Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
2,318
result(s) for
"Crypts"
Sort by:
Walk the wild with me
\"Orphaned when still a toddler, Nicholas Withybeck knows no other home than Locksley Abbey outside Nottingham, England. He works in the scriptorium embellishing illuminated manuscripts with hidden faces of the Wild Folk and whimsical creatures that he sees every time he ventures into the woods and fields. His curiosity leads him into forbidden nooks and crannies both inside and outside the abbey, and he becomes adept at hiding to stay out of trouble. On one of these forays Nick slips into the crypt beneath the abbey. There he finds an altar older than the abbey's foundations, ancient when the Romans occupied England. Behind the bricks around the altar, he finds a palm-sized silver cup. The cup is embellished with the three figures of Elena, the Celtic goddess of crossroads, sorcery, and cemeteries. He carries the cup with him always, listening as the goddess whispers wisdom in the back of his mind. With Elena's cup in his pocket, Nick can see that the masked dancers at the May Day celebration in the local village are actually the creatures of the wood: The Green Man--known to mortals as Little John--and Robin Goodfellow, Herne the Huntsman, dryads, trolls, and water sprites. Theirs are the faces he's seen and drawn into his illuminations. Guided by Elena along secret forest paths, Nick learns that Little John's love has been kidnapped by Queen Mab of the Faeries. The door to the Faery mound will only open when the moons of the two realms align. That time is fast approaching. Nick must release Elena so that she can use sorcery to unlock that door, allowing Nick's band of friends to try to rescue the girl. Will he have the courage to release her as his predecessor did not?\"--Publisher descripton.
Book
A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses colon tumorigenesis via regular exercise
Objective Several epidemiological studies have shown that regular exercise can prevent the onset of colon cancer, although the underlying mechanism is unclear. Myokines are secreted skeletal muscle proteins responsible for some exercise-induced health benefits including metabolic improvement and anti-inflammatory effects in organs. The purpose of this study was to identify new myokines that contribute to the prevention of colon tumorigenesis. Methods To identify novel secreted muscle-derived proteins, DNA microarrays were used to compare the transcriptome of muscle tissue in sedentary and exercised young and old mice. The level of circulating secreted protein acidic and rich in cysteine (SPARC) was measured in mice and humans that performed a single bout of exercise. The effect of SPARC on colon tumorigenesis was examined using SPARC-null mice. The secretion and function of SPARC was examined in culture experiments. Results A single bout of exercise increased the expression and secretion of SPARC in skeletal muscle in both mice and humans. In addition, in an azoxymethane-induced colon cancer mouse model, regular low-intensity exercise significantly reduced the formation of aberrant crypt foci in wild-type mice but not in SPARC-null mice. Furthermore, regular exercise enhanced apoptosis in colon mucosal cells and increased the cleaved forms of caspase-3 and caspase-8 in wild-type mice but not in SPARC-null mice. Culture experiments showed that SPARC secretion from myocytes was induced by cyclic stretch and inhibited proliferation with apoptotic effect of colon cancer cells. Conclusions These findings suggest that exercise stimulates SPARC secretion from muscle tissues and that SPARC inhibits colon tumorigenesis by increasing apoptosis.
Journal Article
Resistant starch supplementation increases crypt cell proliferative state in the rectal mucosa of older healthy participants
There is strong evidence that foods containing dietary fibre protect against colorectal cancer, resulting at least in part from its anti-proliferative properties. This study aimed to investigate the effects of supplementation with two non-digestible carbohydrates, resistant starch (RS) and polydextrose (PD), on crypt cell proliferative state (CCPS) in the macroscopically normal rectal mucosa of healthy individuals. We also investigated relationships between expression of regulators of apoptosis and of the cell cycle on markers of CCPS. Seventy-five healthy participants were supplemented with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design in a randomised, double-blind, placebo-controlled trial (the Dietary Intervention, Stem cells and Colorectal Cancer (DISC) Study). CCPS was assessed, and the expression of regulators of the cell cycle and of apoptosis was measured by quantitative PCR in rectal mucosal biopsies. SCFA concentrations were quantified in faecal samples collected pre- and post-intervention. Supplementation with RS increased the total number of mitotic cells within the crypt by 60 % (P = 0·001) compared with placebo. This effect was limited to older participants (aged ≥50 years). No other differences were observed for the treatments with PD or RS as compared with their respective controls. PD did not influence any of the measured variables. RS, however, increased cell proliferation in the crypts of the macroscopically-normal rectum of older adults. Our findings suggest that the effects of RS on CCPS are not only dose, type of RS and health status-specific but are also influenced by age.
Journal Article
Crypt fusion as a homeostatic mechanism in the human colon
ObjectiveThe crypt population in the human intestine is dynamic: crypts can divide to produce two new daughter crypts through a process termed crypt fission, but whether this is balanced by a second process to remove crypts, as recently shown in mouse models, is uncertain. We examined whether crypt fusion (the process of two neighbouring crypts fusing into a single daughter crypt) occurs in the human colon.DesignWe used somatic alterations in the gene cytochrome c oxidase (CCO) as lineage tracing markers to assess the clonality of bifurcating colon crypts (n=309 bifurcating crypts from 13 patients). Mathematical modelling was used to determine whether the existence of crypt fusion can explain the experimental data, and how the process of fusion influences the rate of crypt fission.ResultsIn 55% (21/38) of bifurcating crypts in which clonality could be assessed, we observed perfect segregation of clonal lineages to the respective crypt arms. Mathematical modelling showed that this frequency of perfect segregation could not be explained by fission alone (p<10−20). With the rates of fission and fusion taken to be approximately equal, we then used the distribution of CCO-deficient patch size to estimate the rate of crypt fission, finding a value of around 0.011 divisions/crypt/year.ConclusionsWe have provided the evidence that human colonic crypts undergo fusion, a potential homeostatic process to regulate total crypt number. The existence of crypt fusion in the human colon adds a new facet to our understanding of the highly dynamic and plastic phenotype of the colonic epithelium.
Journal Article
Are Non-dysplastic Crypts with Corrupted Shapes the Initial Recordable Histological Event in the Development of Sporadic Conventional Adenomas?
Colonic crypts with normal epithelial lining displaying corrupted shapes (called non-dysplastic crypts with corrupted shapes, NDCs) were earlier recorded underneath the adenomatous glands of conventional colon adenomas in rats.
To assess the frequency of NDCs in clinical sporadic conventional (tubular/villous) adenomas.
NDCs found underneath the adenomatous epithelium in 255 sporadic conventional adenomas removed at endoscopy were classified into four groups: i) With fission distortions, ii) with length distortions, iii) with outline distortions, and iv) with axial polarity distortions. In 22 controls, the colonic mucosa proximal or distal to surgically removed colonic adenocarcinomas was scrutinized for NDCs.
Nearly three-quarters of the sporadic conventional adenomas investigated here had three or more NDCs underneath the adenomatous tissue, those with ≥4 NDCs being more frequent (46.3%) than those having 1, 2 or 3 NDCs (p<0.05). Nineteen out of the 22 control colon segments had normal crypts and the remaining three had occasional NDCs (mean=3.7, range=2-5).
NDCs were found underneath the adenomatous glands in all 255 sporadic conventional adenomas. Occasionally, NDCs were present in the mucosa of the stalk of pediculated conventional adenomas. The absence of adenomatous tissue in NDCs of the stalk should rule out the possibility that the adenomatous tissue on top had directly orchestrated the development of NDCs below. Moreover, NDCs rarely occurred in controls. Accordingly, NDCs emerge as a genuine phenomenon of crypt deformation in sporadic conventional adenomas. Considering that human colonic crypts typically divide at most once or twice during a lifetime, with an average crypt cycle length of 36 years, the accumulation of NDCs underneath sporadic conventional adenomas is remarkable. In light of these considerations, it is suggested that these putative mutated NDCs may represent the initial histological recordable event heralding the development of sporadic conventional adenomas in the human colon.
Journal Article
The efficacy of aspirin and metformin combination therapy in patients with rectal aberrant crypt foci: a double-blinded randomized controlled trial
Background
The incidence and mortality rates of colorectal cancer (CRC) continue to increase worldwide. Therefore, new preventive strategies are needed to lower the burden of this disease. Previous studies reported that aspirin could suppress the development of sporadic colorectal adenoma. In addition, metformin is a biguanide derivative that is long widely used for the treatment of diabetes mellitus and has recently been suggested to have a suppressive effect on carcinogenesis and cancer cell growth. Both drugs exhibit a chemopreventive effect, but their efficacy is limited.
Aberrant crypt foci (ACF), defined as lesions containing crypts that are larger in diameter and stain more darkly with methylene blue than normal crypts, are more prevalent in patients with cancer and adenomas, and considered a reliable surrogate biomarker of CRC. Thus, we designed a prospective trial as a preliminary study prior to a CRC chemoprevention trial to evaluate the chemopreventive effect of aspirin combined with metformin on colorectal ACF formation in patients scheduled for polypectomy.
Methods
This study is a double-blind randomized controlled trial that will be conducted in patients with both colorectal ACF and colorectal polyps scheduled for polypectomy. Eligible patients will be recruited for the study and the number of ACF in the rectum will be counted at the baseline colonoscopy. Then, the participants will be allocated to one of the following two groups; the aspirin plus placebo group or the aspirin plus metformin group. Patients in the aspirin plus placebo group will receive oral aspirin (100 mg) and placebo for 8 weeks, and those in the aspirin plus metformin group will receive oral aspirin (100 mg) and metformin (250 mg) for 8 weeks. After 8 weeks of administration, polypectomy will be performed to evaluate changes in the number of ACF, and the cell-proliferative activity in the normal colorectal mucosa and colorectal polyps.
Discussion
This is the first study proposed that will explore the effect of aspirin combined with metformin on the formation of colorectal ACF in humans.
Trial registration
This trial has been registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry as
UMIN000028259
. Registered 17 July 2017.
Journal Article
Wnt5a Potentiates TGF-β Signaling to Promote Colonic Crypt Regeneration After Tissue Injury
Reestablishing homeostasis after tissue damage depends on the proper organization of stem cells and their progeny, though the repair mechanisms are unclear. The mammalian intestinal epithelium is well suited to approach this problem, as it is composed of well-delineated units called crypts of Lieberkühn. We found that Wnt5a, a noncanonical Wnt ligand, was required for crypt regeneration after injury in mice. Unlike controls, Wnt5a-deficient mice maintained an expanded population of proliferative epithelial cells in the wound. We used an in vitro system to enrich for intestinal epithelial stem cells to discover that Wnt5a inhibited proliferation of these cells. Surprisingly, the effects of Wnt5a were mediated by activation of transforming growth factor-ß (TGF-ß) signaling. These findings suggest a Wnt5a-dependent mechanism for forming new crypt units to reestablish homeostasis.
Journal Article
Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells
The intestinal epithelium is maintained by a population of rapidly cycling (Lgr5⁺) intestinal stem cells (ISCs). It has been postulated, however, that slowly cycling ISCs must also be present in the intestine to protect the genome from accumulating deleterious mutations and to allow for a response to tissue injury. Here, we identify a subpopulation of slowly cycling ISCs marked by mouse telomerase reverse transcriptase (mTert) expression that can give rise to Lgr5⁺ cells. mTert-expressing cells distribute in a pattern along the crypt-villus axis similar to long-term label-retaining cells (LRCs) and are resistant to tissue injury. Lineage-tracing studies demonstrate that mTert⁺ cells give rise to all differentiated intestinal cell types, persist long term, and contribute to the regenerative response following injury. Consistent with other highly regenerative tissues, our results demonstrate that a slowly cycling stem cell population exists within the intestine.
Journal Article
Somatic mutation rates scale with lifespan across mammals
The rates and patterns of somatic mutation in normal tissues are largely unknown outside of humans
1
–
7
. Comparative analyses can shed light on the diversity of mutagenesis across species, and on long-standing hypotheses about the evolution of somatic mutation rates and their role in cancer and ageing. Here we performed whole-genome sequencing of 208 intestinal crypts from 56 individuals to study the landscape of somatic mutation across 16 mammalian species. We found that somatic mutagenesis was dominated by seemingly endogenous mutational processes in all species, including 5-methylcytosine deamination and oxidative damage. With some differences, mutational signatures in other species resembled those described in humans
8
, although the relative contribution of each signature varied across species. Notably, the somatic mutation rate per year varied greatly across species and exhibited a strong inverse relationship with species lifespan, with no other life-history trait studied showing a comparable association. Despite widely different life histories among the species we examined—including variation of around 30-fold in lifespan and around 40,000-fold in body mass—the somatic mutation burden at the end of lifespan varied only by a factor of around 3. These data unveil common mutational processes across mammals, and suggest that somatic mutation rates are evolutionarily constrained and may be a contributing factor in ageing.
Whole-genome sequencing is used to analyse the landscape of somatic mutation in intestinal crypts from 16 mammalian species, revealing that rates of somatic mutation inversely scale with the lifespan of the animal across species.
Journal Article
Glycyrrhizic Acid Suppresses the Development of Precancerous Lesions via Regulating the Hyperproliferation, Inflammation, Angiogenesis and Apoptosis in the Colon of Wistar Rats
Colon carcinogenesis is a multistep process and it emanates from a series of molecular and histopathological alterations. Glycyrrhizic acid (GA) is a natural and major pentacyclic triterpenoid glycoside of licorice roots extracts. It has several pharmacological and biological properties such as anti-inflammatory, anti-viral, and anti-cancer. In the present study, we investigated the chemopreventive potential of GA against 1,2-dimethyhydrazine (DMH)-induced precancerous lesions i.e., aberrant crypt foci (ACF) and mucin depleted foci (MDF), and its role in regulating the hyperproliferation, inflammation, angiogenesis and apoptosis in the colon of Wistar rats.
Animals were divided into 5 groups. In group III, IV and V, GA was administered at the dose of 15 mg/kg b. wt. orally while in group II, III and IV, DMH was administered subcutaneously in the groin at the dose of 20 mg/kg b.wt once a week for first 5 weeks and animals were euthanized after 9 weeks.
GA supplementation suppressed the development of precancerous lesions and it also reduced the infiltration of mast cells, suppressed the immunostaining of Ki-67, NF-kB-p65, COX-2, iNOS and VEGF while enhanced the immunostaining of p53, connexin-43, caspase-9 and cleaved caspase-3. GA treatment significantly attenuated the level of TNF-α and it also reduced the depletion of the mucous layer as well as attenuated the shifting of sialomucin to sulphomucin.
Our findings suggest that GA has strong chemopreventive potential against DMH-induced colon carcinogenesis but further studies are warranted to elucidate the precise mechanism of action of GA.
Journal Article