Elderberry (
L.) lipophilic and polar extract dietary supplementation effects were evaluated according to diabetes management indices, using an in vivo model. A research pipeline was constructed, ...that ranged from extract preparation, partial chemical characterization and toxicity evaluation, to examining the elderberry extract dietary supplementation effects on biofluid and tissues. Extracts toxicity was screened using an
bioluminescence model. A concentration of up to 60 mg/L was selected, and rat doses for oral supplementation were computed applying the interspecies correlation between
and rats. Wistar type 2 diabetic rats, induced by streptozotocin (STZ), were fed a high-fat diet and supplemented for 4 weeks at doses of 190 and 350 mg/kg body weight/day of lipophilic and polar extract, respectively. As far as we know, lipophilic elderberry extract supplementation was assessed for the first time, while polar extract was administrated at higher doses and for a shorter period compared to previous studies, aiming to evaluate subacute supplementation effects. The polar extract modulated glucose metabolism by correcting hyperglycemia, while the lipophilic extract lowered insulin secretion. Both extracts lowered insulin resistance, without remarkable alterations to hematological indices, sera lipids and sera and tissular trace element homeostasis. In conclusion, elderberries are a potential source of bioactive compounds for formulations to be used as co-adjuvants in diabetes management.
This study investigated the link between the process performance of two denitrifying phosphorus (P) removal systems and their microbial community structure. Two sequencing batch reactors (SBRs) were ...operated with either acetate or propionate as the sole carbon source, and were gradually acclimatised from anaerobic–aerobic to anaerobic–anoxic conditions. It was found that the propionate SBR was able to sustain denitrifying P removal after acclimatisation, while the enhanced biological phosphorus removal (EBPR) activity in the acetate reactor collapsed after the aerobic phase was eliminated. The results suggested that the anoxic glycogen production rate in the acetate SBR was insufficient to support the anaerobic glycogen demand for acetate uptake. The chemical transformations in each SBR suggested that different types of polyphosphate-accumulating organisms (PAOs) were present in each system, possessing different affinities for nitrate. Microbial characterisation with fluorescence
in situ hybridisation (FISH) revealed that
Accumulibacter was the dominant organism in each reactor, although different cell morphotypes were observed. A coccus morphotype was predominant in the acetate SBR while the propionate SBR was enriched in a rod morphotype. It is hypothesised that the coccus morphotype corresponds to an
Accumulibacter strain that is unable to use nitrate as electron acceptor but is able to use oxygen, and possibly nitrite. The rod morphotype is proposed to be a PAO able to use nitrate, nitrite and oxygen. This hypothesis is in agreement with literature studies focussed on the identity of denitrifying PAOs (DPAOs), as well as a recent metagenomic study on
Accumulibacter.
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•Seven new naphthoquinone esters were synthesized in excellent yields (84–97%).•New non-polymeric chemical additives for petroleum based on naphthoquinone were developed.•Rational ...design and study of the structure-activity relationship was performed.•Excellent results as WAT inhibitors and pour point depressants were obtained.•X-ray diffractions, DSC, TG and molecular modeling studies were realized.
Wax deposition is one of the major flow problems for petroleum transportation and production. In this context, the development of more efficient methods to remediate paraffin precipitation has received great attention within the oil industries. In the present study, eight new long-chain esters were prepared in less than four synthetic steps and in high yields (84–97%). Seven of them contain naphthoquinone nuclei, and one presents a cyclohexyl group. The new molecules were tested as non-polymer wax precipitation inhibitors and pour point depressants. Calorimetric experiments were employed to identify the effect of four pre-determined chemical groups within the molecules and to set out the best components for maximized inhibition: (i) the length of alkyl chain in the ester group, (ii) the length of the alkyl chain separating the polar nuclei and the ester group, (iii) the heteroatom bonded to the polar nuclei, and (iv) the importance of the naphthoquinone nuclei. After determination of the pour point and wax appearance temperature (WAT) of Brazilian oils by differential scanning calorimetry (DSC), the highest efficiency was observed for naphthoquinone esters derived from stearic and palmitic acids when containing two methylene groups as a separator and nitrogen as the heteroatom. These new additives present better results than the commercially available polymer-based inhibitors in all tested samples, even when applied at smaller concentrations, compared to many other polymer-based inhibitors reported in the literature. The importance of the naphthoquinone moiety as the polar portion of the inhibitor was confirmed when it was replaced by a cyclohexyl group. Molecular modeling and X-ray diffraction studies were also carried out to rationalize the relationship between structure and activity and the action mechanism of these new chemical additives.
In2O3 and La3+-doped In2O3 nanostructures were synthesized through a facile and fast chemical route based on the microwave-assisted hydrothermal method combined with rapid thermal treatment in a ...microwave oven. The presence of the La3+ doping process modifies the size and morphology of the In2O3 nanostructures and also stabilizes the rhombohedral (rh) In2O3 phase with respect to the most stable cubic (bcc) polymorph. X-ray diffraction (XRD) patterns and Rietveld refinements, Raman, UV–vis, and energy dispersive X-ray (EDX) spectroscopies, transmission electron (TEM) and field-emission scanning electron (FE-SEM) microscopies, as well as PL emissions have been performed. To complement and rationalize the experimental results, first-principle calculations, based on density functional theory, are carried out to obtain the formation energies of the In2O3 and bcc- and rh-In2O3-doped phases, their geometry and electronic properties. Theoretical results are able to explain the relative stabilization of the rh-phase with respect to the bcc-phase based on the analysis geometry changes and the electronic redistribution induced by the La3+ doping process. In addition, Wulff construction is employed to match the theoretical and experimental morphologies of the cubic phase. The synthesized samples were applied for the O2 evolution reaction (OER). The La3+-doped In2O3 film presents superior electrocatalytic activity, with an onset potential lower than the undoped In2O3 film that can be associated with the increase in electron density caused by the La3+ doping process. This study provides a versatile strategy for obtaining In2O3 and La3+-doped In2O3 nanostructures for practical applications.
No consensus has been reached regarding the influence of the flapless and open-flap surgical techniques on the placement of dental implants. This systematic review compared the effects of flapless ...implant placement and implant placement with elevation of the mucoperiosteal flap in terms of marginal bone loss, implant survival rate and complications rates. This review followed PRISMA guidelines and was registered in PROSPERO with the registration number CRD42017071475. Two independent reviewers performed a comprehensive search of the PubMed/MEDLINE, Scopus, and Cochrane Library databases for studies published until December 2017. The search identified 559 references. After a detailed review, 24 studies were assessed for eligibility. A total of 1025 patients who had received a total of 1873 dental implants were included. There were no significant differences between the flapless and open-flap surgical techniques in terms of implant survival rates (P=0.34; risk ratio (RR): 1.36; confidence interval (CI): 0.72–2.56), marginal bone loss (P=0.23; MD: −0.20; CI: −0.52–0.13), or complication rates (P=0.67; RR: 1.10; CI: 0.70–1.73). The current meta-analysis showed that the implant survival rate, marginal bone levels, and complications of flapless surgery were similar to those of open-flap surgery over a mean follow-up period of 21.62 months.
Summary
Splinted and unsplinted overdenture attachment systems have unique advantages and disadvantages. The aim of the present systematic review was to determine the influence of splinted and ...unsplinted overdenture attachment systems on the marginal bone loss, prosthetic complications and implant survival rate. PubMed/MEDLINE, Scopus and Cochrane databases were searched for articles published up to October 2017, using the following search terms: “overdenture AND attachment OR overdenture AND bar OR overdenture splinted.” The PICO question “Do splinted overdenture attachment systems promote better clinical results in comparison to unsplinted systems?” was evaluated. Eligible studies included randomized controlled clinical trials, prospective studies with at least 10 participants and a minimum follow‐up of 6 months, and studies published in English that compared splinted and unsplinted attachment systems within the same study. The 95% confidence interval (CI) was considered for all outcomes analysed. After completion of the different steps in the article selection process, nine articles were included in the qualitative and quantitative analyses. A total of 984 implants were placed in 380 patients (mean age: 62.8 years). The meta‐analysis demonstrated no statistically significant differences between splinted and unsplinted attachment systems with regard to marginal bone loss (P = .39; MD: −0.11; 95% CI: −0.37 to 0.14), complications (P = .31; RR: 1.26; CI: 0.80‐1.99) and implant survival rate (P = .14; RR: 0.37% CI: 0.10‐1.36). In addition, splinted and unsplinted overdenture attachment systems achieved similar results with regard to marginal bone loss, prosthetic complications and implant survival rate.
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•Ten enamine naphthoquinones were satisfactorily synthesized.•The antiproliferative activity were determined in four human cancer line cell.•Qualitative Structure/Biological Activity ...relationship was made.•Docking indicated that molecules inhibit topoisomerase and thymidylate synthase.
We synthesized ten enamine naphthoquinones with yields ranging from 43 to 76%. These compounds were screened for their in vitro antiproliferative activities by MTT assay against four types of human cancer cell lines: HCT116, PC3, HL60 and SNB19. The naphthoquinones bearing the picolylamine (7) and quinoline (12) moieties were the most actives (IC50 < 24 μM for all the cell lines), which were comparable or better to the values obtained for the control drugs. In silico evaluations allowed us to develop a qualitative Structure-Activity Relationship which suggest that electrostatic features, particularly the C2–C3 internuclear repulsion and the molecular dipole moment, relate to the biological response. Furthermore, Molecular Docking simulations indicate that the synthetic compounds have the potential to act as anticancer molecules by inhibiting topoisomerase-II and thymidylate synthase.
The 17-beta-hydroxysteroid dehydrogenase type 3 (17-β-HSD3) enzyme converts androstenedione to testosterone and is encoded by the HSD17B3 gene. Homozygous or compound heterozygous HSD17B3 mutations ...block the synthesis of testosterone in the fetal testis, resulting in a Disorder of Sex Development (DSD). We describe a child raised as a female in whom the discovery of testes in the inguinal canals led to a genetic study by whole exome sequencing (WES) and to the identification of a compound heterozygous mutation of the HSD17B3 gene (c.608C>T, p.Ala203Val, and c.645A>T, p.Glu215Asp). Furthermore, we review all HSD17B3 mutations published so far in cases of 17-β-HSD3 deficiency. A total of 70 different HSD17B3 mutations have so far been reported in 239 patients from 187 families. A total of 118 families had homozygous mutations, 63 had compound heterozygous mutations and six had undetermined genotypes. Mutations occurred in all 11 exons and were missense (55%), splice-site (29%), small deletions and insertions (7%), nonsense (5%), and multiple exon deletions and duplications (2%). Several mutations were recurrent and missense mutations at codon 80 and the splice-site mutation c.277+4A>T each represented 17% of all mutated alleles. These findings may be useful to those involved in the clinical management and genetic diagnosis of this disorder.
Maladaptive responses to stress adversely affect human behavior, yet the signaling mechanisms underlying stress-responsive behaviors remain poorly understood. Using a conditional gene knockout ...approach, the α isoform of p38 mitogen-activated protein kinase (MAPK) was selectively inactivated by AAV1-Cre-recombinase infection in specific brain regions or by promoter-driven excision of p38α MAPK in serotonergic neurons (by
Slc6a4-Cre or
ePet1-Cre) or astrocytes (by
Gfap-CreERT2). Social defeat stress produced social avoidance (a model of depression-like behaviors) and reinstatement of cocaine preference (a measure of addiction risk) in wild-type mice, but not in mice having p38α MAPK selectively deleted in serotonin-producing neurons of the dorsal raphe nucleus. Stress-induced activation of p38α MAPK translocated the serotonin transporter to the plasma membrane and increased the rate of transmitter uptake at serotonergic nerve terminals. These findings suggest that stress initiates a cascade of molecular and cellular events in which p38α MAPK induces a hyposerotonergic state underlying depression-like and drug-seeking behaviors.
► p38α MAPK is for stress-induced behaviors including depression and addiction ► Selective p38α MAPK deletion in serotonergic neurons produces stress resilience ► p38α MAPK activation translocates the serotonin transporter ► Stress-induced dysphoria is caused by hyposerotoninergic tone
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