Pregnancy outcomes and newborn characteristics in women with follicular fluid thyroid autoantibodies undergoing assisted reproduction

BackgroundHigher levels of thyroid autoantibodies in follicular fluid (FF) of thyroid autoimmunity (TAI) positive women are strongly correlated with serum levels and may have effect on the post-implantation embryo development. Literature highlights that levothyroxine (LT4) treatment may attenuate the risk of adverse pregnancy outcomes. The aim of the study was to estimate the pregnancy and newborn outcomes in women with FF thyroid autoantibodies undergoing assisted reproductive technology (ART).MethodsThe study population included 24 women with confirmed clinical pregnancy, 8 TAI positive and 16 TAI negative women. LT4 supplementation was applied in 20.8% patients, TAI positive.ResultsPregnancy outcomes were: twin pregnancy rate 41.7%, early miscarriage rate 8.3%, late miscarriage rate 4.2%, preterm birth rate 16.7%, term birth rate 70.8%, live birth rate 96.0%. There was significant difference in serum and in FF TgAbs (p< 0.001)between the groups according to TAI, while serum fT₃ was lower in the group with TAI (p = 0.047). Serum P₄ was higher in LT4 treated group (p = 0.005), with TAI, and newborns in this group had higher birth weight (p = 0.001) and height (p = 0.008). Maternal complications occurred in 23.8% of patients. No congenital malformations in newborns were noted.ConclusionsThyroid autoantibodies present in FF may have an effect on the post-implantation embryo development, but have no effect on further course of pregnancy. The special benefit of LT4 treatment for successful ART outcome was demonstrated for newborn anthropometric parameters.     

Inhibition of mTOR-Dependent Autophagy Sensitizes Leukemic Cells to Cytarabine-Induced Apoptotic Death

The present study investigated the role of autophagy, a cellular self-digestion process, in the cytotoxicity of antileukemic drug cytarabine towards human leukemic cell lines (REH, HL-60, MOLT-4) and peripheral blood mononuclear cells from leukemic patients. The induction of autophagy was confirmed by acridine orange staining of intracellular acidic vesicles, electron microscopy visualization of autophagic vacuoles, as well as by the increase in autophagic proteolysis and autophagic flux, demonstrated by immunoblot analysis of p62 downregulation and LC3-I conversion to autophagosome-associated LC3-II in the presence of proteolysis inhibitors, respectively. Moreover, the expression of autophagy-related genes Atg4, Atg5 and Atg7 was stimulated by cytarabine in REH cells. Cytarabine reduced the phosphorylation of the major negative regulator of autophagy, mammalian target of rapamycin (mTOR), and its downstream target p70S6 kinase in REH cells, which was associated with downregulation of mTOR activator Akt and activation of extracellular signal- regulated kinase. Cytarabine had no effect on the activation of mTOR inhibitor AMP-activated protein kinase. Leucine, an mTOR activator, reduced both cytarabine-induced autophagy and cytotoxicity. Accordingly, pharmacological downregulation of autophagy with bafilomycin A1 and chloroquine, or RNA interference-mediated knockdown of LC3β or p62, markedly increased oxidative stress, mitochondrial depolarization, caspase activation and subsequent DNA fragmentation and apoptotic death in cytarabine-treated REH cells. Cytarabine also induced mTOR-dependent cytoprotective autophagy in HL-60 and MOLT-4 leukemic cell lines, as well as primary leukemic cells, but not normal leukocytes. These data suggest that the therapeutic efficiency of cytarabine in leukemic patients could be increased by the inhibition of the mTOR-dependent autophagic response.     

Regulation of early growth and antioxidant defense mechanism of sweet basil seedlings in response to nutrition

Basil cultivars are among most used crops worldwide, but high level of morpho-physiological variations is mainly due to the cultivation characteristics. The present study aimed to investigate the physiological changes and the accumulation of secondary metabolites as a response to prolonged nutrient deprivation in shoots and roots of sweet basil (Ocimum basilicum L. var. minimum). Sweet basil seedlings were grown in media with quarter, half and full strength of micro and macronutrients under different levels of KNO₃ alone or in combination with different levels of NH₄NO₃. Evaluated parameters included characteristics of germination, development of leaves, content of photosynthetic pigments and responses of different parameters related to oxidative stress. While the early growth is influenced mainly due to NH₄NO₃ presence, all the levels of nutrient supply were found to trigger and maintain the antioxidant defence system of sweet basil seedlings. With the variations among seedling parts, the ammonium nutrition was notably enhanced levels of activity of SOD, CAT, A-POX, G-POX and P-POX, but had no effect on total antioxidant activity and total phenolic content, including flavonoids, which is mainly accumulated in nutrient deprived roots. In addition, phenylalanine ammonia-lyase activity was analysed and potential pathways of secondary metabolites synthesis were discussed. The enzymatic and non-enzymatic system in O. basilicum var. minimum seedlings was capable to reverse the stress conditions during growth under nutrient deprivation.     

Synthesis and Spectral Characterization of Asymmetric Azines Containing a Coumarin Moiety: The Discovery of New Antimicrobial and Antioxidant Agents

Nine unsymmetrical azines containing a coumarin moiety were prepared by the reaction of the hydrazone of 4‐hydroxy‐3‐acetylcoumarin with differently substituted aromatic aldehydes. The azines were fully spectrally characterized, including a complete assignment of ¹H‐ and ¹³C‐NMR resonances, and were assessed for their acute toxicities in the Artemia salina model. Their free radical scavenging activities were tested in the DPPH assay, and in vitro antimicrobial activities were determined against seven bacterial and two fungal strains. The azines containing a p‐hydroxyphenyl group were shown to be the most effective antimicrobial agents, and in the case of resistant strains of Staphylococcus aureus and Acinetobacter baumannii, the activity was comparable to that of chloramphenicol. The derivative having a 3,5‐dimethoxy‐4‐hydroxyphenyl group exhibited pronounced antioxidant power reacting rapidly and in 1 : 1 mol ratio with the DPPH radical.     

Potentiometric stripping analysis of zinc and copper in human teeth and dental materials.

Potentiometric stripping analysis (PSA) with oxygen as the oxidant has been used to determine soluble zinc and copper levels in exfoliated human teeth (all of which required extraction for orthodontic reasons) and commercial dental materials. The soluble zinc and copper contents of teeth were slightly below the zinc and copper contents in whole teeth reported by other researchers, except in the case of tooth with removed amalgam filling. Soluble zinc and copper concentrations of the dental materials and metal ceramic crowns were 0.50-6.30, and of 2.00-4.30 microg/g, respectively. The results of this work suggest that PSA may be a good method for zinc and copper leaching studies during the investigation of dental prosthetic materials' biocompatibility. Corrosive action of acidic media as evidenced by SEM micrographs caused the leaching of metal ions from teeth.     

Modulations of the antioxidants defence system in two maize hybrids during flooding stress

Journal of Plant Research - Flooding stress nowadays is one of the major stressors for plants under climate change. This kind of stress may cause severe depression of the plant’s growth...     

Syndecan-4 is essential for development of concentric myocardial hypertrophy via stretch-induced activation of the calcineurin-NFAT pathway

Sustained pressure overload leads to compensatory myocardial hypertrophy and subsequent heart failure, a leading cause of morbidity and mortality. Further unraveling of the cellular processes involved is essential for development of new treatment strategies. We have investigated the hypothesis that the transmembrane Z-disc proteoglycan syndecan-4, a co-receptor for integrins, connecting extracellular matrix proteins to the cytoskeleton, is an important signal transducer in cardiomyocytes during development of concentric myocardial hypertrophy following pressure overload. Echocardiographic, histochemical and cardiomyocyte size measurements showed that syndecan-4(-/-) mice did not develop concentric myocardial hypertrophy as found in wild-type mice, but rather left ventricular dilatation and dysfunction following pressure overload. Protein and gene expression analyses revealed diminished activation of the central, pro-hypertrophic calcineurin-nuclear factor of activated T-cell (NFAT) signaling pathway. Cardiomyocytes from syndecan-4(-/-)-NFAT-luciferase reporter mice subjected to cyclic mechanical stretch, a hypertrophic stimulus, showed minimal activation of NFAT (1.6-fold) compared to 5.8-fold increase in NFAT-luciferase control cardiomyocytes. Accordingly, overexpression of syndecan-4 or introducing a cell-permeable membrane-targeted syndecan-4 polypeptide (gain of function) activated NFATc4 in vitro. Pull-down experiments demonstrated a direct intracellular syndecan-4-calcineurin interaction. This interaction and activation of NFAT were increased by dephosphorylation of serine 179 (pS179) in syndecan-4. During pressure overload, phosphorylation of syndecan-4 was decreased, and association between syndecan-4, calcineurin and its co-activator calmodulin increased. Moreover, calcineurin dephosphorylated pS179, indicating that calcineurin regulates its own binding and activation. Finally, patients with hypertrophic myocardium due to aortic stenosis had increased syndecan-4 levels with decreased pS179 which was associated with increased NFAT activation. In conclusion, our data show that syndecan-4 is essential for compensatory hypertrophy in the pressure overloaded heart. Specifically, syndecan-4 regulates stretch-induced activation of the calcineurin-NFAT pathway in cardiomyocytes. Thus, our data suggest that manipulation of syndecan-4 may provide an option for therapeutic modulation of calcineurin-NFAT signaling.