Lipoteichoic acid and molecular weight of hyaluronic acid could explain the late inflammatory response trigger by hyaluronic acid fillers

Introduction: Hyaluronic acid is a safe dermal filler, but sometimes late granuloma is generated. This adverse effect is an inflammatory process, and its causes are not clear. Late granuloma generation could be due to the reaction to residual components of the bacterial wall present into hyaluronic acid, such as lipoteichoic acid (LTA). Other possibility is hyaluronic acid degraded could be trigger this inflammatory reaction. // Objective: Study possible molecular mechanism that could be implicated into the late granuloma formation. We wonder whereas inflammatory response activation is triggered by lower molecular weight hyaluronic acid or Gram-positive bacterial components as LTA. // Methods: We analyzed one adverse case generated by hyaluronic acid injections. Our study with one nodule through chemical and immunofluorescence histologic technics. // Results: In this case, observe a late granuloma without infectious process. Histological analysis shown few large Langerhans cells around fillers and multiple immunological cells infiltrated. Immunofluorescent study shown immunological cells (CD45 positives cells) with high TLR2 expression (hyaluronic acid and LTA receptor). // Limitations: The difficulty of obtaining biopsy samples of nodules implies that the number of cases analyzed is very low. // Conclusion: New model is proposed in which weight of hyaluronic acid and LTA could be able to trigger inflammation. This process could be mediated by TLR2 expressed in infiltrated immune cells

Alpha-defensins 1-3 release by dendritic cells is reduced by estrogen

<p>Abstract</p> <p>Background</p> <p>During pregnancy the immune system of the mother must protect any activation that may negatively affect the fetus. Changes in susceptibility to infection as well as resolution of some autoimmune disorders represent empirical evidence for pregnancy related alterations in immunity. Sex hormones reach extremely high levels during pregnancy and have been shown to have direct effects on many immune functions including the antiviral response of dendritic cells. Among the immunologically active proteins secreted by monocyte derived DCs (MDDC) are the alpha-defensins 1-3. This family of cationic antimicrobial peptides has a broad spectrum of microbicidal activity and has also been shown to link innate to adaptive immunity by attracting T cells and immature DCs, which are essential for initiating and polarizing the immune response.</p> <p>Methods</p> <p>We compare culture-generated monocyte derived DCs (MDDCs) with directly isolated myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) and measure their alpha-defensins 1-3 secretion by ELISA both, in basal situations and after hormone (E2 or PG) treatments. Moreover, using a cohort of pregnant women we isolated mDCs from blood and also measure the levels of these anti-microbial peptides along pregnancy.</p> <p>Results</p> <p>We show that mDCs and pDCs constitutively produce alpha-defensins 1-3 and at much higher levels than MDDCs. Alpha-defensins 1-3 production from mDCs and MDDCs but not pDCs is inhibited by E2. PG does not affect alpha-defensins 1-3 in any of the populations. Moreover, alpha-defensins 1-3 production by mDCs was reduced in the later stages of pregnancy in 40% of the patients.</p> <p>Conclusions</p> <p>Here, we demonstrate that mDCs and pDCs secrete alpha-defensins 1-3 and present a novel effect of E2 on the secretion of alpha-defensins 1-3 by dendritic cells.</p

El estrés en el ámbito de los profesionales de la salud

Stress among health professionals constitutes a significant problem, because of its strong impact both on them and their patients. This study finds that this syndrome varies according to gender, type of work and job role. We find that primary, secondary and tertiary prevention strategies are effective in minimizing this syndrome. These include better work management, an adjusted work schedule, a balance between work and family life, workforce personnel involvement, and improvement of employment policies which emphasize health promotion.En el ámbito de las profesiones sanitarias, la incidencia del estrés es grave porque no solo afecta al profesional que lo padece, sino también al enfermo que depende de sus cuidados. En cuanto a su incidencia en este gremio, presenta notables diferencias en función del género, ocupación y cargo desempeñado. La prevención es la vía ideal de solución de este problema. Se basa fundamentalmente en una organización del trabajo más racional, el establecimiento de turnos más equilibrados, la conciliación de la vida laboral y familiar, el desarrollo de un ambiente agradable en el puesto de trabajo, la intervención con los propios trabajadores y el desarrollo de políticas sociolaborales promotoras de la salud

Does the ACE I/D polymorphism, alone or in combination with the ACTN3 R577X polymorphism, influence muscle power phenotypes in young, non-athletic adults?

We investigated the association of the angiotensin converting enzyme gene (ACE) insertion/deletion (I/D) polymorphism, alone or in combination with the α-actinin-3 gene (ACTN3) R577X polymorphism, with jumping (vertical squat and counter-movement jump tests) and sprint ability (30 m dash) in non-athletic, healthy young adults [N = 281 (214 male), mean (SD) age 21 (2) years]. We did not observe any effect of the ACE I/D polymorphism on study phenotypes. We repeated the analyses separately in men and women and the results did not materially change. Likewise, the mean estimates of the study phenotypes were similar in subjects with the genotype combinations ACE II + ID and ACTN3 XX or ACE DD and ACTN3 RR + RX. We found no association between the ACE DD and ACTN3 RR + RX genotype combination and performance (≥90th of the sex-specific percentile). In summary, though the ACE I/D polymorphism is a strong candidate to modulate some exercise-related phenotypes or athletic performance status, this polymorphism, alone or in combination with the ACTN3 R577X polymorphism, does not seem to exert a major influence in the muscle ‘explosive’ power of young healthy adults, as assessed during multi-joint exercise tests

Ending preventable maternal mortality: phase II of a multi-step process to develop a monitoring framework, 2016–2030

Background In February 2015, the World Health Organization (WHO) released “Strategies toward ending preventable maternal mortality (EPMM)” (EPMM Strategies), a direction-setting report outlining global targets and strategies for reducing maternal mortality in the Sustainable Development Goal (SDG) period. In May 2015, the EPMM Working Group outlined a plan to develop a comprehensive monitoring framework to track progress toward the achievement of these targets and priorities. This monitoring framework was developed in two phases. Phase I, which focused on identifying indicators related to the proximal causes of maternal mortality, was completed in October 2015. This paper describes the process and results of Phase II, which was completed in November 2016 and aimed to build consensus on a set of indicators that capture information on the social, political, and economic determinants of maternal health and mortality. Findings A total of 150 experts from more than 78 organizations worldwide participated in this second phase of the process to develop a comprehensive monitoring framework for EPMM. The experts considered a total of 118 indicators grouped into the 11 key themes outlined in the EPMM report, ultimately reaching consensus on a set of 25 indicators, five equity stratifiers, and one transparency stratifier. Conclusion The indicators identified in Phase II will be used along with the Phase I indicators to monitor progress towards ending preventable maternal deaths. Together, they provide a means for monitoring not only the essential clinical interventions needed to save lives but also the equally important political, social, economic and health system determinants of maternal health and survival. These distal factors are essential to creating the enabling environment and high-performing health systems needed to ensure high-quality clinical care at the point of service for every woman, her fetus and newborn. They complement and support other monitoring efforts, in particular the “Survive, Thrive, and Transform” agenda laid out by the Global Strategy for Women’s, Children’s and Adolescents’ Health (2016-2030) and the SDG3 global target on maternal mortality

Circular RNA CpG island hypermethylation-associated silencing in human cancer

Noncoding RNAs (ncRNAs), such as microRNAs and long noncoding RNAs (lncRNAs), participate in cellular transformation. Work done in the last decade has also demonstrated that ncRNAs with growth-inhibitory functions can undergo promoter CpG island hypermethylation-associated silencing in tumorigenesis. Herein, we wondered whether circular RNAs (circRNAs), a type of RNA transcripts lacking 5′-3′ ends and forming closed loops that are gaining relevance in cancer biology, are also a target of epigenetic inactivation in tumors. To tackle this issue, we have used cancer cells genetically deficient for the DNA methyltransferase enzymes in conjuction with circRNA expression microarrays. We have found that the loss of DNA methylation provokes a release of circRNA silencing. In particular, we have identified that promoter CpG island hypermethylation of the genes TUSC3 (tumor suppressor candidate 3), POMT1 (protein O-mannosyltransferase 1), ATRNL1 (attractin-like 1) and SAMD4A (sterile alpha motif domain containing 4A) is linked to the transcriptional downregulation of both linear mRNA and the hosted circRNA. Although some circRNAs regulate the linear transcript, we did not observe changes in TUSC3 mRNA levels upon TUSC3 circ104557 overexpression. Interestingly, we found circRNA-mediated regulation of target miRNAs and an in vivo growth inhibitory effect upon TUSC3 circ104557 transduction. Data mining for 5′-end CpG island methylation of TUSC3, ATRNL1, POMT1 and SAMD4A in cancer cell lines and primary tumors showed that the epigenetic defect was commonly observed among different tumor types in association with the diminished expression of the corresponding transcript. Our findings support a role for circRNA DNA methylation-associated loss in human cancer

DNA methylation profiling unveils TGF-ß hyperresponse in tumor associated fibroblasts from lung cancer patients

There is growing interest in defining the aberrant molecular differences between normal and tumor-associated fibroblasts (TAFs) that support tumor progression. For this purpose, we recently conducted a genome-wide DNA methylation profiling of TAFs and paired control fibroblasts (CFs) from non-small cell lung cancer (NSCLC) patients, and reported a widespread hypomethylation concomitantly with focal gain of DNA methylation; in addition, we found evidence that a fraction of lung TAFs are fibrocytes in origin. Of note, the aberrant epigenome of lung TAFs had a global impact in gene expression and a selective impact on the TGF-ß pathway. To get insights on the functional implications of the latter impact, we analyzed the response of lung TAFs to exogenous TGF-ß1 in terms of activation and contractility. We found a larger expression of a panel of activation markers including a-SMA and collagen-I in TAFs compared to control fibroblasts. Likewise, TGF-ß1 elicited a larger contractility in TAFs than in CFs as assessed by traction force microscopy. These findings reveal that lung TAFs are hyperresponsive to TGF-ß1, which may underlie the expansion and/or maintenance of the tumor-promoting desmoplastic stroma in lung cancer.Postprint (author's final draft

Integrando conceptos geológicos a través del juego: R - oca

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Aberrant DNA methylation in non-small cell lung cancer-associated fibroblasts

Epigenetic changes through altered DNA methylation have been implicated in critical aspects of tumor progression, and have been extensively studied in a variety of cancer types. In contrast, our current knowledge of the aberrant genomic DNA methylation in tumor-associated fibroblasts (TAFs) or other stromal cells that act as critical coconspirators of tumor progression is very scarce. To address this gap of knowledge, we conducted genome-wide DNA methylation profiling on lung TAFs and paired control fibroblasts (CFs) from non-small cell lung cancer patients using the HumanMethylation450 microarray. We found widespread DNA hypomethylation concomitant with focal gain of DNA methylation in TAFs compared to CFs. The aberrant DNA methylation landscape of TAFs had a global impact on gene expression and a selective impact on the TGF-β pathway. The latter included promoter hypermethylation-associated SMAD3 silencing, which was associated with hyperresponsiveness to exogenous TGF-β1 in terms of contractility and extracellular matrix deposition. In turn, activation of CFs with exogenous TGF-β1 partially mimicked the epigenetic alterations observed in TAFs, suggesting that TGF-β1 may be necessary but not sufficient to elicit such alterations. Moreover, integrated pathway-enrichment analyses of the DNA methylation alterations revealed that a fraction of TAFs may be bone marrow-derived fibrocytes. Finally, survival analyses using DNA methylation and gene expression datasets identified aberrant DNA methylation on the EDARADD promoter sequence as a prognostic factor in non-small cell lung cancer patients. Our findings shed light on the unique origin and molecular alterations underlying the aberrant phenotype of lung TAFs, and identify a stromal biomarker with potential clinical relevance