Juxtacrine interaction of macrophages and bone marrow stromal cells induce interleukin-6 signals and promote cell migration

The bone marrow contains a heterogeneous milieu of cells, including macrophages, which are key cellular mediators for resolving infection and inflammation. Macrophages are most well known for their ability to phagocytose foreign bodies or apoptotic cells to maintain homeostasis; however, little is known about their function in the bone microenvironment. In the current study, we investigated the in vitro interaction of murine macrophages and bone marrow stromal cells （BMSCs）, with focus on the juxtacrine induction of IL-6 signaling and the resultant effect on BMSC migration and growth. The juxtacrine interaction of primary mouse macrophages and BMSCs activated IL-6 signaling in the co-cultures, which subsequently enhanced BMSC migration and increased BMSC numbers. BMSCs and macrophages harvested from IL-6 knockout mice revealed that IL-6 signaling was essential for enhancement of BMSC migration and increased BMSC numbers via juxtacrine interactions. BMSCs were the main contributor of IL-6 signaling~ and hence activation of the IL-6/ gp130/STAT3 pathway. Meanwhile, macrophage derived IL-6 remained important for the overall production of IL-6 protein in the co-cultures. Taken together, these findings show the function of macmphages as co-inducers of migration and growth of BMSCs, which could directly influence bone formation and turnover.

Histone modifications:Targeting head and neck cancer stem cells

Head and neck squamous cell carcinoma(HNSCC) is the sixth most common cancer worldwide, and is responsible for a quarter of a million deaths annually. The survival rate for HNSCC patients is poor, showing only minor improvement in the last three decades. Despite new surgical techniques and chemotherapy protocols, tumor resistance to chemotherapy remains a significant challenge for HNSCC patients. Numerous mechanisms underlie chemoresistance, including genetic and epigenetic alterations in cancer cells that may be acquired during treatment and activation of mitogenic signaling pathways, such as nuclear factor kappa-light-chain-enhancer-of activated B cell, that cause reduced apoptosis. In addition to dysfunctional molecular signaling, emerging evidence reveals involvement of cancer stem cells(CSCs) in tumor development and in tumor resistance to chemotherapy and radiotherapy. These observations have sparked interest in understanding the mechanisms involved in the control of CSC function and fate. Post-translational modifications of histones dynamically influence gene expression independent of alterations to the DNA sequence. Recent findings from our group have shown that pharmacological induction of posttranslational modifications of tumor histones dynamically modulates CSC plasticity. These findings suggest that a better understanding of the biology of CSCs in response to epigenetic switches and pharmacological inhibitors of histone function may directly translate to the development of a mechanism-based strategy to disrupt CSCs. In this review, we present and discuss current knowledge on epigenetic modifications of HNSCC and CSC response to DNA methylation and histone modifications. In addition, we discuss chromatin modifications and their role in tumor resistance to therapy.

可吸收胶原膜在颊侧袋形瓣引导性骨再生手术中的作用:一项回顾性影像学队列研究

目的:在颊侧袋形瓣引导性骨再生手术基础上,探讨放置可吸收胶原膜是否有利于维持术后牙槽嵴轮廓稳定。方法:收集2019年6月至2023年6月因单颗后牙缺失采用种植体植入同期进行颊侧袋形瓣引导性骨再生手术患者,根据骨粉表面是否覆盖胶原膜分为胶原膜覆盖组和无覆盖组。术前(T0)、术后即刻(T1)和术后3~7个月(T2)拍摄锥形束CT,利用Mimics软件测量种植体光滑-粗糙交界面下不同水平(0、2、4和6 mm)处颊侧骨板厚度(thickness of the buccal bone plate,BBT,分别表示为BBT-0、-2、-4、-6)。结果:收集胶原膜覆盖组15例,无胶原膜覆盖组14例,共计29例患者进行统计分析。在T0、T1和T2三个时间点,不同水平的BBT在两组间差异均无统计学意义(P>0.05)。T2时,BBT-0在胶原膜覆盖组和无覆盖组分别为(1.22±0.55)mm和(1.70±0.97)mm,相应的BBT-2分别为(2.32±0.94)mm和(2.57±1.26)mm。T1~T2愈合阶段不同水平处颊侧骨板吸收的绝对值[(0.47±0.54)~(1.33±0.75)mm]和百分数[(10.04%±24.81%)~(48.43%±18.32%)],以及T0~T2阶段颊侧骨板新骨形成厚度[(1.27±1.09)~(2.75±2.15)mm]在两组间差异均无统计学意义。结论:颊侧袋形瓣引导骨再生手术无论是否使用胶原膜均可有效修复种植体颈部颊侧骨缺损。与无胶原膜覆盖相比,胶原膜覆盖植骨材料不能提高术后牙槽嵴轮廓的稳定性。

Tissue-specific melt electrowritten polymeric scaffolds for coordinated regeneration of soft and hard periodontal tissues

Periodontitis is a chronic inflammatory condition that often causes serious damage to tooth-supporting tissues.The limited successful outcomes of clinically available approaches underscore the need for therapeutics that cannot only provide structural guidance to cells but can also modulate the local immune response.Here,three-dimensional melt electrowritten(i.e.,poly(ε-caprolactone))scaffolds with tissue-specific attributes were engineered to guide differentiation of human-derived periodontal ligament stem cells(hPDLSCs)and mediate macrophage polarization.The investigated tissue-specific scaffold attributes comprised fiber morphology(aligned vs.random)and highly-ordered architectures with distinct strand spacings(small 250μm and large 500μm).Macrophages exhibited an elongated morphology in aligned and highly-ordered scaffolds,while maintaining their round-shape on randomly-oriented fibrous scaffolds.Expressions of periostin and IL-10 were more pronounced on the aligned and highly-ordered scaffolds.While hPDLSCs on the scaffolds with 500μm strand spacing show higher expression of osteogenic marker(Runx2)over 21 days,cells on randomly-oriented fibrous scaffolds showed upregulation of M1 markers.In an orthotopic mandibular fenestration defect model,findings revealed that the tissue-specific scaffolds(i.e.,aligned fibers for periodontal ligament and highly-ordered 500μm strand spacing fluorinated calcium phosphate[F/CaP]-coated fibers for bone)could enhance the mimicking of regeneration of natural periodontal tissues.

前列腺癌骨髓小生境：不仅仅是“沃土”

骨髓中的造血干细胞小生境在过去的几十年中已被广泛地研究了，然而支持转移性前列腺癌生长的骨髓微环境，最近才被认为是一种特殊的“小生境”。新研究表明前列腺癌的播散肿瘤细胞事实上以造血千细胞小生境为目标，替换原有“居住者”的造血干细胞，并占据其已有的小生境空间。这篇综述描述了播散肿瘤细胞作为造血干细胞小生境的分子寄生虫的一些证据和机制。再者，播散肿瘤细胞、造血干细胞和小生境的相互作用可能会为小生境导向的疗法提供新的目标，也可进一步解读复杂的转移性前列腺癌疾病的临床表现。