Life & Health Sciences

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Luminescence Properties of Self-Aggregating Tb III-DOTA-Functionalized Calix[4]arenes


ABSTRACT

Self-aggregating calix[4]arenes carrying four DOTA ligands on the upper rim for stable complexation of paramagnetic Gd III-ions have already been proposed as MRI probes. In this work, we investigate the luminescence properties of Tb III-DOTA-calix[4]arene-4OPr containing four propyl-groups and compare them with those of the analog substituted with a phthalimide chromophore (Tb III-DOTA-calix[4]arene-3OPr-OPhth). We show that, given its four aromatic rings, the calix[4]arene core acts as an effective sensitizer of Tb-centered luminescence. Substituents on the lower rim can modulate the aggregation behavior, which in turn determines the luminescence properties of the compounds. In solid state, the quantum yield of the phthalimide derivative is almost three times as high as that of the propyl-functionalized analog demonstrating a beneficial role of the chromophore on Tb-luminescence. In solution, however, the effect of the phthalimide group vanishes, which we attribute to the large distance between the chromophore and the lanthanide, situated on the opposite rims of the calix[4]arene. Both quantum yields and luminescence lifetimes show clear concentration dependence in solution, related to the strong impact of aggregation on the luminescence behavior. We also evidence the variability in the values of the critical micelle concentration depending on the experimental technique. Such luminescent calix[4]arene platforms accommodating stable lanthanide complexes can be considered valuable building blocks for the design of dual MR/optical imaging probes.


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Agrobiological Interactions of Essential Oils of Two Menthol Mints: Mentha piperita and Mentha arvensis


ABSTRACT

This review article discusses the active constituents and potential of two menthol mint oils, Mentha piperita (MPEO) and Mentha arvensis (MAEO), as natural sources for botanical pesticides. The biological activities of these menthol mint oils, which can be useful in agriculture, have been broadly researched, especially toward phytotoxic microorganisms. To a lesser extent, the insecticidal and herbicidal activities of mint EOs have also been studied. It is apparent that the prospect of using menthol mint oils in agriculture is increasing in popularity. A number of investigations showed that the in vitro efficacy of MPEO and MAEO, as well as that of their main constituent, menthol, is pronounced. The results of in vitro research are useful for choosing EOs for further investigations. However, it is clear that in situ experiments are crucial and should be more extensively developed. At the same time, known techniques are to be applied to this area and new methods should be worked out, aiming at the improvement of EOs’ pesticidal efficacy and cost-effectiveness, for future implementation in agricultural pest control.


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FSH treatment of male idiopathic infertility: Time for a paradigm change


ABSTRACT

Follicle‐stimulating hormone (FSH) has been used in inconclusive clinical trials for male idiopathic infertility in the past. FSH is sometimes prescribed empirically for male idiopathic infertility, showing some improvement in sperm parameters in about half of the patients. In this opinion article, we briefly analyze the pathophysiological evidences in favor of a more aggressive approach in planning future studies on pharmacological FSH use in male infertility, in analogy with the FSH use for multiple follicular growth in women undergoing ovarian stimulation for assisted reproduction. There is sufficient evidence that spermatogenesis does not run at its top in the primate and that some extra FSH can stimulate spermatogenesis over its baseline. Existing data suggest that the pharmacological regimens applied so far were insufficient, both in dosage and in duration, to elicit this response in about half of the patients. A paradigm change is needed now: We should move away from the classical, endocrinological approach, which simply applied the substitutive, therapeutic regimen used in hypogonadotropic hypogonadism, toward testing a ‘testicular hyperstimulation’ scheme for a time sufficient to cover more than only one spermatogenic cycle, a concept to be verified in an appropriately controlled, prospective, randomized clinical trial.


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LAPTM4B gene polymorphism augments the risk of cancer: Evidence from an updated meta‐analysis


ABSTRACT

Lysosome‐associated protein transmembrane‐4 beta (LAPTM4B) has two alleles named as LAPTM4B*1 and LAPTM4B*2 (GenBank No. AY219176 and AY219177). Allele *1 has a single copy of a 19‐bp sequence in the 5` untranslated region (5`UTR), but allele *2 contains tandem repeats of 19‐bp sequence. LAPTM4B gene is located on long chromosome 8 (8q22.1) and contains seven exons that encodes two isoforms of tetratransmembrane proteins, LAPTM4B‐24 and LAPTM4B‐35, with molecular weights of 25 kDa and 35 kDa respectively. The LAPTM4B‐35′s primary structure is formed by 317 amino acid residues, and LAPTM4B‐24 comprised 226 amino acids. LAPTM4B, an integral membrane protein, contains several lysosomal‐targeting motifs at the C terminus and colocalizes with late endosomal and lysosomal markers. LAPTM4B is a proto‐oncogene, which becomes up‐regulated in various cancers. Preceding studies have examined the possible link between LAPTM4B polymorphism and susceptibility to several cancers,but the findings are still inconsistent. Hence, the present meta‐analysis was designed to investigate the impact of LAPTM4B polymorphism on risk of cancer.


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Association of PDCD6 polymorphisms with the risk of cancer: Evidence from a meta-analysis


ABSTRACT

This study was designed to evaluate the relationship between Programmed cell death protein 6 (PDCD6) polymorphisms and cancer susceptibility. The online databases were searched for relevant case-control studies published up to November 2017. Review Manage (RevMan) 5.3 was used to conduct the statistical analysis. The pooled odds ratio (OR) with its 95% confidence interval (CI) was employed to calculate the strength of association. Overall, our results indicate that PDCD6 rs3756712 T>G polymorphism was significantly associated with decreased risk of cancer under codominant (OR = 0.82, 95%CI = 0.70–0.96, p = 0.01, TG vs TT; OR = 0.53, 95%CI = 0.39-0.72, p < 0.0001, GG vs TT), dominant (OR = 0.76, 95%CI = 0.66-0.89, p = 0.0004, TG+GG vs TT), recessive (OR = 0.57, 95%CI = 0.43-0.78, p = 0.0003, GG vs TT+TG), and allele (OR = 0.76, 95%CI = 0.67–0.86, p < 0.00001, G vs T) genetic model. The finding did not support an association between rs4957014 T>G polymorphism of PDCD6, and different cancers risk.


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Structure and properties of slow-resorbing nanofibers obtained by (co-axial) electrospinning as tissue scaffolds in regenerative medicine


ABSTRACT

With the rapid advancement of regenerative medicine technologies, there is an urgent need for the development of new, cell-friendly techniques for obtaining nanofibers—the raw material for an artificial extracellular matrix production. We investigated the structure and properties of PCL10 nanofibers, PCL5/PCL10 core-shell type nanofibers, as well as PCL5/PCLAg nanofibres prepared by electrospinning. For the production of the fiber variants, a 5–10% solution of polycaprolactone (PCL) (Mw = 70,000–90,000), dissolved in a mixture of formic acid and acetic acid at a ratio of 70:30 m/m was used. In order to obtain fibers containing PCLAg 1% of silver nanoparticles was added. The electrospin was conducted using the above-described solutions at the electrostatic field. The subsequent bio-analysis shows that synthesis of core-shell nanofibers PCL5/PCL10, and the silver-doped variant nanofiber core shell PCL5/PCLAg, by using organic acids as solvents, is a robust technique. Furthermore, the incorporation of silver nanoparticles into PCL5/PCLAg makes such nanofibers toxic to model microbes without compromising its biocompatibility. Nanofibers obtained such way may then be used in regenerative medicine, for the preparation of extracellular scaffolds: (i) for controlled bone regeneration due to the long decay time of the PCL, (ii) as bioscaffolds for generation of other types of artificial tissues, (iii) and as carriers of nanocapsules for local drug delivery. Furthermore, the used solvents are significantly less toxic than the solvents for polycaprolactone currently commonly used in electrospin, like for example chloroform (CHCl3), methanol (CH3OH), dimethylformamide (C3H7NO) or tetrahydrofuran (C4H8O), hence the presented here electrospin technique may allow for the production of multilayer nanofibres more suitable for the use in medical field.


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How to make a little worm pump like a big worm


ABSTRACT

Infections with parasitic helminths expose serious health threats to humans and animals alike. Prevention of disease is dependent on the effective treatment using anthelmintics. Unfortunately, anthelmintic resistance (AR) has evolved in many helminth species during the past decades and meanwhile poses a major constraint to established worm control approaches. This project aimed to improve our understanding of the molecular mechanisms by which helminths, particularly the potentially deadly horse parasite Parascaris sp., become capable of withstanding drug treatment. To this end, Parascaris P-glycoproteins (Pgp), belonging to an important group of mediators of anthelmintic resistance, were introduced into the model organism Caenorhabditis elegans using the CRISPR/Cas9 technology. The resulting transgenic lines will subsequently be analyzed to functionally elucidate the role of putatively AR-associated Parascaris Pgp sequence polymorphisms.


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Pleotropism of gonadotropin action


ABSTRACT

Evidence exists that the gonadotropins LH and FSH can substitute to each other under certain circumstances, in addition to the fact that they can act together in granulosa cells. The aim of this study is to investigate how the two human gonadotropins influence each other in granulosa cells expressing both receptors, or by co-culturing cells expressing either the LHCGR or the FSHR (as a model granulosa/theca interaction). Plasmids encoding the c-myc-tagged-LHCGR and the FLAG-tagged FSHR under the control of an inducible coumermycin-responsive or doxycycline-responsive promoter, respectively were produced. These plasmids were used to permanently transfect human granulosa cell-derived KGN cells and HEK293 cells. The following cell lines were obtained and partially characterized: #1 c-myc-tagged-LHCGR-KGN; #2 FLAG-tagged FSHR_HEK293; #3 FLAG-tagged FSHR-KGN; #4 Double, c-myc-tagged-LHCGR and FLAG-tagged FSHR-KGN. After induction of receptor expression, the cell lines #1 and #2 and #3 responded to hCG and FSH stimulation, respectively by producing cAMP. Receptor expression was demonstrated by RT-PCR and flow cytometry. The characterization of the cell line #4 is ongoing. These cell lines are now available for the study of cell signaling and steroid synthesis, as well as in silico modeling, to gain insight into the dynamics of the intertwined cell response to FSH and LH in granulosa cells. These experiments will continue in parallel in both laboratories involved. Our cell lines represent new, very valuable instruments for the study of molecular pharmacology of FSH and LH, in order to improve infertility treatment, (multi)follicular growth for assisted reproduction, ovulation and spermatogenesis.


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Strategies to enhance cosmeceuticals in in vitro cultures of herbal plants


ABSTRACT

Herbal plants accumulate large amounts of phenolics and pentacyclic triterpenes. The present research project deals with the in vitro culture induction from stem and leaf explants of several medicinal plant species of Centre-Val de Loire under various plant growth regulators (PGRs) for the production of antioxidant and anti-ageing compounds. Among all the tested PGRs, auxins and cytokinins used alone or in combination induced callogenesis in stem/leaf-derived explants. Callus culture displayed feasible total phenolic content and antioxidant activity under optimum hormonal combination. HPLC analysis revealed the presence of plectranthoic acid, oleanolic acid, betulinic acid, caffeic acid and rosmarinic acid. Complete antioxidant and anti-aging potential of extracts with very contrasting phytochemical profiles were investigated. Correlation analyses revealed rosmarinic acid as the main contributor for antioxidant activity and anti-aging hyaluronidase, advance glycation end-products inhibition and SIRT1 activation, whereas, pentacyclic triterpenoids were correlated with elastase, collagenase and tyrosinase inhibition. Altogether, these results clearly evidenced the great valorization potential of herbal plants from CVL for the production of antioxidant and anti-aging bioactive extracts for cosmetic applications.


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Characterization of limbic system connectivity through fiber dissection and diffusion imaging techniques


ABSTRACT

Although cortical elements of the limbic system are quite well defined, the underlying white matter pathways are not well detailed. This project aimed to better describe white matter tracts of the limbic system using both fiber dissection, and in and ex vivo Diffusion Weighted Imaging (DWI) techniques. In vivo data (from DWI and neuropsychological evaluations) were obtained from healthy subjects aged 82 and over previously enrolled in the FIBRATLAS project funded by the French Research Agency and run in the host laboratory. Correlations between neuropsychological and white matter characteristics on DWI were examined in this group to infer function of the limbic white matter tracts. Ex vivo data from the FIBRATLAS project database and from the Tours Body Donation Program were examined. The brains were extracted and used to study the anatomy of the limbic white matter tracts employing both DWI and fiber dissection according to a variant of the Klingler’s method.