1‐(2‐Hydroxyethyl)‐2‐imidazolidinone,a heparanase and matrix metalloproteinase inhibitor,improves epidermal basement membrane structure and epidermal barrier function

Daily exposure to sunlight is known to affect the structure and function of the epidermal basement membrane (BM), as well as epidermal differentiation and epidermal barrier function. The aim of this study is to clarify whether the inhibition of BM‐degrading enzymes such as heparanase and matrix metalloproteinase 9 (MMP‐9) can improve the epidermal barrier function of facial skin, which is exposed to the sun on a daily basis. 1‐(2‐hydroxyethyl)‐2‐imidazolidinone (HEI) was synthesized as an inhibitor of both heparanase and MMP‐9. HEI inhibited not only the BM damage at the DEJ but also epidermal proliferation, differentiation, water contents and transepidermal water loss abnormalities resulting from ultraviolet B (UVB). This was determined in this study by the use of UVB‐induced human cultured skins as compared with the control without HEI. Moreover, topical application of HEI improved epidermal barrier function by increasing water content and decreasing transepidermal water loss in daily sun‐exposed facial skin as compared with non‐treated skins. These results suggest that the inhibition of both heparanase and MMP‐9 is an effective way to care for regularly sun‐exposed facial skin by protecting the BM from damage.     

Botulinum toxin blocks mast cells and prevents rosacea like inflammation

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

基质金属蛋白酶在子宫内膜异位症患者中的表达水平及在盆腔粘连中的作用

目的分析基质金属蛋白酶(MMPs)在子宫内膜异位症患者中的表达水平及在盆腔粘连中的作用。方法选取2017年1月-2018年12月在温州市人民医院进行腹腔镜手术的60例子宫内膜异位症患者为观察组,选取同期进行腹腔镜手术的30例非子宫内膜异位症患者为对照组。观察组根据术中盆腔粘连程度分为1组(无或仅有轻度盆腔粘连,子宫内膜异位症Ⅰ~Ⅱ期,24例)和2组(中重度盆腔粘连,子宫内膜异位症Ⅲ~Ⅳ期,36例)。采集3组腹腔液和血清,采用ELISA法检测腹腔液及血清基质金属蛋白酶-2 (MMP-2)、基质金属蛋白酶-3 (MMP-3)、基质金属蛋白酶-7 (MMP-7),血清雌二醇(E2)、黄体生成素(LH)、孕酮(P)、卵泡刺激素(FSH),白细胞介素-6 (IL-6)、白细胞介素-8 (IL-8)、肿瘤坏死因子-α(TNF-α)、C-反应蛋白(CRP)水平。结果 1组腹腔液MMP-2、MMP-3、MMP-7水平显著高于对照组,差异有统计学意义(均P<0. 05),2组腹腔液MMP-2、MMP-3、MMP-7水平显著高于1组(均P<0. 05)。1组血清FSH、LH水平显著高于对照组(均P<0. 05),2组血清FSH、LH水平显著高于1组(均P <0. 05)。1组血清E2、P水平显著低于对照组(均P<0. 05),2组血清E2、P水平显著低于1组(均P<0. 05)。1组血清IL-6、IL-8、TNF-α水平显著高于对照组(均P<0. 05),2组血清IL-6、IL-8、TNF-α水平显著高于1组(均P<0. 05)。结论子宫内膜异位症患者腹腔液中MMPs水平升高,可能与盆腔粘连的发生及严重程度相关。     

Exosomes secreted by prostate cancer cells under hypoxia promote matrix metalloproteinases activity at pre-metastatic niches

Approximately, 30 000 men die from prostate cancer (PCa) every year in the United States, mainly due to the metastasis. Thus, the key events associated with PCa metastasis are under rigorous investigation, with recent studies showing that preparation of pre-metastatic niches (PMN) in distant organs is an important step. However, the molecular basis for PMN preparation is still unclear. Hypoxia in primary tumors promotes aggressiveness; however, its precise role in metastasis is not clear. We recently reported that exosomes secreted by PCa cells under hypoxia promote stemness and invasiveness in naïve PCa cells; however, whether these extracellular vesicles also influence PMN remains unknown. In the present study, we isolated exosomes from human PCa PC3 cells under normoxic (21% O₂, exosomes secreted under normoxic condition [Exo^Normoxic]) and hypoxic (1% O₂, exosomes secreted under hypoxic condition [Exo^Hypoxic]) conditions, and characterized their effect (10 µg exosomes, intraperitoneal (IP) treatment every 48 hours for 4 weeks) on key biomarkers associated with PMN in nude mice. Whole animal fluorescence imaging showed that Exo^Hypoxic treatment promotes matrix metalloproteinases (MMPs) activity in several putative metastatic sites. Histological studies confirmed that Exo^Hypoxic treatment enhanced the level of MMP2, MMP9, and extracellular matrix proteins (fibronectin and collagen) as well as increased the number of CD11b+ cells at selective PMN sites. Furthermore, proteomic profiling of exosomes by liquid chromatography/mass spectrometry identified cargo proteins in Exo^Normoxic and Exo^Hypoxic as well as distinct canonical pathways targeted by them. These results suggest that exosomes secreted by PCa cells under hypoxia plausibly remodel distant PMN, and thus, could be a potential target to control metastatic PCa.     

Matrix metalloproteinase 9 (MMP9) level and MMP9 -1562C>T in patients with obstructive sleep apnea: a systematic review and meta-analysis of case-control studies

BackgroundThe peripheral level of matrix metalloproteinase (MMP)-9 and polymorphism of MMP9 -1562C>T in patients with obstructive sleep apnea (OSA) remains controversial. Therefore, the aims of this systemic review and meta-analysis are to assess the MMP9 level in OSA patients and identify the relationship between MMP9 -1562C>T and OSA susceptibility.MethodsThis systematic review was performed following the PRISMA guideline. We searched for studies in major databases, identifying those indexed from inception to July 3, 2019 which related to MMP9 level, MMP9 -1562C>T and OSA. The pooled standardized mean differences (SMDs) and 95% confidence interval (CI) of MMP9 levels were calculated. In addition, the relationship between MMP9 -1562C>T and OSA susceptibility was assessed by three genetic models. The heterogeneity analysis and calculation of the pooled odds ratio (OR) were also performed, followed by quality assessment using the Newcastle-Ottawa Scale (NOS).ResultsIn sum, our review included 15 eligible studies regarding MMP9 level and three regarding MMP9 -1562C>T. The pooled results showed that peripheral level of MMP9 was increased in OSA patients (SMD = 1.37; 95% CI = 1.15–1.59). Furthermore, significant difference of MMP9 level can be found between severe and mild-to-moderate OSA patients (SMD = 28.17; 95% CI = 4.23–52.11) or between moderate-severe and mild OSA (SMD = 36.62; 95% CI = 12.19–61.04). However, no relationship was observed between MMP9 -1562C>T and OSA susceptibility in three genetic models (Homozygote model, OR = 1.37; 95% CI = 0.87–2.18); (Recessive model, OR = 1.42; 95% CI = 0.83–2.42); (Allele model, OR = 1.07; 95% CI = 0.96–1.18).ConclusionsThis systemic review and meta-analysis indicated that the level of MMP9 was increased in patients with OSA and this increase is relevant to OSA severity. Moreover, the relationship between MMP9 -1562 C>T and OSA susceptibility has currently not been proven by current merging values. Further analyses with larger sample size are required to verify these associations.     

南星骨痛凝胶贴膏对兔膝骨关节炎关节形态及血清IL-1、TNF-α、MMP-13、TIMP-1表达的影响

目的观察南星骨痛凝胶贴膏对兔膝骨关节炎关节形态及血清IL-1、TNF-α、MMP-13、TIMP-1表达的影响,探讨南星骨痛凝胶贴膏治疗兔膝骨关节炎可能的作用机制。方法 18只健康6月龄新西兰兔随机分成3组:空白组(A组)、模型组(B组)、骨痛膏治疗组(C组). BC组用3%木瓜蛋白酶关节腔内注射造模后C组给予南星骨痛凝胶贴膏外敷,给药4周后,用Aloka Latheta LCT-200观察兔膝骨关节影像学改变、用ELISA法检测血清IL-1、TNF-α、MMP-13、TIMP-1含量。结果 C组兔膝关节病变程度较B组轻,C组兔血清中IL-1、TNF-α、MMP-13含量较B组降低(P<0. 05),TIMP-1含量较B组升高(P <0. 05)。结论南星骨痛凝胶贴膏能减轻兔膝关节骨关节炎病变程度,对关节软骨有保护作用,其作用机制可能与抑制炎症因子IL-1、TNF-α及MMP-13表达,增加TIMP-1表达有关。     

多西他赛联合基质金属蛋白酶抑制剂SB-3CT对前列腺癌移植瘤生长的影响

目的 探讨多西他赛联合基质金属蛋白酶抑制剂（SB-3CT）对前列腺癌移植瘤生长的影响及其可能的作用机制。方法 用前列腺癌PC-3细胞建立裸鼠皮下移植瘤模型，随机分为SB-3CT组（注射SB-3CT溶液25 mg/kg），联合用药组（SB-3CT 25 mg/kg+静脉注射多西他赛溶液 10 mg/kg）和空白对照组（注射等量生理盐水），每组5只。测量肿瘤体积和质量并绘制生长曲线。免疫组化检测移植瘤组织中PDK1和PFKFB4的表达。结果 联合用药组、空白对照组和SB-3CT组平均瘤体质量比较差异有统计学意义（F=29.556，P=0.001），且联合用药组的肿瘤生长速度明显较空白对照组和SB-3CT组慢。免疫组化结果显示，PDK1在联合用药组、空白对照组和SB-3CT组的染色评分分别为（2.33±0.47） 分、（6.00±0.81） 分和（4.33±0.48） 分，组间比较差异有统计学意义（F=18.200，P=0.003），且联合用药组评分低于SB-3CT组（P=0.017）；PFKFB4在3组的染色评分分别为（5.33±0.49） 分、（11.33±0.47） 分和（9.00±1.41） 分，组间比较差异有统计学意义（F=17.643，P=0.003），且联合用药组评分低于SB-3CT组（P=0.011）。结论 多西他赛联合基质金属蛋白酶抑制剂SB-3CT对前列腺癌移植瘤生长具有抑制作用，糖代谢相关酶PDK1和PFKFB4表达下调可能是潜在的分子机制。     

清热活血方佐治支气管扩张症急性加重期临床观察

目的:探讨中药清热活血方佐治支气管扩张症急性加重期的临床疗效。方法:选取2016年10月至2018年10月广州中医药大学第二临床医学院收治的支气管扩张症急性加重期患者116例作为研究对象,按照随机数字表法随机分为对照组和观察组,每组58例。对照组给予排痰、抗感染等西医常规治疗;观察组在对照组治疗的基础上给予中药清热活血方治疗,疗程均为2周。比较2组治疗前后中医证候评分、动脉血气分析指标、血清基质金属蛋白酶-9(MMP-9)和基质金属蛋白酶抑制剂-1(TIMP-1)水平,并比较2组治疗总有效率。结果:治疗后观察组咳嗽痰多、痰中带血、发热口渴、胸闷气急、舌苔、脉象各项评分均低于对照组(P<0.01),血气分析指标中氧分压(PaO 2)、血氧饱和度(SaO 2)高于对照组(P<0.01),二氧化碳分压(PaCO 2)低于对照组(P<0.01),血清MMP-9水平低于对照组(P<0.01),TIMP-1水平高于对照组(P<0.01),治疗总有效率高于对照组(P<0.05)。结论:中药清热活血方佐治支气管扩张症急性加重期,可有效缓解症状,改善动脉血气指标,调节MMP-9、TIMP-1平衡,提高临床疗效。     

针灸联合龙胆泻肝汤对子宫脱垂患者血清TGF-β1、MMP-2、TIMP-2表达的影响

目的观察针灸联合龙胆泻肝汤治疗子宫脱垂的临床疗效及对患者血清TGF-β1、MMP-2、TIMP-2表达水平的影响。方法 296例子宫脱垂患者随机分为研究组和对照组,每组148例。对照组采用龙胆泻肝汤治疗,研究组在对照组的基础上采用针灸治疗。观察两组治疗前后的盆底功能障碍评分变化、盆底肌力评分变化及血清转化生长因子-β1 (TGF-β1)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶抑制剂-2(TIMP-2)表达水平变化,并比较两组临床疗效。结果研究组愈显率优于对照组(P<0.05)。两组治疗后盆底功能障碍评分较同组治疗前降低,研究组低于对照组,差异有统计学意义(P<0.05)。研究组治疗后盆底肌力评分高于对照组(P<0.05)。两组治疗后血清TGF-β1、MMP-2、TIMP-2表达水平与同组治疗前比较,差异有统计学意义(P<0.05);研究组治疗后血清TGF-β1、TIMP-2表达水平高于对照组(P><0.05),MMP-2表达水平低于对照组(P<0.05)。结论针灸联合龙胆泻肝汤能显著提高PDF患者的临床疗效,缓解患者的临床症状,改善患者血清TGF-β1、MMP-2、TIMP-2的表达水平。