Application of biomaterial scaffolds in the treatment of spinal cord injury北大核心

BACKGROUND: Due to the weak regeneration ability after spinal cord injury, it is still a difficult medical problem to repair the damaged spinal cord tissue and normalize its function. The rapid development of biological tissue materials and its wide application in medicine provide new therapeutic ideas and methods for spinal cord injury repair. OBJECTIVE: To summarize the research situation of biomaterial scaffolds on nerve tissue regeneration and repair after spinal cord injury, and forecast its development trend, so as to explore the methods of spinal cord injury repair and summarize experience. METHODS: The articles published from January 2011 to January 2021 were retrieved using the advanced retrieval function of PubMed database. The search terms were “spinal cord injury, biomaterials, nerve regeneration, material”. By using the advanced retrieval functions of CNKI, Wanfang, VIP and other databases, relevant articles published from January 2011 to January 2021 were searched, and the search terms were “spinal cord injury, biomaterials, scaffolds”. RESULTS AND CONCLUSION: With further development of the combination of bioengineering research and medicine, biomaterial scaffolds have been widely used in the study of spinal cord injury repair, and the histocompatibility and degradation of biomaterials have been improved. There are many kinds of biomaterials, each of which has its own advantages and disadvantages. It is better to prepare composite scaffolds loaded with seed cells, cytokines or drugs for nerve regeneration. However, how to select the composite scaffold material combination, how to select the seed cells, cytokines or drugs, so as to make the biomaterial scaffold combined with seed cells, cytokines or drugs become the best combination value of in-depth research. In conclusion, biomaterial repair of spinal cord injury is a new idea and may become a breakthrough point to promote the repair of spinal cord injury. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Increased endostatin generation and decreased angiogenesis via MMP-9 by tamoxifen in hormone dependent ovarian cancer

There are several similarities between breast and ovarian cancer but anti-estrogen treatment is rarely used in ovarian cancer. We have previously shown that the most widely used anti-estrogen tamoxifen increased MMP-9 activity and endostatin generation in breast cancer. Here, we show that tamoxifen exposure of highly hormone responsive ovarian cancer cells decreased proliferation, and increased MMP-9 activity leading to increased levels of endostatin both in cell culture in vitro and in solid tumors of nude mice. Tamoxifen exposed tumors also exhibited significantly decreased tumor growth and vascularisation. Moreover, in ascites from ovarian cancer patients, MMP-9 was undetectable in majority of cases but a significant correlation of MMP-2 and endostatin was found. The effects on MMPs and endostatin generation are previously unknown mechanisms of estradiol and tamoxifen in ovarian cancer, which may have therapeutic implications in future anti-cancer options of hormone dependent ovarian cancer.     

An in vitro analysis of murine hemopoietic fibroblastoid progenitors and fibroblastoid cell function during aging

We determined the number of fibroblastoid progenitors (fibroblastoid colony-forming units, CFU-F) in femurs and spleens derived from (CBA X C57BL)F1 mice of different ages. The femoral CFU-F population size increased from 350 at 1 week of age and plateaued at approximately 1900 CFU-F at 8 weeks of age. The mean incidence of CFU-F per 10(6) femoral marrow nucleated cells decreased from 82 at 8 weeks of age to 55 at 70 weeks of age; however, due to an increase in femur cellularity, there was no decrease in the CFU-F population size. The splenic CFU-F population decreased from 1700 at 1 week of age to 180 at 8 weeks of age; no further change was observed in mice up to 70 weeks' old. Analysis of colony-stimulating activity production by fibroblastoid colonies derived from young (6 weeks) and aged (70 weeks) mouse femoral marrow demonstrated no difference. These results indicate that there is no change in CFU-F numbers or fibroblastoid cell colony-stimulating activity production associated with the age-related increase in hemopoietic organ cellularity and hemopoietic progenitor content observed in this mouse strain. There were, however, major changes in the CFU-F population sizes during development of both femoral marrow and spleen in the first 2 months after birth.     

树鼩脑缺血半暗区PAF受体介导的微环境改变及GB保护机制的探讨

目的研究树鼩血栓性脑缺血时,血小板活化因子(PAF)受体活化介导的缺血半暗区微环境改变,并探讨PAF受体拮抗剂—银杏内酯B(ginkgolide,GB)的神经保护机制。方法采用光化学诱导树鼩血栓性局部性脑缺血模型,用3H?PAF放射免疫标记法检测缺血区微环境脑细胞PAF受体亲合性(Kd值)和结合特性(Bm ax值)的变化;用密度梯度法及原子吸收分光法分别测定缺血微环境水含量及Na+、Ca2+含量,并于光化学反应后6 h静注GB(5 mg/Kg),观察其对脑血栓形成后24 h时缺血微环境的改善效应。结果树鼩脑血栓形成后缺血半暗区微环境的改变以24 h为著,脑细胞膜高亲和性、低亲和性PAF受体的Kd值及Bm ax值明显降低,其中Kd1及Bm ax1分别为(0.611±0.9)nM和(419.4±72.6)fmol.mg-1蛋白,Kd2及Bm ax2分别为(4.08±0.5)nM和(676.8±98.66)fmol.mg-1蛋白(与对照组相比P<0.01);GB可促使缺血微环境脑细胞PAF受体Kd及Bm ax的恢复,并具有改善局部脑水肿和缓解Ca2+超载(P均<0.01)。结论PAF受体活化在介导缺血半暗区微环境改变中具有重要作用,GB可改善缺血半暗区微环境和逆转PAF受体活化介导的神经元泵功能障碍。     

Half-life of antigen/major histocompatibility complex class II complexes in vivo: intra- and interorgan variations

We have determined the half-life in vivo of antigen/MHC class II complexes in different organ microenvironments. Mice were “pulsed” with myoglobin intravenously and MHC class II-positive antigen-presenting cell (APC) populations from different organs were isolated after various time intervals. Specific antigen/MHC complexes were quantitated by co-cultivation of the APC subsets with myoglobin-specific T-T hybridoma cells in vitro. Half-lives of antigen/MHC complexes differed both between organs and between compartments of the same organ. Half-lives in peripheral organs (spleen and bone marrow) ranged between 3 and 8 h, whereas in the thymus half-lives between 13 h (cortical epithelial cells) and 22 h (medullary dendritic cells) were observed. Half lives in vivo were independent of antigen processing, since intact protein or antigenic peptides yielded similar values. The considerably longer half-life of peptide/MHC complexes in the thymus as compared to peripheral organs may reflect the distinct role which antigen presentation plays in both organs, i.e. induction of tolerance versus induction of immunity.     

大肠癌肿瘤微环境中Th17细胞与调节性T细胞的作用及临床意义

大肠癌是全球最常见的恶性肿瘤之一,大肠癌的发生、发展与肠内慢性炎症(CRC)密切相关,而部分炎症细胞及其分泌的细胞因子在这一过程中扮演着重要角色,肿瘤浸润效应T细胞与多种类型肿瘤病人的预后密切相关,辅助性T细胞17(Th17)是新近发现的一类CD4+效应T细胞亚群,在炎症、自身免疫性疾病和肿瘤中发挥积极作用.调节性T细胞(Tregs)在功能上是T细胞的免疫抑制亚群,在自身免疫耐受和抗肿瘤免疫中起重要作用.Th17细胞和Treg细胞之间的动态平衡在保持免疫调控功能中至关重要.     

肿瘤相关成纤维细胞与肝癌的关系

我国肝病多发,肝癌一直是国民健康的一大威胁,目前临床针对肝癌的防治手段效果欠佳,随着研究的不断深入,学者们将焦点转向了肿瘤微环境中的肿瘤相关成纤维细胞,越来越多的证据表明肿瘤相关成纤维细胞或可为肝癌防治提供全新靶位。现就肿瘤相关成纤维细胞在肝癌发生发展中的作用及在肝癌治疗中的潜力作一综述。     

Evidence for the disruption of the bone marrow microenvironment by combined exposures to inhaled benzene and ingested ethanol

Studies have been performed to investigate the effects of combined in vivo exposures to inhaled benzene and ingested ethanol on the earliest known murine erythropoietic precursor cells, the Burst Forming Unit — Erythroid (BFU-E) and the Colony Forming Unit — Erythroid (CFU-E). Previously we had determined that murine erythropoietic cell populations were particularly susceptible to combined benzene + ethanol treatments. The most striking example of erythropoietic disruption was the transient appearance of large numbers of nucleated red cells (normoblasts) in the circulating blood. In the present studies, male C57B1/6 mice were exposed to 300 ppm benzene via inhalation for 6 h/d×5 d/wk×9 wks. Groups of mice were also exposed to 5% ethanol in the drinking water 4 d/wk×9 wks. Appropriate controls were also maintained. The hematological assays were performed after 1, 4, and 9 weeks of exposure. After 4 weeks of exposure large numbers of normoblasts appeared in the circulating blood of mice exposed to benzene + ethanol. However, there were no corresponding increases in the numbers of the earliest erythroid progenitor cells in the bone marrow. There were, however, marked increases in the numbers of these cells in the spleen. Previous work in this laboratory had confirmed that the marrow was the source of circulating normoblasts among animals exposed to benzene + ethanol. We conclude, therefore, that circulating normoblasts appear in the peripheral blood because of changes in the bone marrow microenvironment rather than as a consequence of increased erythropoietic proliferation in the marrow.     

Validation of a questionnaire and microenvironmental model for estimating past exposures to ozone

Epidemiology studies of the health effects associated with chronic exposure to ozone are constrained by a lack of validated exposure assessment methods that account for activity patterns and building ventilation, two potentially important predictors of ozone exposure. A pilot study was conducted to evaluate the impact of these parameters on an exposure model, to evaluate how reliably they can be reconstructed, and how this reliability affects estimates of past exposures to ozone. Fourteen subjects completed time-activity diaries and wore personal passive monitors during summer 1996 and reconstructed their activities 1 year later in a questionnaire. These data were used in a microenvironmental exposure model and the results were compared to measured personal exposure. A model using activity patterns, building ventilation, and location-specific ambient ozone data produced mean exposure estimates 18.9 +/- 1.5 ppb ozone greater than personal measurements. A simpler model that omitted variation in indoor ventilation produced exposure estimates 5.0 +/- 1.3 ppb ozone greater than mean measured exposures. The questionnaire was a reliable survey method for reconstructing past activity patterns. However, detailed histories of building ventilation may not be required to reconstruct reliably past exposures to ozone. The simple model was more precise and more practical for implementation in large epidemiological studies of health effects related to chronic exposure to ambient ozone.     

New Approaches to the Treatment of Hepatic Malignancies Angiogenesis and Antiangiogenic Therapy of Colon Cancer Liver Metastasis

The fact that tumor growth and metastatic spread relies on angiogenesis has been widely proven and accepted. The understanding of cancer biology and metastasis formation has led to the development of new therapeutic approaches that target tumor biology. The survival and establishment of metastatic lesions depend on a shift in the normal balance of proangiogenic and antiangiogenic factors that favor angiogenesis. Colorectal cancer is one of the leading cancer deaths worldwide. Angiogenesis has been associated with colon cancer progression and metastatic spread, thereby significantly affecting patient survival. New experimental approaches that inhibit angiogenic processes have demonstrated promising antineoplastic effects on metastatic colorectal cancer and are partially being investigated in clinical trials. This review focuses on angiogenesis in colorectal cancer metastasis formation as a target for antiangiogenic therapy, describing the experience from experimental studies and current clinical trials.