Bilobalide alleviates IL‐17‐induced inflammatory injury in ATDC5 cells by downregulation of microRNA‐125a

Ankylosing spondylitis (AS) is a high disability and greatly destructive disease. In this study, we preliminarily studied the function and mechanism of bilobalide (BIL) on interleukin (IL)‐17‐induced inflammatory injury in ATDC5 cells. CCK‐8 and migration assays were used to detect the functions of IL‐7, BIL, and microRNA (miR)‐125a on cell viability and migration. The miR‐125a level was changed by transfection, and tested by real‐time quantitative polymerase chain reaction. Additionally, Western blot tested the levels of inflammatory factors (IL‐6 and tumor necrosis factor‐α), matrix metalloproteinases (MMPs), and pathway‐related proteins. Moreover, the enzyme‐linked immunosorbent assay also was used to detect inflammatory factor levels. IL‐7 was used to construct an inflammatory injury model in ATDC5 cells. Based on this, BIL inhibited IL‐17‐induced cell viability, migration, and expressions of inflammatory factors and MMPs. Furthermore, we found BIL negatively regulated miR‐125a, and the miR‐125a mimic could partly reverse the effects of BIL on IL‐17‐injury. Finally, we showed that BIL inhibited the c‐Jun N‐terminal kinase (JNK) and nuclear factor kappa B (NF‐κB) pathways, and the miR‐125a mimic had the opposite effect. BIL inhibited IL‐17‐induced inflammatory injury in ATDC5 cells by downregulation of miR‐125a via JNK and NF‐κB signaling pathways.     

癫痫模型大鼠海马CA1网络theta节律断裂的观察*

目的:探究尖波间期和无尖波恢复期颞叶癫痫大鼠模型的海马CA1网络theta节律随癫痫发展进程的变化规律。方法:14只成年雄性Wistar大鼠(200～250 g)麻醉后开颅,在海马的背侧埋入一个双极性钢电极(直径小于1 mm),在颅骨上埋入三个不锈钢皮质电极,在左和右额皮质内分别植入两个电极,在小脑埋入参考电极,粘合颅骨,检测、记录大鼠脑电图;之后腹腔注射癫痫诱发药物,匹罗卡品氢氯化物(pilocarpine hydrochloride,310 mg/kg),30 min后给予大鼠莨菪碱 (scopolamine, 1 mg/kg);借助14只大鼠在嗅行(exploration)时脑深部记录(SEEG),应用Gabor小波时频能量分析估算断裂段数(以350 ms为1段),与总段数的比值定义为断裂比,用来衡量theta节律断裂程度,分别计算了癫痫发展进程的早期(D7)和晚期(D25)中两个邻近尖波之间时间段(定义为尖波间期)和随后无尖波恢复期theta节律断裂比,与注射前脑电图比较。结果:① 与对照脑电图比较,癫痫诱发大鼠的D7和D25的theta节律断裂比显著升高(P＜0.05),并且D7远高于晚期D25;② 在无尖波恢复期,theta节律断裂比与尖波间期相当 (P＜0.05)。结论:癫痫尖波直接导致了theta节律断裂,断裂程度将随癫痫发展进程而动态变化,早期伤害尤其严重。     

Linkage and pyranosyl ring twisting in cyclodextrins

Acylated beta-cyclodextrins (beta-CDs) were studied to gain perspective on maltose octapropanoate, the crystal structure of which was reported in the preceding paper in this issue. Acylated beta-CDs are distorted so we looked at other CDs and gained increased understanding of distortion in CDs and possibly, shapes in starch. Classic CDs have six to eight glucose residues in a doughnut shape that is stabilized by a ring of inter-residue O3,,,O2' hydrogen bonds. On a phi,psi energy map for a maltose analog that does not form hydrogen bonds, classic CD linkages have higher energies than structures that are stabilized by the exo-anomeric effect. In distorted beta-CDs, which lack hydrogen bonding, some linkages attain low-energies from the exo-anomeric effect and acyl stacking. Those linkages result in left-handed helical geometry so other linkages are forced by the CD macrocycle to have counter-balancing right-handed character. Permethylated gamma-CDs have two 'flipping' linkages as do some larger native CDs. Flipping linkages allow two left-handed segments to join into a macrocycle, thus avoiding the higher-energy, right-handed forms. Some glucose rings in derivatized beta-CDs have substantial positive twists of the pseudo torsion angle O1-C1...C4-O4, adding right-handed character to balance the left-handed linkages. In substituted gamma-CD, all residues have negative twists, giving extra left-handed character to the short, pseudo-helical segments. In non-macrocyclic molecules the twists ranged from -14 degrees to +2 degrees , averaging -6.1 degrees. In these beta- and gamma-CDs, the twists ranged from -22 degrees to +16 degrees for (4)C(1) rings, and the (O)S(2) ring in acetylated beta-CD has a twist of +34 degrees . Glucose residues in other CDs were less twisted.     

Cellular-automata models of solid-liquid interfaces

A series of cellular-automata (CA) models have been created, simulating relationships between water (or aqueous solutions) and solid surfaces of differing hydropathic (i.e., hydrophilic or hydrophobic) nature. Both equilibrium- and dynamic-flow models were examined, employing simple breaking and joining rules to simulate the hydropathic interactions. The CA simulations show that water accumulates near hydrophilic surfaces and avoids hydrophobic surfaces, forming concave-up and concave-down meniscuses, resp., under equilibrium conditions. In the dynamic-flow simulations, the flow rate of water was found to increase past a wall surface as the surface became less hydrophilic, reaching a maximum rate when the solid surface was of intermediate hydropathic state, and then declining with further increase in the hydrophobicity of the surface. Solution simulations show that non-polar solutes tend to achieve higher concentrations near hydrophobic-wall surfaces, whereas other hydrophobic/hydrophilic combinations of solutes and surfaces do not show such accumulations. Physical interpretations of the results are presented, as are some possible biological consequences.     

妊娠早期流产的阴道超声影像表现及与血清瘦素、ADAM12、CA-125水平的相关性研究

摘要 目的：探讨妊娠早期流产的阴道超声影像表现及与血清瘦素、融合素 -α（ADAM12）、糖类抗原 -125（CA-125）的相关性。方法：选取 2017年 7月 -2020年 9月于我院就诊的 419例具有早期先兆流产征象的孕妇患者,按妊娠结局分为妊娠早期流产组（流产组,61例）和正常早期妊娠组（正常组,358例）。所有患者均进行阴道超声检查,观察卵黄囊的大小和形态。测定胎儿冠臀长（CRL）、胎囊直径（GSD）、卵黄囊直径（YSD）和胎心率（FHR）。同时检测患者血清瘦素、ADAM12、CA-125水平。采用 Spearman秩相关分析评价阴道超声影像学表现与血清瘦素、ADAM12、CA-125水平的相关性。结果：正常组孕妇超声影像表现可见孕囊形态饱满,孕周和胎芽大小相符,可清晰显示原始心管、卵黄囊和胎心波动。流产组孕妇部分超声影像表现可见卵黄囊过大、过小或未见显示,胎芽略小,卵囊位置位于宫腔中下段,孕囊外形稍欠规则,同时可见原始心管或胎心波动。流产组孕妇平均 CRL、GSD、FHR均显著低于正常组,差异均有统计学意义（P＜0.05）;流产组患者平均 YSD稍低于常组,差异有统计学意义（P＜0.05）。流产组孕妇各孕周 CRL、GSD、FHR均显著低于正常组,差异均有统计学意义（P＜0.05）;流产组患者第 6-7周 YSD高于正常组、第8-9周和第 10-11周 YSD低于正常组,差异均有统计学意义（P＜0.05）。流产组患者血清瘦素、ADAM12水平明显低于正常妊娠组,差异有统计学意义（P＜0.05）,流产组患者血清 CA-125水平明显高于正常妊娠组,差异有统计学意义（P＜0.05）。妊娠早期流产患者阴道超声参数 CRL、GSD、FHR与血清瘦素、ADAM12呈正相关（P＜0.05）,与 CA-125水平呈负相关（P＜0.05）。结论：妊娠早期阴道超声及血清瘦素、ADAM12、CA-125可作为早期流产的有效预测因素,阴道超声参数 CRL、GSD、FHR与血清瘦素、ADAM12、CA-125水平具有相关性,临床可通过测定这些指标以提高妊娠早期流产预测的准确性。     

丁苯酞对颈动脉狭窄大鼠认知功能及海马CA1区神经元凋亡的影响及相关机制研究

摘要 目的：探讨与研究丁苯酞对颈动脉狭窄大鼠认知功能及海马CA1区神经元凋亡的影响及相关机制。方法：将颈动脉狭窄大鼠大鼠（n=42）随机为三组-模型组、低剂量丁苯酞（20 mg/kg）组和高剂量丁苯酞（40 mg/kg）组,每组14只。低剂量丁苯酞组与高剂量丁苯酞组每天给予20 mg/kg、40 mg/kg丁苯酞灌胃治疗,对照组给予等剂量的生理盐水灌胃,持续21 d。结果：低剂量丁苯酞组与高剂量丁苯酞组治疗第7 d、第14 d、第21 d的BBT评分低于模型组（P<0.05）,高剂量丁苯酞组低于低剂量丁苯酞组（P<0.05）。低剂量丁苯酞组与高剂量丁苯酞组治疗第21 d、第28 d的海马CA1区神经元凋亡指数低于模型组,高剂量丁苯酞组低于低剂量丁苯酞组（P<0.05）。低剂量丁苯酞组与高剂量丁苯酞组治疗第21 d、第28 d的脑组织超氧化物歧化酶（Superoxide dismutase,SOD）活性高于模型组（P<0.05）,丙二醛（Malondialdehyde,MDA）活性低于模型组（P<0.05）,高剂量丁苯酞组与低剂量丁苯酞组对比差异都有统计学意义（P<0.05）。低剂量丁苯酞组与高剂量丁苯酞组治疗第21 d、第28 d的海马CA1区BCL2-Associated X（Bax）、B淋巴细胞瘤-2（B-cell lymphoma-2,bcl-2）蛋白相对表达水平高于模型组（P<0.05）,高剂量丁苯酞组高于低剂量丁苯酞组（P<0.05）。结论：丁苯酞在颈动脉狭窄大鼠的应用能提高海马CA1区Bax、Bcl-2蛋白的表达,抑制神经元的凋亡,改善氧化应激状态,从而提高大鼠的认知功能。     

Microvesicles-mediated communication between endothelial cells modulates,endothelial survival,and angiogenic function via transferring of miR-125a-5p

Endothelial cells (ECs) released microvesicles (EMVs) could modulate the functions of target cells by transferring their microRNAs (miRs). We have reported that miR-125a-5p protected EC function. In this study, we determined whether EMVs provided beneficial effects on ECs by transferring miR-125a-5p. Human brain microvessel ECs were transfected with miR-125a-5p mimic or miR-125a-5p short hairpin RNA to obtain miR-125a-5p overexpressing ECs and miR-125a-5p knockdown ECs, and their derived EMVs. For the functional study, ECs or hypoxia/reoxygenation injured ECs were coincubated with various EMVs. The survival and angiogenic function of ECs were measured. Western blot and quantitative real time polymerase chain reaction (qRT-PCR) were used for measuring the levels of phosphoinositide 3-kinase (PI3K), phosphorylation-Akt (p-Akt)/Akt, p-endothelial nitric oxide synthase (p-eNOS), cleaved caspase-3, and miR-125a-5p. PI3K inhibitor was used for pathway analysis. EMVs promoted the proliferation, migration, and tube formation ability of ECs, and alleviated the apoptotic rate of ECs. These effects were associated by an increase in p-Akt/Akt and p-eNOS, and a decrease in cleaved caspase-3 could be abolished by LY294002. Overexpression or downregulation of miR-125a-5p in EMVs promoted or inhibited those effects of EMVs. EMVs could enhance the survival and angiogenic function of ECs via delivering miR-125a-5p to modulate the expression of PI3K/Akt/eNOS pathway and caspase-3.