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S. Kim M.J. Graham R.G. Lee L. Yang S. Kim V. Subramanian J.D. Layne L. Cai R.E. Temel D. Shih A.J. Lusis J.A. Berliner S. Lee 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2019,29(3):306-315
Background and aims
Heparin-binding EGF-like growth factor (HB-EGF) is a representative EGF family member that interacts with EGFR under diverse stress environment. Previously, we reported that the HB-EGF-targeting using antisense oligonucleotide (ASO) effectively suppressed an aortic aneurysm in the vessel wall and circulatory lipid levels. In this study, we further examined the effects of the HB-EGF ASO administration on the development of hyperlipidemia-associated atherosclerosis using an atherogenic mouse model.Methods and results
The male and female LDLR deficient mice under Western diet containing 21% fat and 0.2% cholesterol content were cotreated with control and HB-EGF ASOs for 12 weeks. We observed that the HB-EGF ASO administration effectively downregulated circulatory VLDL- and LDL-associated lipid levels in circulation; concordantly, the HB-EGF targeting effectively suppressed the development of atherosclerosis in the aorta. An EGFR blocker BIBX1382 administration suppressed the hepatic TG secretion rate, suggesting a positive role of the HB-EGF signaling for the hepatic VLDL production. We newly observed that there was a significant improvement of the insulin sensitivity by the HB-EGF ASO administration in a mouse model under the Western diet as demonstrated by the improvement of the glucose and insulin tolerances.Conclusion
The HB-EGF ASO administration effectively downregulated circulatory lipid levels by suppressing hepatic VLDL production rate, which leads to effective protection against atherosclerosis in the vascular wall. 相似文献3.
目的探讨六味能消胶囊联合脂必泰胶囊治疗高脂血症的临床效果。方法选取2017年5月—2018年10月东营市东营区人民医院收治的64例高脂血症患者,随机分为对照组和治疗组,每组各32例。对照组口服脂必泰胶囊,1粒/次,2次/d。治疗组在对照组治疗基础上口服六味能消胶囊,1粒/次,3次/d。两组均连续治疗8周。观察两组的临床疗效,比较两组治疗前后血脂指标、血流变学指标、血小板参数及血清学指标的变化情况。结果治疗后,对照组和治疗组的总有效率分别是75.0%、96.9%,两组比较差异具有统计学意义(P0.05)。治疗后,两组总胆固醇(TC)、非-HDL-C、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平均较治疗前显著降低,而高密度脂蛋白胆固醇(HDL-C)显著升高,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组TC、非-HDL-C、TG、LDL-C水平低于对照组,而HDL-C高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血浆黏度(PV)、红细胞比容(HCT)、聚集指数(RCAI)、平均血小板体积(MPV)、血小板最大聚集率(MAR)均显著降低,而变形指数(RDI)值均显著升高,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,PV、HCT、RCAI、MPV、MAR值均显著低于对照组,而RDI值高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清C反应蛋白(CRP)、内皮素(ET)水平较治疗前均显著降低,而一氧化氮(NO)水平显著增高,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组CRP、ET水平低于对照组,而NO水平高于对照组,两组比较差异有统计学意义(P0.05)。结论六味能消胶囊联合脂必泰胶囊治疗高脂血症具有较好的临床疗效,综合调脂作用显著,可明显纠正患者体内血流变学异常,改善血小板功能及微炎症状态,保护血管内皮功能,具有一定的临床推广应用价值。 相似文献
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Pengkai Cao Yingzhen Niu Chang Liu Xiaomeng Wang Guman Duan Qinghua Mu Xintong Luo Fei Wang 《The Knee》2018,25(1):59-65
Background
Tibial tuberosity–trochlear groove distance(TT-TG) is a measurement to assist in the diagnosis and treatment of patellar instability, however it still has some limitations. Our study was to modify the accepted measurement method and seek a more reliable and standardized method.Methods
The data of 65 healthy controls and 49 patients with bilateral patellar instability from 2010 to 2016 were collected and analyzed by CT. The TT-TG, tibial maximal mediolateral axis (MML), and their ratio [i.e., the modified-TT-TG (M-TT-TG)] were compared between the two groups.Results
The MML (71.9 ± 12.0 vs. 71.3 ± 10.9) was not significantly different between the two groups (P > 0.05). However, the TT-TG(18.1 ± 6.0 vs. 13.1 ± 2.9) and M-TT-TG (0.25 ± 0.08 vs. 0.19 ± 0.04) were significantly different between the two groups (P < 0.05). A TT-TG of > 15 mm was found in 24.5% of healthy controls and 71.5% of patients. The healthy controls with a TT-TG of > 15 mm were compared with the patients; although no significant difference was found in the TT-TG (16.8 ± 1.5 vs. 18.1 ± 6.0), the healthy controls had a significantly larger MML (76.9 ± 12.7 vs. 71.9 ± 10.9) and significantly smaller M-TT-TG (0.22 ± 0.04 vs. 0.25 ± 0.08). A total of 53.1% of patients but only 6.9% of healthy controls had an M-TT-TG of > 0.25.Conclusion
The M-TT-TG is a more reliable and standardized way to measure the effect of the TT-TG with the goal of reducing the false-positive rate associated with the standard measurement technique. The normal M-TT-TG ranges from 0.11 to 0.25, with an M-TT-TG of > 0.25 being associated with patellofemoral malalignment.Level of evidence
III. 相似文献7.
Background
Low-grade malignant endolymphatic sac tumor (ELST) is a rare neoplasm, occurring in the inner ear and invading the temporal bone. This study aims to investigate the clinicopathological features of low-grade malignant ELSTs.Methods
The clinicopathological data of 21 patients with low-grade malignant ELSTs were collected and analyzed.Results
The patients were aged 16–71 years, with an average age of 40.3 years and a median age of 39 years, and the male to female ratio was 1:1.6. There were 13 cases (61.9%) of ELSTs occurring on the left side, 7 cases (33.3%) on the right side, and 1 case (4.8%) on both sides. Blood types O and B were noted in 71.4% of the patients. Immunohistochemistry showed that CK, EMA and Vim were all positive, and S-100 (71.4%, 10/14), CD56 (75.0%, 9/12), NSE (50.0%, 2/4), and GFAP (11.1%, 1/9) were also positive, while Syn, CgA, TTF-1, TG, CD34, and calcitonin were negative. The Ki-67 index was 4.3% on average. Histologically, cells were arranged in a papillary shape often with branches and abundant fibrous axial vessel. Some cells had an expanded different-sized thyroid-follicle-like structure, with the follicles containing red-stained colloids and scallop-like secretary vacuoles. There were expanded cavities. Some cases were in a glandular arrangement, and a few in a nest-like, gland-cystoid arrangement. Most tumors were coated with a monolayer of cubic epithelium, a few cells were flat or columnar, with translucent cytoplasm and light staining. The nuclei were oval, nucleolus was not obvious, chromatin was delicate, and a few nucleoli were small. The tissue was prone to bleeding, with fresh and old bleeding. Approximately half of the patients had necrotic bones, and in some cases the tumor tissue had destroyed the surrounding bone. The background fibrous tissue showed hyperplasia with hyaline degeneration, some had calcification and formation of sandy-gravel bodies. The clinical manifestations were hearing reduction or loss, followed by tinnitus, and accompanied by varying degrees of cranial nerve injury. No patients died during follow-up.Conclusions
Low-grade malignant ELSTs occur most frequently on the left side, with a female preponderance. The disease progressed slowly, with no death, and but relapse in two patients in this series. These tumors are often misdiagnosed. 相似文献8.
Monal Sharma Ranjithkumar Ravichandran Sandhya Bansal Ross M. Bremner Michael A. Smith T. Mohanakumar 《Human immunology》2018,79(9):653-658
Exosomes are extracellular vesicles that express self-antigens (SAgs) and donor human leukocyte antigens. Tissue-specific exosomes can be detected in the circulation following lung, heart, kidney and islet cell transplantations. We collected serum samples from patients who had undergone lung (n?=?30), heart (n?=?8), or kidney (n?=?15) transplantations to isolate circulating exosomes. Exosome purity was analyzed by Western blot, using CD9 exosome-specific markers. Tissue-associated lung SAgs, collagen V (Col-V) and K-alpha 1 tubulin (Kα1T), heart SAgs, myosin and vimentin, and kidney SAgs, fibronectin and collagen IV (Col-IV), were identified using western blot. Lung transplant recipients diagnosed with bronchiolitis obliterans syndrome had exosomes with higher expression of Col-V (4.2-fold) and Kα1T (37.1-fold) than stable. Exosomes isolated from heart transplant recipients diagnosed with coronary artery vasculopathy had a 3.9-fold increase in myosin and a 4.7-fold increase in vimentin compared with stable. Further, Kidney transplant recipients diagnosed with transplant glomerulopathy had circulating exosomes with a 2-fold increased expression of fibronectin and 2.5-fold increase in Col-IV compared with stable. We conclude that circulating exosomes with tissue associated SAgs have the potential to be a noninvasive biomarker for allograft rejection. 相似文献
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Tu X Rhee Y Condon KW Bivi N Allen MR Dwyer D Stolina M Turner CH Robling AG Plotkin LI Bellido T 《BONE》2012,50(1):209-217
Sclerostin, the Wnt signaling antagonist encoded by the Sost gene, is secreted by osteocytes and inhibits bone formation by osteoblasts. Mechanical stimulation reduces sclerostin expression, suggesting that osteocytes might coordinate the osteogenic response to mechanical force by locally unleashing Wnt signaling. To investigate whether sclerostin downregulation is a pre-requisite for load-induced bone formation, we conducted experiments in transgenic mice (TG) engineered to maintain high levels of SOST expression during mechanical loading. This was accomplished by introducing a human SOST transgene driven by the 8 kb fragment of the DMP1 promoter that also provided osteocyte specificity of the transgene. Right ulnae were subjected to in vivo cyclic axial loading at equivalent strains for 1 min/day at 2 Hz; left ulnae served as internal controls. Endogenous murine Sost mRNA expression measured 24 h after 1 loading bout was decreased by about 50% in TG and wild type (WT) littermates. In contrast, human SOST, only expressed in TG mice, remained high after loading. Mice were loaded on 3 consecutive days and bone formation was quantified 16 days after initiation of loading. Periosteal bone formation in control ulnae was similar in WT and TG mice. Loading induced the expected strain-dependent increase in bone formation in WT mice, resulting from increases in both mineralizing surface (MS/BS) and mineral apposition rate (MAR). In contrast, load-induced bone formation was reduced by 70-85% in TG mice, due to lower MS/BS and complete inhibition of MAR. Moreover, Wnt target gene expression induced by loading in WT mice was absent in TG mice. Thus, downregulation of Sost/sclerostin in osteocytes is an obligatory step in the mechanotransduction cascade that activates Wnt signaling and directs osteogenesis to where bone is structurally needed. 相似文献