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..

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..

Morphometric study of uninvolved rectal mucosa 10 cm and 20 cm away from the malignant tumor

Recently, many details of the interplay between tumor cells and tumor-associated stromal elements leading to the progression of malignant disease were elucidated. In contrast, little is known about the role of uninvolved stromal tissue in the remote surrounding of the malignant tumor. Therefore, we performed a computer-aided morphometric study of rectal mucosa in samples taken 10 cm and 20 cm away from the malignant tumor during endoscopic examination of 23 patients older than 60 years. The samples of rectal mucosa from 10 healthy persons of corresponding age subjected to diagnostic rectoscopy during active screening for asymptomatic cancer were used as control. All structural elements of the rectal mucosa were studied and the number of nucleated cells in the lamina propria per 0.1 mm2 of tissue was assessed. Our study revealed a reduced number of cells in the lamina propria of the rectal mucosa 10 cm and 20 cm away from the tumor lesion in both male and female patients. The decreased mucosal height and increased crypt number were registered in female patients 10 cm away from the tumor. The connective tissue of lamina propria showed a disorderly organization: the collagen fibers were frail, loosely arranged and signs of tissue edema were present. Small blood vessels and capillaries were much more frequently seen than in healthy tissue. Our results demonstrate the complex interactions between the cancer and remote mucosal tissue of the affected organ

Lipopolysaccharide induces tumor necrosis factor receptor-1 independent relocation of lymphocytes from the red pulp of the mouse spleen

It is well known that bacterial lipopolysaccharide (LPS) induces migration of several cellular populations within the spleen. However, there are no data about the impact of LPS on B and T lymphocytes present in the red pulp. Therefore, we used an experimental model in which we tested the effects of intravenously injected LPS on the molecular, cellular and structural changes of the spleen, with special reference to the red pulp lymphocytes. We discovered that LPS induced a massive relocation of B and T lymphocytes from the splenic red pulp, which was independent of the tumor necrosis factor receptor-1 signaling axis. Early after LPS treatment, quantitative real-time PCR analysis revealed the elevated levels of mRNA encoding numerous chemokines and proinflammatory cytokines (XCL1, CXCL9, CXCL10, CCL3, CCL4, CCL5, CCL17, CCL20, CCL22, TNFα and LTα) which affect the navigation and activities of B and T lymphocytes in the lymphoid tissues. An extreme increase in mRNA levels for CCL20 was detected in the white pulp of the LPS-treated mice. The CCL20-expressing cells were localized in the PALS. Some smaller CCL20-expressing cells were evenly dispersed in the B cell zone. Thus, our study provides new knowledge of how microbial products could be involved in shaping the structure of lymphatic organs

Altered organization of collagen fibers in the uninvolved human colon mucosa 10 cm and 20 cm away from the malignant tumor

Remodelling of collagen fibers has been described during every phase of cancer genesis and progression. Changes in morphology and organization of collagen fibers contribute to the formation of microenvironment that favors cancer progression and development of metastasis. However, there are only few data about remodelling of collagen fibers in healthy looking mucosa distant from the cancer. Using SHG imaging, electron microscopy and specialized softwares (CT-FIRE, CurveAlign and FiberFit), we objectively visualized and quantified changes in morphology and organization of collagen fibers and investigated possible causes of collagen remodelling (change in syntheses, degradation and collagen cross-linking) in the colon mucosa 10 cm and 20 cm away from the cancer in comparison with healthy mucosa. We showed that in the lamina propria this far from the colon cancer, there were changes in collagen architecture (width, straightness, alignment of collagen fibers and collagen molecules inside fibers), increased representation of myofibroblasts and increase expression of collagen-remodelling enzymes (LOX and MMP2). Thus, the changes in organization of collagen fibers, which were already described in the cancer microenvironment, also exist in the mucosa far from the cancer, but smaller in magnitude

The Effects of Whole Body Gamma Irradiation on Mice, Age-Related Behavioral, and Pathophysiological Changes

We designed a study with the objective to determine the long-term radiation effects of gamma rays, originating from a single shot of Co60 at a dose of 2 Gy on the 7-month-old male mice of the ICR line in 30 days after the irradiation. The aim of this study was to characterize the behavior of animals using the Open Field test, immuno-hematological status, and morpho-functional changes in the central nervous system of mice. Irradiated animals displayed significantly different behavior in the OF in comparison with the control group. The radiation damage was confirmed by assessing the ratio of leukocytes in the peripheral blood of mice at a later date after exposure to Co60. After irradiation, a decrease in the glioneuronal complex was observed in the irritated group as well as histological changes of brain cells. To sum up, not only was the hematological status of mice altered upon the total gamma irradiation, but also their behavior, which was most probably due to significant alterations in the CNS. Graphical Abstract: Study of influence of ionizing radiation on female mice, comparison between different age groups. Open Field test on the 30 days after 2 Gy of γ-rays and histological analysis indicated changes in behavioral patterns, leucocytes, and brain tissue. [Figure not available: see fulltext.] © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature

Photocatalytic decomposition of selected biologically active compounds in environmental waters using TiO 2 /polyaniline nanocomposites: Kinetics, toxicity and intermediates assessment

A comprehensive study of the removal of selected biologically active compounds (pharmaceuticals and pesticides) from different water types was conducted using bare TiO2nanoparticles and TiO2/polyaniline (TP-50, TP-100, and TP-150) nanocomposite powders. In order to investigate how molecular structure of the substrate influences the rate of its removal, we compared degradation efficiency of the initial substrates and degree of mineralization for the active components of pharmaceuticals (propranolol, and amitriptyline) and pesticides (sulcotrione, and clomazone) in double distilled (DDW) and environmental waters. The results indicate that the efficiency of photocatalytic degradation of propranolol and amitriptyline was higher in environmental waters: rivers (Danube, Tisa, and Begej) and lakes (Moharač, and Sot) in comparison with DDW. On the contrary, degradation efficacy of sulcotrione and clomazone was lower in environmental waters. Further, of the all catalysts applied, bare TiO2and TP-100 were found to be most effective in the mineralization of propranolol and amitriptyline, respectively, while TP-150 appeared to be the most efficient in terms of sulcotrione and clomazone mineralization. Also, there was no significant toxicity observed after the irradiation of pharmaceuticals or pesticides solutions using appropriate catalysts on rat hepatoma (H-4-II-E), mouse neuroblastoma (Neuro-2a), human colon adenocarcinoma (HT-29), and human fetal lung (MRC-5) cell lines. Subsequently, detection and identification of the formed intermediates in the case of sulcotrione photocatalytic degradation using bare TiO2and TP-150 showed slightly different pathways of degradation. Furthermore, tentative pathways of sulcotrione photocatalytic degradation were proposed and discussed. Kinetics, toxicity and intermediates assessment of biologically active compounds (pesticides and pharmaceuticals) in environmental waters