Cardiac fibroblasts (CFs) are the primary cell type responsible for cardiac fibrosis during pathological myocardial remodeling. Several studies have illustrated that pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) attenuates cardiac fibrosis in different animal models. However, the effects of pirfenidone on cardiac fibroblast behavior have not been examined. In this study, we investigated whether pirfenidone directly modulates cardiac fibroblast behavior that is important in myocardial remodeling such as proliferation, myofibroblast differentiation, migration and cytokine secretion. Fibroblasts were isolated from neonatal rat hearts and bioassays were performed to determine the effects of pirfenidone on fibroblast function. We demonstrated that treatment of CFs with pirfenidone resulted in decreased proliferation, and attenuated fibroblast α-smooth muscle actin expression and collagen contractility. Boyden chamber assay illustrated that pirfenidone inhibited fibroblast migration ability, probably by decreasing the ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1. Furthermore, pirfenidone attenuated the synthesis and secretion of transforming growth factor-β1 but elevated that of interleukin-10. These direct and pleiotropic effects of pirfenidone on cardiac fibroblasts point to its potential use in the treatment of adverse myocardial remodeling.

Background The use of high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) in patients with COVID-19 is debated. Methods This study was performed in four hospitals of China from January to March 2020. We retrospectively enrolled 23 and 13 COVID-19 patients who used HFNC and NIV as first-line therapy, respectively. Results Among the 23 patients who used HFNC as first-line therapy, 10 experienced HFNC failure and used NIV as rescue therapy. Among the 13 patients who used NIV as first-line therapy, one (8%) used HFNC as rescue therapy due to NIV intolerance. The duration of HFNC + NIV (median 7.1, IQR: 3.5–12.2 vs. 7.3, IQR: 5.3–10.0 days), intubation rate (17% vs. 15%) and mortality (4% vs. 8%) did not differ between patients who used HFNC and NIV as first-line therapy. In total cohorts, 6 (17%) patients received intubation. Time from initiation of HFNC or NIV to intubation was 8.4 days (IQR: 4.4–18.5). And the time from initiation of HFNC or NIV to termination in patients without intubation was 7.1 days (IQR: 3.9–10.3). Among all the patients, C-reactive protein was independently associated with intubation (OR = 1.04, 95% CI: 1.01–1.07). In addition, no medical staff got nosocomial infection who participated in HFNC and NIV management. Conclusions In critically ill patients with COVID-19 who used HFNC and NIV as first-line therapy, the duration of HFNC + NIV, intubation rate and mortality did not differ between two groups. And no medical staff got nosocomial infection during this study.

Hypertensive individuals represent a vulnerable population that merits special attention from healthcare providers and systems. This is especially important given that low health-related quality of life can be a risk factor for subsequent cardiovascular events or complications.

Maternal food restriction (MFR) causes intrauterine growth restriction, a known risk factor for developing chronic lung disease. However, it is unknown whether this negative outcome is gender specific or preventable by blocking the MFR-induced hyperglucocorticoidism. Using a well-established rat model, we used metyrapone (MTP), an inhibitor of glucocorticoid synthesis, to study the MFR-induced lung changes on postnatal day (p) 21 in a gender-specific manner. From embryonic day 10 until delivery, pregnant dams were fed either an ad libitum diet or a 50% caloric restricted diet with or without MTP supplementation. Postnatally, the offspring were fed ad libitum from healthy dams until p21. Morphometric, Western blot, and immunohistochemical analysis of the lungs demonstrated that MTP mitigated the MFR-mediated decrease in alveolar count, decrease in adipogenic protein peroxisome proliferator-activated receptor g, increase in myogenic proteins (fibronectin, a-smooth muscle actin, and calponin), increase in Wnt signaling intermediates (lymphoid enhancer-binding factor 1 and b-catenin), and increase in glucocorticoid receptor (GR) levels. The MFR-induced lung phenotype and the effects of MTP were similar in both genders. To elucidate the mechanism of MFR-induced shift of the adipogenic-to-myogenic phenotype, lung fibroblasts were used to independently study the effects of (1) nutrient restriction and (2) excess steroid exposure. Nutrient deprivation increased myogenic proteins, Wnt signaling intermediates, and GR, all changes blocked by protein supplementation. MTP also blocked, likely by normalizing nicotinamide adenine dinucleotide phosphate levels, the corticosterone-induced increase in myogenic proteins, but had no effect on GR levels. In summary, protein restriction and increased glucocorticoid levels appear to be the key players in MFR-induced lung disease, affecting both genders.