Clinical and hematological characteristics of children infected with the omicron variant of SARS-CoV-2: role of the combination of the neutrophil: lymphocyte ratio and eosinophil count in distinguishing severe COVID-19.

Purpose: Investigate the clinical/hematological characteristics of children infected with the Omicron variant of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and identify an effective indicator to distinguish coronavirus disease 2019 (COVID-19) severity in children. Methods: A retrospective study was conducted through electronic medical records from pediatric patients. The demographic, clinical, and routine blood test (RBT) features of children diagnosed by real-time PCR for SARS-CoV-2 were collected. Results: Data of 261 patients were analyzed. The most common abnormality shown by RBTs was increased monocyte count (68%). Children had "mild-moderate" or "severe" forms of COVID-19. Prevalence of abnormal neutrophil count (p = 0.048), eosinophil count (p = 0.006), mean corpuscular volume (p = 0.033), mean platelet volume (p = 0.006), platelet-large cell ratio (p = 0.043), and red blood cell distribution width-standard deviation (p = 0.031) were significantly different in the two types. A combination of the neutrophil: lymphocyte ratio (NLR) and eosinophil count for diagnosing severe COVID-19 presented the largest AUC (0.688, 95% CI = 0.599-0.777; p < 0.001), and the AUC increased with a decrease in age. Conclusions: Combination of the NLR and eosinophil count might be a promising indicator for identifying severe COVID-19 in children at infection onset.

Cysteine and glycine-rich protein 2 retards platelet-derived growth factor-BB-evoked phenotypic transition of airway smooth muscle cells by decreasing YAP/TAZ activity.

Cysteine and glycine-rich protein 2 (Csrp2) has emerged as a key factor in controlling the phenotypic modulation of smooth muscle cells. The phenotypic transition of airway smooth muscle cells (ASMCs) is a pivotal step in developing airway remodeling during the onset of asthma. However, whether Csrp2 mediates the phenotypic transition of ASMCs in airway remodeling during asthma onset is undetermined. This work aimed to address the link between Csrp2 and the phenotypic transition of ASMCs evoked by platelet-derived growth factor (PDGF)-BB in vitro. The overexpression or silencing of Csrp2 in ASMCs was achieved through adenovirus-mediated gene transfer. The expression of mRNA was measured by quantitative real-time-PCR. Protein levels were determined through Western blot analysis. Cell proliferation was detected by EdU assay and Calcein AM assays. Cell cycle distribution was assessed via fluorescence-activated cell sorting assay. Cell migration was evaluated using the scratch-wound assay. The transcriptional activity of Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) was measured using the luciferase reporter assay. A decline in Csrp2 level occurred in PDGF-BB-stimulated ASMCs. Increasing Csrp2 expression repressed the PDGF-BB-evoked proliferation and migration of ASMCs. Moreover, increasing Csrp2 expression impeded the phenotypic change of PDGF-BB-stimulated ASMCs from a contractile phenotype into a synthetic/proliferative phenotype. On the contrary, the opposite effects were observed in Csrp2-silenced ASMCs. The activity of YAP/TAZ was elevated in PDGF-BB-stimulated ASMCs, which was weakened by Csrp2 overexpression or enhanced by Csrp2 silencing. The YAP/TAZ activator could reverse Csrp2-overexpression-mediated suppression of the PDGF-BB-evoked phenotypic switching of ASMCs, while the YAP/TAZ suppressor could dimmish Csrp2-silencing-mediated enhancement on PDGF-BB-evoked phenotypic switching of ASMCs. In summary, Csrp2 serves as a determinant for the phenotypic switching of ASMCs. Increasing Csrp2 is able to impede PDGF-BB-evoked phenotypic change of ASMCs from a synthetic phenotype into a synthetic/proliferative phenotype through the effects on YAP/TAZ. This work implies that Csrp2 may be a key player in airway remodeling during the onset of asthma.

Risk Factors Associated With Increased Anxiety Sensitivity in Children and Adolescents in Northwest China During COVID-19 Pandemic Lockdown.

Purpose: A large body of evidence has revealed that the sudden outbreak of public health emergencies induces dramatic effects on the mental health of the general public. We aimed to investigate the level of anxiety sensitivity and its risk factors in children and adolescents from northwest China during the COVID-19 pandemic lockdown in early 2020. Methods: A cross-sectional survey was conducted through the Wenjuanxing platform using a convenience sampling method between 18 and 26 February 2020. The self-designed questionnaire contained sociodemographic characteristics, factors associated with the COVID-19 pandemic, and the Childhood Anxiety Sensitivity Index (CASI) scale. The data from 1,091 valid questionnaires from students aged 9-17 years were analyzed using ANOVA, multiple linear regression, and binary logistic regression. Results: The average CASI scores were 11.47 ± 6.631, and 642 students (58.9%) had prominent anxiety sensitivity. Gender, education level, family members participating in anti-COVID-19 work, getting ill and needing medical help during the lockdown, feeling afraid or having heart palpitations on hearing things associated with COVID-19, believing that COVID-19 would have adverse impacts on themselves or their family in the future, and fear of infection were identified as significant factors for elevated levels of anxiety sensitivity (p < 0.05). We established a multiple linear regression model for the anxiety sensitivity score. Risk factors found for anxiety sensitivity in children and adolescents during the COVID-19 lockdown included studying in secondary or high school, becoming ill during the pandemic, feeling afraid or experiencing rapid heartbeat or palpitations on hearing about the COVID-19 pandemic, thinking that COVID-19 would have an adverse impact on themselves or their family in the future, and fear of infection. Conclusions: During the COVID-19 pandemic and home quarantine, scores measuring the prevalence of anxiety sensitivity in children and adolescents from northwest China were elevated. We should develop measures that especially target possible risk factors to intervene against and prevent anxiety sensitivity in children and adolescents in both the current and future pandemics.

Corrigendum: Metformin Ameliorates Inflammation and Airway Remodeling of Experimental Allergic Asthma in Mice by Restoring AMPKα Activity.

[This corrects the article DOI: 10.3389/fphar.2022.780148.].

Metformin Ameliorates Inflammation and Airway Remodeling of Experimental Allergic Asthma in Mice by Restoring AMPKα Activity.

Metformin has been involved in modulating inflammatory state and inhibiting cell proliferation and angiogenesis. This study aimed to determine whether metformin alleviates airway inflammation and remodeling of experimental allergic asthma and elucidate the underlying mechanism. We sensitized and challenged mice with ovalbumin (OVA) to induce allergic asthma. During the challenge period, metformin was administered by intraperitoneal injection. By histopathological and immunohistochemical analyses, metformin-treated mice showed a significant alleviation in airway inflammation, and in the parameters of airway remodeling including goblet cell hyperplasia, collagen deposition and airway smooth muscle hypertrophy compared to those in the OVA-challenged mice. We also observed elevated levels of multiple cytokines (IL-4, IL-5, IL-13, TNF-α, TGF-ß1 and MMP-9) in the bronchoalveolar lavage fluid, OVA-specific IgE in the serum and angiogenesis-related factors (VEGF, SDF-1 and CXCR4) in the plasma from asthmatic mice, while metformin reduced all these parameters. Additionally, the activity of 5'-adenosine monophosphate-activated protein kinase a (AMPKα) in the lungs from OVA-challenged mice was remarkably lower than control ones, while after metformin treatment, the ratio of p-AMPKα to AMPKα was upregulated and new blood vessels in the sub-epithelial area as evidenced by CD31 staining were effectively suppressed. These results indicate that metformin ameliorates airway inflammation and remodeling in an OVA-induced chronic asthmatic model and its protective role could be associated with the restoration of AMPKα activity and decreased asthma-related angiogenesis.

TIPE2 inhibits PDGF-BB-induced phenotype switching in airway smooth muscle cells through the PI3K/Akt signaling pathway.

BACKGROUND: Childhood asthma is a common respiratory disease characterized by airway inflammation. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) has been found to be involved in the progression of asthma. This study aimed to explore the role of TIPE2 in the regulation of airway smooth muscle cells (ASMCs), which are one of the main effector cells in the development of asthma. MATERIALS AND METHODS: ASMCs were transfected with pcDNA3.0-TIPE2 or si-TIPE2 for 48 h and then treated with platelet-derived growth factor (PDGF)-BB. Cell proliferation of ASMCs was measured using the MTT assay. Cell migration of ASMCs was determined by a transwell assay. The mRNA expression levels of calponin and smooth muscle protein 22α (SM22α) were measured using qRT-PCR. The levels of TIPE2, calponin, SM22α, PI3K, p-PI3K, Akt, and p-Akt were detected by Western blotting. RESULTS: Our results showed that PDGF-BB treatment significantly reduced TIPE2 expression at both the mRNA and protein levels in ASMCs. Overexpression of TIPE2 inhibited PDGF-BB-induced ASMC proliferation and migration. In addition, overexpression of TIPE2 increased the expression of calponin and SM22α in PDGF-BB-stimulated ASMCs. However, an opposite effect was observed with TIPE2 knockdown. Furthermore, TIPE2 overexpression blocked PDGF-BB-induced phosphorylation of PI3K and Akt, whereas the expression of p-PI3K and p-Akt were aggravated by TIPE2 knockdown. Additionally, the effects of TIPE2 overexpression and TIPE2 knockdown were altered by IGF-1 and LY294002 treatments, respectively. CONCLUSIONS: Our findings demonstrate that TIPE2 inhibits PDGF-BB-induced ASMC proliferation, migration, and phenotype switching via the PI3K/Akt signaling pathway. Thus, TIPE2 may be a potential therapeutic target for the treatment of asthma.

C1q/TNF-related protein-9 ameliorates hypoxia-induced pulmonary hypertension by regulating secretion of endothelin-1 and nitric oxide mediated by AMPK in rats.

Injury/dysfunction of the endothelium of pulmonary arteries contributes to hypoxia-induced pulmonary hypertension (HPH). We investigated whether C1q/tumor necrosis factor-related protein-9 (CTRP9), a newly identified cardiovascular agent, has protective roles in the development of HPH. HPH was induced in adult male rats by chronic hypobaric hypoxia. CTRP9 overexpression by adeno-associated virus (AAV)-CTRP9 transfection attenuated the increases in right ventricular systolic pressure, right ventricular hypertrophy index, and pulmonary arterial remodeling of rats under hypoxia. Importantly, CTRP9 overexpression improved endothelium-dependent vasodilation in pulmonary arterioles in HPH rats. CTRP9 overexpression enhanced expression of phosphorylated 5'-adenosine monophosphate-activated protein kinase (p-AMPK) and phosphorylated endothelial nitric oxide synthase (p-eNOS), and reduced phosphorylated extracellular signal-regulated protein kinase (p-ERK1/2) expression in pulmonary microvascular endothelial cells (PMVECs) of HPH rats. In cultured PMVECs, CTRP9 not only preserved the decrease of AMPK and eNOS phosphorylation level and nitric oxide (NO) production induced by hypoxia, but also blocked the increase in hypoxia-induced ERK1/2 phosphorylation level and endothelin (ET)-1 production. Furthermore, the effects of CTRP9 were interrupted by inhibitors or knockdown of AMPK. CTRP9 enhances NO production and reduces ET-1 production by regulating AMPK activation. CTRP9 could be a target for HPH.