Consequences of the obesity epidemic on cancer morbidity and mortality are not fully appreciated. Obesity is a risk factor for many cancers, but the mechanisms by which it contributes to cancer ...development and patient outcome have yet to be fully elucidated. Here, we examined the effects of coculturing human-derived adipocytes with established and primary breast cancer cells on tumorigenic potential. We found that the interaction between adipocytes and cancer cells increased the secretion of proinflammatory cytokines. Prolonged culture of cancer cells with adipocytes or cytokines increased the proportion of mammosphere-forming cells and of cells expressing stem-like markers in vitro. Furthermore, contact with immature adipocytes increased the abundance of cancer cells with tumor-forming and metastatic potential in vivo. Mechanistic investigations demonstrated that cancer cells cultured with immature adipocytes or cytokines activated Src, thus promoting Sox2, c-Myc, and Nanog upregulation. Moreover, Sox2-dependent induction of miR-302b further stimulated cMYC and SOX2 expression and potentiated the cytokine-induced cancer stem cell-like properties. Finally, we found that Src inhibitors decreased cytokine production after coculture, indicating that Src is not only activated by adipocyte or cytokine exposures, but is also required to sustain cytokine induction. These data support a model in which cancer cell invasion into local fat would establish feed-forward loops to activate Src, maintain proinflammatory cytokine production, and increase tumor-initiating cell abundance and metastatic progression. Collectively, our findings reveal new insights underlying increased breast cancer mortality in obese individuals and provide a novel preclinical rationale to test the efficacy of Src inhibitors for breast cancer treatment.
Breast cancer continues to be one of the main causes of morbidity and mortality globally and was the leading cause of cancer death in women in Spain in 2020. Early diagnosis is one of the most ...effective methods to lower the incidence and mortality rates of breast cancer. The human metalloproteinases (MMP) mainly function as proteolytic enzymes degrading the extracellular matrix and plays important roles in most steps of breast tumorigenesis. This retrospective cohort study shows the immunohistochemical expression levels of MMP-1, MMP-2, MMP-3, and MMP-9 in 154 women with breast cancer and 42 women without tumor disease. The samples of breast tissue are assessed using several tissue matrices (TMA). The percentages of staining (≤50%–>50%) and intensity levels of staining (weak, moderate, or intense) are considered. The immunohistochemical expression of the MMP-1-intensity (p = 0.043) and MMP-3 percentage (p = 0.018) and intensity, (p = 0.025) present statistically significant associations with the variable group (control–case); therefore, expression in the tumor tissue samples of these MMPs may be related to the development of breast cancer. The relationships between these MMPs and some clinicopathological factors in breast cancer are also evaluated but no correlation is found. These results suggest the use of MMP-1 and MMP-3 as potential biomarkers of breast cancer diagnosis.
Tissue-engineering repair of extrahepatic bile ducts Pérez Alonso, Alejandro José, MD, PhD; Del Olmo Rivas, Carlos, MD; Romero, Ignacio Machado, MD ...
The Journal of surgical research,
2013, January 2013, 2013-Jan, 2013-01-00, 20130101, Letnik:
179, Številka:
1
Journal Article
Recenzirano
Abstract Background In recent years, with the widespread use of laparoscopic cholecystectomy and liver transplantation, complications involving the biliary system are increasing. All techniques ...available have a high risk of recurrence or high-morbidity problems. We developed a three-dimensional collagen duct modified with agarose hydrogel, to substitute the affected extrahepatic bile duct. Materials and methods We used it in 40 guinea pigs and studied the histology and physiology at 4 wk, 3, and 6 mo after transplantation. Blood test, histologic techniques, and cholangiography were performed in all of them. Results All experimental animals survived up to their sacrifices. Our graft showed highly potential applications to treat hepatobiliary diseases that require surgery.
•We investigated the agonist/antagonist activities of ZEN and its metabolites.•Interactions with hERα and hAR were studied by in vitro receptor-specific bioassays.•ZEN and its metabolites behaved as ...full hERα agonists in the E-Screen bioassay.•We found that all six compounds possess hAR-mediated antagonistic activity.•The metabolites ZAN, α-ZAL and β-ZAL were the most potent hAR antagonists.
Zearalenone (ZEN) is a well-known mycotoxin present in numerous agricultural products. Humans and animals are therefore at a risk of exposure to zearalenone through consumption of contaminated food. After intake, ZEN is reduced to α- and β-zearalenol (α-ZEL and β-ZEL), zearalanone (ZAN), and α- and β-zearalanol (α-ZAL and β-ZAL). Although their estrogenicity has been well characterized, much less is known about their interaction with other nuclear receptors. This study was undertaken to investigate interactions of ZEN and its five metabolites, with the human androgen receptor (hAR) and estrogen receptor alpha (hERα). Their ability to induce hAR-mediated reporter gene expression was examined in androgen-sensitive PALM cells, whereas the effects on hERα function were assessed in MCF-7 cells using the E-Screen bioassay. We confirm that ZEN and its metabolites are full agonists for hERα and demonstrate that all six compounds tested possess hAR-mediated antagonistic activity in PALM cells, in which ZAN, α-ZAL, and β-ZAL were the most effective hAR antagonists. Overall, the observed estrogenic and anti-androgenic potencies of ZEN and its metabolites suggest that these compounds may interfere with the endocrine system by various modes of action and that further investigation is warranted into their role as endocrine disrupters in animals and humans.
Detecting and studying pulsars above a few GHz in the radio band is challenging due to the typical faintness of pulsar radio emission, their steep spectra, and the lack of observatories with ...sufficient sensitivity operating at high frequency ranges. Despite the difficulty, the observations of pulsars at high radio frequencies are valuable because they can help us to understand the radio emission process, complete a census of the Galactic pulsar population, and possibly discover the elusive population in the Galactic Centre, where low-frequency observations have problems due to the strong scattering. During the decades of the 1990s and 2000s, the availability of sensitive instrumentation allowed for the detection of a small sample of pulsars above 10 GHz, and for the first time in the millimetre band. Recently, new attempts between 3 and 1 mm (≈86 − 300 GHz) have resulted in the detections of a pulsar and a magnetar up to the highest radio frequencies to date, reaching 291 GHz (1.03 mm). The efforts continue, and the advent of new or upgraded millimetre facilities like the IRAM 30-m, NOEMA, the LMT, and ALMA, warrants a new era of high-sensitivity millimetre pulsar astronomy in the upcoming years.
Abstract
Improving knowledge on the epidemiology and analysing the prognostic factors of severity for injuries caused by fighting bulls in Spain, Portugal and southern France. Observational ...retrospective study including 1239 patients with a reported history of bull horn injuries between January 2012 and November 2019 in Spain, Portugal or southern France. A multiple logistic regression test was used to analyse the prognostic factors of severity and mortality rate of these lesions. The mean accident rate was 9.13% and the mortality rate was 0.48%. The most frequent mechanism of trauma was goring, and the commonest locations of the lesions were thigh and groin. Vascular lesion was found in 20% of thigh/groin gorings. Prognostic factors of severity were vascular lesion, head trauma, fracture, goring injuries and age of the animal. The most reliable prognostic factors of mortality were vascular lesion and goring in the back. Lesions caused by fighting bulls are common in the bullfighting events held in Spain, Portugal and southern France. Although the mortality rate is low, there is a higher morbidity rate, which is conditioned by vascular lesion. All medical teams should include a surgeon experienced in vascular surgery and an anaesthesiologist.
ABSTRACT
We present a multiwavelength observation of a cool core that does not appear to be associated with any galaxy, in a nearby cluster, Abell 1142. Its X-ray surface brightness peak of ≲2 keV is ...cooler than the ambient intracluster gas of ≳3 keV, and is offset from its brightest cluster galaxy (BCG) by 80 kpc in projection, representing the largest known cool core – BCG separation. This BCG-less cool core allows us to measure the metallicity of a cluster centre with a much-reduced contribution from the interstellar medium (ISM) of the BCG. XMM–Newton observation reveals a prominent Fe abundance peak of $1.07^{+0.16}_{-0.15}$ Z⊙ and an α/Fe abundance ratio close to the solar ratio, fully consistent with those found at the centres of typical cool core clusters. This finding hints that BCGs play a limited role in enriching the cluster centres. However, the discussion remains open, given that the α/Fe abundance ratios of the orphan cool core and the BCG ISM are not significantly different. Abell 1142 may have experienced a major merger more than 100 Myr ago, which has dissociated its cool core from the BCG. This implies that the Fe abundance peak in cool core clusters can be resilient to cluster mergers. Our recent Institut de Radio Astronomie Millimétrique 30-m observation did not detect any CO emission at its X-ray peak and we find no evidence for massive runaway cooling in the absence of recent active galactic nucleus feedback. The lack of a galaxy may contribute to an inefficient conversion of the ionized warm gas to the cold molecular gas.
Abstract
We present Event Horizon Telescope (EHT) 1.3 mm measurements of the radio source located at the position of the supermassive black hole Sagittarius A* (Sgr A*), collected during the 2017 ...April 5–11 campaign. The observations were carried out with eight facilities at six locations across the globe. Novel calibration methods are employed to account for Sgr A*'s flux variability. The majority of the 1.3 mm emission arises from horizon scales, where intrinsic structural source variability is detected on timescales of minutes to hours. The effects of interstellar scattering on the image and its variability are found to be subdominant to intrinsic source structure. The calibrated visibility amplitudes, particularly the locations of the visibility minima, are broadly consistent with a blurred ring with a diameter of ∼50
μ
as, as determined in later works in this series. Contemporaneous multiwavelength monitoring of Sgr A* was performed at 22, 43, and 86 GHz and at near-infrared and X-ray wavelengths. Several X-ray flares from Sgr A* are detected by Chandra, one at low significance jointly with Swift on 2017 April 7 and the other at higher significance jointly with NuSTAR on 2017 April 11. The brighter April 11 flare is not observed simultaneously by the EHT but is followed by a significant increase in millimeter flux variability immediately after the X-ray outburst, indicating a likely connection in the emission physics near the event horizon. We compare Sgr A*’s broadband flux during the EHT campaign to its historical spectral energy distribution and find that both the quiescent emission and flare emission are consistent with its long-term behavior.
The Event Horizon Telescope (EHT) is a very long baseline interferometry (VLBI) array that comprises millimeter- and submillimeter-wavelength telescopes separated by distances comparable to the ...diameter of the Earth. At a nominal operating wavelength of ∼1.3 mm, EHT angular resolution (λ/D) is ∼25 as, which is sufficient to resolve nearby supermassive black hole candidates on spatial and temporal scales that correspond to their event horizons. With this capability, the EHT scientific goals are to probe general relativistic effects in the strong-field regime and to study accretion and relativistic jet formation near the black hole boundary. In this Letter we describe the system design of the EHT, detail the technology and instrumentation that enable observations, and provide measures of its performance. Meeting the EHT science objectives has required several key developments that have facilitated the robust extension of the VLBI technique to EHT observing wavelengths and the production of instrumentation that can be deployed on a heterogeneous array of existing telescopes and facilities. To meet sensitivity requirements, high-bandwidth digital systems were developed that process data at rates of 64 gigabit s−1, exceeding those of currently operating cm-wavelength VLBI arrays by more than an order of magnitude. Associated improvements include the development of phasing systems at array facilities, new receiver installation at several sites, and the deployment of hydrogen maser frequency standards to ensure coherent data capture across the array. These efforts led to the coordination and execution of the first Global EHT observations in 2017 April, and to event-horizon-scale imaging of the supermassive black hole candidate in M87.
We present measurements of the properties of the central radio source in M87 using Event Horizon Telescope data obtained during the 2017 campaign. We develop and fit geometric crescent models ...(asymmetric rings with interior brightness depressions) using two independent sampling algorithms that consider distinct representations of the visibility data. We show that the crescent family of models is statistically preferred over other comparably complex geometric models that we explore. We calibrate the geometric model parameters using general relativistic magnetohydrodynamic (GRMHD) models of the emission region and estimate physical properties of the source. We further fit images generated from GRMHD models directly to the data. We compare the derived emission region and black hole parameters from these analyses with those recovered from reconstructed images. There is a remarkable consistency among all methods and data sets. We find that >50% of the total flux at arcsecond scales comes from near the horizon, and that the emission is dramatically suppressed interior to this region by a factor >10, providing direct evidence of the predicted shadow of a black hole. Across all methods, we measure a crescent diameter of 42 3 as and constrain its fractional width to be <0.5. Associating the crescent feature with the emission surrounding the black hole shadow, we infer an angular gravitational radius of GM/Dc2 = 3.8 0.4 as. Folding in a distance measurement of gives a black hole mass of . This measurement from lensed emission near the event horizon is consistent with the presence of a central Kerr black hole, as predicted by the general theory of relativity.
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