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Choline attenuates abdominal aortic coarctation-induced cardiac remodeling and cardiac dysfunction, by amelioration of circadian rhythm disruption and attenuation of calcium-handling protein defects. Modulation of vagal activity by choline may have therapeutic potential for cardiac remodeling and heart failure.
Human corneal keratocytes (HCK) are essential for maintaining corneal structure and transparency. This study shows that the natural antioxidant L-carnitine inhibits stromal scarring by suppressing injury-induced intrinsic transient receptor potential vanilloid type 1 (TRPV1) activity that is linked to induction of myofibroblast transdifferentiation in HCK cells. Blocking TRPV1 activation on keratocytes may therefore be a viable approach to suppress corneal opacification in a clinical setting.
The breast cancer immune microenvironment was analyzed with the nanoString GeoMx® Digital Spatial Profiler (DSP) in cases from the Carolina Breast Cancer Study. Basal-like breast cancers showed increased expression of markers for regulatory T cells. The results were highly reproducible between whole sections and tissue microarrays.
The authors developed a deep-learning-based ductal carcinoma in situ (DCIS) grading system that achieved performance similar to expert observers. To the best of our knowledge, this is the first automated system for the grading of DCIS that could assist pathologists by providing robust and reproducible second opinions on DCIS grade.
Dimethylarginine dimethylamino hydrolase-1 (DDAH-1), as the critical enzyme responsible for asymmetric dimethylarginine (ADMA) degradation, serves as a protective factor for ischemic stroke. DDAH-1 protects ischemia-induced disruption of blood-brain-barrier via regulating ADMA level and preventing tight junction proteins degradation. The supplementation of L-arginine helps restore the function of DDAH-1.
Most current biomedical datasets are rectangular in shape and have few missing data, but the sample sizes are very large. Rigorous analyses of these huge datasets demand considerably more efficient and more accurate machine-learning algorithms to classify outcomes. This paper aims to determine the performance and efficiency of classifying multi-category outcomes of such rectangular data.
This manuscript describes a methodology to quantify the abnormalities in digital cytology images. This automatic AI-system incorporates deep learning structures, mathematical algorithms, and image processing methods to locate and segment abnormal and suspicious cells. Characterized as more informative, objective, and reproducible, it has the potential to assist clinical practice.
The findings of the present study demonstrate that inflammasome NLRP3 deficiency did not attenuate, but enhanced hepatocellular steatosis, injury and death, inflammation, and fibrosis, as well as insulin resistance in both liver and adipose tissues. This effect is probably due to an enhanced inflammatory response with elevated monocyte chemotactic protein-1 and M1 microphages.
Genome-wide association studies have linked Forkhead Box F1 (FOXF1) to Barrett’s esophagus (BE) but functional data are lacking. Using in vitro models and human material, the authors found that FOXF1 promotes columnar phenotype and cell motility in esophageal squamous epithelial cells, which may have a critical role in BE development.
Patient-derived xenograft (PDX) models are valuable platforms to assess preclinical and clinical trials for cancer therapy including lung cancer. The authors clarified that enriched expression of immune system-associated genes such as CD19 and CD23 are the most critical factors to obstacle the PDX generation, particularly in lung squamous cell carcinoma.
The authors report the successful assessment of LD-RT-PCR, a cheap, fast, sensitive, specific, and easily upgradable assay for routine detection of theranostic gene translocations and MET exon 14 skipping in thoracic oncology. It appears to be an excellent cost-effective alternative to FISH and to more expensive and complex assays such as RNA-seq.
PLODs play important roles in cancer progression. In silico analysis of PLOD expression in ovarian cancer was performed. PLOD-enriched pathways and related genes were validated by immunohistochemistry in OvCa tissue blocks and in vivo xenograft murine models. PLODs are generally overexpressed in OvCa and each PLOD may be functionally non-redundant.
Real-time lipid patterns can identify liver tumors and their inter-tumor and intra-tumor heterogeneity. Ceramides and related sphingolipids are a common feature of necrotic tumors and can characterize the tumor phenotype based on metabolic shifts relevant for cell death pathways. Lipid patterns have the potential to improve clinical decision-making in the near future.
Using approaches involving chimeric mice and macrophage-adipocyte cocultures, the authors demonstrate that PFKFB3 disruption only in hematopoietic cells exacerbates the severity of diet-induced adipose tissue inflammation and systemic insulin resistance. Mechanistically, macrophage factors generated in response to PFKFB3 disruption act to enhance adipocyte proinflammatory responses and impair adipocyte insulin signaling.
Recent studies highlight a prominent role of human lung pericytes in lung diseases. However, human lung pericytes usually stop growth within ten passages. This study successfully established an immortalized human lung pericyte cell line, which exhibited sustained proliferation, retained pericyte characteristics and function, is a promising tool for in vitro pericyte studies.
In this study, the authors reveal that the hypoxic microenvironment stimulates glioma to generate miR-1246- and miR-10b-5p-rich exosomes, which are delivered to normoxic glioma cells to promote their migration and invasion by targeting FRK and TFAP2A respectively. Treatment targeting the exosomes and microRNAs may impair the motility of gliomas, providing a novel direction for the development of antitumor therapy.
Tissue cytometry is a promising new microscopy technique that can be used to enumerate and characterize each cell in a tissue. Here the authors describe a complete and accessible pipeline, including methods of sample preparation, microscopy, image analysis, and data analysis for large-scale three-dimensional tissue cytometry of human kidney tissues.
The abnormal differentiation of Th17 cells is a vital promoter of immune thrombocytopenia (ITP) progression. In this study, the authors found that miR-199a-5p is downregulated during ITP. Supplementation of extracellular vesicles (EVs) derived from miR-199a-5p-modified ADSCs markedly repress Th17 differentiation by transferring miR-199a-5p to CD4+T cells, thus ameliorating experimental ITP.