Angiogenesis is promoted by hypoxic cervical carcinoma-derived extracellular vesicles depending on the endothelial cell environment.

INTRODUCTION: Cancer needs perfusion for its growth and metastasis. Cancer cell-derived extracellular vesicles (CA-EVs) alter the tumor microenvironment (TME), potentially promoting angiogenesis. We hypothesize that conditions in the tumor, e.g., hypoxia, and in the target cells of the TME, e.g., nutrient deprivation or extracellular matrix, can affect the angiogenic potential of CA-EVs, which would contribute to explaining the regulation of tumor vascularization and its influence on cancer growth and metastasis. METHODS: CA-EVs were isolated and characterized from cervical carcinoma cell lines HeLa and SiHa cultured under normoxia and hypoxia, and their angiogenic potential was evaluated in vitro in three endothelial cells (ECs) lines and aortic rings, cultured in basal (growth factor-reduced) or complete medium. RESULTS: Hypoxia increased EV production 10-100 times and protein content 2-4 times compared to normoxic CA-EVs. HeLa-EVs contained six times more RNA than SiHa-EVs, and this concentration was not affected by hypoxia. Treatment with CA-EVs increased tube formation and sprouting in ECs and aortic rings cultured in basal medium and long-term stabilized the stablished vascular networks formed by ECs cultured in complete medium. CONCLUSION: Hypoxia differentially affects CA-EVs in a cell line-dependent manner. The cellular environment (nutrient availability and extracellular matrix scaffold) influences the effect of CA-EV on the angiogenic potential of ECs.

Endothelial plasticity across PTEN and Hippo pathways: A complex hormetic rheostat modulated by extracellular vesicles.

Vascularization is a multifactorial and spatiotemporally regulated process, essential for cell and tissue survival. Vascular alterations have repercussions on the development and progression of diseases such as cancer, cardiovascular diseases, and diabetes, which are the leading causes of death worldwide. Additionally, vascularization continues to be a challenge for tissue engineering and regenerative medicine. Hence, vascularization is the center of interest for physiology, pathophysiology, and therapeutic processes. Within vascularization, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and Hippo signaling have pivotal roles in the development and homeostasis of the vascular system. Their suppression is related to several pathologies, including developmental defects and cancer. Non-coding RNAs (ncRNAs) are among the regulators of PTEN and/or Hippo pathways during development and disease. The purpose of this paper is to review and discuss the mechanisms by which exosome-derived ncRNAs modulate endothelial cell plasticity during physiological and pathological angiogenesis, through the regulation of PTEN and Hippo pathways, aiming to establish new perspectives on cellular communication during tumoral and regenerative vascularization.

Current Needs Assessment for Using Lung Clearance Index for Asthma in Clinical Practice.

PURPOSE OF REVIEW: Asthma pathophysiology has shown that remodeling of the bronchial airways mainly affects the small rather than large airways. The severity of asthma is conventionally measured by forced expiratory volume 1 (FEV1) but this maneuver is insensitive to changes in distal airways with smaller diameter. The aim of this review is to evaluate the current evidence supporting LCI as a clinical tool for assessing small airways disease in asthma patients, as well as whether it is useful as a treatment response parameter in severe therapy-resistant asthma (STRA) patients. RECENT FINDINGS: There is an increasing need for novel tests that can assess distal airway disease in asthma. Lung Clearance Index (LCI) may be a useful test for assessing more severe airway obstruction and the persistence of small airway disease. LCI measurement has been shown to be more sensitive than spirometry in cystic fibrosis (CF), but its clinical utility in asthma has not been thoroughly investigated. LCI abnormalities may be a sensitive marker for the persistence of small distal airway disease and may be associated with a more severe asthma endotype unresponsive to inhaled glucocorticoids. There is a need to identify other lung function tests for asthma that can identify early airway remodeling while simultaneously measuring the rate of lung function impairment. When compared to other conventional methods, multiple-breath washout (MBW) measures the lung clearance index (LCI), a more sensitive predictor of early airway disease that is feasible to perform in children. The goal of this review is to evaluate the current evidence of LCI as a clinical tool in asthma patients.

Characterization, cloning, and expression of two diagnostic antigens for Taenia solium tapeworm infection.

Adult and larval stages of Taenia solium cause 2 diseases in humans, i.e., taeniasis and cysticercosis, respectively. Diagnosis and treatment of taeniasis are the ultimate means to eliminate cysticercosis. A serological taeniasis diagnostic test has been developed for laboratory use. However, recombinant forms of the taeniasis diagnostic proteins are required to overcome the limited supply of native proteins and allow the development of a low-cost and field-applicable test with high sensitivity and specificity. Using 2-dimensional electrophoresis of T. solium excretory and secretory (TSES) products from hamster adult tape-worm in vitro cultures, we have identified 5 T. solium-specific protein spots, with molecular weights of 33 kDa (protein isoelectrofocusing point [pI]: 5.6, 5.3, 5.1) and 38 kDa (pI: 4.6, 4.5). Protein sequencing and molecular cloning of these proteins showed that although endowed with different pls, the proteins with the same molecular weights shared the same protein backbone, named TSES33 and TSES38. Their full-length complementary DNAs encode proteins with 267 and 278 amino acids, respectively. TSES33 and TSES38 were expressed in a baculovirus system. Both recombinant proteins were recognized by a panel of taeniasis, but not cysticercosis patient serum samples, indicating that they can potentially replace the native proteins in the development of a more efficacious taeniasis diagnostic test.