五味子甲素在人肝星状细胞中的抗纤维化作用

目的:研究五味子甲素对人肝星状细胞系LX-2细胞的增殖、纤维化指标及凋亡相关蛋白的影响。方法:采用不同浓度的五味子甲素与肝星状细胞LX-2共孵育,MTT法检测五味子甲素对细胞的抑制作用,RT-PCR法和Western blot法测定纤维化指标I型胶原α亚基1(collagen type I alpha 1,collagen I-1)和α-平滑肌动蛋白(α-smooth muscle actin,α-SMA)的表达量,并检测五味子甲素对凋亡相关蛋白Bcl-2和Bax表达量的影响。结果:五味子甲素在不同浓度时可抑制人肝星状细胞系LX-2细胞的增殖,可降低collagenⅠ和α-SMA的mRNA水平和蛋白表达量(P<0.05),并能降低Bcl-2的mRNA水平和蛋白表达量以及Bcl-2/Bax的比值(P<0.05)。结论:五味子甲素可能通过抑制细胞增殖、降低纤维化指标的表达,从而发挥抗肝纤维化的作用。

肝纤维化治疗的研究进展

肝纤维化是由多种致病因素引起的动态且缓慢的肝组织修复过程的一个代偿反应,是发展到肝硬化甚至肝癌的必经阶段。研究认为早期肝纤维化是可逆的,进行有效的抗肝纤维化治疗具有重要意义。本文就目前肝纤维化治疗的研究进展进行综述。

造血干/祖细胞与肿瘤的关系

新近研究发现,骨髓衍生的造血干/祖细胞(bone marrow-derived hematopoietic stem/progenitor cells)可以不断植入肿瘤,参与肿瘤间质和血管生成;持续存在的炎症环境提供了潜在的致癌性条件,使骨髓衍生干细胞可能成为恶性肿瘤起源细胞。VEGFR1+造血祖细胞(vascular endothelial growth factor receptor1positive hematopoiet-ic progenitor cell,VEGFR1+HPC)在肿瘤转移中可能具有决定性作用,肿瘤细胞先突破原发病灶,进入血流,然后停留在另一个预转移场所,在这个场所中,肿瘤细胞先建立造血干祖细胞簇后生长成瘤。

Regulation of Hematopoietic Activity Involving New Interacting Partners (RRAGC &PSMC2, CKAP4 &MANF and CTR9 &CNTNAP2)

Hematopoietic stem cells (HSCs) are tissue-specific cells giving rise to all mature blood cell types regulated by a diverse group of hematopoietic cytokines and growth factors that influences the survival & proliferation of early progenitors and differentiation mechanisms by modulating the functional activities of HSCs. In this study, the functional yet distinctive role of three novel combinations of gene pairs RRAGC & PSMC2;CKAP4 & MANF;and CTR9 & CNTNAP2 have been newly identified. These novel combinations of genes were confirmed and expressed in K562 human leukemic cell line in the presence of cytokine combination (IL-3, FLT-3 and SCF) using RT-PCR and siRNA-mediated gene knock down strategy. This study signifies the synergistic role of gene pairs in different molecular activities like ubiquitination or proteasomal degradation, calcium mobilization, dopamine signaling.

Template sacrificial controlled synthesis of hierarchical nanoporous carbon@NiCo_(2)S_(4)microspheres for high-performance hybrid supercapacitors

Binary transition metal sulfides are hotly investigated in advanced energy storage devices because of their ultra-high reversible capacity.Nevertheless,the unsatisfied rate capability and cycling stability still hinder their practical application.Herein,hierarchical nanoporous carbon@NiCo_(2)S_(4)(HNCMs@NCS)composites with coreshell flower-like structures were prepared by in situ growing of NiCo_(2)S_(4) nanosheets on HNCMs through a hydro thermal-as sis ted template sacrificial method.Benefiting from a synergistic effect between the NiCo_(2)S_(4)shell with high specific capacity and the HNCMs with unique porous structure,the synthesized flower-like HNCMs@NCS composites exhibit extraordinary electrochemical performances,including a high capacity of 346.9 mAh·g^(-1)at 1 A·g^(-1),superb rate property with86.4%initial capacity at 30 A·g^(-1)and predominant cycle stability with 81.2%capacity retention after 5000 cycles.Furthermore,the resulting HNCMs@NCS cathode was coupled with the chemical-activated HNCMs(AHNCMs)anode to construct a hybrid supercapacitor device.The asfabricated device exhibits superior energy density(49.9 Wh·kg^(-1)at 802 W·kg^(-1))and ultra-high power density(24 kW·kg^(-1)at 29.5 Wh·kg^(-1)).This fascinating result further demonstrates the tremendous prospect of the synthesized HNCMs@NCS composites as high-performance supercapacitor electrode materials.

Long-term engraftment of p18^(INK4C)-deficient hematopoietic stem cells is enhanced in the sublethally-irradiated recipients

Non-myeloablative regimens for host conditioning have been widely used in clinical hematopoietic stem cell transplantation due to their reduced toxicity on the recipients. But a milder conditioning regimen may require a higher engrafting ability of donor stem cells in competing with endogenous stem cells. Thus, new strategies for enhancing the competitiveness of donor stem cells in non-myeloablative recipients would have important implications for current clinical stem cell trans- plantation. It is known that the absence of p18INK4C (p18) gene can enhance the self-renewal potential of hematopoietic stem cells (HSCs). We applied the approach of competitive bone marrow trans- plantation to evaluate the impact of p18 gene deletion on long-term engraftment of HSCs in sub- lethally irradiated hosts. We found that p18?/? HSCs had a significant advantage over wild-type HSCs during long-term engraftment in the mouse recipients that received a sub-lethal irradiation (5-Gy). The engraftment efficiency of p18?/? HSCs in the sub-lethally irradiated recipients was similar to that in the lethally irradiated (10-Gy) recipients. Our current study demonstrates that enhanced engraftment of donor HSCs in the absence of p18 does not strictly depend on the dose of irradiation used for host conditioning. Therefore, p18 might serve as a potential drug target for increasing the efficacy of stem cell transplant in the patients that are preconditioned with either a myeloablative or non-myeloablative regimen.

Role of Liver Progenitor Cell in Liver Regeneration Cellular Cross-Talks and Signals

The liver is well known for its ability to regenerate in response to injury. After partial hepatectomy and some chemicals induced acute liver injury, existing hepatocytes can expand to repair the liver function. While adult liver stem/progenitor cells(LPCs) are evoked and differentiate into functional hepatocytes and cholangiocytes to compensate the damaged liver once hepatocyte proliferation is severely impaired. A number of evidences suggest that adjacent hepatic stellate cells(HSCs) or invading leukocytes may be involved in LPCs directed regeneration through governning two major events including fibrogenic and inflammatory responses respectively or simultaneously. As such, a microenvironment(or "niche") composed of different cell sources or factors presents diversity, which eventually mediates LPCs response to biliary or hepatocellular regeneration. This mini review aims at summarizing the latest development on the roles of HSCs, macrophages and lymphocytes as well as corresponding signaling pathways in liver progenitor cells mediated biliary and hepatocellular regeneration, and discussing therapeutic potential of liver progenitor cells in hepatic diseases.

Lymphoid-biased hematopoietic stem cells and myeloid-biased hematopoietic progenitor cells have radioprotection activity

Radioprotection was previously considered as a function of hematopoietic stem cells(HSCs).However,recent studies have reported its activity in hematopoietic progenitor cells(HPCs).To address this issue,we compared the radioprotection activity in 2 subsets of HSCs(nHSC1 and 2 populations)and 4 subsets of HPCs(nHPC1–4 populations)of the mouse bone marrow,in relation to their in vitro and in vivo colony-forming activity.Significant radioprotection activity was detected in the nHSC2 population enriched in lymphoid-biased HSCs.Moderate radioprotection activity was detected in nHPC1 and 2 populations enriched in myeloid-biased HPCs.Low radioprotection activity was detected in the nHSC1 enriched in myeloid-biased HSCs.No radioprotection activity was detected in the nHPC3 and 4 populations that included MPP4(LMPP).Single-cell colony assay combined with flow cytometry analysis showed that the nHSC1,nHSC2,nHPC1,and nHPC2 populations had the neutrophils/macrophages/erythroblasts/megakaryocytes(nmEMk)differentiation potential whereas the nHPC3 and 4 populations had only the nm differentiation potential.Varying day 12 spleen colony-forming units(day 12 CFU-S)were detected in the nHSC1,nHSC2,and nHPC1–3 populations,but very few in the nHPC4 population.These data suggested that nmEMk differentiation potential and day 12 CFU-S activity are partially associated with radioprotection activity.Reconstitution analysis showed that sufficient myeloid reconstitution around 12 to 14 days after transplantation was critical for radioprotection.This study implied that radioprotection is specific to neither HSC nor HPC populations,and that lymphoid-biased HSCs and myeloid-biased HPCs as populations play a major role in radioprotection.

Hemodialysis bilayer bionic blood vessels developed by the mechanical stimulation of hepatitis B viral X(HBX)genetransfected hepatic stellate cells

Artificial vascular graft(AVG)fistula is widely used for hemodialysis treatment in patients with renal failure.However,it has poor elasticity and compliance,leading to stenosis and thrombosis.The ideal artificial blood vessel for dialysis should replicate the structure and components of a real artery,which is primarily maintained by collagen in the extracellular matrix(ECM)of arterial cells.Studies have revealed that in hepatitis B virus(HBV)-induced liver fibrosis,hepatic stellate cells(HSCs)become hyperactive and produce excessive ECM fibers.Furthermore,mechanical stimulation can encourage ECM secretion and remodeling of a fiber structure.Based on the above factors,we transfected HSCs with the hepatitis B viral X(HBX)gene for simulating the process of HBV infection.Subsequently,these HBX-HSCs were implanted into a polycaprolactonepolyurethane(PCL-PU)bilayer scaffold in which the inner layer is dense and the outer layer consists of pores,which was mechanically stimulated to promote the secretion of collagen nanofiber from the HBX-HSCs and to facilitate crosslinking with the scaffold.We obtained an ECM-PCL-PU composite bionic blood vessel that could act as access for dialysis after decellularization.Then,the vessel scaffold was implanted into a rabbit’s neck arteriovenous fistula model.It exhibited strong tensile strength and smooth blood flow and formed autologous blood vessels in the rabbit’s body.Our study demonstrates the use of human cells to create biomimetic dialysis blood vessels,providing a novel approach for creating clinical vascular access for dialysis.