Search

Hypoxia-inducible factors (HIFs) are central regulators of gene expression in response to oxygen deprivation, a common feature in critical illnesses. The significant burden that critical illnesses place on global healthcare systems highlights the need for a deeper understanding of underlying mechanisms and the development of innovative treatment strategies. Among critical illnesses, impaired lung function is frequently linked to hypoxic conditions. This review focuses on the expression and regulation of HIF signalling in experimental models of acute lung injury (ALI) and clinical studies in critically ill patients with acute respiratory distress syndrome (ARDS). We explore the potential dual role of HIF signalling in acute lung inflammation. Furthermore, its role in key biological processes and its potential prognostic significance in clinical scenarios are discussed. Finally, we explore recent pharmacological advancements targeting HIF signalling, which have emerged as promising alternatives to existing therapeutic approaches, potentially enabling more effective management strategies. [ABSTRACT FROM AUTHOR]

The document explores the role of cancer-associated fibroblasts (CAFs) in non-small cell lung cancer (NSCLC) and the significance of molecularly classifying CAF subtypes. CAFs play a crucial role in shaping the tumor microenvironment and supporting cancer growth. The classification of CAFs can predict patient prognosis and responses to various treatment options, highlighting the potential for personalized cancer treatment in NSCLC. The document also discusses the functional diversity of CAFs and the ongoing research to develop effective therapeutic strategies targeting CAFs in various types of malignancies. [Extracted from the article]

The document explores the signaling pathways involved in the reactivation of herpes simplex virus type 1 (HSV-1) from a dormant state in neurons, leading to recurrent outbreaks. It discusses the role of the Wnt/β-catenin pathway, JNK cell stress pathway, and DDR and Akt pathway in triggering viral reactivation. The research highlights potential therapeutic targets within these pathways to prevent HSV-1 reactivation and improve the quality of life for those affected by the virus. The study emphasizes the need for further research to validate these findings and potentially translate them into clinical practice. [Extracted from the article]

Pulmonary fibrosis (PF) is a severe, irreversible lung disease characterized by progressive scarring, with idiopathic pulmonary fibrosis (IPF) being the most prevalent form. IPF's pathogenesis involves repetitive lung epithelial injury leading to fibroblast activation and excessive extracellular matrix (ECM) deposition. The prognosis for IPF is poor, with limited therapeutic options like nintedanib and pirfenidone offering only modest benefits. Emerging research highlights the dysregulation of the yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) signaling pathway as a critical factor in PF. YAP and TAZ, components of the Hippo pathway, play significant roles in cell proliferation, differentiation, and fibrosis by modulating gene expression through interactions with TEA domain (TEAD) transcription factors. The aberrant activation of YAP/TAZ in lung tissue promotes fibroblast activation and ECM accumulation. Targeting the YAP/TAZ pathway offers a promising therapeutic avenue. Preclinical studies have identified potential treatments, such as trigonelline, dopamine receptor D1 (DRD1) agonists, and statins, which inhibit YAP/TAZ activity and demonstrate antifibrotic effects. These findings underscore the importance of YAP/TAZ in PF pathogenesis and the potential of novel therapies aimed at this pathway, suggesting a new direction for improving IPF treatment outcomes. Further research is needed to validate these approaches and translate them into clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer is one of the most lethal forms of malignancies; therefore, new treatment strategies are required to increase the patients' survival. It has been established that different cell types that surround pancreatic cancer cells, thus forming the tumor microenvironment, are responsible for tumorigenicity and inefficacy of treatments, including immunotherapy. In the present review, we aim to summarize current knowledge regarding the molecular mechanisms underpinning the interaction of cancer cells with cells of their microenvironment and discuss associated strategies to improve treatment results. Pancreatic cancer demonstrates an ever-increasing incidence over the last years and represents one of the top causes of cancer-associated mortality. Cells of the tumor microenvironment (TME) interact with cancer cells in pancreatic ductal adenocarcinoma (PDAC) tumors to preserve cancer cells' metabolism, inhibit drug delivery, enhance immune suppression mechanisms and finally develop resistance to chemotherapy and immunotherapy. New strategies target TME genetic alterations and specific pathways in cell populations of the TME. Complex molecular interactions develop between PDAC cells and TME cell populations including cancer-associated fibroblasts, myeloid-derived suppressor cells, pancreatic stellate cells, tumor-associated macrophages, tumor-associated neutrophils, and regulatory T cells. In the present review, we aim to fully explore the molecular landscape of the pancreatic cancer TME cell populations and discuss current TME targeting strategies to provide thoughts for further research and preclinical testing. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is the most lethal gynecological cancer in the developed world. Most cases are diagnosed at late stage III-IV with a very low 5-year overall survival rate. Several studies revealed an elevated risk of OC in users of hormone treatment (HT) compared with non-users. The extended duration of HT is a statistically significant risk factor. Carbohydrate antigen or cancer antigen 125 (CA-125) remains the best screening tool for OC; however, its value is limited due to low specificity, leading to unnecessary interventions, surgeries, and psychological harm. Additionally, the variability of ultrasound interpretation highlights the urgent need to develop a univariate index with higher sensitivity and specificity for early diagnosis of OC in women under HT. Herein we critically review the limitations of biomarkers for the detection of OC aiming to suggest an accurate and cost-effective diagnostic ratio that eliminates the impact of body mass index, age, HT, smoking, and benign ovarian diseases on measurements. Numerous studies combine biomarkers such as CA-125, human epididymis protein 4, and thymidine kinase 1 into diagnostic algorithms. Data suggest that the expression of estrogen receptors may have diagnostic and prognostic value, as the estrogen receptor α (ERα):estrogen receptor β (ERβ) ratio is significantly higher in OC than in normal tissue due to ERβ downregulation. A high positive correlation between expression of CA-125 and carbohydrate antigen or cancer antigen 72 − 4 (CA72-4) with ERα and ERβ, respectively, poses that a novel ratio CA-125:CA72-4 could be nodal for monitoring post-menopausal women under HT. [ABSTRACT FROM AUTHOR]