The Clinical Relevance of the EPH/Ephrin Signaling Pathway in Pediatric Solid and Hematologic Malignancies.

Pediatric neoplasms represent a complex group of malignancies that pose unique challenges in terms of diagnosis, treatment, and understanding of the underlying molecular pathogenetic mechanisms. Erythropoietin-producing hepatocellular receptors (EPHs), the largest family of receptor tyrosine kinases and their membrane-tethered ligands, ephrins, orchestrate short-distance cell-cell signaling and are intricately involved in cell-pattern morphogenesis and various developmental processes. Unraveling the role of the EPH/ephrin signaling pathway in the pathophysiology of pediatric neoplasms and its clinical implications can contribute to deciphering the intricate landscape of these malignancies. The bidirectional nature of the EPH/ephrin axis is underscored by emerging evidence revealing its capacity to drive tumorigenesis, fostering cell-cell communication within the tumor microenvironment. In the context of carcinogenesis, the EPH/ephrin signaling pathway prompts a reevaluation of treatment strategies, particularly in pediatric oncology, where the modest progress in survival rates and enduring treatment toxicity necessitate novel approaches. Molecularly targeted agents have emerged as promising alternatives, prompting a shift in focus. Through a nuanced understanding of the pathway's intricacies, we aim to lay the groundwork for personalized diagnostic and therapeutic strategies, ultimately contributing to improved outcomes for young patients grappling with neoplastic challenges.

Understanding the Role of Connexins in Hepatocellular Carcinoma: Molecular and Prognostic Implications.

Connexins, a family of tetraspan membrane proteins forming intercellular channels localized in gap junctions, play a pivotal role at the different stages of tumor progression presenting both pro- and anti-tumorigenic effects. Considering the potential role of connexins as tumor suppressors through multiple channel-independent mechanisms, their loss of expression may be associated with tumorigenic activity, while it is hypothesized that connexins favor the clonal expansion of tumor cells and promote cell migration, invasion, and proliferation, affecting metastasis and chemoresistance in some cases. Hepatocellular carcinoma (HCC), characterized by unfavorable prognosis and limited responsiveness to current therapeutic strategies, has been linked to gap junction proteins as tumorigenic factors with prognostic value. Notably, several members of connexins have emerged as promising markers for assessing the progression and aggressiveness of HCC, as well as the chemosensitivity and radiosensitivity of hepatocellular tumor cells. Our review sheds light on the multifaceted role of connexins in HCC pathogenesis, offering valuable insights on recent advances in determining their prognostic and therapeutic potential.

Metformin in Esophageal Carcinoma: Exploring Molecular Mechanisms and Therapeutic Insights.

Esophageal cancer (EC) remains a formidable malignancy with limited treatment options and high mortality rates, necessitating the exploration of innovative therapeutic avenues. Through a systematic analysis of a multitude of studies, we synthesize the diverse findings related to metformin's influence on EC. This review comprehensively elucidates the intricate metabolic pathways and molecular mechanisms through which metformin may exert its anti-cancer effects. Key focus areas include its impact on insulin signaling, AMP-activated protein kinase (AMPK) activation, and the mTOR pathway, which collectively contribute to its role in mitigating esophageal cancer progression. This review critically examines the body of clinical and preclinical evidence surrounding the potential role of metformin, a widely prescribed anti-diabetic medication, in EC management. Our examination extends to the modulation of inflammation, oxidative stress and angiogenesis, revealing metformin's potential as a metabolic intervention in esophageal cancer pathogenesis. By consolidating epidemiological and clinical data, we assess the evidence that supports metformin's candidacy as an adjuvant therapy for esophageal cancer. By summarizing clinical and preclinical findings, our review aims to enhance our understanding of metformin's role in EC management, potentially improving patient care and outcomes.

Pulmonary hypertension in patients with interstitial lung disease: a tool for early detection.

Pulmonary hypertension (PH) complicates the treatment of interstitial lung disease (ILD) patients resulting in poor functional status and worse outcomes. Early recognition of PH in ILD is important for initiating therapy and considering lung transplantation. However, no standard exists regarding which patients to screen for PH-ILD or the optimal method to do so. The aim of this study was to create a risk assessment tool that could reliably predict PH in ILD patients. We developed a PH-ILD Detection tool that incorporated history, exam, 6-min walk distance, diffusion capacity for carbon monoxide, chest imaging, and cardiac biomarkers to create an eight-component score. This tool was analyzed retrospectively in 154 ILD patients where each patient was given a score ranging from 0 to 12. The sensitivity (SN) and specificity (SP) of the PH-ILD Detection tool and an area-under-the-curve (AUC) were calculated. In this cohort, 74 patients (48.1%) had PH-ILD. A score of ≥6 on the PH-ILD Detection tool was associated with a diagnosis of PH-ILD (SN: 86.5%; SP: 86.3%; area-under-the-curve: 0.920, p < 0.001). The PH-ILD Detection tool provides high SN and SP for detecting PH in ILD patients. With confirmation in larger cohorts, this tool could improve the diagnosis of PH in ILD and may suggest further testing with right heart catheterization and earlier intervention with inhaled treprostinil and/or lung transplant evaluation.

Detection of Subclinical Coronary Artery Lesions by Framingham Risk Score, Peripheral Artery Atheromatosis and Coronary Artery Calcium Score: A Pilot Study in Asymptomatic Individuals Living with HIV.

The incidence of acute coronary events is increased among people living with HIV (PLWH), but there is no risk estimation score, nor a surrogate biomarker able to predict subclinical coronary artery disease (sCAD). We assessed the performance of: (i) Framingham risk score (FRMs), (ii) peripheral (carotid and femoral) artery atheromatosis, and (iii) coronary artery calcium (CACs) score, to detect the presence of sCAD, in PLWH. In a cohort of PLWH free of cardiovascular disease (CVD), we measured sCAD and CACs by computed tomography, calculated FRMs, and assessed carotid/femoral plaques by ultrasound. In 56 participants (age: 49 ± 10 years, men: 88%, FRMs: 7.2 ± 6.9; mean number of carotid/femoral plaques: 1.4 ± 1.5; CACs >0 present in 59%, median CACs 0.9 [IQR 0-22]): (i) minimal sCAD (stenosis 1%-24%; present in 30%) and mild sCAD (25%-49%, 25%) were effectively detected by FRMs, number of plaques, and CACs [area under the curve (AUC) of CACs was better than that of both FRM and plaques, p < .05]; (ii) moderate sCAD (stenosis 50%-69%; present in 8.9%) was detected by number of plaques and CACs, but similar AUC (0.969 vs. 0.867, respectively, p = NS); and (iii) severe sCAD (70%-99%, present in only 3 [5.4%]) was detected only by CACs. A high prevalence of sCAD in asymptomatic PLWH free of CVD was detected; CACs is a highly efficient biomarker to detect all grades of sCAD, however, the number of carotid/femoral plaques combined is also a very promising-lower cost and radiation free-surrogate biomarker. Future, larger studies are needed to verify these results.

Effects of Full Body Exergaming in Virtual Reality on Cardiovascular and Muscular Parameters: Cross-Sectional Experiment.

BACKGROUND: In recent years, many studies have associated sedentary behavior in front of screens with health problems in infants, children, and adolescents. Yet options for exergaming-playing video games that require rigorous physical exercise-seem to fall short of the physical activity levels recommended by the World Health Organization. OBJECTIVE: The purpose of this study was to investigate the effect of a fully immersive virtual reality (VR)-based training system on cardiovascular and muscular parameters of young adults. METHODS: A cross-sectional experiment design was used to analyze muscle activity (surface electromyography), heart rate, perceived exertion (RPE), cybersickness symptoms, perceived workload, and physical activity enjoyment (PACES) in 33 participants performing two 5-minute flights on a new training device. RESULTS: Participants' performance of the planking position required to play the game resulted in moderate aerobic intensity (108 [SD 18.69] bpm). Due to the mainly isometric contraction of the dorsal muscle chain (with a mean activation between 20.6% [SD 10.57] and 26.7% [SD 17.39] maximum voluntary isometric contraction), participants described the exercise as a moderate to vigorous activity (RPE 14.6 [SD 1.82]). The majority reported that they enjoyed the exercise (PACES 3.74 [SD 0.16]). However, six participants had to drop out because of cybersickness symptoms and two because of muscle pain due to prior injuries. CONCLUSIONS: Our findings suggest that fully immersive VR training systems can contribute to muscle-strengthening activities for healthy users. However, the dropout rate highlights the need for technological improvements in both software and hardware. In prevention and therapy, movement quality is a fundamental part of providing effective resistance training that benefits health. Exergaming on a regular basis has the potential to develop strong muscles and a healthy back. It is essential that future VR-based training systems take into account the recommendations of sport and exercise science.