Prevalence of IMPG1 and IMPG2 Mutations Leading to Retinitis Pigmentosa or Vitelliform Macular Dystrophy in a Cohort of Patients with Inherited Retinal Dystrophies.

Background/objectives: The interphotoreceptor matrix proteoglycans 1 and 2 (IMPG1 and IMPG2) are two interdependent proteoglycans of the interphotoreceptor matrix (IPM). Mutations in IMPG1 or IMPG2 are linked to retinal diseases such as retinitis pigmentosa (RP) and vitelliform macular dystrophy (VMD), yet the specific mutations responsible for each condition remain undefined. This study identifies mutations in IMPG1 and IMPG2 linked to either RP or VMD.

Screening Methods to Discover the FDA-Approved Cancer Drug Encorafenib as Optimally Selective for Metallothionein Gene Loss Ovarian Cancer.

Background/objectives: All 11 metallothionein protein-coding genes are located on human chromosome 16q13. It is unique among human genetics to have an entire pathway's genes clustered in a short chromosomal region. Since solid tumors, particularly high-grade serous ovarian cancer (HGSC), exhibit high rates of monoallelic aneuploidy, this region is commonly lost.

Expanding the Mutation Spectrum for Inherited Retinal Diseases.

Background/objectives: Inherited retinal diseases (IRDs) represent a diverse group of genetic disorders characterized by degeneration of the retina, leading to visual impairment and blindness. IRDs are heterogeneous, sharing common clinical features that can be difficult to diagnose without knowing the genetic basis of the disease. To improve diagnostic accuracy and advance understanding of disease mechanisms, genetic testing was performed for 103 unrelated patients with an IRD at a single clinical site between 30 August 2022 and 5 February 2024.

Sleep Genetics and Cognitive Changes over Time: The Moderating Effect of Age and the Role of Brain.

Background: Sleep plays a crucial role in cognitive performance and cognitive changes in aging. In the current study, we investigated the role of sleep duration genetics in cognitive changes over time and the moderating effect of age.

Methods: Participants were drawn from the Reference Abilities Neural Network and the Cognitive Reserve studies of Columbia University.

Cell Type Specific Suppression of Hyper-Recombination by Human RAD18 Is Linked to Proliferating Cell Nuclear Antigen K164 Ubiquitination.

RAD18 is a conserved eukaryotic E3 ubiquitin ligase that promotes genome stability through multiple pathways. One of these is gap-filling DNA synthesis at active replication forks and in post-replicative DNA. RAD18 also regulates homologous recombination (HR) repair of DNA breaks; however, the current literature describing the contribution of RAD18 to HR in mammalian systems has not reached a consensus.

Development of a Combined 2D-MGD TLC/HPTLC Method for the Separation of Terpinen-4-ol and α-Terpineol from Tea Tree, , Essential Oil.

Tea tree oil (TTO), acquired from (Maiden & Betche) Cheel, Myrtaceae, is a widely utilized essential oil (EO) due to its bioactive properties. The identification and quantification of TTO ingredients is generally performed by GC-MS, which provides the most accurate results. However, in some instances, the cost and time of analysis may pose a challenge.

Feasibility of Ex Vivo Ligandomics.

We developed ligandomics for the in vivo profiling of vascular ligands in mice, discovering secretogranin III (Scg3) as a novel angiogenic factor that selectively binds to retinal vessels of diabetic but not healthy mice. This discovery led to the development of anti-Scg3 therapy for ocular vasculopathies. However, in vivo ligandomics requires intracardial perfusion to remove unbound phage clones, limiting its use to vascular endothelial cells (ECs).

Tetrahydrobiopterin in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Friend or Foe?

Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS) is a chronic multisystem disease characterized by severe muscle fatigue, pain, dizziness, and brain fog. The two most common symptoms are post-exertional malaise (PEM) and orthostatic intolerance (OI). ME/CFS patients with OI (ME+OI) suffer from dizziness or faintness due to a sudden drop in blood pressure while maintaining an upright posture.

Caffeic Acid Phenethyl Ester Protects Neurons Against Oxidative Stress and Neurodegeneration During Traumatic Brain Injury.

Traumatic brain injury (TBI) is an inflammatory disease causing neurodegeneration. One of the consequences of inflammation is an elevated blood level of fibrinogen (Fg). Earlier we found that extravasated Fg induced an increased expression of neuronal nuclear factor kappa B (NF-κB) p65.

Pharmacological Modulation of the Unfolded Protein Response as a Therapeutic Approach in Cutaneous T-Cell Lymphoma.

Cutaneous T-cell lymphoma (CTCL) is a rare T-cell malignancy characterized by inflamed and painful rash-like skin lesions that may affect large portions of the body's surface. Patients experience recurrent infections due to a compromised skin barrier and generalized immunodeficiency resulting from a dominant Th2 immune phenotype of CTCL cells. Given the role of the unfolded protein response (UPR) in normal and malignant T-cell development, we investigated the impact of UPR-inducing drugs on the viability, transcriptional networks, and Th2 phenotype of CTCL.

Characterization of the Sodium Multi-Vitamin Transporter in the Mosquito and Its Capacity to Mobilize Pantothenate and Biotin.

Pantothenate (Pan), or vitamin B5, is essential for the synthesis of co-enzyme A (CoA), acetyl-CoA, and numerous downstream physiological processes. We previously demonstrated that Pan is not only essential for mosquito survival, but also for the development of malaria parasites within the mosquito, suggesting that targeting Pan and CoA biosynthesis may be a novel approach for malaria control. However, little is known about how Pan is acquired and mobilized within the mosquito.

Tryptophan Kynurenine Pathway-Based Imaging Agents for Brain Disorders and Oncology-From Bench to Bedside.

Tryptophan (Trp)-based radiotracers have excellent potential for imaging many different types of brain pathology because of their involvement with both the serotonergic and kynurenine (KYN) pathways. However, radiotracers specific to the kynurenine metabolism pathway are limited. In addition, historically Trp-based radiopharmaceuticals were synthesized with the short-lived isotope carbon-11.

G Protein-Coupled Receptor 17 Inhibits Glucagon-like Peptide-1 Secretion via a Gi/o-Dependent Mechanism in Enteroendocrine Cells.

Gut peptides, including glucagon-like peptide-1 (GLP-1), regulate metabolic homeostasis and have emerged as the basis for multiple state-of-the-art diabetes and obesity therapies. We previously showed that G protein-coupled receptor 17 (GPR17) is expressed in intestinal enteroendocrine cells (EECs) and modulates nutrient-induced GLP-1 secretion. However, the GPR17-mediated molecular signaling pathways in EECs have yet to be fully deciphered.

Neurofilament Light Chain Levels in Serum and Cerebrospinal Fluid Do Not Correlate with Survival Times in Patients with Prion Disease.

Prion diseases, including Creutzfeldt-Jakob disease (CJD), are deadly neurodegenerative disorders characterized by the buildup of abnormal prion proteins in the brain. This accumulation disrupts neuronal functions, leading to the rapid onset of psychiatric symptoms, ataxia, and cognitive decline. The urgency of timely diagnosis for effective treatment necessitates the identification of strongly correlated biomarkers in bodily fluids, which makes our research crucial.

A Predicted Helix-Turn-Helix Core Is Critical for Bacteriophage Kil Peptide to Disrupt Cell Division.

: FtsZ, a eukaryotic tubulin homolog and an essential component of the bacterial divisome, is the target of numerous antimicrobial compounds as well as proteins and peptides, most of which inhibit FtsZ polymerization dynamics. We previously showed that the Kil peptide from bacteriophage λ inhibits cell division by disrupting FtsZ ring assembly, and this inhibition requires the presence of the essential FtsZ membrane anchor protein ZipA. : To investigate Kil's molecular mechanism further, we employed deletions, truncations, and molecular modeling to identify the minimal residues necessary for its activity.

A Review of Therapies for Infection.

is an urgent public health threat that affects approximately half a million patients annually in the United States. Despite concerted efforts aimed at the prevention of infection (CDI), it remains a leading cause of healthcare-associated infections. CDI is associated with significant clinical, social, and economic burdens.

Evaluating Treatment Preferences and the Efficacy of Capsaicin 179 mg Patch vs. Pregabalin in a Randomized Trial for Postsurgical Neuropathic Pain in Breast Cancer: CAPTRANE.

CAPTRANE evaluated the efficacy and tolerability of high-concentration capsaicin patch (HCCP) vs. oral pregabalin for the treatment of postsurgical neuropathic pain (PSNP) following breast cancer surgery. The study was designed with the aim of demonstrating noninferiority of one HCCP against daily pregabalin.

The Homeobox Transcription Factor NKX3.1 Displays an Oncogenic Role in Castration-Resistant Prostate Cancer Cells.

Background/objectives: Prostate cancer (PCa) is the second leading cause of cancer-related death in men. The increase in incidence rates of more advanced and aggressive forms of the disease year-to-year fuels urgency to find new therapeutic interventions and bolster already established ones. PCa is a uniquely targetable disease in that it is fueled by male hormones (androgens) that drive tumorigenesis via the androgen receptor or AR.

Treatment Patterns and Outcomes in Patients with Advanced Biliary Tract Cancers Treated with Gemcitabine-Based Chemotherapy: A Retrospective Study.

Historically, the standard of care for advanced biliary tract cancers (aBTCs) was gemcitabine plus cisplatin (GemCis). Immunotherapy plus GemCis is now recommended as a first-line treatment for aBTCs. Whether patients can tolerate eight cycles of GemCis in clinical practice, as per the Advanced Biliary Cancer (ABC)-02 study, remains to be assessed.

Feasibility and Acceptability of Integrating Acupuncture for Management of Multiple Symptoms in Medically Underserved Breast Cancer Survivors.

Background/objectives: Breast cancer survivors undergoing long-term endocrine therapy often experience multiple symptoms, including pain, fatigue, sleep disturbance, hot flashes, anxiety, and depression. This study explored the feasibility and acceptability of integrating acupuncture for symptom management in medically underserved breast cancer survivors.

Methods: This randomized controlled trial was conducted at two clinics serving medically underserved populations.

IL-1β in Neoplastic Disease and the Role of Its Tumor-Derived Form in the Progression and Treatment of Metastatic Prostate Cancer.

Since its discovery, IL-1β has taken center stage as a key mediator of a very broad spectrum of diseases revolving around immuno-mediated and inflammatory events. Predictably, the pleiotropic nature of this cytokine in human pathology has led to the development of targeted therapeutics with multiple treatment indications in the clinic. Following the accumulated findings of IL-1β's central modulatory role in the immune system and the implication of inflammatory pathways in cancer, the use of IL-1β antagonists was first proposed and then also pursued for oncology disorders.

Activation of Genes by Nuclear Receptor/Specificity Protein (Sp) Interactions in Cancer.

The human nuclear receptor (NR) superfamily consists of 48 genes that are ligand-activated transcription factors that play a key role in maintaining cellular homeostasis and in pathophysiology. NRs are important drug targets for both cancer and non-cancer endpoints as ligands for these receptors can act as agonists, antagonists or inverse agonists to modulate gene expression. With two exceptions, the classical mechanism of action of NRs involves their interactions as monomers, dimers or heterodimers with their cognate response elements (cis-elements) in target gene promoters.

SORL1-Mediated EGFR and FGFR4 Regulation Enhances Chemoresistance in Ovarian Cancer.

Recurrent tumors that are resistant to conventional chemotherapy are a major challenge of ovarian cancer treatment. A better understanding of the underlying molecular mechanisms of chemoresistance is critical for developing more effective targeted therapies for ovarian cancer. In this study, we analyzed the transcriptomic profiles of thirteen pairs of matching primary and recurrent ovarian cancers to identify genes that were upregulated in the recurrent tumors.

Direct Prediction of 48 Month Survival Status in Patients with Uveal Melanoma Using Deep Learning and Digital Cytopathology Images.

Background: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. The median overall survival time for patients who develop metastasis is approximately one year. In this study, we aim to leverage deep learning (DL) techniques to analyze digital cytopathology images and directly predict the 48 month survival status on a patient level.

Unmasking Racial, Ethnic, and Socioeconomic Disparities in United States Chordoma Clinical Trials: Systematic Review.

Background: Chordoma is a rare bone cancer with limited treatment options. Clinical trials are crucial for developing effective therapies, but their success depends on including diverse patient populations. The objective of this study was to systematically evaluate the reporting of racial, ethnic, and socioeconomic diversity in United States clinical trials exploring treatment for chordoma.