How the interplay among the tumor microenvironment and the gut microbiota influences the stemness of colorectal cancer cells

Colorectal cancer(CRC)remains the third most prevalent cancer disease and involves a multi-step process in which intestinal cells acquire malignant characteristics.It is well established that the appearance of distal metastasis in CRC patients is the cause of a poor prognosis and treatment failure.Nevertheless,in the last decades,CRC aggressiveness and progression have been attributed to a specific cell population called CRC stem cells(CCSC)with features like tumor initiation capacity,self-renewal capacity,and acquired multidrug resistance.Emerging data highlight the concept of this cell subtype as a plastic entity that has a dynamic status and can be originated from different types of cells through genetic and epigenetic changes.These alterations are modulated by complex and dynamic crosstalk with environmental factors by paracrine signaling.It is known that in the tumor niche,different cell types,structures,and biomolecules coexist and interact with cancer cells favoring cancer growth and development.Together,these components constitute the tumor microenvironment(TME).Most recently,researchers have also deepened the influence of the complex variety of microorganisms that inhabit the intestinal mucosa,collectively known as gut microbiota,on CRC.Both TME and microorganisms participate in inflammatory processes that can drive the initiation and evolution of CRC.Since in the last decade,crucial advances have been made concerning to the synergistic interaction among the TME and gut microorganisms that condition the identity of CCSC,the data exposed in this review could provide valuable insights into the biology of CRC and the development of new targeted therapies.

Tumor microenvironment involvement in colorectal cancer progression via Wnt/β-catenin pathway:Providing understanding of the complex mechanisms of chemoresistance

Colorectal cancer(CRC)continues to be one of the main causes of death from cancer because patients progress unfavorably due to resistance to current therapies.Dysregulation of the Wnt/β-catenin pathway plays a fundamental role in the genesis and progression of several types of cancer,including CRC.In many subtypes of CRC,hyperactivation of theβ-catenin pathway is associated with mutations of the adenomatous polyposis coli gene.However,it can also be associated with other causes.In recent years,studies of the tumor microenvironment(TME)have demonstrated its importance in the development and progression of CRC.In this tumor nest,several cell types,structures,and biomolecules interact with neoplastic cells to pave the way for the spread of the disease.Cross-communications between tumor cells and the TME are then established primarily through paracrine factors,which trigger the activation of numerous signaling pathways.Crucial advances in the field of oncology have been made in the last decade.This Minireview aims to actualize what is known about the central role of the Wnt/β-catenin pathway in CRC chemoresistance and aggressiveness,focusing on crosscommunication between CRC cells and the TME.Through this analysis,our main objective was to increase the understanding of this complex disease considering a more global context.Since many treatments for advanced CRC fail due to mechanisms involving chemoresistance,the data here exposed and analyzed are of great interest for the development of novel and effective therapies.

水分胁迫对美国凌霄单叶水分利用效率的影响

利用CIRAS-2型便携式光合作用仪对水分胁迫下3年生美国凌霄(Campsis radicans L.Seen)单叶水分利用效率(WUEleaf)的日动态及其与微环境因子的关系进行了测定分析,以阐明其WUEleaf对土壤水分及光照强度的响应规律,探讨美国凌霄维持较高WUEleaf所需的土壤水分和光照条件。结果表明:(1)随着水分胁迫的加重,美国凌霄WUEleaf表现为减弱趋势,但适度的水分胁迫有利于WUEleaf的提高。(2)水分胁迫下,美国凌霄WUEleaf多与空气相对湿度、大气CO2浓度呈极显著正相关,与饱和水汽压差、大气温度、叶温呈极显著负相关;微环境因子对美国凌霄WUEleaf的影响较为复杂,其中大气CO2浓度、胞间CO2浓度、叶温对其影响较大。(3)维持美国凌霄较高WUEleaf的适宜土壤含水量为10.7%～23.1%(相对含水量为39.2%～84.6%),适宜光照强度在600～1 600μmol·m-2·s-1之间。

白桦不同方向功能叶片对微环境因子的光合响应

研究了白桦(Betulaplatyphylla)不同方向功能叶片(东向和南向)以净光合速率(Pn)为主要特征的光合作用日进程响应及净光合速率对环境因子的强度响应。结果表明,白桦的净光合速率与光合有效辐射(PAR)极显著相关(P<0.01),与气温(Ta)显著相关(P<0.05),而与大气相对湿度(RH)不相关。并首次提出了植物功能叶片“微环境”的概念。

Characteristics and regulation of mesenchymal stem cell plasticity by the microenvironment-specific factors involved in the regulation of MSC plasticity

Mesenchymal stem cells(MSCs),multipotent stromal cells,have attracted exten-sive attention in the field of regenerative medicine and cell therapy due to the capacity of self-renewal,multilineage differentiation,and immune regulation.MSCs have different cellular effects in different diseases,and even have markedly different curative effects with different tissue sources,indicating the plasticity of MSCs.The phenotypes,secreted factors,and proliferative,migratory,differentiating,and immunomodulatory effects of MSCs depend on certain mediators present in their microenvironment.Understanding microenvironmental factors and their internal mechanisms in MSC responses may help in subsequent prediction and improvement of clinical benefits.This review highlighted the recent advances in MSC plas-ticity in the physiological and pathological microenvironment and multiple microenviron-mental factors regulating MSC plasticity.It also highlighted some progress in the underlying molecular mechanisms of MSC remodeling in the microenvironment.It might provide refer-ences for the improvement in vitro culture of MSCs,clinical application,and in vivo induction.Copyrightª2020,Chongqing Medical University.Production and hosting by Elsevier B.V.This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).

胆汁淤积性肝硬化来源的微环境因子对肝脏干细胞分化的影响

该研究探讨了胆汁淤积性肝硬化病理微环境来源的细胞因子在胆总管结扎小鼠不同时间点的表达变化,且在体外致力寻找最优的细胞因子组合高效诱导肝脏干细胞HP14-19分化为成熟肝细胞。以Balb/c小鼠胆总管结扎(bile duct ligation,BDL)模拟胆汁淤积性肝硬化病理微环境;免疫组织化学检测胆总管结扎小鼠肝组织中细胞因子EGF、HGF及TGF-α的表达;以小鼠胚胎肝干细胞HP14-19细胞为研究对象,以不同浓度在不同时间点进行荧光素酶报告基因检测ALB-Gluc活性;qRT-PCR、Western blot检测肝细胞相关标志物表达;吲哚菁绿(indocyanine green,ICG)及过碘酸–希夫(periodicacid-schiff,PAS)染色检测肝细胞的成熟功能。结果显示,小鼠胆总管结扎能成功模拟胆汁淤积性肝硬化,并随结扎时间延长肝硬化程度加重;与对照相比,在EGF(10 ng/mL)、HGF(20 ng/mL)、TGF-α(20 ng/mL)单独诱导HP14-19细胞能有效增强ALB-Gluc活性(P<0.05);且在EGF(10 ng/mL)、HGF(20 ng/mL)、TGF-α(20 ng/mL)联合诱导HP14-19细胞时显著增强ALBGluc活性(P<0.05);qRT-PCR、Western-blot显示,ALB、CK18表达随时间增加而增加,而AFP表达则相反。ICG摄取及PAS染色阳性细胞数显著增加(P<0.05)。因此,胆汁淤积性肝硬化病理微环境来源的细胞因子能有效促进肝脏干细胞肝向分化,将对细胞因子联合肝脏干细胞移植治疗胆汁淤积性肝硬化有一定的指导意义。

蛋白质分子间相互作用影响土大黄苷-蛋白质组相互作用的研究

荧光光谱结合全反射傅立叶红外光谱研究土大黄苷(rhaponticin,RT)与混合蛋白质组[BSA(bovine serum albumin)-BLF(bovine lactoferrin)]的相互作用,分析其相互作用的影响因子。荧光光谱实验表明,药物RT猝灭混合蛋白质组的荧光强度,蛋白质组的最大发射波长明显红移,表明RT与蛋白质组之间存在着相互作用,该相互作用受蛋白质组中单组分蛋白质分子间相互作用及不同组分蛋白质分子间相互作用的影响。本工作建议用总体微环境因子(IOM)来定量表达影响RT-混合蛋白质组之间相互作用的溶液微环境因素。全反射傅立叶红外光谱法实验表明,药物RT与混合蛋白质组的相互作用过程中,蛋白质组中各组分蛋白质分子二级构象均发生了变化,分子结构不同,构象变化程度差异明显。蛋白质组中单组分蛋白质分子间的相互作用影响蛋白质分子二级构象变化,浓度与比例不同,相互作用不同,影响分子构象变化程度不同。荧光光谱与红外光谱结果基本一致,可为研究RT与BSA-BLF蛋白质组相互作用提供探讨性参考。