The prevalence of cardiovascular and metabolic diseases is increased in postmenopausal women, which contributes to the burden of illnesses in this period of life. Yerba mate (Ilex paraguariensis) is ...a native bush from Southern South America. Its leaves are rich in phenolic components, which may have antioxidant, vasodilating, hypocholesterolemic, and hypoglycemic proprieties. This post hoc analysis of the case-control study nested in the Obesity and Bone Fracture Cohort evaluated the consumption of yerba mate and the prevalence of hypertension, dyslipidemia, and coronary diseases in postmenopausal women. Ninety-five postmenopausal women were included in this analysis. A questionnaire was applied to evaluate the risk factors and diagnosis of cardiovascular diseases and consumption of yerba mate infusion. Student's t-test and chi-square test were used to assess significant differences between groups. The group that consumed more than 1 L/day of mate infusion had significantly fewer diagnoses of coronary disease, dyslipidemia, and hypertension (P<0.049, P<0.048, and P<0.016, respectively). Furthermore, the serum levels of glucose were lower in the group with a higher consumption of yerba mate infusion (P<0.013). The serum levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides were similar between the groups. This pragmatic study points out the benefits of yerba mate consumption for the cardiovascular and metabolic systems. The ingestion of more than 1 L/day of mate infusion was associated with fewer self-reported cardiovascular diseases and lower serum levels of glucose. Longitudinal studies are needed to evaluate the association between yerba mate infusion and reduction of cardiovascular diseases in postmenopausal women.
Parkinson's disease (PD) is characterized by progressive motor impairment attributed to progressive loss of dopaminergic neurons in the substantia nigra (SN) pars compacta. In addition to an ...accumulation of iron, there is also an increased production of reactive oxygen/nitrogen species (ROS/RNS) and inflammatory markers. These observations suggest that iron dyshomeostasis may be playing a key role in neurodegeneration. However, the mechanisms underlying this metal-associated oxidative stress and neuronal damage have not been fully elucidated. To determine peripheral levels of iron, ferritin, and transferrin in PD patients and its possible relation with oxidative/nitrosative parameters, whilst attempting to identify a profile of peripheral biomarkers in this neurological condition. Forty PD patients and 46 controls were recruited to compare serum levels of iron, ferritin, transferrin, oxidative stress markers (superoxide dismutase (SOD), catalase (CAT), nitrosative stress marker (NOx), thiobarbituric acid reactive substances (TBARS), non-protein thiols (NPSH), advanced oxidation protein products (AOPP), ferric reducing ability of plasma (FRAP) and vitamin C) as well as inflammatory markers (NTPDases, ecto-5'-nucleotidase, adenosine deaminase (ADA), ischemic-modified albumin (IMA) and myeloperoxidase). Iron levels were lower in PD patients, whereas there was no difference in ferritin and transferrin. Oxidative stress (TBARS and AOPP) and inflammatory markers (NTPDases, IMA, and myeloperoxidase) were significantly higher in PD, while antioxidants FRAP, vitamin C, and non-protein thiols were significantly lower in PD. The enzymes SOD, CAT, and ecto-5'-nucleotidase were not different among the groups, although NOx and ADA levels were significantly higher in the controls. Our data corroborate the idea that ROS/RNS production and neuroinflammation may dysregulate iron homeostasis and collaborate to reduce the periphery levels of this ion, contributing to alterations observed in the pathophysiology of PD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Decacene: On‐Surface Generation Krüger, Justus; García, Fátima; Eisenhut, Frank ...
Angewandte Chemie International Edition,
September 18, 2017, Letnik:
56, Številka:
39
Journal Article
Recenzirano
Acenes are intriguing molecules with unique electronic properties. The difficulties in their preparation owing to low stability under ambient conditions are apparent because successful syntheses of ...long unsubstituted acenes are still scarce, in spite of the great attention they have attracted. Only unsubstituted acenes up to heptacene have been isolated in bulk, with nonacene being the largest acene detected to date. Herein we use on‐surface assisted reduction of tetraepoxy decacene precursors on Au(111) as the key step to generate unprecedented decacene which is visualized and its electronic resonances studied by scanning tunneling microscopy (STM) and spectroscopy (STS).
Decathletes: Combined efforts of organic synthesis and on‐surface chemistry have led to the preparation of decacene for the first time. An iterative sequence of aryne cycloadditions was used to synthesize stable tetraepoxy precursors which were reduced on Au(111) to obtain unprecedented decacene as visualized by scanning tunneling microscopy (STM).
Cancer cells secrete factors that influence adjacent cell behavior and can lead to enhanced proliferation and metastasis. To better understand the role of these factors in oncogenesis and disease ...progression, estrogen and progesterone receptor positive MCF-7 cells, triple negative breast cancer MDA-MB-231, DT22, and DT28 cells, and MCF-10A non-transformed mammary epithelial cells were grown in 3D cultures. A special emphasis was placed on triple negative breast cancer since these tumors are highly aggressive and no targeted treatments are currently available. The breast cancer cells secreted factors of variable potency that stimulated proliferation of the relatively quiescent MCF-10A cells. The conditioned medium from each cell line was subjected to mass spectrometry analysis and a variety of secreted proteins were identified including glycolytic enzymes, proteases, protease inhibitors, extracellular matrix proteins, and insulin-like growth factor binding proteins. An investigation of the secretome from each cell line yielded clues about strategies used for breast cancer proliferation and metastasis. Some of the proteins we identified may be useful in the development of a serum-based test for breast cancer detection, diagnosis, prognosis, and monitoring.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The use of broad spectrum chemotherapeutic agents to treat breast cancer results in substantial and debilitating side effects, necessitating the development of targeted therapies to limit tumor ...proliferation and prevent metastasis. In recent years, the list of approved targeted therapies has expanded, and it includes both monoclonal antibodies and small molecule inhibitors that interfere with key proteins involved in the uncontrolled growth and migration of cancer cells. The targeting of plasma membrane proteins has been most successful to date, and this is reflected in the large representation of these proteins as targets of newer therapies. In view of these facts, experiments were designed to investigate the plasma membrane proteome of a variety of human breast cancer cell lines representing hormone-responsive, ErbB2 over-expressing and triple negative cell types, as well as a benign control. Plasma membranes were isolated by using an aqueous two-phase system, and the resulting proteins were subjected to mass spectrometry analysis. Overall, each of the cell lines expressed some unique proteins, and a number of proteins were expressed in multiple cell lines, but in patterns that did not always follow traditional clinical definitions of breast cancer type. From our data, it can be deduced that most cancer cells possess multiple strategies to promote uncontrolled growth, reflected in aberrant expression of tyrosine kinases, cellular adhesion molecules, and structural proteins. Our data set provides a very rich and complex picture of plasma membrane proteins present on breast cancer cells, and the sorting and categorizing of this data provides interesting insights into the biology, classification, and potential treatment of this prevalent and debilitating disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Endogenous small RNAs (endo-siRNAs) interact with Argonaute (AGO) proteins to mediate sequence-specific regulation of diverse biological processes. Here, we combine deep-sequencing and genetic ...approaches to explore the biogenesis and function of endo-siRNAs in C. elegans. We describe conditional alleles of the Dicer-related helicase, drh-3, that abrogate both RNA interference and the biogenesis of endo-siRNAs, called 22G-RNAs. DRH-3 is a core component of RNA-dependent RNA polymerase (RdRP) complexes essential for several distinct 22G-RNA systems. We show that, in the germline, one system is dependent on worm-specific AGOs, including WAGO-1, which localizes to germline nuage structures called P granules. WAGO-1 silences certain genes, transposons, pseudogenes, and cryptic loci. Finally, we demonstrate that components of the nonsense-mediated decay pathway function in at least one WAGO-mediated surveillance pathway. These findings broaden our understanding of the biogenesis and diversity of 22G-RNAs and suggest additional regulatory functions for small RNAs.
With the wide availability of massively parallel sequencing technologies, genetic mapping has become the rate limiting step in mammalian forward genetics. Here we introduce a method for real-time ...identification of N -ethyl- N -nitrosourea-induced mutations that cause phenotypes in mice. All mutations are identified by whole exome G1 progenitor sequencing and their zygosity is established in G2/G3 mice before phenotypic assessment. Quantitative and qualitative traits, including lethal effects, in single or multiple combined pedigrees are then analyzed with Linkage Analyzer, a software program that detects significant linkage between individual mutations and aberrant phenotypic scores and presents processed data as Manhattan plots. As multiple alleles of genes are acquired through mutagenesis, pooled “superpedigrees” are created to analyze the effects. Our method is distinguished from conventional forward genetic methods because it permits (1) unbiased declaration of mappable phenotypes, including those that are incompletely penetrant (2), automated identification of causative mutations concurrent with phenotypic screening, without the need to outcross mutant mice to another strain and backcross them, and (3) exclusion of genes not involved in phenotypes of interest. We validated our approach and Linkage Analyzer for the identification of 47 mutations in 45 previously known genes causative for adaptive immune phenotypes; our analysis also implicated 474 genes not previously associated with immune function. The method described here permits forward genetic analysis in mice, limited only by the rates of mutant production and screening.
Significance In forward genetics, a mutagen is used to randomly induce germline mutations that cause variant phenotypes. Forward genetics permits discovery of genes necessary for biological phenomena, but identifying the mutations that cause variant phenotypes is time-consuming and in the past usually occurred long after the phenotype was first recognized. Here we introduce a method and software tool, Linkage Analyzer, for identifying causative mutations present in the germline of mutant mice concurrent with recognition of variant phenotypes. It requires knowledge of genotype at all mutation sites in members of a pedigree prior to phenotypic assessment. Using this method and software, forward genetic studies in mice are limited only by the rates of mutant production and screening.
Background
Endotracheal intubation is a commonly performed procedure in neonates, the risks of which are well‐described. Some endotracheal tubes (ETT) are equipped with a cuff that can be inflated ...after insertion of the ETT in the airway to limit leak or aspiration. Cuffed ETTs have been shown in larger children and adults to reduce gas leak around the ETT, ETT exchange, accidental extubation, and exposure of healthcare workers to anesthetic gas during surgery. With improved understanding of neonatal airway anatomy and the widespread use of cuffed ETTs by anesthesiologists, the use of cuffed tubes is increasing in neonates.
Objectives
To assess the benefits and harms of cuffed ETTs (inflated or non‐inflated) compared to uncuffed ETTs for respiratory support in neonates.
Search methods
We searched CENTRAL, PubMed, and CINAHL on 20 August 2021; we also searched trial registers and checked reference lists to identify additional studies.
Selection criteria
We included randomized controlled trials (RCTs), quasi‐RCTs, and cluster‐randomized trials comparing cuffed (inflated and non‐inflated) versus uncuffed ETTs in newborns. We sought to compare 1. inflated, cuffed versus uncuffed ETT; 2. non‐inflated, cuffed versus uncuffed ETT; and 3. inflated, cuffed versus non‐inflated, cuffed ETT.
Data collection and analysis
We used the standard methods of Cochrane Neonatal. Two review authors independently assessed studies identified by the search strategy for inclusion, extracted data, and assessed risk of bias. We used the GRADE approach to assess the certainty of evidence.
Main results
We identified one eligible RCT for inclusion that compared the use of cuffed (inflated if ETT leak greater than 20% with cuff pressure 20 cm H2O or less) versus uncuffed ETT. The author provided a spreadsheet with individual data. Among 76 infants in the original manuscript, 69 met the inclusion and exclusion criteria for this Cochrane Review. We found possible bias due to lack of blinding and other bias.
We are very uncertain about frequency of postextubation stridor, because the confidence intervals (CI) of the risk ratio (RR) were very wide (RR 1.36, 95% CI 0.35 to 5.25; risk difference (RD) 0.03, −0.11 to 0.18; 1 study, 69 participants; very low‐certainty evidence).
No neonate was diagnosed with postextubation subglottic stenosis; however, endoscopy was not available to confirm the clinical diagnosis.
We are very uncertain about reintubation for stridor or subglottic stenosis because the CIs of the RR were very wide (RR 0.27, 95% CI 0.01 to 6.49; RD −0.03, 95% CI −0.11 to 0.05; 1 study, 69 participants; very low‐certainty evidence).
No neonate had surgical intervention (e.g. endoscopic balloon dilation, cricoid split, tracheostomy) for stridor or subglottic stenosis (1 study, 69 participants).
Neonates randomized to cuffed ETT may be less likely to have a reintubation for any reason (RR 0.06, 95% CI 0.01 to 0.45; RD −0.39, 95% CI −0.57 to −0.21; number needed to treat for an additional beneficial outcome 3, 95% CI 2 to 5; 1 study, 69 participants; very low‐certainty evidence).
We are very uncertain about accidental extubation because the CIs of the RR were wide (RR 0.82, 95% CI 0.12 to 5.46; RD −0.01, 95% CI −0.12 to 0.10; 1 study, 69 participants; very low‐certainty evidence).
We are very uncertain about all‐cause mortality during initial hospitalization because the CIs of the RR were extremely wide (RR 2.46, 95% CI 0.10 to 58.39; RD 0.03, 95% CI −0.05 to 0.10; 1 study, 69 participants; very low‐certainty evidence).
There is one ongoing trial. We classified two studies as awaiting classification because outcome data were not reported separately for newborns and older infants.
Authors' conclusions
Evidence for comparing cuffed versus uncuffed ETTs in neonates is limited by a small number of babies in a single RCT with possible bias. There is very low certainty evidence for all outcomes of this review. CIs of the estimate for postextubation stridor were wide. No neonate had clinical evidence for subglottic stenosis; however, endoscopy results were not available to assess the anatomy.
Additional RCTs are necessary to evaluate the benefits and harms of cuffed ETTs (inflated and non‐inflated) in the neonatal population. These studies must include neonates and be conducted both for short‐term use (in the setting of the operating room) and chronic use (in the setting of chronic lung disease) of cuffed ETTs.
Abstract IgA nephropathy (IgAN) is the most prevalent form of chronic glomerulonephritis in the world. The underlying pathogenesis of this autoimmune disease comprises the formation of immune ...complexes, including glycan-specific IgA1 or IgG antibodies and an aberrant glycosylation of IgA1. Until now, anatomopathological analysis of renal biopsies is essential for the diagnosis of IgAN and different histological classification systems have been proposed, e.g. the Oxford classification. However, a percutaneous renal biopsy is frequently not performed for several reasons and the Oxford classification system has some limitations. Since the poor prognosis of IgAN patients is partly the result of a delayed diagnosis, there is an urgent need for reliable noninvasive biomarkers that might be applicable in routine clinical practice. This article reviews the advances on the understanding of the underlying pathophysiological mechanisms of IgAN and discusses in depth the recent development of new biomarkers, including the use of proteomics and microRNAs.
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