10 research outputs found
Carbosilane Dendrimer 2G-NN16 Represses Tc17 Differentiation in Primary T CD8+ Lymphocytes
We studied changes in gene expression induced by the
carbosilane
dendrimer 2G-NN16 to evaluate their potential as a vehicle for gene
therapy and as medication. Global gene expression profiles on CD8+
T lymphocytes reveal that ribosomal proteins are induced in the presence
of 2G-NN16. IL17A and IL17F, the principal interleukins secreted by
Tc17 cells, a subset of CD8+ T lymphocytes, were down-regulated when
cultured in the presence of this dendrimer. Microarray results were
confirmed by real time quantitative reverse transcriptase polymerase
chain reaction (qRT-PCR). 2G-NN16 also showed a high potential for
in vitro inhibition of Tc17 differentiation of CD8+ T lymphocytes
in the presence of the Tc17 differentiation molecules IL6 and TGF-B1.
These findings suggest that 2G-NN16 could facilitate drug delivery
and may be used to treat inflammatory processes driven by Tc17 cells
Effects of Hydroxytyrosol and Hydroxytyrosol Acetate Administration to Rats on Platelet Function Compared to Acetylsalicylic Acid
Magnetic Interactions in the Double Perovskites R<sub>2</sub>NiMnO<sub>6</sub> (R = Tb, Ho, Er, Tm) Investigated by Neutron Diffraction
R<sub>2</sub>NiMnO<sub>6</sub> (R = Tb, Ho, Er, Tm) perovskites have been
prepared by soft-chemistry techniques followed by high oxygen-pressure
treatments; they have been investigated by X-ray diffraction, neutron
powder diffraction (NPD), and magnetic measurements. In all cases
the crystal structure is defined in the monoclinic <i>P</i>2<sub>1</sub>/<i>n</i> space group, with an almost complete
order between Ni<sup>2+</sup> and Mn<sup>4+</sup> cations in the octahedral
perovskite sublattice. The low temperature NPD data and the macroscopic
magnetic measurements indicate that all the compounds are ferrimagnetic,
with a net magnetic moment different from zero and a distinct alignment
of Ni and Mn spins depending on the nature of the rare-earth cation.
The magnetic structures are different from the one previously reported
for La<sub>2</sub>NiMnO<sub>6</sub>, with a ferromagnetic structure
involving Mn<sup>4+</sup> and Ni<sup>2+</sup> moments. This spin alignment
can be rationalized taking into account the Goodenough–Kanamori
rules. The magnetic ordering temperature (<i>T</i><sub>CM</sub>) decreases abruptly as the size of the rare earth decreases, since <i>T</i><sub>CM</sub> is mainly influenced by the superexchange
interaction between Ni<sup>2+</sup> and Mn<sup>4+</sup> (Ni<sup>2+</sup>–O–Mn<sup>4+</sup> angle) and this angle decreases
with the rare-earth size. The rare-earth magnetic moments participate
in the magnetic structures immediately below <i>T</i><sub>CM</sub>
Improved Efficiency of Ibuprofen by Cationic Carbosilane Dendritic Conjugates
In
order to improve the efficiency of the anti-inflammatory drug
ibuprofen, cationic carbosilane dendrimers and dendrons with ibuprofen
at their periphery or at their focal point, respectively, have been
synthesized, and the release of the drug was studied using HPLC. Macrophages
were used to evaluate the anti-inflammatory effect of the ibuprofen-conjugated
dendritic systems and compared with mixtures of non-ibuprofen dendritic
systems in the presence of the drug. The cationic ibuprofen-conjugated
dendron was the compound that showed higher anti-inflammatory properties.
It reduces the LPS-induced <i>COX-2</i> expression and decreases
the release of several inflammatory cytokines such as TNFα,
IL-1β, IL-6, and CCL3. These results open new perspectives in
the use of these compounds as drug carriers
Magnetic Silica Nanoparticle Cellular Uptake and Cytotoxicity Regulated by Electrostatic Polyelectrolytes–DNA Loading at Their Surface
Magnetic silica nanoparticles show great promise for drug delivery. The major advantages correspond to their magnetic nature and ease of biofunctionalization, which favors their ability to interact with cells and tissues. We have prepared magnetic silica nanoparticles with DNA fragments attached on their previously polyelectrolyte-primed surface. The remarkable feature of these materials is the compromise between the positive charges of the polyelectrolytes and the negative charges of the DNA. This dual-agent formulation dramatically changes the overall cytotoxicity and chemical degradation of the nanoparticles, revealing the key role that surface functionalization plays in regulating the mechanisms involved
Sepsis of Patients Infected by SARS-CoV-2: Real-World Experience From the International HOPE-COVID-19-Registry and Validation of HOPE Sepsis Score
Background: Patients with sepsis with a concomitant coronavirus (COVID-19) infection are related to a high morbidity and mortality rate. We investigated a large cohort of patients with sepsis with a concomitant COVID-19, and we developed a risk score for the estimation of sepsis risk in COVID-19.Methods: We conducted a sub-analysis from the international Health Outcome Predictive Evaluation Registry for COVID-19 (HOPE-COVID-19-Registry, NCT04334291). Out of 5,837 patients with COVID-19, 624 patients were diagnosed with sepsis according to the Sepsis-3 International Consensus.Results: In multivariable analysis, the following risk factors were identified as independent predictors for developing sepsis: current smoking, tachypnoea (>22 breath per minute), hemoptysis, peripheral oxygen saturation (SpO(2)) <92%, blood pressure (BP) (systolic BP <90 mmHg and diastolic BP <60 mmHg), Glasgow Coma Scale (GCS) <15, elevated procalcitonin (PCT), elevated troponin I (TnI), and elevated creatinine >1.5 mg/dl. By assigning odds ratio (OR) weighted points to these variables, the following three risk categories were defined to develop sepsis during admission: low-risk group (probability of sepsis 3.1-11.8%); intermediate-risk group (24.8-53.8%); and high-risk-group (58.3-100%). A score of 1 was assigned to current smoking, tachypnoea, decreased SpO(2), decreased BP, decreased GCS, elevated PCT, TnI, and creatinine, whereas a score of 2 was assigned to hemoptysis.Conclusions: The HOPE Sepsis Score including nine parameters is useful in identifying high-risk COVID-19 patients to develop sepsis. Sepsis in COVID-19 is associated with a high mortality rate
Characteristic Phenolic Composition of Single-Cultivar Red Wines of the Canary Islands (Spain)
Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial
Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kid-ney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagli-flozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a random-ized controlled trial. Setting & Participants: Participants in the CREDENCE trial. Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kid-ney failure, doubling of serum creatinine con-centration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Out-comes were evaluated by age at baseline (<60, 60-69, and >_70 years) and sex in the intention-to-treat population using Cox regression models.Results: The mean age of the cohort was 63.0 & PLUSMN; 9.2 years, and 34% were female. Older age and female sex were independently associ-ated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (acomposite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.4 8-0.82], and 0.89 [0.61-1.29] for ages <60, 60-69, and >_70 years, respectively; P = 0.3 for interaction) or sexes (HRs, 0.71 [95% CI, 0.5 4-0.95] and 0.69 [0.56-0.8 4] in women and men, respectively; P = 0.8 for interaction). No differences in safety outcomes by age group or sex were observed.Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791