Towards Clinical Application: Calcium Waves for In Vitro Qualitative Assessment of Propagated Primary Human Corneal Endothelial Cells.

Corneal endothelium cells (CECs) regulate corneal hydration between the leaky barrier of the corneal endothelium and the ionic pumps on the surface of CECs. As CECs do not regenerate, loss of CECs leads to poor vision and corneal blindness. Corneal transplant is the only treatment option; however, there is a severe shortage of donor corneas globally.

Counterproductive effects of anti-CD38 and checkpoint inhibitor for the treatment of NK/T cell lymphoma.

Introduction: Natural killer/T cell lymphoma (NKTL) is an aggressive malignancy associated with poor prognosis. This is largely due to limited treatment options, especially for relapsed patients. Immunotherapies like immune checkpoint inhibitors (ICI) and anti-CD38 therapies have shown promising but variable clinical efficacies.

Endoplasmic reticulum stress enhances the expression of TLR3-induced TSLP by airway epithelium.

Thymic stromal lymphopoietin (TSLP) is an epithelial-derived pleiotropic cytokine that regulates T-helper 2 (Th2) immune responses in the lung and plays a major role in severe uncontrolled asthma. Emerging evidence suggests a role for endoplasmic reticulum (ER) stress in the pathogenesis of asthma. In this study, we determined if ER stress and the unfolded protein response (UPR) signaling are involved in TSLP induction in the airway epithelium.

Bilobed Flap Coverage for the Reconstruction of Dorsal Soft Tissue Defect Over the Proximal Phalanx: A Case Report.

Soft tissue defects over the dorsal finger are common and may result from trauma, burns, or surgical management of infections and tumors. We present a case where a bilobed flap was used for the reconstruction of a soft tissue defect dorsal to the proximal phalanx of the ring finger and discuss the design of this flap. The defect was secondary to a collar button abscess of the right third webspace and the surgical debridement required to control the infection.

Early Visibility of Cellular Aggregates and Changes in Central Corneal Thickness as Predictors of Successful Corneal Endothelial Cell Injection Therapy.

(1) Background: Cell injection therapy is an emerging treatment for bullous keratopathy (BK). Anterior segment optical coherence tomography (AS-OCT) imaging allows the high-resolution assessment of the anterior chamber. Our study aimed to investigate the predictive value of the visibility of cellular aggregates for corneal deturgescence in an animal model of bullous keratopathy.

Chronic exposure to low-level lipopolysaccharide dampens influenza-mediated inflammatory response A20 and PPAR network.

Influenza A virus (IAV) infection leads to severe inflammation, and while epithelial-driven inflammatory responses occur activation of NF-κB, the factors that modulate inflammation, particularly the negative regulators are less well-defined. In this study we show that A20 is a crucial molecular switch that dampens IAV-induced inflammatory responses. Chronic exposure to low-dose LPS environment can restrict this excessive inflammation.

Evaluation of tracer kinetic parameters in cervical cancer using dynamic contrast-enhanced MRI as biomarkers in terms of biological relevance, diagnostic performance and inter-center variability.

Objectives: This study assessed the clinical value of parameters derived from dynamic contrast-enhanced (DCE) MRI with respect to correlation with angiogenesis and proliferation of cervical cancer, performance of diagnosis and reproducibility of DCE-MRI parameters across MRI scanners.

Materials And Methods: A total of 113 patients with cervical carcinoma from two centers were included in this retrospective study. The DCE data were centralized and processed using five tracer kinetic models (TKMs) (Tofts, Ex-Tofts, ATH, SC, and DP), yielding the following parameters: volume transfer constant (Ktrans), extravascular extracellular volume (Ve), fractional volume of vascular space (Vp), blood flow (Fp), and permeability surface area product (PS).

A Game of Infection - Song of Respiratory Viruses and Interferons.

Humanity has experienced four major pandemics since the twentieth century, with the 1918 Spanish flu, the 2002 severe acute respiratory syndrome (SARS), the 2009 swine flu, and the 2019 coronavirus disease (COVID)-19 pandemics having the most important impact in human health. The 1918 Spanish flu caused unprecedented catastrophes in the recorded human history, with an estimated death toll between 50 - 100 million. While the 2002 SARS and 2009 swine flu pandemics caused approximately 780 and 280,000 deaths, respectively, the current COVID-19 pandemic has resulted in > 6 million deaths globally at the time of writing.

Cell therapy in corneal endothelial disease.

Purpose Of Review: Endothelial keratoplasty is the current gold standard for treating corneal endothelial diseases, achieving excellent visual outcomes and rapid rehabilitation. There are, however, severe limitations to donor tissue supply and uneven access to surgical teams and facilities across the globe. Cell therapy is an exciting approach that has shown promising early results.

Atypical microbial keratitis.

Atypical microbial keratitis refers to corneal infections caused by micro-organisms not commonly encountered in clinical practice. Unlike infections caused by common bacteria, cases of atypical microbial keratitis are often associated with worse clinical outcomes and visual prognosis. This is due to the challenges in the identification of causative organisms with standard diagnostic techniques, resulting in delays in the initiation of appropriate therapies.

Human platelet lysate as a replacement for fetal bovine serum in human corneal stromal keratocyte and fibroblast culture.

The isolation and propagation of primary human corneal stromal keratocytes (CSK) are crucial for cellular research and corneal tissue engineering. However, this delicate cell type easily transforms into stromal fibroblasts (SF) and scar inducing myofibroblasts (Myo-SF). Current protocols mainly rely on xenogeneic fetal bovine serum (FBS).

Evolution of therapies for the corneal endothelium: past, present and future approaches.

Corneal endothelial diseases are leading indications for corneal transplantations. With significant advancement in medical science and surgical techniques, corneal transplant surgeries are now increasingly effective at restoring vision in patients with corneal diseases. In the last 15 years, the introduction of endothelial keratoplasty (EK) procedures, where diseased corneal endothelium (CE) are selectively replaced, has significantly transformed the field of corneal transplantation.

Cellular therapy of corneal epithelial defect by adipose mesenchymal stem cell-derived epithelial progenitors.

Background: Persistent epithelial defects (PED), associated with limbal stem cell deficiency (LSCD), require ocular surface reconstruction with a stable corneal epithelium (CE). This study investigated CE reformation using human adipose mesenchymal stem cells (ADSC), which derived epithelial progenitors via mesenchymal-epithelial transition (MET).

Methods: STEMPRO human ADSC were cultured with specific inhibitors antagonizing glycogen synthase kinase-3 and transforming growth factor-β signaling, followed by culture under a defined progenitor cell targeted-epithelial differentiation condition to generate epithelial-like cells (MET-Epi), which were characterized for cell viability, mesenchymal, and epithelial phenotypes using immunofluorescence and flow cytometry.

Characterization of Human Transition Zone Reveals a Putative Progenitor-Enriched Niche of Corneal Endothelium.

The corneal endothelium regulates corneal hydration to maintain the transparency of cornea. Lacking regenerative capacity, corneal endothelial cell loss due to aging and diseases can lead to corneal edema and vision loss. There is limited information on the existence of corneal endothelial progenitors.

Posterior Eye Shape Measurement With Retinal OCT Compared to MRI.

Purpose: Posterior eye shape assessment by magnetic resonance imaging (MRI) is used to study myopia. We tested the hypothesis that optical coherence tomography (OCT), as an alternative, could measure posterior eye shape similarly to MRI.

Methods: Macular spectral-domain OCT and brain MRI images previously acquired as part of the Singapore Epidemiology of Eye Diseases study were analyzed.

Structure-Activity Relationship Studies of Mitogen Activated Protein Kinase Interacting Kinase (MNK) 1 and 2 and BCR-ABL1 Inhibitors Targeting Chronic Myeloid Leukemic Cells.

Clinically used BCR-ABL1 inhibitors for the treatment of chronic myeloid leukemia do not eliminate leukemic stem cells (LSC). It has been shown that MNK1 and 2 inhibitors prevent phosphorylation of eIF4E and eliminate the self-renewal capacity of LSCs. Herein, we describe the identification of novel dual MNK1 and 2 and BCR-ABL1 inhibitors, starting from the known kinase inhibitor 2.

Novel Ultrasound Joint Selection Methods Using a Reduced Joint Number Demonstrate Inflammatory Improvement when Compared to Existing Methods and Disease Activity Score at 28 Joints.

Objective: A pilot study testing novel ultrasound (US) joint-selection methods in rheumatoid arthritis.

Methods: Responsiveness of novel [individualized US (IUS) and individualized composite US (ICUS)] methods were compared with existing US methods and the Disease Activity Score at 28 joints (DAS28) for 12 patients followed for 3 months. IUS selected up to 7 and 12 most ultrasonographically inflamed joints, while ICUS additionally incorporated clinically symptomatic joints.

Noncoding RNA Expression Aberration Is Associated with Cancer Progression and Is a Potential Biomarker in Esophageal Squamous Cell Carcinoma.

Esophageal cancer is one of the most common cancers worldwide. Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancer in Eastern Asian countries. Several types of noncoding RNAs (ncRNAs) function as key epigenetic regulators of gene expression and are implicated in various physiological processes.

Amino-terminal p53 mutations lead to expression of apoptosis proficient p47 and prognosticate better survival, but predispose to tumorigenesis.

Whereas most mutations in p53 occur in the DNA-binding domain and lead to its functional inactivation, their relevance in the amino-terminal transactivation domain is unclear. We show here that amino-terminal p53 (ATp53) mutations often result in the abrogation of full-length p53 expression, but concomitantly lead to the expression of the amino-terminally truncated p47 isoform. Using genetically modified cancer cells that only express p47, we demonstrate it to be up-regulated in response to various stimuli, and to contribute to cell death, through its ability to selectively activate a group of apoptotic target genes.

Consumption Of Specific Foods And Beverages And Excess Weight Gain Among Children And Adolescents.

Efforts are under way to identify successful strategies to reduce long-term childhood obesity risk, such as ways to improve diet quality. To identify foods and beverages associated with excess weight gain, we used cohort data from the Avon Longitudinal Study of Parents and Children in the United Kingdom. We quantified the associations between changes in or levels of consumption of twenty-seven food and beverage groups and excess weight gain in three-year periods among youth ages 7-13.

Determinants of optical coherence tomography-derived minimum neuroretinal rim width in a normal Chinese population.

Purpose: To characterize an optical coherence tomography (OCT)-derived parameter, Bruch's membrane opening-minimum rim width (BMO-MRW), and its association with demographic and clinical parameters in normal Chinese subjects.

Methods: Right eyes of 466 consecutive healthy subjects from a population-based study of Singaporean Chinese underwent Cirrus OCT imaging. The retinal internal limiting membrane (ILM) and BMO were automatically delineated using the built-in Cirrus algorithm.

Pathogenesis of cholangiocarcinoma: From genetics to signalling pathways.

Cholangiocarcinoma (CCA) is a malignant tumour of bile duct epithelial cells with dismal prognosis and rising incidence. Chronic inflammation resulting from liver fluke infection, hepatitis and other inflammatory bowel diseases is a major contributing factor to cholangiocarcinogenesis, likely through accumulation of serial genetic and epigenetic alterations resulting in aberration of oncogenes and tumour suppressors. Recent studies making use of advances in high-throughput genomics have revealed the genetic landscape of CCA, greatly increasing our understanding of its underlying biology.

Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes.

Gastric cancer, a leading cause of cancer-related deaths, is a heterogeneous disease. We aim to establish clinically relevant molecular subtypes that would encompass this heterogeneity and provide useful clinical information. We use gene expression data to describe four molecular subtypes linked to distinct patterns of molecular alterations, disease progression and prognosis.

Analysis of wntless (WLS) expression in gastric, ovarian, and breast cancers reveals a strong association with HER2 overexpression.

The oncogenic role of WNT is well characterized. Wntless (WLS) (also known as GPR177, or Evi), a key modulator of WNT protein secretion, was recently found to be highly overexpressed in malignant astrocytomas. We hypothesized that this molecule may be aberrantly expressed in other cancers known to possess aberrant WNT signaling such as ovarian, gastric, and breast cancers.