Heparan sulfate proteoglycans undergo differential expression alterations in left sided colorectal cancer, depending on their metastatic character

Abstract Background Heparan sulfate proteoglycans (HSPGs) are complex molecules which play a role in the invasion and growth and metastatic properties of cancerous cells. In this work we analyze changes in the patterns of expression of HSPGs in left sided colorectal cancer (LSCRC), both metastatic and non-metastatic, and the results are also compared with those previously obtained for right sided tumors (RSCRCs). Methods Eighteen LSCRCs were studied using qPCR to analyze the expression of both the proteoglycan core proteins and the enzymes involved in heparan sulfate chain biosynthesis. Certain HSPGs also carry chondroitin sulfate chains and so we also studied the genes involved in its biosynthesis. The expression of certain genes that showed significant expression differences were also analysed using immunohistochemical techniques. Results Changes in proteoglycan core proteins were dependent on their location, and the main differences between metastatic and non-metastatic tumors affected cell-surface glypicans, while other molecules were quite similar. Glypicans were also responsible for the main differences between RS- and LS- malignances. Regarding the biosynthesis of heparan sulfate chains, differential alterations in transcription depending on the presence or not of metastasis affected genes involved in the modification of uronic acid (epimerization and 2-O sulfation), and some isoforms responsible for sulfation of glucosamine (NDST1, HS6ST1). Moreover, in RSCRCs differences were preferentially found in the expression of genes involved in C6 and C3 sulfation of glucosamine, but not in NDSTs or SULFs. Finally, synthesis of chondroitin sulfate showed some alterations, which affected various steps, including polimerization and the modification of chains, but the main variations dependent on the presence of metastases were epimerization and 6C sulfation; however, when compared with RSCRCs, the essential divergences affected polymerization of the chains and the 6C sulfation of the galactosamine residue. Conclusions We evidenced alterations in the expression of HSPGs, including the expression of cell surface core proteins, many glycosiltransferases and some enzymes that modify the GAG chains in LSCRCs, but this was dependent on the metastatic nature of the tumor. Some of these alterations are shared with RSCRCs, while others, focused on specific gene groups, are dependent on tumor localization

Cycloidal Domains in the Magnetization Reversal Process of Ni80Fe20/Nd16Co84/Gd12Co88 Trilayers

The magnetization reversal of each individual layer in magnetic trilayers ( permalloy / Nd Co / Gd Co ) is investigated in detail with x-ray microscopy and micromagnetic calculations. Two sequential inversion mechanisms are identified. First, magnetic vortex-antivortex pairs move along the field direction while inverting the magnetization of magnetic stripes until they are pinned by defects. The vortex-antivortex displacements are reversible within a field interval which allows their controlled motion. Second, as the reversed magnetic field increases, cycloidal domains appear in the permalloy layer as a consequence of the dissociation of vortex-antivortex pairs due to pinning. The field range where magnetic vortices and antivortices are effectively guided by the stripe pattern is of the order of tens of mT for the Ni Fe layer, as estimated from the stability of cycloid domains in the sample

Home‑based prehabilitation improves physical conditions measured by ergospirometry and 6MWT in colorectal cancer patients: a randomized controlled pilot study

Purpose/background Prehabilitation aims to improve physical condition in the preoperative period and, therefore, decrease the loss of cardiopulmonary capacity postoperatively, with the aim of reducing complications and promoting an early recovery. This study aims to evaluate the impact of home-based prehabilitation on the physical condition of patients treated surgically for colorectal cancer. Methods A prospective and randomized clinical study was conducted on 60 patients during two periods from October 2018 to February 2019 and from September 2019 to September 2020, in a single university hospital. Patients were randomized into two study groups (30 per group): prehabilitation vs. standard care. Changes in physical condition, measured at diagnosis, the day before surgery, and at 6–8 weeks after surgery using the cardiopulmonary exercise testing (CPET) and the 6-minute walk test (6MWT) were evaluated. Results Prehabilitation reduced postoperative complications (17.4% vs. 33.3%, p = 0.22) and hospital stay (5.74 vs. 6.67 days, p = 0.30). 6MWT showed a signifcant improvement in the prehabilitation group (+78.9 m). Six weeks after surgery, prehabilitation showed a signifcant improvement in the 6MWT (+68.9 m vs. −27.2 m, p = 0.01). Signifcant diferences were also observed in the ergospirometry between the diagnosis and postoperative study (+0.79 METs vs. −0.84 METs, p = 0.001). A strong correlation was observed between CPET and 6MWT (0.767 (p < 0.001)). Conclusion Home prehabilitation achieved lower overall postoperative complications than standard care and reached signifcant improvements in 6MWT and CET. A strong correlation was observed between CET and 6MWT, which allows validation of 6MWT as a valid and reliable measure of functional exercise capacity in colorectal patients when other, more specifc and expensive tests are not available

Tunable ferromagnetic resonance in coupled trilayers with crossed in-plane and perpendicular magnetic anisotropies

An original approach to tune the ferromagnetic resonance frequency of a soft magnetic Ni80Fe20 (Permalloy = Py) film with in-plane magnetic anisotropy (IMA) based on the controlled coupling to a hard magnetic NdCox film with perpendicular magnetic anisotropy (PMA) through a nonmagnetic Al spacer is studied. Using the transverse magneto-optical Kerr effect (T-MOKE), alternating gradient magnetometry (AGM), and vector network analyzer ferromagnetic resonance (VNA-FMR) spectroscopy, the influence of both the Co concentration and the Al spacer thickness on the static and dynamic magnetic properties of the coupled IMA/PMA system is investigated. Compared to a single Py film, two striking effects of the coupling between IMA and PMA layers can be observed in their FMR spectra. First, there is a significant increase in the zero-field resonance frequency from 2.0 GHz up to 6.4 GHz, and second, an additional frequency hysteresis occurs at low magnetic fields applied along the hard axis. The maximum frequency difference between the frequency branches for increasing and decreasing magnetic fields is as high as 1 GHz, corresponding to a tunability of about 20% at external fields of typically less than ±70 mT. The origin of the observed features in the FMR spectra is discussed by means of magnetization reversal curves

Neuroendocrine tumors show altered expression of chondroitin sulfate, glypican 1, glypican 5, and syndecan 2 depending on their differentiation grade

Neuroendocrine tumors (NETs) are found throughout the body and are important as they give rise to distinct clinical syndromes. Glycosaminoglycans, in proteoglycan (PG) form or as free chains, play vital roles in every step of tumor progression. Analyzing tumor samples with different degrees of histological differentiation we determined the existence of important alterations in chondroitin sulfate (CS) chains. Analysis of the transcription of the genes responsible for the production of CS showed a decline in the expression of some genes in poorly differentiated compared to well-differentiated tumors. Using anti-CS antibodies, normal stroma was always negative whereas tumoral stroma always showed a positive staining, more intense in the highest grade carcinomas, while tumor cells were negative. Moreover, certain specific cell surface PGs experienced a drastic decrease in expression depending on tumor differentiation. Syndecan 2 levels were very low or undetectable in healthy tissues, increasing significantly in well-differentiated tumors, and decreasing in poorly differentiated NETs, and its expression levels showed a positive correlation with patient survival. Glypican 5 appeared overexpressed in high-grade tumors with epithelial differentiation, and not in those that displayed a neuroendocrine phenotype. In contrast, normal neuroendocrine cells were positive for glypican 1, displaying intense staining in cytoplasm and membrane. Low-grade NETs had increased expression of this PG, but this reduced as tumor grade increased, its expression correlating positively with patient survival. Whilst elevated glypican 1 expression has been documented in different tumors, the downregulation in high-grade tumors observed in this work suggests that this proteoglycan could be involved in cancer development in a more complex and context-dependent manner than previously though

Cardiotrophin-1 opposes renal fibrosis in mice: Potential prevention of chronic kidney disease

[EN]Chronic kidney disease is characterized by tubulointerstitial fibrosis involving inflammation, tubular apoptosis, fibroblast proliferation and extracellular matrix accumulation. Cardiotrophin-1, a member of the interleukin-6 family of cytokines, protects several organs from damage by promoting survival and anti-inflammatory effects. However, whether cardiotrophin-1 participates in the response to chronic kidney injury leading to renal fibrosis is unknown. We hypothesized and assessed the potential role of cardiotrophin-1 in a mice model of tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO). Three days after UUO, obstructed kidneys from cardiotrophin-1-/- mice show higher expression of inflammatory markers IL-1β, Cd68, ICAM-1, COX-2 and iNOs, higher activation of NF-κB, higher amount of myofibroblasts and higher severity of tubular damage and apoptosis, compared with obstructed kidneys from wild-type littermates. In a later stage, obstructed kidneys from cardiotrophin-1-/- mice show higher fibrosis than obstructed kidneys from wild-type mice. Interestingly, administration of exogenous cardiotrophin-1 prevents the increased fibrosis resulting from the genetic knockout of cardiotrophin-1 upon UUO, and supplementation of wild-type mice with exogenous cardiotrophin-1 further reduces the renal fibrosis induced by UUO. In vitro, renal myofibroblasts from cardiotrophin-1-/- mice have higher collagen I and fibronectin expression and higher NF-κB activation than wild-type cells. Cardiotrophin-1 participates in the endogenous response that opposes renal damage by counteracting the inflammatory, apoptotic and fibrotic processes. And exogenous cardiotrophin-1 is proposed as a candidate for the treatment and prevention of chronic renal fibrosis

Productos biodegradables “Eco Product”

Hasta la actualidad la contaminación por residuos plásticos es un problema para el medio ambiente, no solo por su larga duración, sino también por su proceso de producción. Hoy en día este problema ha llevado a que la población tome conciencia del daño y efectos que puede causar a corto y mediano plazo. Identificamos que existe la necesidad de sustituir los utensilios de plástico porque estos componen una de las principales causas de contaminación ambiental. Esta problemática nos da una oportunidad de negocio y ha despertado el interés por desarrollar y comercializar utensilios biodegradables (platos, cubiertos y vasos) a base del tallo de las plantas de plátano, que a corto o mediano plazo nos generará ingresos económicos altos, donde además buscamos crear una empresa responsable y que genere conciencia en los consumidores. Para lograr el posicionamiento efectivo de Eco Product, resaltaremos sus ventajas competitivas frente a los de la competencia, las cuales son, brindar un producto con durabilidad y calidad en consistencia, y contribuir al manejo responsable de desechos plástico. En este plan de negocio, identificamos a todos los grupos de interés de Eco Product, asimismo, se propone estrategias para gestionar la relación con dichos grupos, se busca establecer lazos y compromisos que contribuyan al desarrollo conjunto de nuestro negocio. Se estima una inversión de 139,973, para que Eco Product inicie con sus operaciones. El negocio entregará al inversionista una rentabilidad promedio anual de 12.96%.Until now, pollution by plastic waste is a problem for the environment, not only because of its long duration, but also because of its production process. Today this problem has made the population aware of the damage and effects that it can cause in the short and medium term. We identify that there is a need to replace plastic utensils because they are one of the main causes of environmental pollution. This problem gives us a business opportunity and has aroused interest in developing and marketing biodegradable utensils (plates, cutlery and glasses) based on the stem of banana plants, which in the short or medium term will generate high economic income, where in addition We seek to create a responsible company that generates awareness in consumers. To achieve the effective positioning of Eco Products, we will highlight its competitive advantages over those of the competition, which are, to provide a product with durability and quality in consistency, and to contribute to the responsible management of plastic waste. In this business plan, we identify all the Eco Product stakeholders, and strategies are also proposed to manage the relationship with these groups, it seeks to establish ties and commitments that contribute to the joint development of our business. An investment of 139,973 is estimated for Eco Product to start its operations. The business will provide the investor with an average annual profitability of 12.96%.Trabajo de investigació

A system dynamics model to predict the human monocyte response to endotoxins

System dynamics is a powerful tool that allows modeling of complex and highly networked systems such as those found in the human immune system. We have developed a model that reproduces how the exposure of human monocytes to lipopolysaccharides (LPSs) induces an inflammatory state characterized by high production of tumor necrosis factor alpha (TNFα), which is rapidly modulated to enter into a tolerant state, known as endotoxin tolerance (ET). The model contains two subsystems with a total of six states, seven flows, two auxiliary variables, and 14 parameters that interact through six differential and nine algebraic equations. The parameters were estimated and optimized to obtain a model that fits the experimental data obtained from human monocytes treated with various LPS doses. In contrast to publications on other animal models, stimulation of human monocytes with super-low-dose LPSs did not alter the response to a second LPSs challenge, neither inducing ET, nor enhancing the inflammatory response. Moreover, the model confirms the low production of TNFα and increased levels of C-C motif ligand 2 when monocytes exhibit a tolerant state similar to that of patients with sepsis. At present, the model can help us better understand the ET response and might offer new insights on sepsis diagnostics and prognosis by examining the monocyte response to endotoxins in patients with sepsisThis work was supported by grants from the “Instituto de Salud Carlos III” (ISCiii), “Fondo de Investigación Sanitaria” (FIS), and Fondos FEDER (PI14/01234, PIE15/00065) to EL-C. EA work contract is supported by the Torres Quevedo program from “Ministerio de Economía y Competitividad” (SPTQ1300X006175XV0). VT work contract is supported by the “Ministerio de Economía y Competitividad” (PTA2013-8265-I

Revealing 3D magnetization of thin films with soft X-ray tomography: magnetic singularities and topological charges

The knowledge of how magnetization looks inside a ferromagnet is often hindered by the limitations of the available experimental methods which are sensitive only to the surface regions or limited in spatial resolution. Here we report a vector tomographic reconstruction based on soft X-ray transmission microscopy and magnetic dichroism data, which has allowed visualizing the three-dimensional magnetization in a ferromagnetic thin film heterostructure. Different non-trivial topological textures have been resolved and the determination of their topological charge has allowed us to identify a Bloch point and a meron-like texture. Our method relies only on experimental data and might be of wide application and interest in 3D nanomagnetism