Factors Involved in Decision-Making Dilemmas Faced by Parents of Children with Severe Asthma in PICU During the Development of Discharge Care Plans: A Phenomenological Study.

Purpose: This study aims to explore the complicated decision-making dilemma and challenges confronted by parents of children suffering from severe asthma within the Pediatric Intensive Care Unit (PICU) when participating in the development of their children's discharge care plans. Patients and Methods: Employing a phenomenological methodology, a purposive sampling was performed to engage with 17 parents who participated in in-depth and semi-structured interviews between October 2022 and February 2023. The transcripts of these interviews were transcribed into textual data, which was then subjected to Colaizzi's seven-step analysis for meticulous coding and comprehensive thematic elucidation. Results: The comprehensive analysis of the factors involved in the intricate decision-making dilemmas faced by parents of children with severe asthma during the process of crafting discharge care plans in the PICU revealed five themes and eight sub-themes: 1) Complexity of asthma-related information; 2) Insufficient provision of comprehensive decision-making support; 3) Encountering negative emotions and wavering confidence; 4) Navigating realistic constraints impacting both parents and HCPs; 5) Balancing the advantages and disadvantages of various plans. Conclusion: Parents of children with severe asthma in the PICU encounter intricate and multifaceted decision-making dilemmas while engaging in the formulation of discharge care plans. These complexities significantly dampen their decision-making enthusiasm and introduce potential risks to the children's prognosis and recovery. In the future, it is imperative to leverage the guidance provided by healthcare professionals (HCPs) in the decision-making process, develop tailored decision support tools specifically designed for the formulation of discharge care plans for children with severe asthma in the PICU.

Betaine protects rats against ischemia/reperfusion injury-induced brain damage.

Brain ischemia and reperfusion (I/R) injury may lead to a poor prognosis for ischemic stroke, which could be alleviated by antioxidants with diminished oxidative stress. Betaine is a natural nutrient found in beetroot and seafood to improve cognitive performance in the elderly. The present study investigated whether betaine could protect the brain from I/R injury. Results showed that betaine treatment could reduce H2O2-induced cell death in the PC12 cell line. Pretreatment with betaine reduced the brain infarct volume and neuronal apoptosis in a rat I/R injury model induced by 2-h middle cerebral artery occlusion (MCAO). Biochemical analyses indicated that betaine treatment decreased proinflammatory cytokine production and reduced oxidative stress after I/R injury. Betaine increased the expression of antioxidative enzymes, such as glutathione peroxidase 4 (Gpx4) and superoxide dismutase 1 (Sod1), and antioxidative nonenzymatic genes, such as 3-mercaptopyruvate sulfurtransferase (Mpst), methionine sulfoxide reductases b1 (Msrb1), and Msrb2. These data suggest that betaine exerts a neuroprotective effect in I/R injury through enzymatic and nonenzymatic antioxidative systems and anti-inflammatory mechanisms.NEW & NOTEWORTHY These data suggested that betaine exerted a neuroprotective effect in I/R injury through enzymatic and nonenzymatic antioxidative systems.

miR-4429 sensitized cervical cancer cells to irradiation by targeting RAD51.

Cervical cancer (CC) is a prevalent malignancy in women, with the feature of metastasis and easy recurrence is responsible for a large proportion of global cancer deaths. Radiotherapy is one of the common treatment tools for CC patients with unresectable tumors. However, radio-resistance in patients could be a major reason for recurrence. Therefore, it is of significance to tunnel the molecular mechanism of radio-resistance in CC. MicroRNAs (miRNAs) are increasingly reported in the regulation of cancer progression and cellular response to radiotherapy and chemotherapy. miR-4429 is a newly discovered miRNA acting as a tumor-suppressor gene in multiple cancers, but its function in CC has never been explored yet. The current study tried to explore the role of miR-4429 in cell radio-sensitivity in CC. First, we validated the downregulation of miR-4429 in CC cells. Importantly, the association of miR-4429 with radio-resistance was validated by identifying the downregulation of miR-4429 in radio-resistant CC cells. Gain- and loss-of-function assays validated that miR-4429 sensitized CC cells to irradiation. Through bioinformatics tools, RAD51 recombinase (RAD51) was identified to be a target for miR-4429. RAD51 is known to be a crucial regulator for DNA damage repair and has been reported to influence cell radio-resistance in cancers, including in CC. Luciferase reporter assay confirmed the interaction between miR-4429 and RAD51. Finally, rescue assays indicated that miR-4429 promoted CC cell radio-sensitivity through RAD51. Consequently, our study showed that miR-4429 sensitized CC cells to irradiation by targeting RAD51, providing a potential therapeutic target for CC patients.

miR-499-5p suppresses C-reactive protein and provides neuroprotection in hypoxic-ischemic encephalopathy in neonatal rat.

Perinatal hypoxic-ischemic encephalopathy (HIE) is associated with high neonatal mortality and permanent neurologic deficit. Recent data suggested microRNAs (miRNAs) may have essential functions in the regulation of HIE. This study aims to investigate the functional role of miR-499-5p and the underlying mechanism in regulating neonatal hypoxia-ischemia (HI)-induced brain injury. Dual-luciferase reporter assay and western blotting assay were performed to investigate the relationship between miR-499-5p and C-reactive protein (CRP). TUNEL staining assay was applied to evaluate neuronal cell apoptosis in the hippocampus after administration of miR-499-5p in HIE rat model. Neurobehavioral assays were conducted to evaluate the effect of miR-499-5p on the neurological functions of rat pups with HI-induced brain injury. Our study showed that miR-499-5p regulated CRP expression in L-02 cells and rat HIE model. The miR-499-5p treatment resulted in significant reduction of neuronal cell apoptosis and the infarct size of the brain. Furthermore, administration of miR-499-5p significantly improved spatial learning ability, spatial memory, and locomotor function of rat pups with HIE. Our data demonstrated that miR-499-5p have a neuroprotective effect in HI-induced brain injury in rat pups, which suggests a potential therapeutic application of miR-499-5p in the treatment of neonatal HIE.

Hyperoside protects rat ovarian granulosa cells against hydrogen peroxide-induced injury by sonic hedgehog signaling pathway.

Sustained exogenous stimuli induce oxidative stress in granulosa cells and cause cell apoptosis, thereby resulting in follicular atresia. Hyperoside is a natural flavonoid that possesses anti-oxidant activity. The present study aimed to evaluate the effect of hyperoside on hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis in granulosa cells. Cell viability was measured using MTT assay. The malondialdehyde (MDA) level and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were detected to reflect the oxidative stress. Flow cytometry was performed to measure the apoptotic rate. Western blot was carried out to determine the expression of Bcl-2, Bax, Sonic hedgehog (SHH), Gli1, and smoothened (SMO). The mRNA levels of SHH, Gli1, and SMO were analyzed using qRT-PCR. We found that hyperoside improved cell viability in H2O2-stimulated granulosa cells. The increased MDA level and decreased activities of SOD, GSH-Px, and CAT caused by H2O2 stimulation were reversed by hyperoside treatment. The apoptotic rate of H2O2-stimulated granulosa cells was reduced after treatment with hyperoside. Hyperoside treatment caused a decrease in Bax expression and an increase in Bcl-2 expression in H2O2-stimulated granulosa cells. The mRNA and protein levels of SHH, Gli1, and SMO in H2O2-stimulated granulosa cells were elevated by hyperoside treatment. Suppression of SHH pathway by cyclopamine attenuated the protective effects of hyperoside on H2O2-induced injury. In short, hyperoside protected granulosa cells from H2O2-induced cell apoptosis and oxidative stress via activation of the SHH signaling pathway.

Effect of ß-patchoulene on cerebral ischemia-reperfusion injury and the TLR4/NF-κB signaling pathway.

ß-patchoulene (ß-PAE), an active constituent of the Pogostemon cablin, is well known for its anti-inflammatory and antioxidative functions in various diseases. However, little is known about the impact of ß-PAE on the cerebral ischemia-reperfusion (I/R) injury. The current study aimed to determine the neuroprotective effect of ß-PAE and the underlying mechanisms on cerebral I/R injury. Following pretreatment with ß-PAE (10 mg/kg body weight) by tail intravenous injection for 1 h, Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2 h and reperfusion for 24 h. The results indicated that pretreatment with ß-PAE could diminish the infarct volume, decrease the brain water content, reduce the neurological deficit score and restore the mitochondrial membrane potential, compared with the untreated I/R injury group. Furthermore, cell apoptosis was markedly suppressed by ß-PAE, and this effect was associated with the decreased apoptosis regulator BAX/apoptosis regulator Bcl-2 expression ratio and caspase-3 activity. In addition, ß-PAE significantly inhibited the release of proinflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1ß and IL-6. Superoxide generation and malondialdehyde levels were reduced while the levels of glutathione peroxidase and superoxide dismutase were elevated following treatment with ß-PAE, indicating the antioxidative role of ß-PAE in cerebral I/R injury. Furthermore, the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway was inhibited by ß-PAE, as demonstrated by the decreased TLR4 expression and nuclear translocation of p65, and increased IκBα level. Taken together, the results suggested that ß-PAE may exhibit a neuroprotective effect on cerebral I/R injury in rats through inactivating the TLR4/NF-κB signaling pathway.