趋化因子CXCL5在肾癌中的表达及临床意义

目的:明确趋化因子配体5(CXC-chemokine ligand 5,CXCL5)在肾癌中的表达情况,探讨其与临床病理特征的关系以及在肿瘤预后评估中的意义。方法:通过检索Cbio Portal数据库,分析CXCL5表达与肾癌进展和预后的关系。收集2012年11月至2014年6月天津医科大学肿瘤医院收治的105例肾癌患者的临床病理资料,62例组织标本中CXCL5表达患者作为试验组,选择正常肾脏和癌旁组织标本各20例作为对照组,采用免疫组织化学染色和实时定量RT-PCR法评价。根据CXCL5表达水平将患者分为高、中、低表达组,分析各组的表达情况与临床病理特征之间的关系,利用Kaplan-Meier生存分析评价CXCL5表达与患者术后生存率的关系。结果:数据库中的结果显示,CXCL5突变患者的总生存期与无病生存期明显缩短(P<0.05),疾病复发风险明显增加(P<0.05);而且,CXCL5 mRNA表达水平与肿瘤转移、分期、阳性淋巴结数量、患者总生存状态均有一定相关性。免疫组织化学法结果显示,肾癌组织中CXCL5的表达明显高于正常肾脏组织和癌旁组织(P<0.05);亚组分析显示,CXCL5的表达水平与临床分期、Fuhrman分级呈正相关(P<0.05)。此外,表达CXCL5的肾癌患者5年生存率(65%)明显低于不表达CXCL5的患者(79%),两者比较差异具有统计学意义(P<0.05)。结论:CXCL5在肾癌中高表达,其表达水平与临床分期和病理分级呈正相关,且与不良预后相关。因此,CXCL5有望成为判断肾癌预后的预测指标和新的治疗靶点。

An infusible biologically active adhesive for chemotherapy-related heart failure in elderly rats

Chemotherapy-induced cardiotoxicity with subsequent heart failure(HF)is a major cause of morbidity and mortality in cancer survivors worldwide.Chemotherapy-induced HF is exceptionally challenging as it generally manifests in patients who are typically not eligible for left ventricular device implantation or heart transplantation.To explore alternative treatment strategies for cancer survivors suffering from chemotherapy-induced HF,we developed a minimally invasive infusible cardiac stromal cell secretomes adhesive(MISA)that could be delivered locally through an endoscope-guided intrapericardial injection.To mimic the typical clinical presentation of chemotherapy-induced HF in elder patients,we established an aged rat model in which restrictive cardiomyopathy with sequential HF was induced via consecutive doxorubicin injections.In vitro,we prove that MISA not only enhanced cardiomyocytes proliferation potency and viability,but also inhibited their apoptosis.In vivo,we prove that MISA improved the ventricular contractility indexes and led to beneficial effects on histological and structural features of restrictive cardiomyopathy via promoting cardiomyocyte proliferation,angiogenesis,and mitochondrial respiration.Additionally,we also evaluated the safety and feasibility of MISA intrapericardial delivery in a healthy porcine model with an intact immune system.In general,our data indicates that MISA has a strong potential for translation into large animal models and ultimately clinical applications for chemotherapy-induced HF prior to the final option of heart transplantation.

Advances in biomaterials and regenerative medicine for primary ovarian insufficiency therapy

Primary ovarian insufficiency(POI)is an ovarian dysfunction that affects more than 1%of women and is characterized by hormone imbalances that afflict women before the age of 40.The typical perimenopausal symptoms result from abnormal levels of sex hormones,especially estrogen.The most prevalent treatment is hormone replacement therapy(HRT),which can relieve symptoms and improve quality of life.However,HRT cannot restore ovarian functions,including secretion,ovulation,and fertility.Recently,as part of a developing field of regenerative medicine,stem cell therapy has been proposed for the treatment of POI.Thus,we recapitulate the literature focusing on the use of stem cells and biomaterials for POI treatment,and sum up the underlying mechanisms of action.A thorough understanding of the work already done can aid in the development of guidelines for future translational applications and clinical trials that aim to cure POI by using regenerative medicine and biomedical engineering strategies.

A trifunctional contraceptive gel enhances the safety and quality of sexual intercourse

Current contraceptive methods come with a number of drawbacks,including low efficacy,in the case of commercial contraceptive gels,and a reduction in the quality of sexual intercourse,in the case of condoms.Adding pharmacologically-active agents to contraceptive gels holds the potential to improve sexual experience,and hardbor safety and hygiene.In this study,we fabricated a carbomer-based contraceptive gel consisting of three agents:tenofovir,gossypol acetate,and nitroglycerin(TGN),with pH adjusted to 4.5(to be compatible with the vagina).In vitro,the gossypol component of the contraceptive gel proved to be an effective spermicide.When the concentration of gossypol acetate was 10 mg/ml,the spermicidal ability reached 100%after 30 s.In addition,tenofovir in the gel significantly inhibited lentiviral transfection efficiency in cell-containing media.In 6 pairs of rats,the gel successfully prevented all females from conceiving after successful mating.Moreover,increased sexual frequency and enhanced erection,which were promoted by the nitroglycerin in the components,were observed in male rats that had the gel applied to their penises.This novel TGN contraceptive gel yielded a higher contraceptive success rate than that of the commercial contraceptive gel(Contragel®).In addition,it has the added benefits to prevent sexually transmitted diseases and improve male libido and erectile function during sexual intercourse.Combining three FDA-approved and marketed agents together,our trifunctional TGN gel has a great potential for further translation and commercialization.

In situ cardiac regeneration by using neuropeptide substance P and IGF-1C peptide eluting heart patches

Cardiovascular diseases cause huge socio-economic burden worldwide.Although a mammalian myocardium has its own limited healing capability,scaffold materials capable of releasing stem cell recruiting/engrafting factors may facilitate the regeneration of the infarcted myocardium.The aim of this research was to develop cardiac patches capable of simultaneously eluting substance P(SP)and insulin-like growth factor-1C(IGF-1C)peptide.Polycaprolactone/collagen type 1-based patches with or without SP and IGF-1C peptide were fabricated by co-electrospinning,which exhibited nanofibrous morphology.SP and IGF-1C/SP patches recruited significantly higher numbers of bone marrow-mesenchymal stem cells than that of the negative control and patch-only groups in vitro.The developed patches were transplanted in an infarcted myocardium for up to 14 days.Mice underwent left anterior descending artery ligation and received one of the following treatments:(i)sham,(ii)saline,(iii)patch-only,(iv)IGF-1C patch,(v)SP patch and(vi)IGF-1C/SP patch.SP and IGF-1C/SP patch-treated groups exhibited better heart function and attenuated adverse cardiac remodeling than that of the saline,patch-only and individual peptide containing cardiac patches.SP patch and IGF-1C/SP patch-treated groups also showed higher numbers of CD31-positive vessels and isolectin B4-positive capillaries than that of other groups.IGF-1C/SP-treated group also showed thicker left ventricular wall in comparison to the saline and patch-only groups.Moreover,IGF-1C/SP patches recruited significantly higher numbers of CD29-positive cells and showed less numbers of Tunel-positive cells compared with the other groups.These data suggest that SP and IGF-1C peptides may act synergistically for in situ tissue repair.

Comparison of extruded cell nanovesicles and exosomes in their molecular cargos and regenerative potentials

Extracellular vesicles(EVs)generated from mesenchymal stem cells(MSCs)play an essential role in modulating cell–cell communication and tissue regeneration.The clinical translation of EVs is constrained by the poor yield of EVs.Extrusion has recently become an effective technique for producing a large scale of nanovesicles(NVs).In this study,we systematically compared MSC NVs(from extrusion)and EVs(from natural secretion).Proteomics and RNA sequencing data revealed that NVs resemble MSCs more closely than EVs.Additionally,microRNAs in NVs are related to cardiac repair,fibrosis repression,angiogenesis.Lastly,intravenous delivery of MSC NVs improved heart repair and cardiac function in a mouse model of myocardial infarction.

Light-triggered NO-releasing nanoparticles for treating mice with liver fibrosis

Liver fibrosis, resulting from chronic liver damage and characterized by the accumulation of extracellular matrix (ECM) proteins, is a characteristic of most types of chronic liver diseases. The activation of hepatic stellate cells (HSC) is considered an essential pathological hallmark in liver fibrosis. Although nitric oxide (NO) can effectively induce HSC apoptosis, the systemic administration of NO is ineffective and may cause severe complications such as hypotension. To overcome this limitation, nanoparticles were designed to target HSCs and release NO locally under the exposure of near infrared light (NIR). To achieve this, upconversion nanoparticle (UCNP) cores were enveloped in mesoporous silica shells (UCNP@mSiO2), which were modified with hyaluronic acid (HA-UCNP@mSiO2) and Roussin’s black salt (RBS). HA molecules recognize and bind to CD44 proteins, which are overexpressed on activated HSCs. Under exposure to a 980-nm NIR laser, the UCNP cores convert the 980-nm wavelength into ultraviolet (UV) light, which then energizes the RBS (NO donors), resulting in an efficient release of NO inside of the HSCs. Once released, NO triggers HSC apoptosis and reverses the liver fibrosis. This targeted and controlled release method provides the theoretical and experimental basis for novel therapeutic approaches to treat hepatic fibrosis.