Transplant of insulin‐like growth factor‐1 expressing bone marrow stem cells improves functional regeneration of injured rat uterus by NF‐κB pathway

To investigate the potential beneficial effect of insulin‐like growth factor‐1 (IGF‐1) in BMSC transplantation therapy of uterus injury and the underlying molecular mechanisms, rat BMSCs were isolated and cultured. The relative expressions of IGF‐1 and IL‐10 were determined by RT‐PCR and immunoblotting. The secretory IL‐10 and released E2 were measured using ELISA kits. The relative vWF and α‐SMA expressions were determined by immunohistochemistry. The direct binding of NF‐κB subunit p50 with IL‐10 promoter was analysed by chromatin immunoprecipitation assay. The regulation of IL‐10 expression by p50 was interrogated by luciferase reporter assay. Our data demonstrated that IGF‐1 expression in BMSCs induced IL‐10 expression and secretion, which was further enhanced by E2‐PLGA. IGF‐1 overexpression improved BMSCs transplantation therapy in rat uterus injury. We further demonstrated that both inhibition and knockdown of p50 abolished IGF‐1‐induced expression and secretion of IL‐10 in BMSCs, which consequently compromised the IGF‐1 conferred therapeutic benefits against uterus injury. Furthermore, we elucidated that p50 regulated IL‐10 expression via direct association with its promoter. Our data suggested that transplantation of IGF‐1 overexpressing BMSCs improved functional regeneration of injured uterus by inducing IL‐10 expression and secretion via activation of NF‐κB signalling.     

Effect of cell therapy with allogeneic osteoblasts on bone repair of rat calvaria defects

Background aims

Regenerative medicine strategies based on cell therapy are considered a promising approach to repair bone defects. The aims of this study were to evaluate the effect of subculturing on the osteogenic potential of osteoblasts derived from newborn rat calvaria and the effect of these osteoblasts on bone repair of rat calvaria defects.

Phenotypic and functional characterization of mesenchymal stromal cells isolated from pediatric patients with severe idiopathic nephrotic syndrome

Background

Idiopathic nephrotic syndrome (INS) is one of the most common renal diseases in the pediatric population; considering the role of the immune system in its pathogenesis, corticosteroids are used as first-line immunosuppressive treatment. Due to its chronic nature and tendency to relapse, a significant proportion of children experience co-morbidity due to prolonged exposure to corticosteroids and concomitant immunosuppression with second-line, steroid-sparing agents. Mesenchymal stromal cells (MSCs) are multipotent cells that represent a key component of the bone marrow (BM) microenvironment; given their unique immunoregulatory properties, their clinical use may be exploited as an alternative therapeutic approach in INS treatment.

Local delivery of tetramethylpyrazine eliminates the senescent phenotype of bone marrow mesenchymal stromal cells and creates an anti‐inflammatory and angiogenic environment in aging mice

Aging drives the accumulation of senescent cells (SnCs) including stem/progenitor cells in bone marrow, which contributes to aging‐related bone degenerative pathologies. Local elimination of SnCs has been shown as potential treatment for degenerative diseases. As LepR⁺ mesenchymal stem/progenitor cells (MSPCs) in bone marrow are the major population for forming bone/cartilage and maintaining HSCs niche, whether local elimination of senescent LepR⁺ MSPCs delays aging‐related pathologies and improves local microenvironment need to be well defined. In this study, we performed local delivery of tetramethylpyrazine (TMP) in bone marrow of aging mice, which previously showed to be used for the prevention and treatment of glucocorticoid‐induced osteoporosis (GIOP). We found the increased accumulation of senescent LepR⁺ MSPCs in bone marrow of aging mice, and TMP significantly inhibited the cell senescent phenotype via modulating Ezh2‐H3k27me3. Most importantly, local delivery of TMP improved bone marrow microenvironment and maintained bone homeostasis in aging mice by increasing metabolic and anti‐inflammatory responses, inducing H‐type vessel formation, and maintaining HSCs niche. These findings provide evidence on the mechanisms, characteristics and functions of local elimination of SnCs in bone marrow, as well as the use of TMP as a potential treatment to ameliorate human age‐related skeletal diseases and to promote healthy lifespan.     

Micro-CT监测尼古丁对大鼠正畸牙移动过程中牙周改建的影响

目的:探讨不同摄取量的尼古丁对大鼠正畸过程牙周改建的影响。方法:选择120只雄性Wistar大鼠并将其随机分为四组:A组-空白对照,B组-正畸模型,C组-正畸并0.01 mg/m L尼古丁给药,D组-正畸并1 mg/m L尼古丁给药。分别于实验开始后第1、3、7、14、21天通过Micro-CT和HE染色观察模型牙齿移动距离和牙周组织改变并通过ELISA实验检测IL-17的表达。结果:Micro-CT扫描显示:正畸建模组相对于空白对照组在牙移动距离、骨体积分数、骨密度等指标均有明显变化,变化最大幅度发生在D组,B、C两组之间的差异没有统计学意义(P0.05)。21天,D组移动距离达到0.80±0.06 mm,明显高于B、C组(P0.05)。相较于空白对照组(A组),B、C、D三组Micro-CT测量的骨体积分数、骨密度、骨小梁厚度均降低,D组骨密度值降至1108.36±8.86mg/cm3。HE染色结果显示:D组在21天时破骨细胞增多并出现牙根吸收陷窝伴牙周膜纤维排列混乱;ELISA检测显示B、C组IL-17的含量在第7天时达到峰值,D组则在14天含量最高。结论:高浓度的尼古丁可加速正畸牙齿的移动速度及牙槽骨吸收,增加牙周组织中的破骨细胞及IL-17表达水平。     

仙灵骨葆胶囊联合透明质酸钠对膝骨关节炎患者关节功能、炎症因子及生活质量的影响

目的:观察仙灵骨葆胶囊联合透明质酸钠对膝骨关节炎(KOA)患者关节功能、炎症因子及生活质量的影响,为临床用药提供依据。方法:选取我院骨科于2014年12月-2016年12月间收治的72例KOA患者作为研究对象。采用随机数字表法将患者分为透明质酸钠组(采用透明质酸钠治疗,n=36)和联合组(采用仙灵骨葆胶囊与透明质酸钠联合治疗,n=36)。检测并比较两组患者治疗前及治疗1个月后的超敏C反应蛋白(hs-CRP)水平、肿瘤坏死因子-α(TNF-α)水平。分别于治疗前、治疗1个月后以及治疗6个月后采用生活质量调查表(SF-36)中文版评价患者生活质量,同时采用视觉模拟评估法(VAS)以及膝关节功能评定量表(Lysholm)对膝关节功能进行综合评定。治疗结束后随访半年,观察患者不良反应发生情况。结果:治疗1个月后,两组患者hs-CRP、TNF-α水平均明显下降,且联合组患者hs-CRP、TNF-α水平明显低于透明质酸钠组患者(P0.05)。两组治疗6个月后的VAS评分明显低于治疗1个月后的VAS评分,Lysholm评分均明显高于治疗1个月后的Lysholm评分(P0.05)。治疗1个月后和治疗6个月后,联合组患者VAS评分均明显低于透明质酸钠组患者同期VAS评分,而Lysholm评分均明显高于透明质酸钠组患者同期Lysholm评分(P0.05)。两组治疗6个月后SF-36量表各维度评分均高于治疗1个月后的评分(P0.05)。联合组患者治疗1个月后及治疗6个月后的躯体功能、躯体角色功能、躯体疼痛、总体健康、社会功能和心理健康评分均明显高于透明质酸钠组(均P0.05)。两组均无严重不良反应发生,且不良反应发生情况无明显差异(P0.05)。结论:仙灵骨葆胶囊联合透明质酸钠治疗膝骨关节炎对患者炎症反应、关节功能及生活质量有持续的改善作用,同时安全可靠,值得推广应用。     

银杏达莫联合通痹胶囊治疗冠心病心绞痛的临床疗效及对血清IL-1β、TNF-α、ET-1、MMP-9水平的影响

目的:研究银杏达莫联合通痹胶囊治疗冠心病心绞痛的临床疗效及对血清白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、内皮素-1(ET-1)、基质金属蛋白酶-9(MMP-9)水平的影响。方法:选取2015年8月至2016年7月我院收治的84例冠心病心绞痛患者,根据患者入院顺序分为观察组和对照组,42例每组。对照组使用通痹胶囊完成治疗,观察组在此基础上联合银杏达莫完成治疗。比较两组患者临床疗效、心绞痛发作次数、持续时间、ST段下移程度、血清IL-1β、TNF-α、ET-1、MMP-9水平的变化。结果:治疗后,观察组临床总有效率显著高于对照组[92.86%(39/42)比66.67%(28/42)](P0.05);两组患者心绞痛发作次数、持续时间、ST段下移程度、血清IL-1β、TNF-α、ET-1、MMP-9水平均较治疗前显著降低(P0.05),且观察组以上指标均明显低于对照组(P0.05)。观察组和对照组的不良反应发生率比较差异无统计学意义(P0.05)。结论:银杏达莫联合通痹胶囊治疗冠心病心绞痛能有效改善患者临床症状并提高临床疗效,可能与其显著降低患者血清IL-1β、TNF-α、ET-1、MMP-9水平有关。     

Coordinated regulation of the dorsal‐ventral and anterior‐posterior patterning of Xenopus embryos by the BTB/POZ zinc finger protein Zbtb14

During early vertebrate embryogenesis, bone morphogenetic proteins (BMPs) belonging to the transforming growth factor‐β (TGF‐β) family of growth factors play a central role in dorsal–ventral (DV) patterning of embryos, while other growth factors such as Wnt and fibroblast growth factor (FGF) family members regulate formation of the anterior–posterior (AP) axis. Although the establishment of body plan is thought to require coordinated formation of the DV and AP axes, the mechanistic details underlying this coordination are not well understood. Here, we show that a Xenopus homologue of zbtb14 plays an essential role in the regulation of both DV and AP patterning during early Xenopus development. We show that overexpression of Zbtb14 promotes neural induction and inhibits epidermal differentiation, thereby regulating DV patterning. In addition, Zbtb14 promotes the formation of posterior neural tissue and suppresses anterior neural development. Consistent with this, knock‐down experiments show that Zbtb14 is required for neural development, especially for the formation of posterior neural tissues. Mechanistically, Zbtb14 reduces the levels of phosphorylated Smad1/5/8 to suppress BMP signaling and induces an accumulation of β‐Catenin to promote Wnt signaling. Collectively, these results suggest that Zbtb14 plays a crucial role in the formation of DV and AP axes by regulating both the BMP and Wnt signaling pathways during early Xenopus embryogenesis.