Both melanoma cells and tissues were allowed to interact with an identical pool of billions of human-safe phage nanofiber clones with each genetically displaying a unique 12-mer peptide at the tips, respectively, resulting in the discovery of bionanofibers displaying a melanoma cell/tissue dual-homing peptide for personalized targeted melanoma therapy.
An unprecedented asymmetric-electrolyte electrolyzer is proposed using an acidic cathode for the hydrogen evolution reaction (HER) and an alkaline anode for the urea oxidation reaction (UOR), which significantly decreases the electrical energy required for electrolytic hydrogen production.
Endothelial progenitor cells (EPCs) are the key cells of postnatal neovascularization, and mesenchymal stem cells (MSCs) possess pluripotent differentiation capacity and contribute to tissue regeneration and wound healing. Both EPCs and MSCs are critical to the wound repair process, which is hindered in diabetes mellitus. Diabetes has been shown to decrease the function of these progenitor cells, whereas estrogen has beneficial wound healing effects. However, the role of estrogen in modulating EPC and MSC biology in diabetes is unknown. We investigated the effect of estrogen on improving bone marrow (BM)-derived EPC and MSC function using a murine diabetic wound healing model.
Female diabetic db+/db+ and nondiabetic control mice were wounded cutaneously and treated with topical estrogen or placebo cream. On day 5 after wounding, BM cells were harvested to quantify EPC number and colony-forming units of EPCs and MSCs. Wound healing rate was concurrently studied. Vessel density and scar density were then quantified using whole body perfusion and laser confocal microscopy. EPC recruitment was documented by immunohistochemistry to identify CD34- and vascular endothelial growth factor receptor 2-positive cells in the vessel wall. Data were analyzed by analysis of variance.
Topical estrogen significantly increased colony-forming units of both EPCs and MSCs compared with placebo treatment, indicating improved viability and proliferative ability of these cells. Consistently, increased recruitment of EPCs to diabetic wounds and higher vessel density were observed in estrogen-treated compared with placebo-treated mice. Consequently, topical estrogen significantly accelerated wound healing as early as day 6 after wounding. In addition, scar density resulting from collagen deposition was increased in the estrogen-treated group, reflecting increased MSC activity and differentiation.
Estrogen treatment increases wound healing and wound neovascularization in diabetic mice. Our data implicate that these beneficial effects may be mediated through improving the function of BM-derived EPCs and MSCs.
A phytochemical investigation of twigs of Podocarpus nagi resulted in the identification of eight new type B nagilactones (1-8), all bearing a 7α,8α-epoxy-9(11)-enolide substructure, along with two known analogs (9-10). Their structures were determined on the basis of spectroscopic analysis, including HRESIMS, IR and NMR experiments, and X-ray crystallographic analysis. In vitro cytotoxic assay exhibited that compounds 1, 2, 9 and 10 could induce antiproliferation against three different types of human cancer cells while compounds 3 and 5 were inactive. Notably, the IC50 value of compound 1 is 0.208μM for A431 human epidermoid carcinoma cells, reaching the same level as the positive control combretastatin A-4 (0.104μM). Furthermore, compound 1 performed a strong inhibition of cancer cells by triggering apoptosis and arresting the cell cycle at G1 phase. These results unfold potential anticancer therapeutic applications of type B nagilactones.
How to read Uyghur text from biomedical graphic images is a challenge problem due to the complex layout and cursive writing of Uyghur. In this paper, we propose a system that extracts text from Uyghur biomedical images, and matches the text in a specific lexicon for semantic analysis. The proposed system possesses following distinctive properties: first, it is an integrated system which firstly detects and crops the Uyghur text lines using a single fully convolutional neural network, and then keywords in the lexicon are matched by a well-designed matching network. Second, to train the matching network effectively an online sampling method is applied, which generates synthetic data continually. Finally, we propose a GPU acceleration scheme for matching network to match a complete Uyghur text line directly rather than a single window. Experimental results on benchmark dataset show our method achieves a good performance of F-measure 74.5%. Besides, our system keeps high efficiency with 0.5s running time for each image due to the GPU acceleration scheme.
Mitotic arrest deficiency protein 1 (Mad1) is associated with microtubule-unattached kinetochores in mitotic cells and is a component of the spindle assembly checkpoint (SAC). Here, we have studied the phosphorylation of Mad1 and mapped using liquid chromatography-tandem mass spectrometry several phosphorylated amino acids in this protein. One phosphorylated residue, Thr680, was characterized to be important for the kinetochore localization of Mad1 and its SAC function. We also found that in mitotic cells Mad1 co-immunoprecipitated with Plk1. Depletion of cellular Plk1 using small interfering RNAs and inhibition of the kinase activity of Plk1 using a kinase-dead mutant or a small molecule inhibitor attenuated Mad1 phosphorylation and its association with kinetochores. Collectively, these findings indicate mechanistic roles contributed by protein phosphorylation and Plk1 to the SAC activity of Mad1.
Two compounds belonging to a new group of diterpene alkaloids, kaurines A and B (1 and 2), and an alkaloid bearing a succinimide moiety (3) were obtained from Isodon rubescens. Their structures and absolute configurations were determined by spectroscopy and quantum-chemical computational (13)C NMR and ECD data analysis. These alkaloids differ from known diterpene alkaloids and diterpenoids and are presumably biosynthesized from ent-kaurane diterpenoids.
T cell immunoglobulin mucin-3 (Tim-3) is an immune checkpoint inhibitor and its dysregulation has been related to T cell tolerance and many immune disorders, such as tumors and infection tolerance. However, the physiopathology roles of Tim-3 in innate immunity remain elusive. Here, we demonstrate that Tim-3 inhibits macrophage phagocytosis of L. monocytogenes by inhibiting the nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway and increases bacterial burden. Tim-3 signaling promotes Nrf2 degradation by increasing its ubiquitination and, as a result, decreasing its nuclear translocation. CD36 and heme oxygenase-1 (HO-1), two downstream molecules in the Tim-3-Nrf2 signaling axis, are involved in the Tim-3- mediated immune evasion of L. monocytogenes both in vitro and in vivo. We here identified new mechanisms by which Tim-3 induces infection tolerance. By modulating the Tim-3 pathway, we demonstrate the feasibility of manipulating macrophage function as a potent tool for treating infectious diseases, such as Listeria infection.
This study aims to investigate cellular immunity and clinical efficacy of ShenQi FuZheng Injection (SFI) in the associated chemotherapy of colorectal cancer (CRC).
PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Full-text Database (VIP), WanFang Database and Chinese Biomedical Literature Database (CBM) searches were undertaken to identify randomized controlled trials of SFI plus chemotherapy versus chemotherapy alone in CRC patients. The quality of each trial was assessed according to the Jadad's scale, and Review Manager 5 was used to statisitically analyze the outcomes.
Eight studies involving 722 patients were included in this review. The meta-analyses suggested there was a significantly higher overall response rate (OR 1.89; CI: 1.10-3.24; p = 0.02), grades of KPS (OR 2.35; CI: 1.55-3.56; p<0.01), CD3+cells (MD 10.29; CI: 8.46-12.12; p<0.01), CD4+cells (MD 7.06; CI: 5.33-8.794; p<0.01), CD4/CD8+cells (MD 0.32; CI: 0.25-0.40; p<0.01), NK+ (MD 7.20; CI: 2.02-12.37, p = 0.006), WBC (MD 1.24; CI: 0.59-1.89; p<0.01), HB (MD 14.55; CI: 7.47-21.63; p<0.01), and PLT (MD 19.05; CI: 4.29-33.81; p = 0.01), but lower severe toxicity for leukocytopenia (OR 0.37; CI: 0.17-0.80; p = 0.01), thrombocytopenia (OR 0.32; CI: 0.14-0.74; p = 0.008), gastrointestinal toxicity (OR 0.48; CI: 0.24-0.96; p = 0.04), when chemotherapy combined with SFI was compared with chemotherapy alone. There were similarities between two groups in liver dysfunction (OR 0.44; CI: 0.18-1.08; p = 0.07) and CD8+ (MD 0.54; CI: -1.89-2.96; p = 0.66). Also, there was presence of heterogeneity in the CD8 results; after the sensitivity analysis, the result of CD8+ was reversed (MD 1.57; CI: 0.32-2.81; p = 0.01). There was no significant publication bias across studies according to the Egger's (P = 0.19) and Begg's test (P = 0.23).
SFI enhances chemotherapy efficiency as they are combined and used in the treatment of colorectal cancer patients. At the same time, SFI also improves patients' immunity function.
Globally, cardio-cerebrovascular diseases (CCVDs) are the leading cause of death, and thus the development of novel strategies for preventing and treating such diseases is in urgent need. Traditional Chinese medicine (TCM), used for thousands of years in Asia and other regions, has been proven effective in certain disorders. As a long-time medicinal herb in TCM, Ginkgo biloba leaves (GBLs), have been widely used to treat various diseases including CCVDs. However, the underlying molecular mechanisms of medicinal herbs in treating these diseases are still unclear. Presently, by incorporating pharmacokinetic prescreening, target fishing, and network analysis, an innovative systems-pharmacology platform was introduced to systematically decipher the pharmacological mechanism of action of GBLs for the treatment of CCVDs. The results show that GBLs exhibit a protective effect on CCVDs probably through regulating multiple pathways and hitting on multiple targets involved in several biological pathways. Our work successfully explains the mechanism of efficiency of GBLs for treating CCVDs and, meanwhile, demonstrates that GDJ, an injection generated from GBLs, could be used as a preventive or therapeutic agent in cerebral ischemia. The approach developed in this work offers a new paradigm for systematically understanding the action mechanisms of herb medicine, which will promote the development and application of TCM.