Light-dark shift promotes colon carcinogenesis through accelerated colon aging.

Colorectal cancer (CRC) is the third most common cancer worldwide, with rising prevalence among younger adults. Several lifestyle factors, particularly disruptions in circadian rhythms by light-dark (LD) shifts, are known to increase CRC risk. Epidemiological studies previously showed LD-shifts are associated with increased risk of CRC.

Exosomal Galectin-3 promotes peritoneal metastases in gastric adenocarcinoma via microenvironment alterations.

Peritoneal carcinomatosis (PC) in gastric adenocarcinoma (GAC) is the most common metastatic site and leads to a short median survival. Exosomes have been shown to remodel the microenvironment, facilitating tumor metastases. However, the functional component in GAC cell-derived exosomes that remodel the landscape in the peritoneal cavity remains unclear.

Optimal size and PEG coating of gold nanoparticles for prolonged blood circulation: a statistical analysis of published data.

This study presents a statistical analysis of how gold nanoparticle (GNP) size and polyethylene glycol (PEG) coating molecular weight (MW) affect the circulation of nanoparticles in blood. We showed a non-linear relationship with interaction between GNP size and PEG MW. The findings revealed a threshold effect, and recommendations for GNP coating are discussed.

Myristoylated Eepd1 Enhances Lipolysis and Thermogenesis through PKA Activation to Combat Obesity.

Middle-aged obesity, characterized by excessive fat accumulation and systemic energy imbalance, often precedes various health complications. Recent research has unveiled a surprising link between DNA damage response and energy metabolism. Here, we explore the role of Eepd1, a DNA repair enzyme, in regulating adipose tissue function and obesity onset.

Injectable ionic hydrogel conductors: Advancing material design to transform cardiac pacing.

Direct pacing of the mid myocardium where re-entry originates can be used to prevent ventricular arrhythmias and circumvent the need for painful defibrillation or cardiac ablation. However, there are no pacing electrodes small enough to navigate the coronary veins that cross these culprit scar regions. To address this need, we have developed an injectable ionically conductive hydrogel electrode that can fill the epicardial coronary veins and transform them into flexible electrodes.

Tissue-Engineered Therapeutics for Lymphatic Regeneration: Solutions for Myocardial Infarction and Secondary Lymphedema.

The lymphatic system, which regulates inflammation and fluid homeostasis, is damaged in various diseases including myocardial infarction (MI) and breast-cancer-related lymphedema (BCRL). Mounting evidence suggests that restoring tissue fluid drainage and clearing excess immune cells by regenerating damaged lymphatic vessels can aid in cardiac repair and lymphedema amelioration. Current treatments primarily address symptoms rather than underlying causes due to a lack of regenerative therapies, highlighting the importance of the lymphatic system as a promising novel therapeutic target.

Lipid nanoparticles deliver DNA-encoded biologics and induce potent protective immunity.

Lipid nanoparticles (LNPs) for mRNA delivery have advanced significantly, but LNP-mediated DNA delivery still faces clinical challenges. This study compared various LNP formulations for delivering DNA-encoded biologics, assessing their expression efficacy and the protective immunity generated by LNP-encapsulated DNA in different models. The LNP formulation used in Moderna's Spikevax mRNA vaccine (LNP-M) demonstrated a stable nanoparticle structure, high expression efficiency, and low toxicity.

NADH-bound AIF activates the mitochondrial CHCHD4/MIA40 chaperone by a substrate-mimicry mechanism.

Mitochondrial metabolism requires the chaperoned import of disulfide-stabilized proteins via CHCHD4/MIA40 and its enigmatic interaction with oxidoreductase Apoptosis-inducing factor (AIF). By crystallizing human CHCHD4's AIF-interaction domain with an activated AIF dimer, we uncover how NADH allosterically configures AIF to anchor CHCHD4's β-hairpin and histidine-helix motifs to the inner mitochondrial membrane. The structure further reveals a similarity between the AIF-interaction domain and recognition sequences of CHCHD4 substrates.

Placebo nonresponders: An experimental investigation on their unreliability over time.

In order to disentangle the effects of drugs from placebo responses, several approaches have been used, such as a placebo run-in phase in which only placebo nonresponders, or poor responders, are considered for further randomization to either placebo or active treatment. This study is aimed at investigating the variability of placebo nonresponders obtained through the classical placebo run-in paradigm (group RUN) and through mismatch conditioning (group MIS), as done in our previous study. To do this, we simulated a real clinical trial in the laboratory, in which the placebo responders of both groups were discarded and the remaining nonresponders of both groups RUN and MIS were randomized to either continuing on placebo (groups RUN-P and MIS-P, respectively) or receiving topical 0.

DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.

Predictive Value of FDG Uptake on PET for Future Immune Checkpoint Inhibitor-Mediated Colitis: A Case Series.

: Immune-mediated colitis (IMC) is a common immune-related adverse event during immune checkpoint inhibitor (ICI) therapy. This case series and review aimed to highlight atypical cases of IMC and explore the potential of PET/CT to predict imminent ICI colitis. : Through a descriptive, retrospective study at a tertiary cancer center, we identified adult patients receiving ICIs for any cancer between 2010 and 2022 who also underwent PET/CT for routine cancer surveillance during this time.

Impact of American Thyroid Association's Revised Cancer Management Guidelines on Thyroid Cancer Incidence Trends: A Retrospective Cohort Study, 2000-2020.

The past four decades have seen a steady increase in thyroid cancer in the United States (US). This study investigated the impact of the American Thyroid Association (ATA)'s revised cancer management guidelines on thyroid cancer incidence trends and how the trends varied by socioeconomic, histologic, geographic, and racial and ethnic characteristics from 2000 to 2020. We used data from the Surveillance, Epidemiology, and End Results (SEER) database to identify thyroid cancer cases diagnosed among US patients between 2000 and 2020.

Novel Computational and Artificial Intelligence Models in Cancer Research.

The ICIBM 2023 marked the 11th annual conference of its kind, with the ICIBM recently becoming the official conference of the International Association for Intelligent Biology and Medicine (IAIBM), showcasing cutting-edge advancements at the intersection of computation and biomedical research [...

Role of Mutation in the Development of Eleven Different Cancers.

: With the rise in prevalence of diagnostic genetic techniques like RNA sequencing and whole exome sequencing (WES), as well as biological treatment regiments for cancer therapy, several genes have been implicated in carcinogenesis. This review aims to update our understanding of the Neurofibromatosis 2 (NF2) gene and its role in the pathogenesis of various cancers. : A comprehensive search of five online databases yielded 43 studies that highlighted the effect of sporadic NF2 mutations on several cancers, including sporadic meningioma, ependymoma, schwannoma, mesothelioma, breast cancer, hepatocellular carcinoma, prostate cancer, glioblastoma, thyroid cancer, and melanoma.

Radiosurgery for Intracranial Meningiomas: A Review of Anatomical Challenges and an Update on the Evidence.

Radiation has been used to treat meningiomas since the mid-1970s. Traditionally, radiation was reserved for patients unfit for major surgery or those with surgically inaccessible tumors. With an increased quantity and quality of imaging, and an aging population, there has been a rise in incidentally diagnosed meningiomas with smaller tumors at diagnosis time.

Epigenetic Modulation with 5-Aza-CdR Prevents Metabolic-Associated Fatty Liver Disease Promoted by Maternal Overnutrition.

Background/objectives: This study builds on previous findings from mouse models, which showed that maternal overnutrition induced by a high-fat diet (HFD) promotes metabolic-associated fatty liver disease (MAFLD) in offspring, linked to global DNA hypermethylation. We explored whether epigenetic modulation with 5-Aza-CdR, a DNA methylation inhibitor, could prevent MAFLD in offspring exposed to maternal overnutrition.

Methods: The offspring mice from dams of maternal overnutrition were fed either a chow diet or a high-fat diet (HFD) for 10 weeks.

Loss of CHOP Prevents Joint Degeneration and Pain in a Mouse Model of Pseudoachondroplasia.

Pseudoachondroplasia (PSACH), a severe dwarfing condition characterized by impaired skeletal growth and early joint degeneration, results from mutations in cartilage oligomeric matrix protein (COMP). These mutations disrupt normal protein folding, leading to the accumulation of misfolded COMP in chondrocytes. The MT-COMP mouse is a murine model of PSACH that expresses D469del human COMP in response to doxycycline and replicates the PSACH chondrocyte and clinical pathology.

Encapsulation of Moringa oleifera aqueous extract in silver chitosan metallopolymer nanocomposites for anti-cancer activity.

The growing interest in plant-derived compounds and synthesis of metallopolymer nanocomposites (MPNCs) especially silver chitosan nanocomposites (AgCS-NCs) emerges as a useful platform to encapsulate and deliver plant-based anticancer drugs. This work presents the synthesis of AgCS-NCs by using Moringa oleifera aqueous leaf extract (MOAE) and the effect of concentration of MOAE on physicochemical properties of AgCS-NCs followed by its anticancer effect on MCF-7 cell line. The results of UV-visible spectroscopy (UV-Vis) and Scanning electron microscopy (SEM) showed successful formation of AgCS-NCs.

Lead time trajectory of blood-based protein biomarkers for detection of pancreatic cancer based on repeat testing.

In the current study, we assessed whether repeated measurements of a panel of protein biomarkers with relevance to pancreatic ductal adenocarcinoma (PDAC) improves lead time performance for earlier detection over a single timepoint measurement. Specifically, CA125, CEA, LRG1, REG3A, THBS2, TIMP1, TNRFSF1A as well as CA19-9 were assayed in serially collected pre-diagnostic plasma from 242 PDAC cases and 242 age- and sex-matched non-case control participants in the PLCO cohort. We compared performance estimates of a parametric empirical Bayes (PEB) algorithm, which incorporates participant biomarker history, to that of a single-threshold (ST) method.

Molecular dynamics at immune synapse lipid rafts influence the cytolytic behavior of CAR T cells.

Chimeric antigen receptor T cells (CART) targeting CD19 through CD28.ζ signaling induce rapid lysis of leukemic blasts, contrasting with persistent tumor control exhibited by 4-1BB.ζ-CART.

The adiponectin-PPARγ axis in hepatic stellate cells regulates liver fibrosis.

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear.

Extracorporeal Membrane Oxygenation in Children with Pulmonary Atresia and Intact Ventricular Septum: Mortality and Associated Outcomes.

Data on outcomes of extracorporeal membrane oxygenation (ECMO) are limited in patients with pulmonary atresia intact ventricular septum (PAIVS). The objective of this study was to describe the use of ECMO and the associated outcomes in patients with PAIVS. We retrospectively reviewed neonates with PAIVS who received ECMO between 2009 and 2019 in 19 US hospitals affiliated with the Collaborative Research for the Pediatric Cardiac Intensive Care Society (CoRe-PCICS).

Endoglin as a predictive biomarker for pemetrexed sensitivity in non-small-cell lung cancer: a cellular study.

Objective: Based on our previous research, which demonstrated that elevated plasma endoglin (ENG) levels in lung cancer patients were associated with a better prognosis, increased sensitivity to pemetrexed, and enhanced tumor suppression, this study aims to validate these findings at the cellular level. The focus is on membrane and extracellular ENG and their influence on drug response and tumor cell behavior in non-small cell lung cancer (NSCLC) cells.

Methods: The correlation between ENG expression and pemetrexed-induced cytotoxicity in eight human non-squamous subtype NSCLC cell lines was analyzed.

An Ontology-Based Approach for Understanding Appendicectomy Processes and Associated Resources.

Background: Traditional methods for analysing surgical processes often fall short in capturing the intricate interconnectedness between clinical procedures, their execution sequences, and associated resources such as hospital infrastructure, staff, and protocols.

Aim: This study addresses this gap by developing an ontology for appendicectomy, a computational model that comprehensively represents appendicectomy processes and their resource dependencies to support informed decision making and optimise appendicectomy healthcare delivery.

Methods: The ontology was developed using the NeON methodology, drawing knowledge from existing ontologies, scholarly literature, and de-identified patient data from local hospitals.