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71.
72.
Dongzheng Gai Jin-Ran Chen James P. Stewart Intawat Nookaew Hasem Habelhah Cody Ashby Fumou Sun Yan Cheng Can Li Hongwei Xu Bailu Peng Tarun K. Garg Carolina Schinke Sharmilan Thanendrarajan Maurizio Zangari Fangping Chen Bart Barlogie Frits van Rhee Guido Tricot John D. Shaughnessy Jr. Fenghuang Zhan 《The Journal of clinical investigation》2022,132(18)
Osteolytic bone disease is a hallmark of multiple myeloma (MM). A significant fraction (~20%) of MM patients do not develop osteolytic lesions (OLs). The molecular basis for the absence of bone disease in MM is not understood. We combined PET-CT and gene expression profiling (GEP) of purified BM CD138+ MM cells from 512 newly diagnosed MM patients to reveal that elevated expression of cystatin M/E (CST6) was significantly associated with the absence of OL in MM. An enzyme-linked immunosorbent assay revealed a strong correlation between CST6 levels in BM serum/plasma and CST6 mRNA expression. Both recombinant CST6 protein and BM serum from patients with high CST6 significantly inhibited the activity of the osteoclast-specific protease cathepsin K and blocked osteoclast differentiation and function. Recombinant CST6 inhibited bone destruction in ex vivo and in vivo myeloma models. Single-cell RNA-Seq showed that CST6 attenuates polarization of monocytes to osteoclast precursors. Furthermore, CST6 protein blocks osteoclast differentiation by suppressing cathepsin-mediated cleavage of NF-κB/p100 and TRAF3 following RANKL stimulation. Secretion by MM cells of CST6, an inhibitor of osteoclast differentiation and function, suppresses osteolytic bone disease in MM and probably other diseases associated with osteoclast-mediated bone loss. 相似文献
73.
目的:使用转基因斑马鱼模型筛选冠心宁片中具有抗血栓活性的组分及药效物质,并探讨其作用机制。方法:将斑马鱼胚胎分为对照组、造模组、给药组及阳性药组,使用苯肼诱导血栓模型。通过荧光显微成像结合血红蛋白染色对冠心宁片各组分抗血栓作用进行定性和定量分析。进一步探寻活性组分中起抗血栓作用的主要成分。最后进行活性氧(ROS)检测及脂质氧化损伤丙二醛(Malondialdehyde,MDA)分析,探讨其抗血栓机制。结果:实验结果显示冠心宁片水溶性组分可显著减少外周血红细胞聚集(P<0.01),增加回心血量,且效果呈剂量依赖性。因多糖为冠心宁片水溶性成分中的主要物质,进一步实验发现丹参多糖和川芎多糖也具有抗血栓活性,且能显著降低斑马鱼的氧化应激水平,丹参多糖还具有下调胚胎脂质过氧化水平的作用。结论:丹参多糖和川芎多糖为冠心宁片水溶性组分中具有抗血栓作用的活性化合物,可能与其抑制氧化应激作用有关,具有开发为抗血栓治疗先导物的潜在应用前景。 相似文献
74.
目的 探讨饮酒对红细胞免疫及其调节功能的影响.方法 对饮酒组(94人)和对照组(62人)健康成人分别检测其红细胞受体花环率(RBC-C3bRR)、红细胞免疫复合物花环率(RBC-ICR)、红细胞免疫增强因子(EF)及抑制因子(IF)的变化.结果 饮酒组的RBC-C3bRR、EF水平低于非饮酒组(P均<0.01),而RBC-ICR水平则高于非饮酒对照组(P<0.01);相关分析表明RBC-C3bRR、EF水平与饮酒量及饮酒时间负相关,而RBC-ICR、IF水平则与被动饮酒量及饮酒时间呈正相关.结论 长期大量饮酒可引起继发性免疫功能低下及降低红细胞免疫调节能力. 相似文献
75.
Yusuf Cem Yilmaz Sefik Can Ipek Muhammet Derda Ozer Tugba Celebi 《Indian journal of ophthalmology》2022,70(5):1556
Purpose:To evaluate corneal densitometry (CD) of patients with arcus senilis (AS) and its association with the serum lipid markers.Methods:This is a cross-sectional, case-control study. The AS diagnosis was made clinically. Forty-five eyes of 45 patients with AS and 38 eyes of 38 age-matched control subjects with no noticeable AS were enrolled in the study. All participants underwent detailed ophthalmologic examination along with corneal Scheimpflug imaging with CD measurement. The evaluated serum lipid markers of the participants included total cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and very-low-density lipoprotein (VLDL). The Spearman correlation analysis was used to correlate the serum lipid values and the CD. P < 0.05 was defined as statistically significant.Results:The male to female ratio was 26/19 and 14/24 in the study and control groups, respectively (P = 0.057). The mean age was 59.56 ± 8.7 and 56.47 ± 8.6 years in the study and control groups, respectively (P = 0.117). The mean total CD values in the zones extending from 2 to 12 mm were higher in the study group than in the control group (P < 0.001). The serum HDL level was found to be significantly decreased in the study group compared to the control group (P = 0.048 and Z = −1.976). There was a significant positive correlation between the serum triglyceride level and the CD value of the outermost zone (10–12 mm) (r = 0.334 and P = 0.025).Conclusion:The CD of patients with AS was found to increase not only in the peripheral zone but also in the cornea’s paracentral zone compared to the healthy controls. The serum triglyceride level should give an insight into the intensity of arcus senilis. The serum HDL levels were decreased in patients with AS. 相似文献
76.
The aim of this study was to examine the effect of chronotype on addictive eating behavior and BMI in university students. A questionnaire on their sociodemographic characteristics and eating habits, as well as the three-factor eating questionnaire (TFEQ) and the morningness-eveningness questionnaire (MEQ), were given to students at Üsküdar University. Data were analyzed with IBM SPSS 26.0. This study included a total of 850 students, 46.8% of whom were male and 53.2% were female. The mean BMI was 22.94 ± 3.30 kg/m2. As the BMI values of students increased, there was a decrease of 25.6% in the TFEQ scores, regardless of gender (s = −0.256; p < 0.001), and an increase of 10.6% in their chronotype scores, meaning that the students tended to be morning types (s = 0.106; p < 0.01). A significantly negative, very weak correlation was found between the students’ TFEQ and MEQ scores (s = −0.123; p < 0.001). The students’ BMI (p < 0.01) and TFEQ scores (p < 0.001) were affected by their MEQ scores in a statistically significant way. It was found that each 1-point increase in the MEQ score led to a 4.0% increase in the BMI score and a 15.8% decrease in the TFEQ score. It was observed that the morning-type students tended to be obese in terms of their BMI, and these students demonstrated fewer addictive eating behaviors. 相似文献
77.
应用体外抗血小板聚集生物活性检测方法,并结合化学指纹图谱进行谱效相关分析,探索何首乌抗血小板聚集的活性物质。采用体外抗血小板聚集法进行检测,何首乌50%乙醇提取物的抗血小板聚集作用强于10%或90%的乙醇提取物,超声提取优于回流提取。对正交试验的不同提取物进行抗血小板聚集活性评价,抑制率在32.03%~74.56%。谱效相关分析结果表明,反式二苯乙烯苷、顺式二苯乙烯苷、儿茶素与抗血小板聚集活性的相关系数较高且具有统计学意义,分别为0.963(P0.01),0.902(P0.01)和0.656(P0.05);进一步对上述3种与活性相关系数较高化合物的单体进行活性验证,均有较好的抗血小板聚集活性;最后根据3种单体化合物在何首乌中的含量差异计算相对活性贡献度可知,反式二苯乙烯苷是何首乌体外抗血小板聚集的主要活性物质。 相似文献
78.
活血祛痰法逆转高血压左心室肥厚的实验研究 总被引:20,自引:0,他引:20
严灿 《中国中医基础医学杂志》1999,(4):25-27
目的探讨活血祛痰治法逆转高血压左心室肥厚(LeftVentricularHypertrophy,LVH)的作用机理。方法采用14周龄自发性高血压大鼠(SpontaneouslyHypertensiveRat,SHR)。观察采用活血祛痰治法及组方治疗前后大鼠血压(BloodPresure,BP)、左室重/体重(LeftVentricularMass/BodyWeight,LVM/BW)、左室壁相对厚度(LeftVentricularWalThickness,LVWT)、心肌Ca2+含量,以及心肌过氧化脂质(Lipidperoxidation,LPO)和超氧化物歧化酶活性(Superoxidedismutase,SOD)等的变化。结果14周龄SHR已形成LVH,心肌Ca2+含量增高,心肌LPO含量升高而SOD活性下降。经活血祛痰治法及其组方治疗后,SHR血压下降,LVH明显消退,心肌Ca2+含量下降,心肌LPO含量下降而SOD活性升高。结论活血祛痰治法及其组方可逆转高血压LVH,其作用机理与其降低血压和心肌Ca2+含量,改善心肌顺应性以及抗氧自由基损伤有关。 相似文献
79.
反复心理应激大鼠血浆和下丘脑单胺神经递质的变化及加味四逆散的影响 总被引:13,自引:0,他引:13
目的 :观察反复心理应激大鼠血浆和下丘脑内DA、5 HT、E、NE的变化以及加味四逆散的影响。方法 :采用限制大鼠活动空间的方法造成反复心理应激的动物模型 ;血浆和下丘脑内DA、5 HT、E、NE含量测定采用电化学高效液相色谱分析方法。结果 :反复心理应激大鼠血浆DA、5 HT含量明显降低 ,NE、E含量则明显升高 ,下丘脑DA和 5 HT含量明显降低。加味四逆散可以升高应激大鼠下丘脑和血浆中DA、5 HT含量 ,并能降低血浆中NE、E含量 ,升高下丘脑和血浆 5 HT/NE以及血浆 5 HT/E ,作用优于人参总皂甙。结论 :加味四逆散可显著增强反复心理应激状态大鼠的抗应激能力 ,其机制与其升高中枢和血浆中 5 HT及DA含量 ,降低血浆中NE和E含量有关。 相似文献
80.
Chuan Xie Siyu Zhang Wei Zhang Chunxia Wu Can Yong Yuhao Sun Zhengxing Zeng Qian Zhang Zixin Huang Tian Chen Yuanyuan Zhang 《Chemical biology & drug design》2020,96(2):836-849
The issue of antibiotic resistance is becoming progressively serious these days, and the feasible solution to address it is to develop and discover novel antibiotics. The diterpene natural pleuromutilin is a prominent candidate for its special mode of action by inhibiting protein synthesis. In this study, a series of novel pleuromutilin derivatives with chalcone moiety was designed and synthesized, and their antibacterial activities were assessed in vitro. As suggested from the results, most of compounds exhibited potent activities against two methicillin‐resistant Staphylococcus aureus (MRSA) ATCC 33591 and 43300. The further modification of the chalcone structure, aza‐cyclic derivatives were afforded and then assessed, and potent activities against the tested strains were reported. The preliminary docking studies were conducted to explore the interactions between target molecules and binding site. 相似文献