Adjusting the Balance between Effective Loading and Vector Migration of Macrophage Vehicles to Deliver Nanoparticles

The nature of macrophage allows the possibility that this cell type could be used as drug delivery system to track therapeutic drug nanoparticles (NPs) in cancer. However, there is no existing research on the regulation between effective loading of NPs and targeted delivery of macrophages. Here, we investigated the important parameters of intracellular NP quantity and the vector migration rate. Macrophage loading capacity was obtained by comparing the uptake quantity of varisized NPs, and the delivery ability of loaded cells was determined by measuring vector migration rates. We observed a positive correlation between the size of NPs and directed macrophage migration. Our findings suggest that the molecular mechanism of migration vector rate regulation involved increased expression levels of colony-stimulating factor-1 (CSF-1) receptor and integrin induced by 100-nm and 500-nm particles. The ability of macrophages uptake to varisized NPs showed the opposite trend, with the increased vector rate of cell migration influenced by NPs. We are able to demonstrate the important balance between effective macrophage loading and targeted delivery. By adjusting the balance parameters, it will be possible to utilize NPs in macrophage-mediated disease diagnosis and therapy.     

乏情和发情初产母猪下丘脑–垂体–卵巢轴中lincRNAs表达谱比较分析

初产母猪断奶后能否正常发情对养猪生产影响重大,也是初产母猪被淘汰的主要原因。本研究以乏情和发情初产母猪为研究对象,首次利用RNA-seq技术对其下丘脑-垂体-卵巢轴中的基因间长链非编码RNAs(long intergenic noncoding RNAs,lincRNAs)进行筛选比较,得到lincRNAs的表达图谱,并对其特征和功能进行了初步分析。结果显示,在乏情和发情初产母猪下丘脑–垂体–卵巢轴中鉴定得到3519个lincRNAs,以发情组为对照共有17个lincRNAs存在差异表达,其中12个表达上调,5个表达下调(FC≥2,P<0.05)。选择4个差异表达的lincRNAs经qRT-PCR验证,其表达水平与测序结果基本一致。对这17个差异表达的lincRNAs进行GO分析、KEGG通路分析及lincRNA-mRNA共表达网络分析,发现这些lincRNAs主要与猪卵母细胞减数分裂成熟、卵巢细胞分化及颗粒细胞凋亡等生殖活动相关。本研究结果丰富了猪lincRNAs数据资源,为进一步深入研究初产母猪的生殖机能提供了理论依据。     

SmMYB98b positive regulation to tanshinones in Salvia miltiorrhiza Bunge hairy roots

Plant Cell, Tissue and Organ Culture (PCTOC) - Tanshinones are major secondary metabolites in Salvia miltiorrhiza Bunge, the traditional Chinese medicinal plant Danshen. Increasing the production...     

Transforming growth factor-β promotes the function of HIV-specific CXCR5+CD8 T cells

HIV replication can be inhibited by CXCR5⁺CD8 T cells (follicular cytotoxic T cell [TFC]) which transfer into B-cell follicles where latent HIV infection persists. However, how cytokines affect TFC remain unclear. Understanding which cytokines show the ability to affect TFC could be a key strategy toward curing HIV. Similar mechanisms could be used for the growth and transfer of TFCs and follicular helper T (TFH) cells; as a result, we hypothesized that cytokines IL-6, IL-21, and transforming growth factor-β (TGF-β), which are necessary for the differentiation of TFH cells, could also dictate the development of TFCs. In this work, lymph node mononuclear cells and peripheral blood mononuclear cells from HIV-infected individuals were cocultured with IL-6, IL-21, and TGF-β. We then carried out T-cell receptor (TCR) repertoire analysis to compare the differences between CXCR5^– and CXCR5⁺CD8 T cells. Our results showed that the percentage and function of TFC can be enhanced by stimulation with TGF-β. Besides, TGF-β stimulation enhanced the diversity of TCR and complementarity-determining region 3 sequences. HIV DNA showed a negative correlation with TFC. The use of TGF-β to promote the expression of CXCR5⁺CD8 T cells could become a new treatment approach for curing HIV.     

A prognostic eight-gene expression signature for patients with breast cancer receiving adjuvant chemotherapy

Breast cancer is a popularly diagnosed malignant tumor. Genomic profiling studies suggest that breast cancer is a disease with heterogeneity. Chemotherapy is one of the chief means to treat breast cancer, while its responses and clinical outcomes vary largely due to the conventional clinicopathological factors and inherent chemosensitivity of breast cancer. Using the least absolute shrinkage and selection operator (LASSO) Cox regression model, our study established a multi-mRNA-based signature model and constructed a relative nomogram in predicting distant-recurrence-free survival for patients receiving surgery and following chemotherapy. We constructed a signature of eight mRNAs (IPCEF1, SYNDIG1, TIGIT, SPESP1, C2CD4A, CLCA2, RLN2, and CCL19) with the LASSO model, which was employed to separate subjects into groups with high- and low-risk scores. Obvious differences of distant-recurrence-free survival were found between these two groups. This eight-mRNA-based signature was independently associated with the prognosis and had better prognostic value than classical clinicopathologic factors according to multivariate Cox regression results. Receiver operating characteristic results demonstrated excellent performance in diagnosing 3-year distant-recurrence by the eight-mRNA signature. A nomogram that combined both the eight-mRNA-based signature and clinicopathological risk factors was constructed. Comparing with an ideal model, the nomograms worked well both in the training and validation sets. Through the results that the eight-mRNA signature effectively classified patients into low- and high-risk of distant recurrence, we concluded that this eight-mRNA-based signature played a promising predictive role in prognosis and could be clinically applied in breast cancer patients receiving adjuvant chemotherapy.     

An in situ collagen-HA hydrogel system promotes survival and preserves the proangiogenic secretion of hiPSC-derived vascular smooth muscle cells

Human-induced pluripotent stem cell-derived vascular smooth muscle cells (hiPSC-VSMCs) with proangiogenic properties have huge therapeutic potential. While hiPSC-VSMCs have already been utilized for wound healing using a biomimetic collagen scaffold, an in situ forming hydrogel mimicking the native environment of skin offers the promise of hiPSC-VSMC mediated repair and regeneration. Herein, the impact of a collagen type-I-hyaluronic acid (HA) in situ hydrogel cross-linked using a polyethylene glycol-based cross-linker on hiPSC-VSMCs viability and proangiogenic paracrine secretion was investigated. Our study demonstrated increases in cell viability, maintenance of phenotype and proangiogenic growth factor secretion, and proangiogenic activity in response to the conditioned medium. The optimally cross-linked and functionalized collagen type-I/HA hydrogel system developed in this study shows promise as an in situ hiPSC-VSMC carrier system for wound regeneration.     

Deregulation of UCA1 expression may be involved in the development of chemoresistance to cisplatin in the treatment of non-small-cell lung cancer via regulating the signaling pathway of microRNA-495/NRF2

Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer death worldwide. As a platinum-based chemotherapeutic drug, cisplatin has been used for over 30 years in NSCLC treatment while its effects are diminished by drug resistance. Therefore, we aimed to study the potential role of UCA1 in the development of chemoresistance against cisplatin. Real-time polymerase chain reaction, western-blot analysis, and immunofluorescence were used to study the involvement of UCA1, miR-495, and NRF2 in chemoresistance against cisplatin. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to determine the effect of cisplatin on cell proliferation. Computational analysis and luciferase assay were carried out to explore the interaction among UCA1, miR-495, and NRF2. The cisplatin-R group exhibited lower levels of UCA1 and NRF2 expression but a higher level of miR-495 expression than the cisplatin-S group. The growth rate and half-maximal inhibitory concentration of cellular dipeptidyl peptidase (cisplatinum) of the cisplatin-R group were much higher than those in the cisplatin-S group. MiR-495 contained a complementary binding site of UCA1, and the luciferase activity of wild-type UCA1 was significantly reduced after the transfection of miR-495 mimics. MiR-495 directly targeted the 3′-untranslated region (3′-UTR) of NRF2, and the luciferase activity of wild-type NRF2 3′-UTR was evidently inhibited by miR-495 mimics. Finally, UCA1 and NRF2 expressions in the effective group were much lower than that in the ineffective group, along with a much higher level of miR-495 expression. We suggested for the first time that high expression of UCA1 contributed to the development of chemoresistance to cisplatin through the UCA1/miR-495/NRF2 signaling pathway.