No abstract

BackgroundDesigner self-assembling peptide nanofibers (SAPNFs) as a novel kind of emerging nanomaterial have received more and more attention in the field of nanomedicine in recent years. However, a simple method to monitor and image SAPNFs is still currently absent.MethodsRADA16-I, a well-studied ionic complementary peptide was used as a model to check potential amyloid-like staining properties of SAPNFs. Thioflavin-T (ThT) and Congo red (CR) as specific dyes for amyloid-like fibrils were used to stain RADA16-I nanofibers in solution, combined with drugs or cells, or injected in vivo as hydrogels. Fluorescent spectrometry and fluorescent microscopy were used to check ThT-binding property, and polarized light microscopy was used to check CR-staining property.ResultsThT binding with the nanofibers showed enhanced and blue-shifted fluorescence, and specific apple-green birefringence could be observed after the nanofibers were stained with CR. Based on these properties we further showed that ThT-binding fluorescence intensity could be used to monitor the forming and changing of nanofibers in solution, while fluorescent microscopy and polarized light microscopy could be used to image the nanofibers as material for drug delivery, 3D cell culture, and tissue regeneration.ConclusionOur results may provide convenient and reliable tools for detecting SAPNFs, which would be helpful for understanding their self-assembling process and exploring their applications.

Background The effects of neuromuscular blocking agents (NMBAs) on adult patients with acute respiratory distress syndrome (ARDS) remain unclear. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate its effect on mortality. Methods We searched the Cochrane (Central) database, Medline, Embase, the Chinese Biomedical Literature Database (SinoMed), WanFang data and ClinicalTrials from inception to June 2019, with language restriction to English and Chinese. We included published RCTs and eligible clinical trials from ClinicalTrials.gov that compared NMBAs with placebo or usual treatment in adults with ARDS. We pooled data using random-effects models. The primary outcome was mortality. The secondary outcomes were the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO 2 /FIO 2), total positive end expiratory pressure (PEEP), plateau pressure (Pplat), days free of ventilator at day 28, barotrauma and ICU-acquired weakness. Results We included 6 RCTs (n = 1557). Compared with placebo or usual treatment, NMBAs were associated with lower 21 to 28-day mortality (RR 0.72, 95% CI 0.53-0.97, I2 = 59%). NMBAs significantly improved oxygenation (Pao2:Fio2 ratios) at 48 hours (MD 27.26 mm Hg, 95% CI 1.67, 52.84, I2 = 92%) and reduced the incidence of barotrauma (RR 0.55, 95% CI 0.35, 0.85, I2 = 0). However, NMBAs had no effect on oxygenation (Pao2:Fio2 ratios) (MD 18.41 mm Hg, 95% CI-0.33, 37.14, I2 = 72%) at 24 hours. We also found NMBAs did not affect total PEEP, plateau pressure, days free of ventilation at day 28 and ICU-acquired weakness.

Cognitive impairments induced by severe acute pancreatitis (SAP) are severe complications, for which there are a lack of effective pharmacological treatment strategies. Berberine is an isoquinoline alkaloid extracted from the Chinese herb, Coptis rhizome, which exhibits numerous biological effects on gastrointestinal disorders. However, the effects of berberine on SAP‑induced cognitive impairments remain unknown. The present study aimed to investigate the effects of berberine on cognitive impairments associated with SAP. Wistar rats were randomly divided into Sham, Sham + berberine, SAP and SAP + berberine groups. Rats were intraperitoneally injected with L‑arginine (3 g/kg) to induce SAP. Subsequently, selected rats were intragastrically administered berberine (100 mg/kg) once daily for 6 consecutive days. Disease severities of rats were investigated 48 h post‑induction of SAP via determination of serum amylase levels and hematoxylin and eosin staining. Survival rates, performance of behavioral tests (automated rotarod and fear conditioning tests), blood brain barrier (BBB) permeability, and the expression levels of tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β in hippocampal tissues were also determined. Proteins associated with apoptosis and necroptosis in the hippocampal tissues of SAP rats, including caspase‑3, receptor‑interacting protein kinase (RIP)1 and RIP3, were detected via western blotting. The results revealed that treatment with L‑arginine induced SAP, which subsequently resulted in increased BBB permeability, mortality rates and cognitive deficits in rats. The expression levels of TNF‑α, IL‑1β, caspase‑3, RIP1 and RIP3 were significantly increased in the hippocampal tissues of SAP rats, thus suggesting that neuroinflammation, apoptosis and necroptosis may be involved in neurodegeneration associated with the development of SAP. Notably, administration of berberine protected the integrity of the BBB, decreased levels of brain inflammation and mortality rates, and attenuated increased levels of proteins associated with apoptosis and necroptosis and cognitive deficits associated with SAP in rats. The results of the present study demonstrated that daily treatment with berberine may attenuate cognitive deficits and reduce associated mortality via exhibition of anti‑neuroinflammatory effects and attenuation of neuronal apoptosis and necroptosis in the hippocampal tissues of SAP rats.