Ultrasound combined with SDF‐1α chemotactic microbubbles promotes stem cell homing in an osteoarthritis model

Osteoarthritis (OA) is a common joint disease in the middle and old age group with obvious cartilage damage, and the regeneration of cartilage is the key to alleviating or treating OA. In stem cell therapy, bone marrow stem cell (BMSC) has been confirmed to have cartilage regeneration ability. However, the role of stem cells in promoting articular cartilage regeneration is severely limited by their low homing rate. Stromal cell‐derived factor‐1α (SDF‐1α) plays a vital role in MSC migration and involves activation, mobilization, homing and retention. So, we aim to develop SDF‐1α‐loaded microbubbles MB(SDF‐1α), and to verify the migration of BMSCs with the effect of ultrasound combined with MB(SDF‐1α) in vitro and in vivo. The characteristics of microbubbles and the content of SDF‐1α were examined in vitro. To evaluate the effect of ultrasound combined with chemotactic microbubbles on stem cell migration, BMSCs were injected locally and intravenously into the knee joint of the OA model, and the markers of BMSCs in the cartilage were detected. We successfully prepared MB(SDF‐1α) through covalent bonding with impressive SDF‐1α loading efficacy loading content. In vitro study, ultrasound combined with MB(SDF‐1α) group can promote more stem cell migration with highest migrating cell counts, good cell viability and highest CXCR4 expression. In vivo experiment, more BMSCs surface markers presented in the ultrasound combined with MB(SDF‐1α) group with or without exogenous BMSCs administration. Hence, ultrasound combined with MB(SDF‐1α) could promote the homing of BMSCs to cartilage and provide a novel promising therapeutic approach for OA.     

Gastrodin relieves inflammation injury induced by lipopolysaccharides in MRC‐5 cells by up‐regulation of miR‐103

The beneficial function of gastrodin towards many inflammatory diseases has been identified. This study designed to see the influence of gastrodin in a cell model of chronic obstructive pulmonary disease (COPD). MRC‐5 cells were treated by LPS, before which gastrodin was administrated. The effects of gastrodin were evaluated by conducting CCK‐8, FITC‐PI double staining, Western blot, qRT‐PCR and ELISA. Besides this, the downstream effector and signalling were studied to decode how gastrodin exerted its function. And dual‐luciferase assay was used to detect the targeting link between miR‐103 and lipoprotein receptor‐related protein 1 (LRP1). LPS induced apoptosis and the release of MCP‐1, IL‐6 and TNF‐α in MRC‐5 cells. Pre‐treating MRC‐5 cells with gastrodin attenuated LPS‐induced cell damage. Meanwhile, p38/JNK and NF‐κB pathways induced by LPS were repressed by gastrodin. miR‐103 expression was elevated by gastrodin. Further, the protective functions of gastrodin were attenuated by miR‐103 silencing. And LRP1 was a target of miR‐103 and negatively regulated by miR‐103. The in vitro data illustrated the protective function of gastrodin in LPS‐injured MRC‐5 cells. Gastrodin exerted its function possibly by up‐regulating miR‐103 and modulating p38/JNK and NF‐κB pathways.     

Use of Tregs as a cell‐based therapy via CD39 for benign prostate hyperplasia with inflammation

Benign prostatic hyperplasia (BPH) occurs most commonly among older men, often accompanied by chronic tissue inflammation. Although its aetiology remains unclear, autoimmune dysregulation may contribute to BPH. Regulatory T cells (Tregs) prevent autoimmune responses and maintain immune homeostasis. In this study, we aimed to investigate Tregs frequency, phenotype, and function in BPH patients and to evaluate adoptive transfer Tregs for immunotherapy in mice with BPH via CD39. Prostate specimens and peripheral blood from BPH patients were used to investigate Treg subsets, phenotype and Treg‐associated cytokine production. Sorted CD39^+/? Tregs from healthy mice were adoptively transferred into mice before or after testosterone propionate administration. The Tregs percentage in peripheral blood from BPH patients was attenuated, exhibiting low Foxp3 and CD39 expression with low levels of serum IL‐10, IL‐35 and TGF‐β. Immunohistochemistry revealed Foxp3+ cells were significantly diminished in BPH prostate with severe inflammatory. Although the Tregs subset was comprised of more effector/memory Tregs, CD39 was still down‐regulated on effector/memory Tregs in BPH patients. Before or after testosterone propionate administration, no alterations of BPH symptoms were observed due to CD39‐ Tregs in mice, however, CD39⁺Tregs existed more potency than Tregs to regulate prostatic hyperplasia and inhibit inflammation by decreasing IL‐1β and PSA secretion, and increasing IL‐10 and TGF‐β secretion. Furthermore, adoptive transfer with functional Tregs not only improved prostate hyperplasia but also regulated muscle cell proliferation in bladder. Adoptive transfer with Tregs may provide a novel method for the prevention and treatment of BPH clinically.     

Exogenous neuritin treatment improves survivability and functions of Schwann cells with improved outgrowth of neurons in rat diabetic neuropathy

Pathogenesis and treatment for diabetic neuropathy are still complex. A deficit of neurotrophic factors affecting Schwann cells is a very important cause of diabetic neuropathy. Neuritin is a newly discovered potential neurotrophic factor. In this study, we explored the effect of exogenous neuritin on survivability and functions of diabetic Schwann cells of rats with experimental diabetic neuropathy. Diabetic neuropathy was induced in rats. 12‐week diabetic rats contrasted with non‐diabetic normal rats had decreased levels of serum neuritin and slowed nerve conduction velocities (NCVs). Schwann cells isolated from these diabetic rats and cultured in high glucose showed reduced cell neuritin mRNA and protein and supernatant neuritin protein, increased apoptosis rates, increased caspase‐3 activities and progressively reduced viability. In contrast, exogenous neuritin treatment reduced apoptosis and improved viability, with elevated Bcl‐2 levels (not Bax) and decreased caspase‐3 activities. Co‐cultured with diabetic Schwann cells pre‐treated with exogenous neuritin in high glucose media, and diabetic DRG neurons showed lessened decreased neurite outgrowth and supernatant NGF concentration occurring in co‐culture of diabetic cells. Exogenous neuritin treatment ameliorated survivability and functions of diabetic Schwann cells of rats with diabetic neuropathy. Our study may provide a new mechanism and potential treatment for diabetic neuropathy.     

Protective Antioxidant Effects of Amentoflavone and Total Flavonoids from Hedyotis diffusa on H2O2‐Induced HL‐O2 Cells through ASK1/p38 MAPK Pathway

In this study, total flavonoids and total triterpenoid acid were extracted with ethyl acetate from Hedyotis diffusa Willd, and hepatoprotective activities of them and five compounds from total flavonoids against H₂O₂ induced hepatocyte damage on HL‐02 cells were determined. In particular, amentoflavone and total flavonoids had influence on the leakage of ALT, AST, LDH, the activities of SOD and the content of MDA. They effectively reduced the loss of MMP, the release of Cyt C, and then inhibited activation of caspase‐3/caspase‐9 cascade in hepatotoxic cells. The contents of ROS were significantly reduced to inhibit p38 in amentoflavone and flavonoids groups which decreased ASK1 and p‐p38 levels through increasing thioredoxin Trx1 and reductase TrxR1. These results suggesting that the antioxidant protection of amentoflavone and flavonoids might be reducing ROS to inhibit the H₂O₂‐induced upstream of pathway via increasing levels of Trx1 and TrxR1, which were pivotal in blocking the down streaming effectors of ASK1/p38 MAPK pathway and alleviating hepatotoxicity.     

Robust Swing‐Structured Triboelectric Nanogenerator for Efficient Blue Energy Harvesting

Ocean wave energy is a promising renewable energy source, but harvesting such irregular, “random,” and mostly ultra‐low frequency energies is rather challenging due to technological limitations. Triboelectric nanogenerators (TENGs) provide a potential efficient technology for scavenging ocean wave energy. Here, a robust swing‐structured triboelectric nanogenerator (SS‐TENG) with high energy conversion efficiency for ultra‐low frequency water wave energy harvesting is reported. The swing structure inside the cylindrical TENG greatly elongates its operation time, accompanied with multiplied output frequency. The design of the air gap and flexible dielectric brushes enable mininized frictional resistance and sustainable triboelectric charges, leading to enhanced robustness and durability. The TENG performance is controlled by external triggering conditions, with a long swing time of 88 s and a high energy conversion efficiency, as well as undiminished performance after continuous triggering for 4 00 000 cycles. Furthermore, the SS‐TENG is demonstrated to effectively harvest water wave energy. Portable electronic devices are successfully powered for self‐powered sensing and environment monitoring. Due to the excellent performance of the distinctive mechanism and structure, the SS‐TENG in this work provides a good candidate for harvesting blue energy on a large scale.     

喉罩通气下七氟醚全凭吸入麻醉在小儿先天性心脏病介入手术的临床麻醉效果

目的:探讨喉罩通气下七氟醚全凭吸入麻醉在小儿先天性心脏病介入手术的临床麻醉效果。方法:选取2017年4月～2019年5月期间我院收治的行先天性心脏病介入手术患儿98例,根据随机数字表法将其分为对照组(n=49)和研究组(n=49)。对照组给予氯胺酮诱导,全凭丙泊酚维持,面罩吸氧;研究组给予全凭七氟醚诱导、维持,喉罩通气。比较两组患儿麻醉前(T0)、切皮前(T1)、切皮后1 min(T2)、切皮后30 min(T3)、术后(T4)的血流动力学指标[平均动脉压(MAP)、心率(HR)]及应激反应指标[血糖、皮质醇],记录两组患儿手术时间、麻醉诱导时间、术后苏醒时间等围术期指标情况。记录两组围术期不良反应发生情况。结果:研究组手术时间、麻醉诱导时间、术后苏醒时间均短于对照组(P0.05)。两组T0时间点血糖、MAP、皮质醇、HR比较差异无统计学意义(P0.05);对照组T1～T4时间点MAP、血糖、皮质醇、HR均较T0升高(P0.05);研究组T1～T4时间点血糖、MAP、皮质醇、HR与T0时间点比较无差异(P0.05);研究组T1～T4时间点血糖、MAP、皮质醇、HR低于对照组(P0.05)。两组不良反应发生率比较无差异(P0.05)。结论:小儿先天性心脏病介入手术中应用喉罩通气下七氟醚全凭吸入麻醉,诱导迅速且安全、术后苏醒快、手术时间短,可有效维持血流动力学稳定,减少应激反应。     

幽门螺杆菌感染性胃癌组织中cyclinD1、MMP-9的表达及其临床意义

目的:探讨幽门螺杆菌(HP)感染性胃癌组织中细胞周期蛋白D1(cyclinD1)、基质金属蛋白酶-9(MMP-9)的表达及其临床意义。方法:选取2016年12月到2018年6月期间在兰州大学第一医院接受治疗的胃癌患者80例,收集其手术切除的病理组织。采用C-14呼气试验和改良Giemsa染色检测患者HP感染的情况,采用免疫组化法检测胃癌组织中cyclinD1、MMP-9表达情况。分析HP感染、cyclinD1、MMP-9表达与胃癌患者临床病理特征的关系,并分析胃癌患者HP感染与cyclinD1、MMP-9表达的相关性。结果:80例胃癌患者HP感染阳性56例(70.00%),阴性24例(30.00%)。有淋巴结转移、浸润深度为T3+T4的胃癌患者的HP感染阳性率高于无淋巴结转移、浸润深度为T1+T2的胃癌患者(P0.05)。80例胃癌患者cyclinD1阳性表达45例(56.25%),阴性表达35例(43.75%),MMP-9阳性表达65例(81.25%),阴性表达15例(18.75%),TNM临床分期为III+IV期、分化程度为低分化、有淋巴结转移、浸润深度为T3+T4的胃癌患者的cyclinD1、MMP-9阳性表达率明显高于TNM临床分期为I+II期、分化程度为中高分化、无淋巴结转移、浸润深度为T1+T2的胃癌患者(P0.05)。HP感染阳性患者的cyclinD1阳性表达率和MMP-9阳性表达率均明显高于HP感染阴性患者(P0.05)。Pearson相关分析显示,胃癌患者HP感染与cyclinD1、MMP-9表达均呈正相关(P0.05)。结论:胃癌患者的HP感染情况与淋巴结转移、浸润深度有关,cyclinD1和MMP-9的表达与TNM临床分期、分化程度、淋巴结转移、浸润深度有关,且胃癌患者HP感染与cyclinD1、MMP-9表达均呈正相关。