop a dorsal fin.

A latent transfer learning method for estimating hospital-specific post-acute healthcare demands following SARS-CoV-2 infection.

The long-term complications of COVID-19, known as the post-acute sequelae of SARS-CoV-2 infection (PASC), significantly burden healthcare resources. Quantifying the demand for post-acute healthcare is essential for understanding patients' needs and optimizing the allocation of valuable medical resources for disease management. Driven by this need, we developed a heterogeneous latent transfer learning framework (Latent-TL) to generate critical insights for individual health systems in a distributed research network.

A developmental biliary lineage program cooperates with Wnt activation to promote cell proliferation in hepatoblastoma.

Cancers evolve not only through the acquisition and clonal transmission of somatic mutations but also by epigenetic mechanisms that modify cell phenotype. Here, we use histology-guided and spatial transcriptomics to characterize hepatoblastoma, a childhood liver cancer that exhibits significant histologic and proliferative heterogeneity despite clonal activating mutations in the Wnt/β-catenin pathway. Highly proliferative regions with embryonal histology show high expression of Wnt target genes, the embryonic biliary transcription factor SOX4, and striking focal expression of the growth factor FGF19.

Neurofilament light chain: a biomarker at the crossroads of clarity and confusion for gene-directed therapies.

Neurofilament light chain (NfL) is a promising biomarker for neurodegenerative diseases, measurable in both CSF and blood upon neuroaxonal damage. While CSF analysis was traditionally used, blood-based assays now offer a less invasive alternative. NfL levels correlate with disease severity and progression in conditions like Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis and Huntington's disease.

Regulated GATA1 expression as a universal gene therapy for Diamond-Blackfan anemia.

Gene therapy using hematopoietic stem and progenitor cells is altering the therapeutic landscape for patients with hematologic, immunologic, and metabolic disorders but has not yet been successfully developed for individuals with the bone marrow failure syndrome Diamond-Blackfan anemia (DBA). More than 30 mutations cause DBA through impaired ribosome function and lead to inefficient translation of the erythroid master regulator GATA1, providing a potential avenue for therapeutic intervention applicable to all patients with DBA, irrespective of the underlying genotype. Here, we report the development of a clinical-grade lentiviral gene therapy that achieves erythroid lineage-restricted expression of GATA1.

GPR68 supports AML cells through the calcium/calcineurin pro-survival pathway and confers chemoresistance by mediating glucose metabolic symbiosis.

Accumulating evidence demonstrates that the "Warburg effect" that glycolysis is enhanced even in the presence of oxygen existed in hematopoietic malignancies, contributing to extracellular acidosis. G-protein coupled receptor 68 (GPR68), as a proton sensing GPCR responding to extracellular acidosis, is expected to play a critical role in hematopoietic malignancies. In the present study, we found that GPR68 was overexpressed in acute myeloid leukemia (AML) cells, and GPR68 deficiency impaired AML cell survival in vitro and cell engraftment in vivo.

Quantifying tumor specificity using Bayesian probabilistic modeling for drug and immunotherapeutic target discovery.

In diseases such as cancer, the design of new therapeutic strategies requires extensive, costly, and unfortunately sometimes deadly testing to reveal life threatening off-target effects. We hypothesized that the disease specificity of targets can be systematically learned for all genes by jointly evaluating complementary molecular measurements of healthy tissues using a hierarchical Bayesian modeling approach. Our method, BayesTS, integrates protein and gene expression evidence and includes tunable parameters to moderate tissue essentiality.

The unique functions of Runx1 in skeletal muscle maintenance and regeneration are facilitated by an ETS interaction domain.

The conserved Runt-related (RUNX) transcription factor family are master regulators of developmental and regenerative processes. Runx1 and Runx2 are expressed in satellite cells (SCs) and in skeletal myotubes. Here, we examined the role of Runx1 in mouse satellite cells to determine the role of Runx1 during muscle differentiation.

The Innate Immune System Surveillance Biomarker p87 in African Americans and Caucasians with Small High-Grade Dysplastic Adenoma [SHiGDA] and Right-Sided Colon Mutations May Explain the Presence of Multiple Cancers Revealing an Important Minority of Patients with Mutations and Colorectal Neoplasia.

Unlabelled: Colorectal cancer (CRC) outcomes in terms of incidence and mortality are significantly worse in African Americans than other Americans. While differences in primary preventions for neoplasia (diet, obesity remediation, aspirin prophylaxis) are being elucidated, genetic mutations affecting premalignant lesions and immune response mechanisms may possibly also explain the increased incidence and mortality, particularly from right-sided disease.

Objective: Our team therefore examined colonic segments seeking to test the hypothesis that the immune response and somatic genetic profiles of the colonic anatomic segments may vary and thus account for variations in neoplasia risk among the various colonic segments revealing an antigenic relationship with precancerous lesions.

Single cell RNA-seq reveals cellular and transcriptional heterogeneity in the splenic CD11bLy6C monocyte population expanded in sepsis-surviving mice.

Background: Sepsis survivors exhibit immune dysregulation that contributes to poor long-term outcomes. Phenotypic and functional alterations within the myeloid compartment are believed to be a contributing factor. Here we dissect the cellular and transcriptional heterogeneity of splenic CD11bLy6C myeloid cells that are expanded in mice that survive the cecal ligation and puncture (CLP) murine model of polymicrobial sepsis to better understand the basis of immune dysregulation in sepsis survivors.

Synthetic hydrogel substrate for human induced pluripotent stem cell definitive endoderm differentiation.

Human induced pluripotent stem cells (hiPSCs) can give rise to multiple lineages derived from three germ layers, endoderm, mesoderm and ectoderm. Definitive endoderm (DE) cell types and tissues have great potential for regenerative medicine applications. Current hiPSC differentiation protocols focus on the addition of soluble factors; however, extracellular matrix properties are known to also play a role in dictating cell fate.

Treatment of Short Stature in Aggrecan-deficient Patients With Recombinant Human GH: 3-year Response.

Context: Patients with aggrecan (ACAN) deficiency present with dominantly inherited short stature, as well as early-onset joint disease.

Objective: The objective of this study was to evaluate the efficacy and safety of recombinant human GH (rhGH) on linear growth in ACAN-deficient children.

Methods: Open-label, single-arm, prospective study over 3 years recruiting 10 treatment-naïve patients with heterozygous mutations in , age ≥2 years, prepubertal, and normal IGF-I concentration.

A primer on the pleiotropic endocrine fibroblast growth factor FGF19/FGF15.

Fibroblast Growth Factor 19 (FGF19) is a member of the Fibroblast Growth Factor (FGF) family, known for its role in various cellular processes including embryonic development and metabolic regulation. FGF19 functions as an endocrine factor, influencing energy balance, bile acid synthesis, glucose and lipid metabolism, as well as cell proliferation. FGF19 has a conserved structure typical of FGFs but exhibits unique features.

Utility of Serum Matrix Metalloproteinase-7 as a Biomarker in Cholestatic Infants with Congenital Heart Disease.

Background: Matrix metalloproteinase 7 (MMP-7) is a novel biomarker for diagnosis of biliary atresia (BA), the most common cholestatic liver disease in infancy. There is a pressing need to determine the utility of MMP-7 levels in infants with congenital heart disease (CHD) to avoid unnecessary invasive diagnostic procedures in this high-risk population. We investigated the utility of MMP-7 in discriminating BA from non-BA cholestasis in infants with CHD and whether MMP-7 elevation was present in infants requiring treatment for clinically significant PH.