Apoptotic body engulfment by a human stellate cell line is profibrogenic

Hepatocyte apoptosis and stellate cell activation are both features of chronic liver diseases, but a relationship between these events has not been explored. In macrophages, engulfment of apoptotic bodies induces expression of transforming growth factor-beta (TGF-beta), a profibrogenic cytokine. We examined whether a similar response occurs in stellate cells. Fluorescently labeled hepatocyte apoptotic bodies were added to cultures of primary and immortalized human stellate cells. Stellate cells, but not hepatocytes, readily engulfed apoptotic bodies in a time-dependent manner as assessed by confocal microscopy. The activation of primary and immortalized human stellate cells after incubation with apoptotic bodies, as well as their fibrogenic activity, was indicated by an increase in alpha-smooth muscle actin (primary cells), TGF-beta1, and collagen alpha1(I) mRNA (primary and immortalized cells). The profibrogenic response was dependent upon apoptotic body engulfment, because nocodazole, a microtubule-inhibiting agent, blocked both the engulfment and the increase of TGF-beta1 and collagen alpha1(I) mRNA. As described in primary rodent stellate cells, up-regulation of collagen alpha1(I) mRNA was inhibited by a PI-3K inhibitor (LY294002) and a p38 mitogen-activated protein kinase inhibitor (SB203580) in LX-1 cells. In conclusion, these data support a model in which engulfment of hepatocyte apoptotic bodies by stellate cells leads to a fibrogenic response by eliciting a kinase-signaling pathway.     

The development of mouse APECED models provides new insight into the role of AIRE in immune regulation

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy is a rare recessive autoimmune disorder caused by a defect in a single gene called AIRE (autoimmune regulator). Characteristics of this disease include a variable combination of autoimmune endocrine tissue destruction, mucocutaneous candidiasis and ectodermal dystrophies. The development of Aire-knockout mice has provided an invaluable model for the study of this disease. The aim of this review is to briefly highlight the strides made in APECED research using these transgenic murine models, with a focus on known roles of Aire in autoimmunity. The findings thus far are compelling and prompt additional areas of study which are discussed.     

Glucose metabolic changes in stress

Provision of a better understanding of the pathogenic pathways underlying injured sugar metabolism during stress should ideally translate into a more rational approach to the provision of nutritional support. Patients with burns, trauma, severe injuries or infections commonly develop a hypermetabolic state that is associated with several changes in carbohydrate metabolism. The hypermetabolic state is induced either by the area of injury and by organs involved in the immunologic response to stress; further it determines a glycemic milieu which will be directed toward satisfaction of the requirements for glucose as an energy support.     

Artificial Anisotropy in Ge2Sb2Te5 Thin Films after Femtosecond Laser Irradiation

Ge₂Sb₂Te₅ (GST225) looks to be a promising material for rewritable memory devices due to its relatively easy processing and high optical and electrophysical contrast for the crystalline and amorphous phases. In the present work, we combined the possibilities of crystallization and anisotropic structures fabrication using femtosecond laser treatment at the 1250 nm wavelength of 200 nm thin amorphous GST225 films on silicon oxide/silicon substrates. A raster treatment mode and photoexcited surface plasmon polariton generation allowed us to produce mutually orthogonal periodic structures, such as scanline tracks (the period is 120 ± 10 μm) and laser-induced gratings (the period is 1100 ± 50 nm), respectively. Alternating crystalline and amorphous phases at the irradiated surfaces were revealed according to Raman spectroscopy and optical microscopy studies for both types of structures. Such periodic modulation leads to artificial optical and electrophysical anisotropy. Reflectance spectra in the near infrared range differ for various polarizations of probing light, and this mainly results from the presence of laser-induced periodic surface structures. On the other hand, the scanline tracks cause strong conductivity anisotropy for dc measurements in the temperature range of 200–400 K. The obtained results are promising for designing new GST225-based memory devices in which anisotropy may promote increasing the information recording density.     

Mirau-based line-field confocal optical coherence tomography for three-dimensional high-resolution skin imaging

SignificanceLine-field confocal optical coherence tomography (LC-OCT) is a recently introduced high-resolution imaging modality based on a combination of low-coherence optical interferometry and reflectance confocal optical microscopy with line illumination and line detection. Capable of producing three-dimensional (3D) images of the skin with cellular resolution, in vivo, LC-OCT has been mainly applied in dermatology and dermo-cosmetology. The LC-OCT devices capable of acquiring 3D images reported so far are based on a Linnik interferometer using two identical microscope objectives. In this configuration, LC-OCT cannot be designed to be a very compact and light device, and the image acquisition speed is limited.AimThe objective of this work was to develop a more compact and lighter LC-OCT device that is capable of acquiring images faster without significant degradation of the resolution and with optimized detection sensitivity.ApproachWe developed an LC-OCT device based on a Mirau interferometer using a single objective. Dynamic adjustment of the camera frequency during the depth scan is implemented, using a faster camera and a more powerful light source. The reflectivity of the beam-splitter in the Mirau interferometer was optimized to maximize the detection sensitivity. A galvanometer scanner was incorporated into the device for scanning the illumination line laterally. A stack of adjacent B-scans, constituting a 3D image, can thus be acquired.ResultsThe device is able to acquire and display B-scans at 17 fps. 3D images with a quasi-isotropic resolution of ∼1.5μm (1.3, 1.9, and 1.1μm in the x,y, and z directions, respectively) over a field of 940μm×600μm×350μm (x×y×z) can be obtained. 3D imaging of human skin at cellular resolution, in vivo, is reported.ConclusionsThe acquisition rate of the B-scans, at 17 fps, is unprecedented in LC-OCT. Compared with the conventional LC-OCT devices based on a Linnik interferometer, the reported Mirau-based LC-OCT device can acquire B-scans ∼2 times faster. With potential advantages in terms of compactness and weight, a Mirau-based device could easily be integrated into a smaller and lighter handheld probe for use by dermatologists in their daily medical practice.     

A biaryl xanthone derivative having axial chirality from Penicillium vinaceum

A new xanthone derivative having axial chirality was isolated from Penicillium vinaceum. Owing to the axial chirality, its structure, including absolute configuration, was determined by means of extensive spectroscopic data, such as UV, IR, MS, and 1D and 2D NMR spectra, and computational chiroptical methods. The new compound, (a R)-2'-methoxyvinaxanthone, has a structure containing two aromatic moieties with substituents hindering rotation about the biaryl axis. The compound gave positive results in a sea urchin egg test ( Paracentrotus lividus) and a crown gall tumor on potato disks test (Agrobacterium tumefaciens).     

Left ventricular isovolumic relaxation and renin-angiotensin system in the growth restricted fetus

OBJECTIVE: To determine left ventricular isovolumic relaxation time (LV IRT) in normally developing and growth restricted fetuses (FGR) as an indicator of fetal cardiac afterload and neonatal systolic blood pressure. STUDY DESIGN: A prospective longitudinal study in 124 normally developing and 47 growth restricted fetuses (FGR). LV IRT, fetal heart rate (FHR) and umbilical artery pulsatility index (PI) were determined at 2-3 week intervals starting at 22-26 weeks of gestation until delivery. Renin and angiotensin I levels were measured by radioimmunoassay in umbilical venous blood after delivery. Systolic blood pressure was measured at day 1 and day 5 of postnatal life. To evaluate the association between LV IRT, gestational age and FHR, bivariate regression analyses were performed. RESULTS: Mean LV IRT (62+/-8ms) was 29 percent longer in FGR as compared to the normal subset (47+/-6ms) at all gestational ages (p<0.001). Mean postnatal active plasma renin level (7.78+/-S.D. 1.03ng/ml) and postnatal angiotensin I level (4.21+/-0.70ng/ml) in the FGR subset were significantly higher (p<0.001) than in the normal subset (4.81+/-1.04ng/ml, renin and 2.69+/-0.44ng/ml, angiotensin I). There was a significant difference (p<0.01) in systolic blood pressure between the two subsets on postnatal day 1 (FGR 52+/-6mmHg vs. normal 46+/-4mmHg) and day 5 (FGR 76+/-5mmHg vs. normal 60+/-6mmHg). CONCLUSION: Left ventricular isovolumic relaxation time may act as a sensitive index of increased arterial afterload in the growth retarded fetus and may herald raised systolic blood pressure in the early neonatal period.     

Acute Mediastinitis – Outcomes and Prognostic Factors of Surgical Therapy (A Single-Center Experience)

Purpose: The aims of this work were the retrospective analysis of a cohort of patients with acute mediastinitis treated at the authors’ worksite over a 15-year period and the identification of factors that significantly affect the outcomes of the therapy.Methods: During the period 2006–2020, 80 patients with acute mediastinitis were treated. Within the cohort, the following were observed: the causes and the type of acute mediastinitis, length of anamnesis, comorbidities, diagnostic methods, time from the diagnosis to surgery, types and number of surgical procedures, results of microbiological tests, complications, and outcomes of the treatment.Results: The most common type of acute mediastinitis was descending mediastinitis (48.75%). A total of 116 surgical procedures were performed. Ten patients in the cohort died (12.5%). Patients older than 60 years were at a 6.8 times higher risk of death. Patients with more than two comorbidities were at a 14.3 times higher risk of death. The presence of yeasts in the culture material increased the risk of death by 4.4 times.Conclusion: Early diagnosis, removal of the cause of mediastinitis, sufficient mediastinal debridement, and multiple drainage thereof with the possibility of continual postoperative lavage are essential for the successful treatment of acute mediastinitis.