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How to eradicate Helicobacter pylori (H. pylori) in vivo with antibiotic resistance owns tremendous clinical requirement. Herein, gold nanostars were conjugated with acid-sensitive cis-aconitic anhydride modified anti-H. pylori polyclonal antibodies, resultant pH sensitive gold nanostars@H. pylori-antibodies nanoprobes (GNS@Ab) were employed for the theranostics of H. pylori in vivo. Photoacoustic imaging confirmed that prepared GNS@Ab could target actively H. pylori in the stomach. GNS@Ab nanoprobes could kill H. pylori in vivo in model animals under NIR laser irradiation, all GNS@Ab nanoprobes could be excreted out of gut within 7 days after oral administration. Gastric local lesion caused by H. pylori restored to normal status within one month. GNS@Ab nanoprobes within therapeutic doses did not damage intestinal bacteria imbalance. Forty clinical specimens of H. pylori with antibiotic resistance were verified validity of GNS@Ab nanoprobes. Prepared oral pH-sensitive GNS@Ab nanoprobes own clinical translational potential in the theranostics of H. pylori in near future., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Preeclampsia, a serious pregnancy-associated syndrome, is the leading cause of maternal and perinatal morbidity and mortality. Significant exacerbation of the hypercoagulation status as well as imbalanced steroid hormones have been reported in developed preeclampsia. However, it remains unclear whether the two pathological changes are directly associated., Method and Results: Our proteomic analysis revealed a significantly elevated SerpinF2/α2-antiplasmin level in preeclampsia plasma. Measurement of the longitudinally gestational change of plasmin-α2-antiplasmin (PAP) complex, testosterone, estradiol in preeclampsia patients and normal pregnant women demonstrated that the circulating PAP and testosterone levels in the early-onset preeclampsia (E-PE) patients were substantially higher, whereas estradiol concentration was significantly lower than that in normal pregnant controls from early pregnancy throughout gestation. Correlation analysis revealed that circulating PAP is in positive correlation with the concentration of testosterone, and in negative correlation with estradiol in E-PE patients. In E-PE placenta, the productions and activities of 17β-hydroxysteroid dehydrogenases 3 and aromatase, the essential enzymes for testosterone and estradiol synthesis, were compromised. In human renal and trophoblastic cells, testosterone and estradiol could regulate SerpinF2 expression in opposite ways. In addition, obvious fibrin deposition was colocalized with SerpinF2 in intervillous spaces and the area surrounding syncytiotrophoblasts in E-PE placenta., Conclusion: The findings reveal a tight correlation between the imbalanced steroid hormone production and the procoagulation factor in E-PE patients, which provide potential biomarkers to predict preeclampsia, and bring new insight into the pathogenesis of preeclampsia.

Objective: The signalling of the receptor tyrosine kinase Met is critical in promoting trophoblast cell invasion, and the deficiency in HGF/Met signalling is associated with preeclampsia. The semaphorin family member semaphorin4D (sema4D) and its receptor Plexin-B1 have been reported to control tumour cell invasion by coupling with Met. We hypothesized that sema4D/Plexin-B1 may promote trophoblast invasion by activating Met, and downregulation of sema4D/Plexin-B1 may account for the deficiency in Met signalling in preeclamptic placenta., Methods: In this study, Met and Erk activation and the expression of sema4D/Plexin-B1 in normal and preeclamptic placentas were comparably measured. The role of sema4D in trophoblast cell invasion and tubulogenesis was examined in vitro using the Transwell invasion assay and tube formation assay in trophoblast-endothelial cell co-culture model., Results: Met, sema4D and Plexin-B1 co-localized in various subtypes of human trophoblast cells, including villous trophoblasts and extravillous trophoblasts (EVTs). In early-onset preeclampsia (E-PE) placentas, the phosphorylated Met and Erk as well as sema4D and Plexin-B1 were much lower than those in gestational week-matched preterm-labour (PTL) placentas. In human trophoblast HTR8/SVneo cell line, sema4D could promote Met and Erk phosphorylation as well as enhance trophoblast cell invasion and tubulogenesis with endothelial cells. Moreover, the effect of sema4D on HTR8/SVneo could be blocked by knocking down Met with specific siRNA., Conclusion: The crosstalk between sema4D and Met could transactivate Met to promote trophoblast cell invasion and differentiation, and decreased expression of sema4D and Plexin-B1 may be responsible for the deficiency in Met signalling and the development of preeclampsia.

The development of multifunctional nanoparticles for tumor theranostics has become a research hotspot. Despite the advantages of non-invasive precision diagnostics and efficient drug-delivery, these nanoparticles bring two significant issues: (i) a potential toxic effect and (ii) difficult clearance. To solve these issues, carbon dots (C-dots) are key potential candidates owing to their unique properties, such as excellent biocompatibility and rapid renal clearance. However, their small size leads to a short circulation time in the blood, which causes non-sufficient tumor accumulation for antitumor therapy. To reach the balance between an efficient accumulation in a tumor and rapid clearance from the body, herein we report a new multifunctional nanoprobe: photosensitizer (chlorine e6, Ce6)-loaded assembled C-dots (A-C-dots@Ce6). The A-C-dots@Ce6 were assembled from negatively-charged discrete C-dots using Gd3+ ions as a "glue". which also provided another function of in vivo nanoprobe monitoring via magnetic resonance (MR) imaging. Moreover, the nanoprobe exhibited an acidic pH-dependent disassembly and drug-release property. Benefiting from these advantages, the nanoprobe showed a targeted antitumor effect in A549 tumor-bearing mice under laser irradiation and gradual disassembly in the tumor for later body clearance. Therefore, the nanoprobe potentially provides a new strategy to solve the above balance issue, and brightens the future for antitumor monitoring and treatment.

The development of targeted nanoprobes is a promising approach to cancer diagnostics and therapy. In the present work, a novel multifunctional photo/magnet-diagnostic nanoprobe (MNPs-PEG 2K -FA@Ce6) has been developed. This nanoprobe is built using folic acid (FA), bifunctional polyethylene glycol (PEG 2K ) and photosensitizer chlorin e6 (Ce6). The MNPs-PEG 2K -FA@Ce6 nanoprobes are superparamagnetic, can be synthesized on a large scale by a one-pot hydrothermal process without further surface modification and are stable in an aqueous environment for eight months. Compared with free Ce6 nanoprobes in vitro studies, the MNPs-PEG 2K -FA@Ce6 nanoprobes significantly enhance cellular uptake efficiency and promote the effectiveness of photodynamic therapy (PDT) with the assistance of 633 nm laser irradiation. The unique nanoprobes show superior penetration and a retention time of more than six days with less accumulation in the liver allowing highly effective tumor recognition and monitoring. Additionally, there was little damage to healthy organs or tissues. These exciting new nanoprobes could be potential building blocks to develop new clinical therapies and translational medicine.

MicroRNA (miRNA) biomarkers display great potential for cancer diagnosis and prognosis. The development of rapid and specific methods for miRNA detection has become a hotspot. Herein, hairpin DNA-templated silver nanoclusters (AgNCs/HpDNA) were prepared and integrated into strand-displacement amplification (SDA) as a novel beacon for miRNA detection. The light-up platform was established based on guanine (G)-rich fluorescence enhancement that essentially converted the excitation/emission pair of AgNCs/HpDNAs from a shorter wavelength to a longer wavelength, and then achieved fluorescent enhancement at longer wavelength. On the basis of the validation of the method, the single and duplex detection were conducted in two plasma biomarkers (miR-16-5p and miR-19b-3p) for the diagnosis of gastric cancer. The probe (AgNCs/RED 16(7s)C) utilized for miR-16-5p detection adopted a better conformation with high specificity to recognize single-base mismatches by producing dramatically opposite signals (increase or decrease at 580 nm ex/640 nm em) while the probe (AgNCs/GRE 19b(5s)C) for miR-19b-3p generated dual signals (increase at 490 nm ex/570 nm em and decrease at 430 nm ex/530 nm em) with bright fluorescence in one reaction during the amplification, but unexpectedly was partially digested. This is for the first time to allow the generation of enhanced fluorescent AgNCs and the target recognition integrated into a single process, which offers great opportunity for specific miRNA detection in an easy and rapid way.