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[EN] Silica mesoporous microparticles loaded with both rhodamine B fluorophore (S1) or hydrocortisone (S2), and capped with an olsalazine derivative, are prepared and fully characterized. Suspensions of Si and S2 in water at an acidic and a neutral pH show negligible dye/drug release, yet a notable delivery took place when the reducing agent sodium dithionite is added because of hydrolysis of an azo bond in the capping ensemble. Additionally, olsalazine fragmentation induced 5-aminosalicylic acid (5-ASA) release. In vitro digestion models show that S1 and S2 solids are suitable systems to specifically release a pharmaceutical agent in the colon. In vivo pharmacokinetic studies in rats show a preferential rhodamine B release from Si in the colon. Moreover, a model of ulcerative colitis is induced in rats by oral administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS) solutions, which was also used to prove the efficacy of S2 for colitis treatment. The specific delivery of hydrocortisone and 5-ASA from S2 material to the colon tissue in injured rats markedly lowers the colon/body weight ratio and the clinical activity score. Histological studies showed a remarkable reduction in inflammation, as well as an intensive regeneration of the affected tissues. ; We thank the Generalitat Valenciana (Project PROMETE02018/024) and the Spanish Government (Projects AGL2015-70235-C2-2-R and MAT2015-64139-C4-1-R (MINECO/FEDER)) for support. A.H.T. thanks the Spanish MEC for his FPU fellowship. The authors also thank the support of the Electron Microscopy Service at the UPV. The SCSIE (of the Universitat de Valencia) is also gratefully acknowledged for all the equipment used. NMR spectra were measured at the U26 facility of ICTS "NANBIOSIS" at the Universitat de Valencia. ; Hernández Teruel, A.; Pérez-Esteve, É.; González-Álvarez, I.; González-Álvarez, M.; Costero Nieto, AM.; Ferri, D.; Gaviña, P. (2019). Double Drug Delivery Using Capped Mesoporous Silica Microparticles for the Effective Treatment of Inflammatory Bowel ...

2418 2429 16 6 ; S ; [EN] Silica mesoporous microparticles loaded with both rhodamine B fluorophore (S1) or hydrocortisone (S2), and capped with an olsalazine derivative, are prepared and fully characterized. Suspensions of Si and S2 in water at an acidic and a neutral pH show negligible dye/drug release, yet a notable delivery took place when the reducing agent sodium dithionite is added because of hydrolysis of an azo bond in the capping ensemble. Additionally, olsalazine fragmentation induced 5-aminosalicylic acid (5-ASA) release. In vitro digestion models show that S1 and S2 solids are suitable systems to specifically release a pharmaceutical agent in the colon. In vivo pharmacokinetic studies in rats show a preferential rhodamine B release from Si in the colon. Moreover, a model of ulcerative colitis is induced in rats by oral administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS) solutions, which was also used to prove the efficacy of S2 for colitis treatment. The specific delivery of hydrocortisone and 5-ASA from S2 material to the colon tissue in injured rats markedly lowers the colon/body weight ratio and the clinical activity score. Histological studies showed a remarkable reduction in inflammation, as well as an intensive regeneration of the affected tissues. We thank the Generalitat Valenciana (Project PROMETE02018/024) and the Spanish Government (Projects AGL2015-70235-C2-2-R and MAT2015-64139-C4-1-R (MINECO/FEDER)) for support. A.H.T. thanks the Spanish MEC for his FPU fellowship. The authors also thank the support of the Electron Microscopy Service at the UPV. The SCSIE (of the Universitat de Valencia) is also gratefully acknowledged for all the equipment used. NMR spectra were measured at the U26 facility of ICTS "NANBIOSIS" at the Universitat de Valencia. Hernández Teruel, A.; Pérez-Esteve, É.; González-Álvarez, I.; González-Álvarez, M.; Costero Nieto, AM.; Ferri, D.; Gaviña, P. (2019). Double Drug Delivery Using Capped Mesoporous Silica Microparticles for the Effective Treatment of ...

MCM-41 silica nanoparticles were used as inorganic scaffolding to prepare a nanoscopic-capped hybrid material S1, which was able to release an entrapped cargo in the presence of certain enzymes, whereas in the absence of enzymes, a zero release system was obtained. S1 was prepared by loading nanoparticles with Safranine O dye and was then capped with a gluconamide derivative. In the absence of enzymes, the release of the dye from the aqueous suspensions of S1 was inhibited as a result of the steric hindrance imposed by the bulky gluconamide derivative, the polymerized gluconamide layer and the formation of a dense hydrogen-bonded network around the pore outlets. Upon the addition of amidase and pronase enzymes, delivery of Safranine O dye was observed due to the enzymatic hydrolysis of the amide bond in the anchored gluconamide derivative. S1 nanoparticles were not toxic for cells, as demonstrated by cell viability assays using HeLa and MCF-7 cell lines, and were associated with lysosomes, as shown by confocal microscopy. Finally, the S1¿CPT material loaded with the cytotoxic drug camptothecin and capped with the gluconamide derivative was prepared. The HeLa cells treated with S1¿CPT underwent cell death as a result of material internalization, and of the subsequent cellular enzyme-mediated hydrolysis and aperture of the molecular gate, which induced the release of the camptothecin cargo. ; We thank the Spanish Government (Project MAT2009-14564-C04 and SAF2010-15512) and the Generalitat Valenciana (Project PROMETEO/2009/016and/2010/005) for support. I. C. thanks the Universitat Politecnica de Valencia for her fellowship. L. M. thanks the Generalitat Valenciana for her post-doctoral VALi+d contract. E. A. and C. T. also thank the CIBER-BBN for contracts. We thank Eva Maria Lafuente Villarreal and Alberto Hernandez Cano from the Confocal Microscopy service of CIPF and the Electronic Microscopy service of UPV for their technical support. ; Candel Busquets, I.; Aznar Gimeno, E.; Mondragón Martínez, L.; De La Torre ...

Abstract
The aim of this study is to investigate the protective effect of polyethylene glycol capped gold nanoparticles (PEG-AuNPs) on renal ischemia–reperfusion injury (I/R)–induced acute kidney injury (AKI) in diabetic mice via the activation of adenosine 5′ monophosphate–activated protein kinase—nuclear factor erythroid-2-related factor-2 (AMPK-Nrf2) pathway. Diabetes was induced in male mice (12/group) by streptozotocin (50 mg/kg) for 5 consecutive days. After 4 weeks, the mice have intravenously received doses of PEG-AuNPs (40, 150, and 400 µg/kg body weight) for 3 consecutive days, and then animals were subjected to 30 min ischemia and 48 h reperfusion. Following the treatment with three different doses of PEG-AuNPs, the levels of blood urea nitrogen (BUN) and creatinine were reduced. Obvious reduction in renal tubular atrophy, glomerular damage, mitochondrial damage, and necrotic area were ultra-structurally detected, and renal interstitial inflammation and apoptosis were diminished. Moreover, PEG-AuNPs increased the recovering of damaged renal cells, suppressed significantly levels of malondialdehyde (MDA), downregulated significantly the level of inflammatory cytokines (TNF-α and IL-1β), and upregulated the AMPK-Nrf2 pathway. PEG-AuNPs exhibited a promising alternative therapeutic target for diabetic renal I/R-induced AKI through upregulation of AMPK/PI3K/AKT path which additionally stimulated Nrf2-regulated antioxidant enzymes in a dose-dependent manner.
Graphical abstract

[EN] Apoptotic signaling pathways are altered in numerous pathologies such as cancer. In this scenario, caspase-9/PP2Ac alpha interaction constitutes a key target with pharmacological interest to re-establish apoptosis in tumor cells. Very recently, a short peptide (C9h) known to disrupt caspase-9/PP2Ac alpha interaction with subsequent apoptosis induction was described. Here, we prepared two sets of mesoporous silica nanoparticles loaded with safraninO (S2) or with C9h peptide (S4) and functionalized with epsilon-polylysine as capping unit. Aqueous suspensions of both nanoparticles showed negligible cargo release whereas in the presence of pronase, a marked delivery of safraninO or C9h was observed. Confocal microscopy studies carried out with HeLa cells indicated that both materials were internalized and were able to release their entrapped cargos. Besides, a marked decrease in HeLa cell viability (ca. 50%) was observed when treated with C9h-loaded S4 nanoparticles. Moreover, S4 provides peptide protection from degradation additionally allowing for a dose reduction to observe an apoptotic effect when compared with C9h alone or in combination with a cell-penetrating peptide (i.e., Mut3DPT-C9h). Flow cytometry studies, by means of Annexin V-FITC staining, showed the activation of apoptotic pathways in HeLa as a consequence of S4 internalization, release of C9h peptide and disruption of caspase-9/PP2Ac alpha interaction. ; The authors wish to express their gratitude to the Spanish government (Projects MAT2015-64139-C4-1, SAF2012-31405, SAF2015-67077-R, AGL2015-70235-C2-2-R (MINECO/FEDER)), the Generalitat Valencia (Projects PROMETEOII/2014/047, PROMETEO/2012/061) and the CIBER-BBN for their support. C.T. is grateful to the Spanish Ministry of Science and Innovation for her Ph.D. fellowship. ; De La Torre-Paredes, C.; Domínguez-Berrocal, L.; Murguía, JR.; Marcos Martínez, MD.; Martínez-Máñez, R.; Bravo, J.; Sancenón Galarza, F. (2018). epsilon-Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C9h ...

Carbon pricing regimes are often preceded and accompanied by companion policies, which can include regulatory standards, subsidies, and additional carbon pricing policies. While carbon pricing programs hold the advantage of identifying least-cost means of reducing carbon emissions, non-price based companion policies provide other advantages, such as addressing other externalities besides the social cost of carbon emissions, targeting specific technologies, addressing impacts on disadvantaged communities, and providing additional incentives for behavioral changes when carbon prices are too low to adequately do so. Companion policies therefore do play an important role in meeting climate goals, but some inefficiencies are expected when carbon pricing and companion policies interact. The two North American carbon pricing programs we discuss, the Regional Greenhouse Gas Initiative (RGGI) and the Western Climate Initiative (WCI), are cap-and-trade programs composed of individual states and provinces that pursue their own climate objectives and policies in addition to participating in emissions trading. RGGI affects the electricity sector in nine eastern US states, and virtually all allowances are auctioned in this program. The WCI is an economy-wide program covering California, Quebec and Ontario, where most allowance are auctioned. The companion policies in those jurisdictions are challenged by the waterbed effect, in which emissions reductions by one facility in a capped system are offset by increased emissions by another facility, leaving total emissions unchanged at least in the short run. Both trading programs reduce the waterbed effect by implementing a price floor in allowance auctions, below which emissions allowances are not sold. RGGI also plans to adopt an Emissions Containment Reserve (ECR), an additional price step above the price floor, applying to about 10 percent of allowances that will not sell at prices below this level. The auction price floors have been binding in both programs, and subsequently prices have risen off the price floor. These mechanisms cause the supply of allowances to decrease in response to lower demand, allowing the trading programs to capture some of the emissions reductions from companion policies through price suppression, but also maintain the buoyancy of the programs by supporting the price despite lack of allowance scarcity and guarantee a stream of revenue for programs supported by auction revenue. Companion policies have been fundamental to the design of the RGGI and WCI programs. In RGGI, most auction revenues are invested in energy efficiency, which by design pushes down electricity demand and allowance prices. In this context, the price floor and ECR provide guardrails for the allowance price path. In California, the largest jurisdiction in the WCI, over 80 percent of emissions reductions under the cap are attributable to regulatory measures. California estimates that these measures have a cost per ton of avoided carbon emissions that is greater than the cap-and-trade allowance price. However, these companion policies achieve essential ancillary benefits such as air quality improvements and investments in low carbon infrastructure. An important part of California's policy is the focus of companion policies and spending of auction revenues to address emissions outcomes in disadvantaged communities. The European Union's Emissions Trading System (ETS) faces the same challenge from the waterbed effect. The EU and its member states have pursued companion policies that reduce emissions at specific facilities in their jurisdictions but do not affect the volume of emissions allowances in the market. This effect contributes to the large surplus of allowances and the low allowance price that the EU ETS market has experienced over the past years. The EU has hence adopted a mechanism called a Market Stability Reserve (MSR), in which allowances are temporarily withheld from auction based on the number of (surplus) allowances in circulation. Beginning in 2023, when the MSR reaches a certain volume, some allowances can be permanently cancelled. This mechanism provides some responsiveness of allowance supply to reduced demand. We find through our modeling of MSR outcomes from 2018-2030 that the waterbed effect is diminished but still exists to some extent. We also find that additional emissions reductions have a greater impact on allowance supply the sooner they are taken. Our analysis of the North American and European Union cap-and-trade experiences provide a number of insights that are useful to Sweden in achieving its commitment to reach net-zero greenhouse gas emissions by 2045. ; Carbon pricing regimes are often preceded and accompanied by companion policies, which can include regulatory standards, subsidies, and additional carbon pricing policies. In this report, we discuss the mechanisms of companion (overlapping) policies, describe the experiences in North America and the European Union with cap and trade and companion policies, and suggest a conceptual framework to address the complications raised by companion policies.

AbstractThe antagonistic side effects of chemical medications led to the search for safe strategies such as biogenic agents. Correspondingly, this study aims to create biogenic, appropriate, auspicious and innovative therapeutic agents likeGalaxaura elongata{GE}, Turbinaria ornata{TO} andEnteromorpha flexuosa{EF} macroalgae-based silver nanoparticles (Ag-NPs). The Ag+reduction and the creation of Ag[GE]-NPs, Ag[TO]-NPs and Ag[EF]-NPs have been validated using UV–visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM) and zeta potential analysis, and the chemical composition of macroalgae crude extracts was estimated through gas chromatography–mass spectrometry (GC–MS). Further, macroalgae-based Ag-NPs were tested for their free radical scavenging activity DPPH, ABTS, anticancer activity in human liver carcinoma (HepG2) cell line, distinctive inflammation forms and elevated α-amylase. Results showed that the biosynthesized Ag-NPs have unique mechanical and physicochemical characters attributed to their high relative surface area, nanosized dimensions and spherical shape. At dose of 200 µg/mL, the DPPH radical scavenging capacity was maximized with Ag[TO]-NPs (67.26%); however, Ag[EF]-NPs was the most potent as ABTs scavenger (97.74%). Additionally, Ag[GE]-NPs had the maximum proteinase inhibitory action with 59.78%. The 1000 µg/mL of Ag[GE]-NPs, Ag[TO]-NPs and Ag[EF]-NPs revealed significant inhibitions of cell growth of HepG2 resulting in cell viabilities 5.92%, 4.44% and 11.33%, respectively. These findings suggest that macroalgae bio-capped Ag-NPs have magnificent biological potentials for safe biomedical applications.

Changing the Medicaid program is a top priority for the Republican party. Common themes from GOP proposals include converting Medicaid from a jointly financed entitlement benefit to a form of capped federal financing. While proponents of this reform argue that it would provide greater flexibility and a more predictable budget for state governments, serious consequences would likely result for Medicaid enrollees and state governments. Under all three scenarios promoted by Republicans--block grants, capped allotments, and per capita caps—most states would face increased costs. For all three scenarios, the capped nature of the funding guarantees that the real value of funds would decrease in future years relative to what would be expected from growth under the current program. Although the federal government would undoubtedly realize savings from all three scenarios, the impact might lead states to reduce benefits and services, create waiting lists, impose cost-sharing on a traditionally low-income enrollee population, or impose other obstacles to coverage. Nationally, as many as 20.5 million Americans stand to lose coverage under the proposed Medicaid changes. In California, up to 6 million people could lose coverage if changes to the Medicaid program were coupled with the repeal of coverage for the expansion population.

Changing the Medicaid program is a top priority for the Republican party. Common themes from GOP proposals include converting Medicaid from a jointly financed entitlement benefit to a form of capped federal financing. While proponents of this reform argue that it would provide greater flexibility and a more predictable budget for state governments, serious consequences would likely result for Medicaid enrollees and state governments. Under all three scenarios promoted by Republicans--block grants, capped allotments, and per capita caps—most states would face increased costs. For all three scenarios, the capped nature of the funding guarantees that the real value of funds would decrease in future years relative to what would be expected from growth under the current program. Although the federal government would undoubtedly realize savings from all three scenarios, the impact might lead states to reduce benefits and services, create waiting lists, impose cost-sharing on a traditionally low-income enrollee population, or impose other obstacles to coverage. Nationally, as many as 20.5 million Americans stand to lose coverage under the proposed Medicaid changes. In California, up to 6 million people could lose coverage if changes to the Medicaid program were coupled with the repeal of coverage for the expansion population.

Changing the Medicaid program is a top priority for the Republican party. Common themes from GOP proposals include converting Medicaid from a jointly financed entitlement benefit to a form of capped federal financing. While proponents of this reform argue that it would provide greater flexibility and a more predictable budget for state governments, serious consequences would likely result for Medicaid enrollees and state governments. Under all three scenarios promoted by Republicans--block grants, capped allotments, and per capita caps—most states would face increased costs. For all three scenarios, the capped nature of the funding guarantees that the real value of funds would decrease in future years relative to what would be expected from growth under the current program. Although the federal government would undoubtedly realize savings from all three scenarios, the impact might lead states to reduce benefits and services, create waiting lists, impose cost-sharing on a traditionally low-income enrollee population, or impose other obstacles to coverage. Nationally, as many as 20.5 million Americans stand to lose coverage under the proposed Medicaid changes. In California, up to 6 million people could lose coverage if changes to the Medicaid program were coupled with the repeal of coverage for the expansion population.

[EN] The development of new strategies to detect microRNAs (miRNAS) has become an important challenge in thebiomedical ¿eld. We report herein the use of oligonucleotide-gated silica nanoparticles for the detection ofmiRNA-145. In the proposed design, mesoporous silica nanoparticles (MSNs) are loaded with a ¿uorescentreporter (rhodamine B) and pores are blocked by speci¿c DNA oligonucleotides. The opening of the gated systemand dye delivery is selectively controlled by DNA-miRNA recognition. Moreover, the use of DNA capture probesable to form duplex or triplex structures between target miRNA and the complementary oligonucleotides hasbeen studied. By this simple procedure a limit of detection as low as 0.25 pM was found for miRNA. The methodwas successfully applied to detect miRNA-145 in serum samples, which demonstrates the high potential of thesecapped materials to detect miRNA for diagnostic purposes ; We thank the Spanish Government (projects MAT2015-64139-C4-1-R and CTQ2014-52588-R (MINECO/FEDER)), the Generalitat Valenciana (project PROMETEOII/2014/047) and the Generalitat de Catalunya (2014/SGR/624) for support. A.R. thanks UPV for her predoctoral fellowship. S.S. thanks the Instituto de Salud Carlos III and the European Social Fund for the financial support "Sara Borrell" (CD16/000237). V.C.-N. thanks Ministerio de Educacion, Cultura y Deporte for his predoctoral grant. The authors also thank the Electron Microscopy Service at the UPV for support. ; Ribes, À.; Santiago Felipe, S.; Aviñó, A.; Candela-Noguera, V.; Eritja, R.; Sancenón Galarza, F.; Martínez-Máñez, R. (2018). Design of oligonucleotide-capped mesoporous silica nanoparticles for the detection of miRNA-145 by duplex and triplex formation. Sensors and Actuators B Chemical. 277:598-603. https://doi.org/10.1016/j.snb.2018.09.026 ; S ; 598 ; 603 ; 277

[EN] CuII-macrocycle functionalized hexametaphosphate-capped silica mesoporous nanoparticles have been prepared and used for the selective and sensitive detection of hydrogen sulfide in aqueous environments. The possibility of using different metal complexes combined with different capping anions and choice of different dyes or other sensing molecules as indicators makes this new protocol highly appealing for the preparation of new sensing systems for sulfide detection in different environments. ; Financial support from the Spanish Government (Project MAT2012-38429-C04-01) and the Generalitat Valencia (Project PROMETEOII/2014/047) is gratefully acknowledged. S.E. is grateful to the Generalitat Valenciana for his Santiago Grisolia fellow. ; El Sayed Shehata Nasr, S.; Milani, M.; Licchelli, M.; Martínez-Máñez, R.; Sancenón Galarza, F. (2015). Hexametaphosphate-Capped Silica Mesoporous Nanoparticles Containing CuII Complexes for the Selective and Sensitive Optical Detection of Hydrogen Sulfide in Water. Chemistry - A European Journal. 21(19):7002-7006. https://doi.org/10.1002/chem.201500360 ; S ; 7002 ; 7006 ; 21 ; 19