The Morphological Analysis of the Collagen Fiber Straightness in the Healthy Uninvolved Human Colon Mucosa Away From the Cancer

The morphological method—based on the topology and singularity theory and originally developed for the analysis of the scattering experiments—was extended to be applicable for the analysis of biological data. The usefulness of the topological viewpoint was demonstrated by quantification of the changes in collagen fiber straightness in the human colon mucosa (healthy mucosa, colorectal cancer, and uninvolved mucosa far from cancer). This has been done by modeling the distribution of collagen segment angles by the polymorphic beta-distribution. Its shapes were classified according to the number and type of critical points. We found that biologically relevant shapes could be classified as shapes without any preferable orientation (i.e. shapes without local extrema), transitional forms (i.e. forms with one broad local maximum), and highly oriented forms (i.e. forms with two minima at both ends and one very narrow maximum between them). Thus, changes in the fiber organization were linked to the metamorphoses of the beta-distribution forms. The obtained classification was used to define a new, shape-aware/based, measure of the collagen straightness, which revealed a slight and moderate increase of the straightness in mucosa samples taken 20 and 10 cm away from the tumor. The largest increase of collagen straightness was found in samples of cancer tissue. Samples of healthy individuals have a uniform distribution of beta-distribution forms. We found that this distribution has the maximal information entropy. At 20 cm and 10 cm away from cancer, the transition forms redistribute into unoriented and highly oriented forms. Closer to cancer the number of unoriented forms decreases rapidly leaving only highly oriented forms present in the samples of the cancer tissue, whose distribution has minimal information entropy. The polarization of the distribution was followed by a significant increase in the number of quasi-symmetrical forms in samples 20 cm away from cancer which decreases closer to cancer. This work shows that the evolution of the distribution of the beta-distribution forms—an abstract construction of the mind—follows the familiar laws of statistical mechanics. Additionally, the polarization of the beta-distribution forms together with the described change in the number of quasi-symmetrical forms, clearly visible in the parametric space of the beta-distribution and very difficult to notice in the observable space, can be a useful indicator of the early stages in the development of colorectal cancer

Structural and cellular changes of the uninvolved colonic mucosa from patients with colorectal adenocarcinoma

U novije vreme sve češći predmet istraživanja su interakcije između tumorskih ćelija i vezivno-tkivnih elemenata koji čine stromu tumora. Pored istraživanja interakcija tumorskih ćelija i stromalnih elemenata samog tumora u progresiji maligne bolesti, pokazano je da postoje promene u nezahvaćenoj sluznici u neposrednoj okolini tumora (tzv. prelaznoj sluznici). Međutim, zanemareno je proučavanje nezahvaćene sluznice na većoj udaljenosti od tumora. U literaturi izostaju jasni podaci o tome da li su promene opisane u prelaznoj sluznici ograničene samo na neposrednu blizinu tumora ili postoje u nezahvaćenoj sluznici i na većoj udaljenosti od malignog tumora. Uprkos ovome, pojedini istraživači ovu sluznicu koriste kao normalno, nepromenjeno tkivo. Za proučavanje udaljene nezahvaćene sluznice u okolini tumora odabrali smo debelo crevo, pošto je ovaj organ često zahvaćen malignom bolešću, a primarna tumorska lezija i nezahvaćeni deo organa su relativno lako dostupni. Ciljevi istraživanja. Detektovanje i kvantifikovanje promena epitelnih ćelija debelog creva (promene u sekreciji sulfomucina i sijalomucina, proliferaciji i fraktalnoj dimenziji jedara epitelnih ćelija) i strukturnih (krvni i limfni sudovi, kolagena, retikularna vlakana, periostin i hijaluronska kiselina) i celularnih elemenata (fibroblasti, miofibroblasti, makrofazi, T-limfociti, B-limfociti, plazma ćelije i dendritske ćelije) lamine proprije sluznice debelog creva na udaljenosti 10 cm i 20 cm od tumora i poređenje sa laminom proprijom sluznice debelog creva uzetom sa iste lokacije kod pacijenata bez malignog tumora. Materijal i metode. Uzorci sluznice debelog creva, na udaljenosti 10 cm i 20 cm kaudalno od primarne tumorske lezije, dobijeni su biopsijom u Centru za gastroenterologiju i hepatologiju Kliničko-bolničkog cenra „Zvezdara“ u Beogradu prilikom dijagnostičkog pregleda osoba sa malignim tumorom ovog organa (n=40). Kao kontrola korišćeni su uzorci sluznice debelog creva 50 zdravih osoba sa familijarnim opterećenjem za malignitet creva...Recently, increasingly frequent subjects of research are interplays between tumor cells and tumor-associated stromal elements. In addition to investigating the interaction of tumor cells and tumor-associated stromal elements in the progression of malignant disease, it has been shown that there are changes in uninvolved mucosa in the close vicinity of the tumor (so-called transitional mucosa). However, no attention has been devoted to the studies of uninvolved tissue in the remote surrounding of the tumor. In the literature, there is no clear indication whether the changes in the transitional mucosa are limited only to the immediate proximity of the tumor, or they also exist in the uninvolved mucosa at a greater distance from the malignant tumor. Despite this, some researchers use this remote mucosa as normal, unchanged tissue. To study the uninvolved mucosa at a greater distance from the malignant tumor, we selected colon, as this organ is often affected by malignant disease, and both the primary tumor and the uninvolved mucosa are relatively easy to access. Aims. Determination and quantification of changes of colonic epithelial cells (changes in sulfomucin and sialomucin secretion, proliferation and fractal dimension of nuclei) and structural (blood and lymphatic vessels, collagen, reticular fibers, periostin and hyaluronic acid) and cellular elements (fibroblasts, myofibroblasts, macrophages, Tlymphocytes, B-lymphocytes, plasma cells and dendritic cells) of colonic lamina propria at a distance 10 cm and 20 cm away from the tumor, and comparison with mucosa taken from the same location from patients without malignant tumor. Materials and methods. Tissue samples of colonic mucosa 10 cm and 20 cm away in caudal direction from the tumor, were endoscopically collected at the Center for Gastroenterology and Hepatology, Zvezdara Clinical Center, Belgarde, during diagnostic examination of patients with colorectal adenocarcinoma (n=40). As control, the samples of colonic mucosa taken from 50 healthy persons, with a family history of intestinal malgnancy, were used..

Multiple Roles of LOXL2 in the Progression of Hepatocellular Carcinoma and Its Potential for Therapeutic Targeting

LOXL2, a copper-dependent amine oxidase, has emerged as a promising therapeutic target in hepatocellular carcinoma (HCC). Increased LOXL2 expression in HCC has been linked with an aggressive phenotype and represents a poor prognostic factor. Here, we focus on the mechanisms through which LOXL2 orchestrates multiple oncogenic functions in HCC development. We performed a review of the current knowledge on the roles LOXL2 performs in the modulation of the HCC tumor microenvironment, formation of premetastatic niches, and epithelial–mesenchymal transition. We also highlighted the complex interplay between LOXL2 and hypoxia, angiogenesis, and vasculogenic mimicry in HCC. At the end of the review, we summarize the current LOXL2 inhibitors and discuss their potential in HCC precision treatment

Chokeberry (Aronia melanocarpa) fruit extract modulates immune response in vivo and in vitro

Chokeberry (Aronia melanocarpa) is known for its anti-oxidant, anti-inflammatory and anti-diabetic properties. Since the effects of chokeberry extract on the immune response have been only sporadically assessed, our aim was to investigate chokeberry fruit water extract on the immune response in vivo and in vitro. When administered orally to healthy mice, the extract exerted immunomodulatory effects in the gut evidenced by the altered proportion of macrophages, dendritic cells and T cells. Importantly, oral consumption of the chokeberry extract resulted in blood glucose level increase in C57BL/6 mice with chemically-induced diabetes. These in vivo results were corroborated by observed up-regulation of nitric oxide and interelukin-1β production in macrophages and dendritic cells, up-regulated phagocytic activity of macrophages, increased T and B lymphocytes proportions and differentiation of interferon-γ-producing T cells in vitro. The obtained results imply that our chokeberry extract stimulates pro-inflammatory properties in immune cells of innate and adaptive immunity

Effect of calcination temperature on the photoactivities of ZnO nanoparticles for degradation of the herbicide clomazone

The introduction of huge amount of organic pollutants such as dyes, pharmaceuticals, pesticides, etc. to the environment has caused many diseases to both aquatic and terrestrial lives due to their carcinogenic, toxic, and mutagenic poisonous nature. As environmental friendly and easy operational techniques, photocatalysis with semiconductors has been regarded as the most advanced and effective technique to replace the traditional methods used for the removal of organic pollutants [1-4]. Calcination temperature plays a key role in the crystallinity and photocatalytic activities of semiconductor photocatalysts [1]. The aim of this work was to investigate removal of the herbicide clomazone from double distilled water in the presence of novel ZnO nanoparticles under simulated sunlight. The ZnO photocatalysts were synthesized by precipitation method from the water and ethanol solutions of the acetate precursor and calcinated at 300–700 °C. The performances of the applied photocatalysts were correlated with their physic chemical properties. The efficiency of elimination the herbicide from double distilled water was monitored by UFLC–DAD technique

Health-related quality of life in elderly patients hospitalized with chronic heart failure

Background: Chronic heart failure is a very common condition in the elderly, characterized not only by high mortality rates, but also by a strong impact on health-related quality of life (HRQOL). Previous studies of HRQOL in elderly heart failure subjects have included mostly outpatients, and little is known about determinants of HRQOL in hospitalized elderly population, especially in Serbia. In this study, we tried to identify factors that influence HRQOL in elderly patients hospitalized with chronic heart failure in Serbia. Methods: The study population consisted of 136 patients aged 65 years or older hospitalized for chronic heart failure. HRQOL was assessed using the Minnesota Living with Heart Failure questionnaire. Predictors of HRQOL were identified by multiple linear regression analysis. Results: Univariate analysis showed that patients with lower income, a longer history of chronic heart failure, and longer length of hospital stay, as well as those receiving aldosterone antagonists and digoxin, taking multiple medications, in a higher NYHA class, and showing signs of depression and cognitive impairment had significantly worse HRQOL. Presence of depressive symptoms (P lt 0.001), higher NYHA class (P=0.021), lower income (P=0.029), and longer duration of heart failure (P=0.049) were independent predictors of poor HRQOL. Conclusion: Depressive symptoms, higher NYHA class, lower income, and longer duration of chronic heart failure are independent predictors of poor HRQOL in elderly patients hospitalized with chronic heart failure in Serbia. Further, there is an association between multiple medication usage and poor HRQOL, as well as a negative impact of cognitive impairment on HRQOL. Hence, measures should be implemented to identify such patients, especially those with depressive symptoms, and appropriate interventions undertaken in order to improve their HRQOL

Comparative Study on the Removal Efficiency of Clomazone and Amitriptyline via Adsorption and Photocatalysis in Aqueous Media: Kinetic Models and Toxicity Assessment

This study aimed to compare the effectiveness of adsorption and photocatalysis techniques at removing the herbicide clomazone (CLO) and the antidepressant known as amitriptyline (AMI) from water. This study employed kinetic models to analyze the removal processes and assess the potential toxicity of the treated water. The structure and morphology of the prepared multi-walled carbon nanotubes were characterized as adsorbents by transmission electron microscopy, X-ray diffraction, Fourier transform infrared techniques, and Raman spectroscopy. The adsorption kinetics of CLO and AMI were studied on the pristine and functionalized multi-walled carbon nanotubes. Kinetic studies were performed by modeling the obtained experimental data using three kinetic models: pseudo-first-order, pseudo-second-order, and Elovich kinetic models. On the other hand, the efficiency of CLO and AMI photodegradation was examined as a function of the type of irradiation (UV and simulated solar irradiation) and type of TiO2 photocatalyst (Aeroxide and Kronos). Under the experimental conditions employed, the reaction followed pseudo-first-order kinetics. Additionally, in order to assess the toxicity of water containing CLO, AMI, and their intermediates, toxicity assessments were conducted using human fetal lung fibroblast cells. The results obtained indicate the effectiveness of both methods and provide valuable insights into their removal mechanisms, contributing to the advancement of sustainable water treatment strategies

The Role of Macrophage Migration Inhibitory Factor in the Function of Intestinal Barrier.

Macrophage migration inhibitory factor (MIF) is a multifunctional protein that is involved in the development of gut-related inflammation. To investigate the role of MIF in the function of the intestinal barrier, we have explored intestinal permeability and gut-associated immune response in MIF-deficient (MIF-KO) mice. The absence of MIF provoked impairment of tight and adherens epithelial junctions in the colon through the disturbance of E-cadherin, zonula occludens-1, occludin and claudin-2 expression, which lead to the increase of intestinal barrier permeability. In these circumstances the diversity and content of gut microbiota in MIF-KO mice was considerably different compared to wild type mice. This change in microbiota was accompanied by an increased intestinal IgA concentration and a higher production of pro-inflammatory cytokines TNF and IFN-γ in mesenteric lymph nodes of MIF-KO mice. The forced changes of microbiota executed by antibiotics prevented the "leakage" of the barrier in MIF-KO mice, probably through up-regulation of occludin expression and normalization of cellular pore diameters. In addition, cytokine secretion was normalized after the treatment with antibiotics. These results suggest that MIF participates in the maintenance of physiological microbiota diversity and immunosurveillance, which in turn enables the proper intestinal barrier function

Zirconia based photocatalysts in degradation of selected herbicides

Hydrothermally synthesized zirconia nanopowders: pure and doped with Si4+ ions were spectroscopically characterized and used as photocatalysts for degradation of herbicides sulcotrione and fluroxypyr. Zirconia is wide band gap ceramic (Eg ~ 5 eV) however, synthesized nanopowders showed unexpected, modest absorbance in visible light range. That fact inspired photocatalytical degradation of herbicides with wide utilization, using solar irradiation (SI) in laboratory conditions. In the scope of this study, degradation of herbicides was only slightly achieved (irradiation time 2h).XV International Conference on Fundamental and Applied Aspects of Physical Chemistry : Proceedings. Vol. 1, September 20-24,2021, Belgrad