A major problem in cancer treatment is the multidrug resistance. siRNA inhibitors have great advantages to solve the problem, if the bottleneck of their delivery could be well addressed by the ...various nanocarriers. Moreover, co-delivery of siRNA together with the various anticancer agents in one nanocarrier may maximize their additive or synergistic effect. This review provides a comprehensive summary on the state-of-the-art of the nanocarriers, which may include prodrugs, micelles, liposomes, dendrimers, nanohydrogels, solid lipid nanoparticles, nanoparticles of biodegradable polymers and nucleic acid nanocarriers for delivery of siRNA and co-delivery of siRNA together with anticancer agents with focus on synthesis of the nanocarrier materials, design and characterization, in vitro and in vivo evaluation, and prospect and challenges of nanocarriers.
Two X-ray sources were recently discovered by Irwin et al. that are compact companions to elliptical galaxies showing ultraluminous flares with fast rise (∼minute) and decay (∼hour), and with a peak ...luminosity ∼1040-41 erg s−1. Together with two other sources found earlier, they constitute a new type of fast transients that cannot be attributed to neutron stars, but might be due to intermediate-mass black holes (IMBHs; ). The flaring behavior is recurrent for at least two sources. If the flare represents a short period of accretion onto an IMBH during the periastron passage of a donor star on an eccentric (i.e., repeating) or parabolic (non-repeating) orbit, we argue that the flare's rise time corresponds to the duration during which the donor's tidally stripped mass joins a residual disk at the pericenter. This duration is in turn equal to three other timescales: the duration of stripping, the sound crossing time of the donor, and the circular orbit time at the pericenter radius. Only a white dwarf (WD) can have a sound crossing time as short as one minute. Therefore, the donor must be a WD and it was stripped of ∼10−10 M upon each passage at several to tens of Schwarzschild radii from the IMBH. The flux decay corresponds to the viscous drainage of the supplied mass toward the hole. Aided by long-term X-ray monitoring, this type of fast transient would be an ideal target for next-generation gravitational wave detectors.
The substantial heterogeneity and hierarchical organization in liver cancer support the theory of liver cancer stem cells (LCSCs). However, the relationship between chronic hepatic inflammation and ...LCSC generation remains obscure. Here, we observed a close correlation between aggravated inflammation and liver progenitor cell (LPC) propagation in the cirrhotic liver of rats exposed to diethylnitrosamine. LPCs isolated from the rat cirrhotic liver initiated subcutaneous liver cancers in nonobese diabetic/severe combined immunodeficient mice, suggesting the malignant transformation of LPCs toward LCSCs. Interestingly, depletion of Kupffer cells in vivo attenuated the LCSC properties of transformed LPCs and suppressed cytokeratin 19/Oval cell 6–positive tumor occurrence. Conversely, LPCs cocultured with macrophages exhibited enhanced LCSC properties. We further demonstrated that macrophage‐secreted tumor necrosis factor‐α triggered chromosomal instability in LPCs through the deregulation of ubiquitin D and checkpoint kinase 2 and enhanced the self‐renewal of LPCs through the tumor necrosis factor receptor 1/Src/signal transducer and activator of transcription 3 pathway, which synergistically contributed to the conversion of LPCs to LCSCs. Clinical investigation revealed that cytokeratin 19/Oval cell 6–positive liver cancer patients displayed a worse prognosis and exhibited superior response to sorafenib treatment. Conclusion: Our results not only clarify the cellular and molecular mechanisms underlying the inflammation‐mediated LCSC generation but also provide a molecular classification for the individualized treatment of liver cancer. (Hepatology 2017;66:1934–1951)
Exosomes derived from bone marrow mesenchymal stem cells can inhibit neuroinflammation through regulating microglial phenotypes and promoting nerve injury repair. However, the underlying molecular ...mechanism remains unclear. In this study, we investigated the mechanism by which exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation. Our in vitro co-culture experiments showed that bone marrow mesenchymal stem cells and their exosomes promoted the polarization of activated BV2 microglia to their anti-inflammatory phenotype, inhibited the expression of proinflammatory cytokines, and increased the expression of anti-inflammatory cytokines. Our in vivo experiments showed that tail vein injection of exosomes reduced cell apoptosis in cortical tissue of mouse models of traumatic brain injury, inhibited neuroinflammation, and promoted the transformation of microglia to the anti-inflammatory phenotype. We screened some microRNAs related to neuroinflammation using microRNA sequencing and found that microRNA-181b seemed to be actively involved in the process. Finally, we regulated the expression of miR181b in the brain tissue of mouse models of traumatic brain injury using lentiviral transfection. We found that miR181b overexpression effectively reduced apoptosis and neuroinflamatory response after traumatic brain injury and promoted the transformation of microglia to the anti-inflammatory phenotype. The interleukin 10/STAT3 pathway was activated during this process. These findings suggest that the inhibitory effects of exosomes derived from bone marrow mesenchymal stem cells on neuroinflamation after traumatic brain injury may be realized by the action of miR181b on the interleukin 10/STAT3 pathway.
Oral chemotherapy is an important topic in the 21st century medicine, which may radically change the current regimen of chemotherapy and greatly improve the quality of life of the patients. ...Unfortunately, most anticancer drugs, especially those of high therapeutic efficacy such as paclitaxel and docetaxel, are not orally bioavailable due to the gastrointestinal (GI) drug barrier. The molecular basis of the GI barrier has been found mainly due to the multidrug efflux proteins, i.e. P-type glycoproteins (P-gp), which are rich in the epithelial cell membranes in the GI tract. Medical solution for oral chemotherapy is to apply P-gp inhibitors such as cyclosporine A, which, however, suppress the body's immune system either, thus causing medical complication. Pharmaceutical nanotechnology, which is to apply and further develop nanotechnology to solve the problems in drug delivery, may provide a better solution and thus change the way we make drug and the way we take drug. This review is focused on the problems encountered in oral chemotherapy and the pharmaceutical nanotechnology solutions such as prodrugs, nanoemulsions, dendrimers, micelles, liposomes, solid lipid nanoparticles and nanoparticles of biodegradable polymers. Proof-of-concept in vitro and in vivo results for oral delivery of anticancer drugs by the various nanocarriers, which can be found so far from the literature, are provided.
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Biochar（BC）, known as the new black gold, is a stable, novel carbonaceous by-product that is synthesized through pyrolysis of biological materials in the absence of O_2.Recently, an emerging interest ...in the application of BC as a robust soil amendment has given rise to a broad research area in science and technology.It is considered a promising remediation option for heavy metal（HM）-contaminated soils to reduce HM bioavailability to plants.Remediation efficacy of BC depends on the porosity, composition,pyrolysis temperature, feedstock, and residence time of pyrolysis.This review article aimed to present an overview of BC use in the immobilization of HMs, i.e., Cd, As, Pb, Zn, Ni, Cu, Mn, Cr, and Sb, in contaminated soils.The remaining uncertain factors, including the specific soil HM immobilization mechanisms, long-term beneficial effects, and potential environmental risks associated with BC application are analyzed.Future research must be conducted to ensure that the management of environmental pollution is in accord with ecological sustainability and adaptation of the black gold biotechnology on a commercial basis for immobilization of HMs in contaminated soils.
Most marine fish species express life-history changes across temperature gradients, such as faster growth, earlier maturation, and higher mortality at higher temperature. However, such climate-driven ...effects on life histories and population dynamics remain unassessed for most fishes. For 332 Indo-Pacific fishes, we show positive effects of temperature on body growth (but with decreasing asymptotic length), reproductive rates (including earlier age-at-maturation), and natural mortality for all species, with the effect strength varying among habitat-related species groups. Reef and demersal fishes are more sensitive to temperature changes than pelagic and bathydemersal fishes. Using a life table, we show that the combined changes of life histories upon increasing temperature tend to facilitate population growth for slow life-history populations, but reduce it for fast life-history ones. Within our data, lower proportions (25-30%) of slow life-history fishes but greater proportions of fast life-history fishes (42-60%) show declined population growth rates under 1 °C warming. Together, these findings suggest prioritizing sustainable management for fast life-history species.
The molecular mechanisms underlying estrogen receptor (ER)‐positive breast carcinogenesis and endocrine therapy resistance remain incompletely understood. Here, we report that circPVT1, a circular ...RNA generated from the lncRNA PVT1, is highly expressed in ERα‐positive breast cancer cell lines and tumor samples and is functionally important in promoting ERα‐positive breast tumorigenesis and endocrine therapy resistance. CircPVT1 acts as a competing endogenous RNA (ceRNA) to sponge miR‐181a‐2‐3p, promoting the expression of ESR1 and downstream ERα‐target genes and breast cancer cell growth. Furthermore, circPVT1 directly interacts with MAVS protein to disrupt the RIGI–MAVS complex formation, inhibiting type I interferon (IFN) signaling pathway and anti‐tumor immunity. Anti‐sense oligonucleotide (ASO)‐targeting circPVT1 inhibits ERα‐positive breast cancer cell and tumor growth, re‐sensitizing tamoxifen‐resistant ERα‐positive breast cancer cells to tamoxifen treatment. Taken together, our data demonstrated that circPVT1 can work through both ceRNA and protein scaffolding mechanisms to promote cancer. Thus, circPVT1 may serve as a diagnostic biomarker and therapeutic target for ERα‐positive breast cancer in the clinic.
Synopsis
Estrogen receptor (ER)α, encoded by ESR1, promotes mammary malignancies and is targeted in cancer therapy; however, resistance arises frequently. This study reports a novel circRNA, termed circPVT1, with dual mechanisms to enhance ER‐positive breast tumorigenesis, suggesting therapeutic opportunities.
CircPVT1 is highly expressed in ERα‐positive breast tumor patients.
CircPVT1 sponges miR‐181a‐2‐3p to stabilize ESR1 mRNA, activating the expression of estrogen/ERα‐target genes.
CircPVT1 interacts with MAVS protein to disrupt RIGI–MAVS complex formation, repressing the expression of type I IFN and interferon‐stimulated genes.
ASO‐targeting circPVT1 suppresses ERα‐positive breast cancer cell and tumor growth.
Circular RNA circPVT1 has dual function in aggravating ER+ mammary gland malignancies.
The electrochemical reduction of carbon dioxide (CO2) to ethylene creates a carbon‐neutral approach to converting carbon dioxide into intermittent renewable electricity. Exploring efficient ...electrocatalysts with potentially high ethylene selectivity is extremely desirable, but still challenging. In this report, a laboratory‐designed catalyst HKUST‐1@Cu2O/PTFE‐1 is prepared, in which the high specific surface area of the composites with improved CO2 adsorption and the abundance of active sites contribute to the increased electrocatalytic activity. Furthermore, the hydrophobic interface constructed by the hydrophobic material polytetrafluoroethylene (PTFE) effectively inhibits the occurrence of hydrogen evolution reactions, providing a significant improvement in the efficiency of CO2 electroreduction. The distinctive structures result in the remarkable hydrocarbon fuels generation with high Faraday efficiency (FE) of 67.41%, particularly for ethylene with FE of 46.08% (−1.0 V vs RHE). The superior performance of the catalyst is verified by DFT calculation with lower Gibbs free energy of the intermediate interactions with improved proton migration and selectivity to emerge the polycarbon（C2+） product. In this work, a promising and effective strategy is presented to configure MOF‐based materials with tailored hydrophobic interface, high adsorption selectivity and more exposed active sites for enhancing the efficiency of the electroreduction of CO2 to C2+ products with high added value.
Elaborate design of core–shell catalyst HKUST‐1@Cu2O/PTFE‐1 with hydrophobic interface exhibits outstanding electrocatalytic activities for hydrocarbon fuels with high Faraday efficiency of 67.41% in CO2 electroreduction, benefiting from the improved CO2 adsorption, the abundance of synergistic active sites and blocking the supply of protons and electrons to inhibit HER.
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