The Effects of Insulin-Like Growth Factor I and BTP-2 on Acute Lung Injury

Acute lung injury (ALI) afflicts approximately 200,000 patients annually and has a 40% mortality rate. The COVID-19 pandemic has massively increased the rate of ALI incidence. The pathogenesis of ALI involves tissue damage from invading microbes and, in severe cases, the overexpression of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). This study aimed to develop a therapy to normalize the excess production of inflammatory cytokines and promote tissue repair in the lipopolysaccharide (LPS)-induced ALI. Based on our previous studies, we tested the insulin-like growth factor I (IGF-I) and BTP-2 therapies. IGF-I was selected, because we and others have shown that elevated inflammatory cytokines suppress the expression of growth hormone receptors in the liver, leading to a decrease in the circulating IGF-I. IGF-I is a growth factor that increases vascular protection, enhances tissue repair, and decreases pro-inflammatory cytokines. It is also required to produce anti-inflammatory 1,25-dihydroxyvitamin D. BTP-2, an inhibitor of cytosolic calcium, was used to suppress the LPS-induced increase in cytosolic calcium, which otherwise leads to an increase in proinflammatory cytokines. We showed that LPS increased the expression of the primary inflammatory mediators such as toll like receptor-4 (TLR-4), IL-1β, interleukin-17 (IL-17), TNF-α, and interferon-γ (IFN-γ), which were normalized by the IGF-I + BTP-2 dual therapy in the lungs, along with improved vascular gene expression markers. The histologic lung injury score was markedly elevated by LPS and reduced to normal by the combination therapy. In conclusion, the LPS-induced increases in inflammatory cytokines, vascular injuries, and lung injuries were all improved by IGF-I + BTP-2 combination therapy.     

Focal Ischemic Injury to the Early Neonatal Rat Brain Models Cognitive and Motor Deficits with Associated Histopathological Outcomes Relevant to Human Neonatal Brain Injury

Neonatal arterial ischemic stroke is one of the more severe birth complications. The injury can result in extensive neurological damage and is robustly associated with later diagnoses of cerebral palsy (CP). An important part of efforts to develop new therapies include the on-going refinement and understanding of animal models that capture relevant clinical features of neonatal brain injury leading to CP. The potent vasoconstrictor peptide, Endothelin-1 (ET-1), has previously been utilised in animal models to reduce local blood flow to levels that mimic ischemic stroke. Our previous work in this area has shown that it is an effective and technically simple approach for modelling ischemic injury at very early neonatal ages, resulting in stable deficits in motor function. Here, we aimed to extend this model to also examine the impact on cognitive function. We show that focal delivery of ET-1 to the cortex of Sprague Dawley rats on postnatal day 0 (P0) resulted in impaired learning in a touchscreen-based test of visual discrimination and correlated with important clinical features of CP including damage to large white matter structures.     

Human-Induced Neural and Mesenchymal Stem Cell Therapy Combined with a Curcumin Nanoconjugate as a Spinal Cord Injury Treatment

We currently lack effective treatments for the devastating loss of neural function associated with spinal cord injury (SCI). In this study, we evaluated a combination therapy comprising human neural stem cells derived from induced pluripotent stem cells (iPSC-NSC), human mesenchymal stem cells (MSC), and a pH-responsive polyacetal–curcumin nanoconjugate (PA-C) that allows the sustained release of curcumin. In vitro analysis demonstrated that PA-C treatment protected iPSC-NSC from oxidative damage in vitro, while MSC co-culture prevented lipopolysaccharide-induced activation of nuclear factor-κB (NF-κB) in iPSC-NSC. Then, we evaluated the combination of PA-C delivery into the intrathecal space in a rat model of contusive SCI with stem cell transplantation. While we failed to observe significant improvements in locomotor function (BBB scale) in treated animals, histological analysis revealed that PA-C-treated or PA-C and iPSC-NSC + MSC-treated animals displayed significantly smaller scars, while PA-C and iPSC-NSC + MSC treatment induced the preservation of β-III Tubulin-positive axons. iPSC-NSC + MSC transplantation fostered the preservation of motoneurons and myelinated tracts, while PA-C treatment polarized microglia into an anti-inflammatory phenotype. Overall, the combination of stem cell transplantation and PA-C treatment confers higher neuroprotective effects compared to individual treatments.     

Hydrogen Sulfide Metabolite,Sodium Thiosulfate: Clinical Applications and Underlying Molecular Mechanisms

Thiosulfate in the form of sodium thiosulfate (STS) is a major oxidation product of hydrogen sulfide (H₂S), an endogenous signaling molecule and the third member of the gasotransmitter family. STS is currently used in the clinical treatment of acute cyanide poisoning, cisplatin toxicities in cancer therapy, and calciphylaxis in dialysis patients. Burgeoning evidence show that STS has antioxidant and anti-inflammatory properties, making it a potential therapeutic candidate molecule that can target multiple molecular pathways in various diseases and drug-induced toxicities. This review discusses the biochemical and molecular pathways in the generation of STS from H₂S, its clinical usefulness, and potential clinical applications, as well as the molecular mechanisms underlying these clinical applications and a future perspective in kidney transplantation.     

氧糖剥夺条件下PC12细胞RAGE的表达及对其损伤的影响

目的探讨大鼠肾上腺嗜铬细胞瘤(PC12)细胞在氧糖剥夺(OGD)的条件下,晚期糖基化终产物受体(RAGE)的表达及其对PC12细胞损伤的影响。方法PC12细胞随机分为3组:OGD培养组(PC12细胞在无血清无糖的DMEM培养液中厌氧培养);封闭RAGE的OGD培养组(PC12细胞在加5μg/mlRAGE抗体的无血清无糖DMEM培养液中厌氧培养);对照组(PC12细胞在无血清无糖DMEM培养液中培养)。免疫组化法检测RAGE表达。收集细胞上清液,检测乳酸脱氢酶(LDH)活性和一氧化氮(NO)含量,并对细胞死亡率进行检测。结果在OGD条件下PC12细胞培养8、11、20h均有RAGE表达,与对照组相比表达均明显增加,OGD培养组与封闭RAGEOGD培养组相比,LDH活性差异显著。随着厌氧时间的延长,PC12细胞死亡率明显增高,封闭RAGEOGD培养组与OGD培养组相比,PC12细胞死亡率明显降低。NO含量差异无显著意义,但与对照组相比差异显著。结论在OGD条件下,PC12细胞RAGE表达增高。RAGE的表达对细胞的损伤起促进作用。     

Police officer in-vehicle discomfort: Appointments carriage method and vehicle seat features

Musculoskeletal pain is commonly reported by police officers. A potential cause of officer discomfort is a mismatch between vehicle seats and the method used for carrying appointments. Twenty-five police officers rated their discomfort while seated in: (1) a standard police vehicle seat, and (2) a vehicle seat custom-designed for police use. Discomfort was recorded in both seats while wearing police appointments on: (1) a traditional appointments belt, and (2) a load-bearing vest/belt combination (LBV). Sitting in the standard vehicle seat and carrying appointments on a traditional appointments belt were both associated with significantly elevated discomfort. Four vehicle seat features were most implicated as contributing to discomfort: back rest bolster prominence; lumbar region support; seat cushion width; and seat cushion bolster depth. Authorising the carriage of appointments using a LBV is a lower cost solution with potential to reduce officer discomfort. Furthermore, the introduction of custom-designed vehicle seats should be considered.     

除草剂对不同栽培方式水稻药害的评价

选取酰胺类、磺酰脲类、硫代氨基甲酸酯类、杂环类、脲类、苯氧羧酸类等常用化学除草剂,以超常规剂量用移液和喷雾两种方式对抛栽和直播籼、粳稻进行药剂试验。研究结果明确了各种除草剂对水稻的药害症状;籼粳稻对各药剂的敏感差异;以及清水冲洗、搁田、施肥等措施对某些除草剂品种造成的水稻药害的缓解作用。     

采用听觉外周模型改进电子耳蜗CIS方案

提出了一种改进的CIS电子耳蜗的脉冲刺激方案。利用听觉外周模型产生一种符合听神经发放机制的刺激脉冲序列来刺激电极,代替传统的均匀交替刺激方案,不仅可以通过包络而且可以通过脉冲间隔来传递语音信息,确保了语音的空间编码和时间编码。听觉仿真实验表明,相对于其他两种方案,方案可以有效地传递更多更丰富的语音信息,在汉语声调识别实验中至少提高19.2%识别率,在可懂度的对比实验中具有最高可懂度。     

Duration of slip-resistant shoe usage and the rate of slipping in limited-service restaurants: results from a prospective and crossover study

Several studies have indicated that slip-resistant shoes may have a positive effect on reducing the risk of slips and falls, a leading cause of injury at work. Few studies, however, have examined how duration of shoe usage affects their slip-resistance properties. This study examined the association between the duration of slip-resistant shoes usage and the self-reported rate of slipping in limited-service restaurant workers. A total of 475 workers from 36 limited-service restaurants in the USA were recruited to participate in a 12-week prospective study of workplace slipping. Of the 475 participants, 83 reported changing to a new pair of shoes at least once during the 12-week follow-up. The results show that slip-resistant shoes worn for less than six months were moderately more effective than those worn for more than six months. Changing to a new pair of shoes among those wearing slip-resistant shoes at baseline was associated with a 55% reduction in the rate of slipping (RR = 0.45, 95% CI = 0.23–0.89). Further research is needed to develop criteria for the replacement of slip-resistant shoes.

Practitioner Summary: The duration of usage impacts the slip-resistance properties of slip-resistant shoes. Slip-resistant shoes worn for less than six months were moderately more effective in reducing slips than slip-resistant shoes worn for more than six months. Shoe use policies should not only encourage or require their use but also include guidance on replacing slip-resistant shoes at regular intervals.     

数据挖掘预测模型在脑损伤患者认知功能康复中的应用

为了更好地预测后天性脑损伤ABI(Acquired Brain Injury)患者认知功能康复的影响因素,提出基于决策树(DT)、多层感知器(MLP)和广义回归神经网络(GRNN)的三种预测模型。借助于10折交叉验证测试算法,通过专一性、灵敏度和精度分析以及混淆矩阵分析对模型的性能进行测试,从而获得新的知识以评估和改善认知功能康复过程中的有效性。实验结果表明,基于DT的模型的模拟结果明显比其他模型更为优越,预测平均精度可高达90.38%。