Epidermal Growth Factor Receptor Inhibition Is Protective in Hyperoxia-Induced Lung Injury.

AIMS: Studies have linked severe hyperoxia, or prolonged exposure to very high oxygen levels, with worse clinical outcomes. This study investigated the role of epidermal growth factor receptor (EGFR) in hyperoxia-induced lung injury at very high oxygen levels (\u3e95%). RESULTS: Effects of severe hyperoxia (100% oxygen) were studied in mice with genetically inhibited EGFR and wild-type littermates. Despite the established role of EGFR in lung repair, EGFR inhibition led to improved survival and reduced acute lung injury, which prompted an investigation into this protective mechanism. Endothelial EGFR genetic knockout did not confer protection. EGFR inhibition led to decreased levels of cleaved caspase-3 and poly (ADP-ribosyl) polymerase (PARP) and decreased terminal dUTP nick end labeling- (TUNEL-) positive staining in alveolar epithelial cells and reduced ERK activation, which suggested reduced apoptosis CONCLUSION: In conditions of severe hyperoxia (\u3e95% for \u3e24 h), EGFR inhibition led to improved survival, decreased lung injury, and reduced cell death. These findings further elucidate the complex role of EGFR in acute lung injury

Alveolar type II epithelial cell FASN maintains lipid homeostasis in experimental COPD

20 p.-7 fig.Alveolar epithelial type II (AEC2) cells strictly regulate lipid metabolism to maintain surfactant synthesis. Loss of AEC2 cell function and surfactant production are implicated in the pathogenesis of the smoking-related lung disease chronic obstructive pulmonary disease (COPD). Whether smoking alters lipid synthesis in AEC2 cells and whether altering lipid metabolism in AEC2 cells contributes to COPD development are unclear. In this study, high-throughput lipidomic analysis revealed increased lipid biosynthesis in AEC2 cells isolated from mice chronically exposed to cigarette smoke (CS). Mice with a targeted deletion of the de novo lipogenesis enzyme, fatty acid synthase (FASN), in AEC2 cells (FasniΔAEC2) exposed to CS exhibited higher bronchoalveolar lavage fluid (BALF) neutrophils, higher BALF protein, and more severe airspace enlargement. FasniΔAEC2 mice exposed to CS had lower levels of key surfactant phospholipids but higher levels of BALF ether phospholipids, sphingomyelins, and polyunsaturated fatty acid–containing phospholipids, as well as increased BALF surface tension. FasniΔAEC2 mice exposed to CS also had higher levels of protective ferroptosis markers in the lung. These data suggest that AEC2 cell FASN modulates the response of the lung to smoke by regulating the composition of the surfactant phospholipidome.This work was supported by the National Natural Science Foundation of China (81925001 to JFX and 81800063 to LCF) and by the NIH grant P01 HL114501 (AMKC). SMC is supported by Science Foundation Ireland (Future Research Leaders Grant FRL4862). MP is supported by NIH grant K08 HL157728.Peer reviewe

MIF is a common genetic determinant of COVID-19 symptomatic infection and severity

Genetic predisposition to coronavirus disease 2019 (COVID-19) may contribute to its morbidity and mortality. Because cytokines play an important role in multiple phases of infection, we examined whether commonly occurring, functional polymorphisms in macrophage migration inhibitory factor (MIF) are associated with COVID-19 infection or disease severity.This work was supported by National Institute of Health (NIH) [1R01-AR078334 (RB), 5R01-AI51306 (RB), R01-HL155948 (MS, RB), 1R01AG056728 (IK), T32AR07107 (JPY) and KL2 TR001862 (JJS)]; the European Commission (DB) – NextGenerationEU (Regulation EU 2020/2094) through CSIC's Global Health Platform (PTI Salud Global), and Junta de Castilla y León (Programa Estratégico Instituto de Biología y Genética Molecular (IBGM), Junta de Castilla y León (CCVC8485); and the National Natural Science Foundation of China [#81901669 (WF)].Peer reviewe

Perception on the use of abdominal band or bigkis for babies among women of reproductive age on selected barangays on the City of Dasmariñas, Cavite

This study utilized a non-experimental, descriptive type of research, which covered a group of women aging 15-49, who were considered to be in their reproductive age with or without a child or children who may either be biological or adopted, within the selected barangays on the City of Dasmariñas, Cavite. The respondents were chosen using non-probability, quota-convenience sampling. The researchers used a self-made questionnaire for gathering the data. Data was analysed using frequency distribution, percentage, mean, t-test, and Analysis of Variance. Majority of the women of productive age were 18 to 34 years old, married with children, high school graduates, unemployed, middle child of the family, and Caviteños. There respodents have moderate perception on the use of abdominal band or bigkis for their babies. There were significant differences in the perception of women of reproductive age on the use of abdominal band or bigkis for babies when the respondents were grouped according to age, ordinal position, educational attainment, civil status, ethnic group, and employment status

Parentification Experiences of Filipino Young Professional Daughters During the COVID-19 Pandemic

Parentification refers to parent-child role reversal wherein the child adopts the parent's role instrumentally or emotionally. This role reversal practice between the parent and the child is not uncommon in certain cultures. The cultural dynamics and familial obligations at play have positive and negative outlooks with varying effects. This study focused on the effects of instrumental parentification experiences on psychological resilience and interpersonal relationships among selected Filipino young professional daughters during the COVID-19 pandemic. Using purposive sampling, 19 Filipino young professional daughters from Metro Manila, Philippines, were selected for the study. Online interviews were conducted and thematic analysis was employed to process the data. Findings showed that most of the daughters, with “utang na loob” (indebtedness) value system, wholeheartedly accepted instrumental parentification. Thus, more tasks and responsibilities were shouldered by them due to the COVID-19 lockdown wherein older parents need to stay at home due to the fear of contracting the disease. Almost all shared that the COVID-19 pandemic tested their parent-child relationship. A few expressed that it made them let go of personal growth opportunities and experienced problems with their parents' relationship, given the uncertainties brought by the COVID-19 pandemic. Nevertheless, they shared that they could not leave their ageing parents in this time of COVID-19 pandemic and that with proper balancing of tasks and responsibilities at home and at work, parentification made them to become more self-reliant, mature Faster, and responsible daughters

Macrophage-derived PDGF-B induces muscularization in murine and human pulmonary hypertension

Excess macrophages and smooth muscle cells (SMCs) characterize many cardiovascular diseases, but crosstalk between these cell types is poorly defined. Pulmonary hypertension (PH) is a lethal disease in which lung arteriole SMCs proliferate and migrate, coating the normally unmuscularized distal arteriole. We hypothesized that increased macrophage platelet-derived growth factor–B (PDGF-B) induces pathological SMC burden in PH. Our results indicate that clodronate attenuates hypoxia-induced macrophage accumulation, distal muscularization, PH, and right ventricle hypertrophy (RVH). With hypoxia exposure, macrophage Pdgfb mRNA was upregulated in mice, and LysM‑Cre mice carrying floxed alleles for hypoxia-inducible factor 1a, hypoxia-inducible factor 2a, or Pdgfb had reduced macrophage Pdgfb and were protected against distal muscularization and PH. Conversely, LysM‑Cre von-Hippel Lindaufl/fl mice had increased macrophage Hifa and Pdgfb and developed distal muscularization, PH, and RVH in normoxia. Similarly, Pdgfb was upregulated in macrophages from human idiopathic or systemic sclerosis–induced pulmonary arterial hypertension patients, and macrophage-conditioned medium from these patients increased SMC proliferation and migration via PDGF-B. Finally, in mice, orotracheal administration of nanoparticles loaded with Pdgfb siRNA specifically reduced lung macrophage Pdgfb and prevented hypoxia-induced distal muscularization, PH, and RVH. Thus, macrophage-derived PDGF-B is critical for pathological SMC expansion in PH, and nanoparticle-mediated inhibition of lung macrophage PDGF-B has profound implications as an interventional strategy for PH

Parentification Experiences of Filipino Young Professional Daughters During the COVID-19 Pandemic

Parentification refers to parent-child role reversal wherein the child adopts the parent's role instrumentally or emotionally. This role reversal practice between the parent and the child is not uncommon in certain cultures. The cultural dynamics and familial obligations at play have positive and negative outlooks with varying effects. This study focused on the effects of instrumental parentification experiences on psychological resilience and interpersonal relationships among selected Filipino young professional daughters during the COVID-19 pandemic.  Using purposive sampling, 19 Filipino young professional daughters from Metro Manila, Philippines, were selected for the study. Online interviews were conducted and thematic analysis was employed to process the data. Findings showed that most of the daughters, with “utang na loob” (indebtedness) value system, wholeheartedly accepted instrumental parentification. Thus, more tasks and responsibilities were shouldered by them due to the COVID-19 lockdown wherein older parents need to stay at home due to the fear of contracting the disease. Almost all shared that the COVID-19 pandemic tested their parent-child relationship. A few expressed that it made them let go of personal growth opportunities and experienced problems with their parents' relationship, given the uncertainties brought by the COVID-19 pandemic. Nevertheless, they shared that they could not leave their ageing parents in this time of COVID-19 pandemic and that with proper balancing of tasks and responsibilities at home and at work, parentification made them to become more self-reliant, mature faster, and responsible daughters

Differential regulation of macrophage activation by the MIF cytokine superfamily members MIF and MIF-2 in adipose tissue during endotoxemia

Sepsis is a leading cause of death worldwide and recent studies have shown white adipose tissue (WAT) to be an important regulator in septic conditions. In the present study, the role of the inflammatory cytokine macrophage migration inhibitory factor (MIF) and its structural homolog D-dopachrome tautomerase (D-DT/MIF-2) were investigated in WAT in a murine endotoxemia model. Both MIF and MIF-2 levels were increased in the peritoneal fluid of LPS-challenged wild-type mice, yet, in visceral WAT, the proteins were differentially regulated, with elevated MIF but downregulated MIF-2 expression in adipocytes. Mif gene deletion polarized adipose tissue macrophages (ATM) toward an anti-inflammatory phenotype while Mif-2 gene knockout drove ATMs toward a pro-inflammatory phenotype and Mif-deficiency was found to increase fibroblast viability. Additionally, we observed the same differential regulation of these two MIF family proteins in human adipose tissue in septic vs healthy patients. Taken together, these data suggest an inverse relationship between adipocyte MIF and MIF-2 expression during systemic inflammation, with the downregulation of MIF-2 in fat tissue potentially increasing pro-inflammatory macrophage polarization to further drive adipose inflammation