AIM: To investigate whether defi ciency of expressionof cytochrome c oxidase I (CcOI) in colonic crypts is associated with colon cancer.METHODS: The pattern and level of expression of CcOI in non-neoplastic colonic cr...AIM: To investigate whether defi ciency of expressionof cytochrome c oxidase I (CcOI) in colonic crypts is associated with colon cancer.METHODS: The pattern and level of expression of CcOI in non-neoplastic colonic crypts,and in dysplastic tissues,was assessed using standard immunohis-tochemical methods.Biopsies were obtained from individuals undergoing colonoscopies for screening purposes or for a medically indicated reason.Tissue samples were also obtained from surgical colonic resections.Samples from resections were taken from colonic mucosa 1 and 10 cm from tumors and from the tumors themselves.Samples were evaluated for frequency of crypts with reduced or absent expression of CcOI.In most crypts the loss was apparent throughout the entire crypt,while in a small minority the loss was segmental.The strong immunoreactivity using this monoclonal antibody makes the scoring unambiguous.The percent of crypts with reduced or absent expression of CcOI or (infrequent) segmented loss of expression was then calculated.Data analyses were performed using SPSS statistical package 17.0.RESULTS: The average frequency of CcOI deficient crypts (CcOI-DC) is low in individuals between 20 and 39 years of age,with 0.48% ± 0.40% CcOI-DC for women and 1.80% ± 0.35% for men.CcOI-DC increases after age 40 years,so that between the ages of 40 and 44 years the average frequency of CcOI- DC goes up to 5.89% ± 0.84% in women and 2.15% ± 1.27% in men.By 80-84 years of age,the average frequency of CcOI-DC goes up in women to 15.77% ± 0.97% and in men to 22.6% ± 0.65%.The increases in CcOI-DC from ages 40-44 years compared to 80-84 years in women and men are significantly different with P < 0.01.For women over age 60 years,deficiency of CcOI expression is greater in those women who have had a cancer in their colon.The frequency of CcOI-DC,measured in men,increased in tissues adjacent to colon cancer,being 4.03% ± 0.27% in individuals free of neoplasia in the age range 55-64 yearsand 14.13% ± 0.35% in resected histologically normal tissue of men with cancer in the same age range,P < 0.001.Similar signifi cant differences were noted in older age ranges.The frequency of CcOI-DC crypts in the cecum and sigmoid colon of an individual are signifi cantly correlated,with an R2 = 0.414 for women and R2 = 0.528 for men,P < 0.001.This suggests that the factors determining the level of CcOI deficiency act throughout the colon.Most defective crypts are in clusters of two or more,a likely consequence of crypt fission.In the non-neoplastic margins of cancers,crypts are frequently defi cient for CcOI,and such crypts may appear in large clusters,some containing more than 100 defi cient crypts.CcOI defi ciency is also apparent in colon cancers and sometimes involves a large section of the tumor.Overall,CcOI deficient cells can be visualized in segments of crypts,in whole crypts that increase in frequency with age,in crypts undergoing f ission,in clusters of crypts where the clusters increase in size with age,in increased frequency near tumors,in large clusters in the intimate margins of tumors,and in the tumors themselves.There is no clear dividing line between early stages that can be considered aspects of aging and later stages that can be considered aspects of the progression to cancer.This ambiguity may re ect a rather general situation leading to adult cancer where the early stages of cellular change appear to be relatively innocuous features of the aging process but over decades may evolve into malignancy.CONCLUSION: CcOI defi cient crypts increase in frequency with age,and clusters of defi cient crypts are associated with,and may give rise to,colon cancer.展开更多
The pathogenesis of colon cancer involves sequential and multistep progression of epithelial cells initiated to a cancerous state with defined precancerous intermediaries. Aberrant crypt foci （ACF） represent the ear...The pathogenesis of colon cancer involves sequential and multistep progression of epithelial cells initiated to a cancerous state with defined precancerous intermediaries. Aberrant crypt foci （ACF） represent the earliest identifiable intermediate precancerous lesions during colon carcinogenesis in both laboratory animals and humans. ACF are easily induced by colon-specific carcinogens in rodents and can be used to learn more about the process of colon carcinogenesis. For over two decades, since its first discovery, azoxymethane （AOM）-induced rodent ACF have served as surrogate biomarkers in the screening of various anticarcinogens and carcinogens. Several dietary constituents and phytochemicals have been tested for their colon cancer chemopreventive efficacy using the ACF system. There has been substantial effort in defining and refining ACF in terms of understanding their molecular make-up, and extensive research in this field is currently in progress. In chemoprevention studies, AOM-induced rat ACF have been very successful as biomarkers, and have provided several standardized analyses of data. There have been several studies that have reported that ACF data do not correlate to actual colon tumor outcome, however, and hence there has been an ambiguity about their role as biomarkers. The scope of this mini-review is to provide valuable insights and limitations of AOM-induced rat ACF as biomarkers in colon cancer chemoprevention studies. The role of the dynamics and biological heterogeneity of ACF is critical in understanding them as biomarkers in chemoprevention studies.展开更多
AIM:To characterize aberrant crypt focus (ACF) in adjoining mucosa in sporadic colorectal carcinoma and to evaluate fragile histidine triad (Fhit) protein and Ki67. METHODS:ACF was identified grossly and classified hi...AIM:To characterize aberrant crypt focus (ACF) in adjoining mucosa in sporadic colorectal carcinoma and to evaluate fragile histidine triad (Fhit) protein and Ki67. METHODS:ACF was identified grossly and classified histologically in 75 resected specimens. ACF was typed into hyperplastic ACF (HACF) and dysplastic ACF (DACF). Sections of ACF, carcinoma and normal colonic mucosa as control were studied for Fhit and Ki67 expressions by immunohistochemistry and were grouped according to staining intensity and the number of positive stained cells observed in different histological groups. Comparison was done between the different groups by Pearson's χ 2 test and γ test for the ordinal data. P value < 0.05 was considered as significant.RESULTS:Age range was 40 to 86 years in males (mean = 43.36) and 45 to 70 years in females (mean = 56). HACF was identified in all cases studied in the non-tumorous colonic mucosa; ACF was observed as non-contiguous scattered foci, which supports the hypothesis of acquisition of single focus monoclonality by colonic epithelial cells in tumor generation. Twenty-four (32%) had DACF and were observed as closure to carcinoma foci. Intensity of Fhit expression:(1) HACF 40% exhibited strong intensity, similar to normal, moderate in 36% and weak in 24%; (2) DACF strong in 25%, moderate in 37.5% and weak in 37.5%; and (3) carcinoma negative in 16%, strong in 43% and moderate and weak in 28.5% each. Significant difference was observed in intensity of the Fhit protein expressions by HACF and DACF (P < 0.05). Tumor in older patients showed a stronger Fhit intensity compared to younger patients (P = 0.036). Vegetarian diet intake and nonsmokers showed stronger Fhit intensities. Advanced stage tumor, non-vegetarian diet and younger age was associated with loss of Fhit protein. Ki67 positivity was an extended crypt pattern in HACF and DACF showed extension up to the neck region of the crypts and surface epithelium. Carcinomas showed a marked increase in Ki67 expression (P < 0.05). Fhit protein had an inverse association with Ki67 expression. CONCLUSION:Weaker Fhit intensity was associated with smoking, non-vegetarian diet intake and increasing Ki67 expression. Loss of Fhit protein expression is possibly influenced by environmental factors like smoking and non-vegetarian diet intake.展开更多
AIM:To evaluate whether crypt abscesses frominflammatory bowel disease(IBD)patients containbacteria and to establish their nature.METHODS:We studied 17 ulcerative colitis patients,11 Crohn's disease patients,7 pat...AIM:To evaluate whether crypt abscesses frominflammatory bowel disease(IBD)patients containbacteria and to establish their nature.METHODS:We studied 17 ulcerative colitis patients,11 Crohn's disease patients,7 patients with acute selflimited colitis(ASLC)and normal colonic biopsies from5 subjects who underwent colonoscopy for colon cancer screening.A fluorescent in situ hybridization techniquewas applied to colonic biopsies to assess the microbiotacomposition of the crypts and crypt abscesses.RESULTS:Crypts colonized by bacteria were observedin 42.9%and 3.6%of ASLC and IBD patients,respectively(P=0.019).Crypt abscesses colonized bybacteria were observed in 28.6%and 0.0%of ASLCand IBD patients,respectively(P=0.035).CONCLUSION:These results do not support thehypothesis that crypt abscesses in IBD are the resultof localized dysbiosis arising from persistence of livingbacteria colonizing the crypts.展开更多
AIM:To clarify the relationship of human rectal aberrant crypt foci and formation of colorectal polyp.METHODS:Eighty-nine subjects were recruited from the population of Japanese individuals who underwent polypectomy a...AIM:To clarify the relationship of human rectal aberrant crypt foci and formation of colorectal polyp.METHODS:Eighty-nine subjects were recruited from the population of Japanese individuals who underwent polypectomy at Yokohama City University Hospital.All patients had baseline adenomas removed at year 0 colonoscopy.Aberrant crypt foci(ACF) were defined as lesions in which the crypts were more darkly stained with methylene blue than normal crypts and had larger diameters,often with oval or slit-like lumens and a thicker epithelial lining.RESULTS:A total of 366 ACFs were identified in 89 patients;all had baseline adenomas removed at the first examination(year 0) colonoscopy and returned for the second(year 1).ACF in the lower rectum were assessed at year 0 and study group were divided into two groups depend on ACF numbers,0-3 or over 3.All participants were examined in the number and maximum size of adenoma.There was no statistical difference in number and maximum size of ACF at year 0,however,maximum size of adenoma was larger in over 3 group than 0-3 group at year 1.CONCLUSION:The number of ACF may be a predictive factor of relatively large adenoma incidence in the pilot phase study.展开更多
Dear Editor,Cryptozoospermia is defined as the apparent absence of spermatozoa from fresh semen samples,but they can.be found in centrifuged pellets.1 It is usually caused by a spermatogenic disorder,while cryptozoosp...Dear Editor,Cryptozoospermia is defined as the apparent absence of spermatozoa from fresh semen samples,but they can.be found in centrifuged pellets.1 It is usually caused by a spermatogenic disorder,while cryptozoospermia associated with seminal duct obstruction is less common.2 Because of the extremely low sperm counts in semen samples,men with cryptozoospermia are often reliant on intracytoplasmic sperm injection(ICSI)for paternity.展开更多
The effect of fermented milk on micronuclei andapoptosis induced by DimethyIhydraziine(DMH)in thecolon crypt cells of mouse was studied.Fermented milk,milk and tap water were fed to three groups of C57BL mice.The anim...The effect of fermented milk on micronuclei andapoptosis induced by DimethyIhydraziine(DMH)in thecolon crypt cells of mouse was studied.Fermented milk,milk and tap water were fed to three groups of C57BL mice.The animals were given DMH i.p.at a dosage of 20mg/kg onthe 7th day.The animals were sacrificed 24 hours展开更多
The intestinal epithelial lining plays a central role in the digestion and absorption of nutrients,but exists in a harsh luminal environment that necessitates continual renewal.This renewal process involves epithelial...The intestinal epithelial lining plays a central role in the digestion and absorption of nutrients,but exists in a harsh luminal environment that necessitates continual renewal.This renewal process involves epithelial cell proliferation in the crypt base and later cell migration from the crypt base to the luminal surface.This process is dependent on multi-potent progenitor cells,or stem cells,located in each crypt.There are about 4 to 6 stem cells per crypt,and these stem cells are believed to generate distinct end-differentiated epithelial cell types,including absorptive cells,goblet cells,enteroendocrine cells and Paneth cells,while also maintaining their own progenitor cell state.Earlier studies suggested that intestinal stem cells were located either in the crypt base interspersed between the Paneth cells [i.e.crypt base columnar(CBC) cell model] or at an average position of 4 cells from the crypt base [i.e.label-retaining cells(LRC +4) model].Recent studies have employed biomarkers in the in vivo mammalian state to more precisely evaluate the location of these progenitor cells in the intestinal crypt.Most notable of these novel markers are Lgr5,a gene that encodes a G-protein-coupled receptor with expression restricted to CBC cells,and Bmi 1,which encodes a chromatin remodeling protein expressed by LRC.These studies raise the possibility that there may be separate stem cell lines or different states of stem cell activation involved in the renewal of normal mammalian intestinal tract.展开更多
Background:Ventricular crypts are quite a common finding during cardiac imaging,but their etiology is unclear.A possible final result of a spontaneous ventricular septal defect closure has been supposed but never inve...Background:Ventricular crypts are quite a common finding during cardiac imaging,but their etiology is unclear.A possible final result of a spontaneous ventricular septal defect closure has been supposed but never investigated in earlier studies.Method:From January 1997 to December 2020,all newborns diagnosed to have a ventricular septal defect were prospectively entered in our database and those with an isolated defect were included in the study.Ventricular septal defects were classified into four types:perimembranous,trabecular muscular,inlet and outlet.A long-term follow up was performed in order to visualize the possible residual formation of a septal myocardial crypt.Results:A total of 376 isolated ventricular septal defects(314 muscular and 54 perimembranous,4 inlet,4 outlet)were detected.Follow up ranged from 1 to 23 years and showed that,among muscular type,a spontaneous closure occurred in 284(91%),26 did not close(8,28%),2 required surgical intervention(0,63%),3 were lost at follow up(0,95%).During this period,after spontaneous defect closure closure,20 crypts were found(6,4%).Conclusion:This study shows that a muscular ventricular septal defect may evolve in the 6.4%of cases in a residual septal crypt.Although septal crypts occur more frequently in patients affected by hypertrophic and hypertensive cardiomyopathy,they may also represent the evolution of a spontaneous closure of a muscular interventricular defect.展开更多
In this paper epithelial cell necroses(apoptosis)of mouse intestinal crypts induced by βRays fromtritiated water(HTO)was reported.The resultsshowed that the number of apoptotic cells perintestinal crypt 20 hrs after ...In this paper epithelial cell necroses(apoptosis)of mouse intestinal crypts induced by βRays fromtritiated water(HTO)was reported.The resultsshowed that the number of apoptotic cells perintestinal crypt 20 hrs after injection of展开更多
AIM:To study the genetic alteration in ACF and to define the possibility that ACF may be a very early morphological lesion with molecular changes,and to explore the relationship between ACF and colorectal adenoma even...AIM:To study the genetic alteration in ACF and to define the possibility that ACF may be a very early morphological lesion with molecular changes,and to explore the relationship between ACF and colorectal adenoma even carcinoma. METHODS: DNA from 35 CRC, 15 adenomas, 34 ACF and 10 normal mucus was isolated by means of microdissection. Direct gene sequencing of K-ras gene including codon 12, 13 and 61 as well as the mutation cluster region (MCR) of APC gene was performed. RESULTS: K-ras gene mutation frequency in ACF, adenoma and carcinoma was 17.6% (6/34), 13.3% (2/15), and 14.3% (5/35) respectively, showing no difference (P 】 0.05) in K-ras gene mutation among three pathologic procedures. The K-ras gene mutation in adenoma, carcinoma and 4 ACF restricted in codon 12 (GGT GAT), but the other 2 mutations from ACF located in codon 13 (GGC GAC). K-ras gene mutation was found more frequently in older patients and patients with polypoid cancer. No mutation in codon 61 was found in the three tissue types. Mutation rate of APC gene in adenoma and carcinoma was 22.9% (8/35) and 26.7% (4/15), which was higher than ACF (2.9%) (P 【0.05). APC gene mutation in carcinoma was not correlated with age of patients, location, size and differentiation of tumor. CONCLUSION: ACF might be a very early morphological lesion in the tumorogenesis of colorectal tumor. The morphological feature and gene mutation status was different in ACF and adenoma. ACF is possibly putative microadenoma that might be the precursor of adenoma. In addition, the development of a subgroup of colorectal carcinomas might undergo a way of normal epithelium ACF carcinomas .展开更多
Reportedly,proteins involved in lipid metabolism change significantly in the jejunal crypt cells of earlyweaned piglets,but the exact lipid profile change remains uncertain.In the present study,32 piglets weaned at 21...Reportedly,proteins involved in lipid metabolism change significantly in the jejunal crypt cells of earlyweaned piglets,but the exact lipid profile change remains uncertain.In the present study,32 piglets weaned at 21 d of age were randomly divided into 4 groups with 8 replicates.The jejunal crypt cells of a group of piglets on the post-weaning day(PWD)1,3,7,and 14 were isolated per time point.Crypt cell lipid profiles were analyzed using ultra-high-performance liquid chromatography coupled with hybrid quadrupole time-of-flight mass spectrometry.This study showed that piglets suffered the greatest weaning stress on PWD 3 in terms of the lowest relative weight of the small intestine,the highest relative weight of the spleen,and the highest levels of malondialdehyde,cholesterol,and low-density lipoprotein cholesterol.The lipid profile of jejunal crypt cells including carnitine,sulfatide,sphingomyelin,hexosylceramide,and ceramide greatly changed after weaning,especially between PWD3 and 14(P<0.05).The differential lipid species between these 2 d were mainly involved in the glycerophospholipid metabolism pathway.In addition,potential lipid biomarkers for weaning stress in crypt cells such as phosphatidylcholine(PC)(9:0/26:1),PC(17:0/18:2),carnitine(24:0),carnitine(22:0),sphingomyelin(d14:1/22:0),PC(P-18:0/18:4),phosphatidylethanolamine(P-16:0/20:4),phosphatidylinositol(15:1/24:4),and dihexosylceramide(d14:1/26:1)were identified.The changes in lipid profile might be related to the inflammation caused by early weaning.These findings might provide new therapeutical targets for intestinal dysfunctions caused by weaning stress.展开更多
Intestinal cancers are developed from intestinal epithelial stem cells(ISCs)in intestinal crypts through a multi-step process involved in genetic mutations of oncogenes and tumor suppressor genes.ISCs play a key role ...Intestinal cancers are developed from intestinal epithelial stem cells(ISCs)in intestinal crypts through a multi-step process involved in genetic mutations of oncogenes and tumor suppressor genes.ISCs play a key role in maintaining the homeostasis of gut epithelium.In 2009,Sato et al established a three-dimensional culture system,which mimicked the niche microenvironment by employing the niche factors,and successfully grew crypt ISCs into organoids or Mini-guts in vitro.Since then,the intestinal organoid technology has been used to delineate cellular signaling in ISC biology.However,the cultured organoids consist of heterogeneous cell populations,and it was technically challenging to introduce genomic changes into three-dimensional organoids.Thus,there was a technical necessity to develop a twodimensional ISC culture system for effective genomic manipulations.In this study,we established a conditionally immortalized mouse intestinal crypt(ciMIC)cell line by using a piggyBac transposon-based SV40 T antigen expression system.We showed that the ciMICs maintained long-term proliferative activity under two-dimensional niche factor-containing culture condition,retained the biological characteristics of intestinal epithelial stem cells,and could form intestinal organoids in three-dimensional culture.While in vivo cell implantation tests indicated that the ciMICs were non-tumorigenic,the ciMICs overexpressing oncogenic b-catenin and/or KRAS exhibited high proliferative activity and developed intestinal adenoma-like pathological features in vivo.Collectively,these findings strongly suggested that the engineered ciMICs should be used as a valuable tool cell line to dissect the genetic and/or epigenetic underpinnings of intestinal tumorigenesis.展开更多
基金Supported by Grants from the National Institutes of Health (5 R01 CA119087)Arizona Biomedical Research Commission Grant #0803Veterans Affairs Merit Review Grant 0142 administered by the Southern Arizona Veterans Affairs Health Care System and from Biomedical Diagnostics and Research, Inc., Tucson, AZ 85719
文摘AIM: To investigate whether defi ciency of expressionof cytochrome c oxidase I (CcOI) in colonic crypts is associated with colon cancer.METHODS: The pattern and level of expression of CcOI in non-neoplastic colonic crypts,and in dysplastic tissues,was assessed using standard immunohis-tochemical methods.Biopsies were obtained from individuals undergoing colonoscopies for screening purposes or for a medically indicated reason.Tissue samples were also obtained from surgical colonic resections.Samples from resections were taken from colonic mucosa 1 and 10 cm from tumors and from the tumors themselves.Samples were evaluated for frequency of crypts with reduced or absent expression of CcOI.In most crypts the loss was apparent throughout the entire crypt,while in a small minority the loss was segmental.The strong immunoreactivity using this monoclonal antibody makes the scoring unambiguous.The percent of crypts with reduced or absent expression of CcOI or (infrequent) segmented loss of expression was then calculated.Data analyses were performed using SPSS statistical package 17.0.RESULTS: The average frequency of CcOI deficient crypts (CcOI-DC) is low in individuals between 20 and 39 years of age,with 0.48% ± 0.40% CcOI-DC for women and 1.80% ± 0.35% for men.CcOI-DC increases after age 40 years,so that between the ages of 40 and 44 years the average frequency of CcOI- DC goes up to 5.89% ± 0.84% in women and 2.15% ± 1.27% in men.By 80-84 years of age,the average frequency of CcOI-DC goes up in women to 15.77% ± 0.97% and in men to 22.6% ± 0.65%.The increases in CcOI-DC from ages 40-44 years compared to 80-84 years in women and men are significantly different with P < 0.01.For women over age 60 years,deficiency of CcOI expression is greater in those women who have had a cancer in their colon.The frequency of CcOI-DC,measured in men,increased in tissues adjacent to colon cancer,being 4.03% ± 0.27% in individuals free of neoplasia in the age range 55-64 yearsand 14.13% ± 0.35% in resected histologically normal tissue of men with cancer in the same age range,P < 0.001.Similar signifi cant differences were noted in older age ranges.The frequency of CcOI-DC crypts in the cecum and sigmoid colon of an individual are signifi cantly correlated,with an R2 = 0.414 for women and R2 = 0.528 for men,P < 0.001.This suggests that the factors determining the level of CcOI deficiency act throughout the colon.Most defective crypts are in clusters of two or more,a likely consequence of crypt fission.In the non-neoplastic margins of cancers,crypts are frequently defi cient for CcOI,and such crypts may appear in large clusters,some containing more than 100 defi cient crypts.CcOI defi ciency is also apparent in colon cancers and sometimes involves a large section of the tumor.Overall,CcOI deficient cells can be visualized in segments of crypts,in whole crypts that increase in frequency with age,in crypts undergoing f ission,in clusters of crypts where the clusters increase in size with age,in increased frequency near tumors,in large clusters in the intimate margins of tumors,and in the tumors themselves.There is no clear dividing line between early stages that can be considered aspects of aging and later stages that can be considered aspects of the progression to cancer.This ambiguity may re ect a rather general situation leading to adult cancer where the early stages of cellular change appear to be relatively innocuous features of the aging process but over decades may evolve into malignancy.CONCLUSION: CcOI defi cient crypts increase in frequency with age,and clusters of defi cient crypts are associated with,and may give rise to,colon cancer.
基金Supported by Health Canada,Government of Canada,Canada
文摘The pathogenesis of colon cancer involves sequential and multistep progression of epithelial cells initiated to a cancerous state with defined precancerous intermediaries. Aberrant crypt foci （ACF） represent the earliest identifiable intermediate precancerous lesions during colon carcinogenesis in both laboratory animals and humans. ACF are easily induced by colon-specific carcinogens in rodents and can be used to learn more about the process of colon carcinogenesis. For over two decades, since its first discovery, azoxymethane （AOM）-induced rodent ACF have served as surrogate biomarkers in the screening of various anticarcinogens and carcinogens. Several dietary constituents and phytochemicals have been tested for their colon cancer chemopreventive efficacy using the ACF system. There has been substantial effort in defining and refining ACF in terms of understanding their molecular make-up, and extensive research in this field is currently in progress. In chemoprevention studies, AOM-induced rat ACF have been very successful as biomarkers, and have provided several standardized analyses of data. There have been several studies that have reported that ACF data do not correlate to actual colon tumor outcome, however, and hence there has been an ambiguity about their role as biomarkers. The scope of this mini-review is to provide valuable insights and limitations of AOM-induced rat ACF as biomarkers in colon cancer chemoprevention studies. The role of the dynamics and biological heterogeneity of ACF is critical in understanding them as biomarkers in chemoprevention studies.
文摘AIM:To characterize aberrant crypt focus (ACF) in adjoining mucosa in sporadic colorectal carcinoma and to evaluate fragile histidine triad (Fhit) protein and Ki67. METHODS:ACF was identified grossly and classified histologically in 75 resected specimens. ACF was typed into hyperplastic ACF (HACF) and dysplastic ACF (DACF). Sections of ACF, carcinoma and normal colonic mucosa as control were studied for Fhit and Ki67 expressions by immunohistochemistry and were grouped according to staining intensity and the number of positive stained cells observed in different histological groups. Comparison was done between the different groups by Pearson's χ 2 test and γ test for the ordinal data. P value < 0.05 was considered as significant.RESULTS:Age range was 40 to 86 years in males (mean = 43.36) and 45 to 70 years in females (mean = 56). HACF was identified in all cases studied in the non-tumorous colonic mucosa; ACF was observed as non-contiguous scattered foci, which supports the hypothesis of acquisition of single focus monoclonality by colonic epithelial cells in tumor generation. Twenty-four (32%) had DACF and were observed as closure to carcinoma foci. Intensity of Fhit expression:(1) HACF 40% exhibited strong intensity, similar to normal, moderate in 36% and weak in 24%; (2) DACF strong in 25%, moderate in 37.5% and weak in 37.5%; and (3) carcinoma negative in 16%, strong in 43% and moderate and weak in 28.5% each. Significant difference was observed in intensity of the Fhit protein expressions by HACF and DACF (P < 0.05). Tumor in older patients showed a stronger Fhit intensity compared to younger patients (P = 0.036). Vegetarian diet intake and nonsmokers showed stronger Fhit intensities. Advanced stage tumor, non-vegetarian diet and younger age was associated with loss of Fhit protein. Ki67 positivity was an extended crypt pattern in HACF and DACF showed extension up to the neck region of the crypts and surface epithelium. Carcinomas showed a marked increase in Ki67 expression (P < 0.05). Fhit protein had an inverse association with Ki67 expression. CONCLUSION:Weaker Fhit intensity was associated with smoking, non-vegetarian diet intake and increasing Ki67 expression. Loss of Fhit protein expression is possibly influenced by environmental factors like smoking and non-vegetarian diet intake.
文摘AIM:To evaluate whether crypt abscesses frominflammatory bowel disease(IBD)patients containbacteria and to establish their nature.METHODS:We studied 17 ulcerative colitis patients,11 Crohn's disease patients,7 patients with acute selflimited colitis(ASLC)and normal colonic biopsies from5 subjects who underwent colonoscopy for colon cancer screening.A fluorescent in situ hybridization techniquewas applied to colonic biopsies to assess the microbiotacomposition of the crypts and crypt abscesses.RESULTS:Crypts colonized by bacteria were observedin 42.9%and 3.6%of ASLC and IBD patients,respectively(P=0.019).Crypt abscesses colonized bybacteria were observed in 28.6%and 0.0%of ASLCand IBD patients,respectively(P=0.035).CONCLUSION:These results do not support thehypothesis that crypt abscesses in IBD are the resultof localized dysbiosis arising from persistence of livingbacteria colonizing the crypts.
基金Supported by Grant-in-Aid for Research on the Third Term Comprehensive Control Research for Cancer from the Ministry of Health,Labour and Welfare,Japan to Nakajima Aa grant from the National Institute of Biomedical Innovation (NBIO) to Nakajima Aa grant from the Ministry of Education,Culture,Sports,Science and Technology,Japan (KIBAN-B) to Nakajima A and (KIBAN-C) to Takahashi H
文摘AIM:To clarify the relationship of human rectal aberrant crypt foci and formation of colorectal polyp.METHODS:Eighty-nine subjects were recruited from the population of Japanese individuals who underwent polypectomy at Yokohama City University Hospital.All patients had baseline adenomas removed at year 0 colonoscopy.Aberrant crypt foci(ACF) were defined as lesions in which the crypts were more darkly stained with methylene blue than normal crypts and had larger diameters,often with oval or slit-like lumens and a thicker epithelial lining.RESULTS:A total of 366 ACFs were identified in 89 patients;all had baseline adenomas removed at the first examination(year 0) colonoscopy and returned for the second(year 1).ACF in the lower rectum were assessed at year 0 and study group were divided into two groups depend on ACF numbers,0-3 or over 3.All participants were examined in the number and maximum size of adenoma.There was no statistical difference in number and maximum size of ACF at year 0,however,maximum size of adenoma was larger in over 3 group than 0-3 group at year 1.CONCLUSION:The number of ACF may be a predictive factor of relatively large adenoma incidence in the pilot phase study.
基金supported by Clinical Research Innovation Plan of Shanghai General Hospital(No.CTCCR-2019C04 and No.KD007-ly01)Shanghai Sailing Program(No.20YF1439500)National Science Foundation for Young Scientists of China(No.82001530).
文摘Dear Editor,Cryptozoospermia is defined as the apparent absence of spermatozoa from fresh semen samples,but they can.be found in centrifuged pellets.1 It is usually caused by a spermatogenic disorder,while cryptozoospermia associated with seminal duct obstruction is less common.2 Because of the extremely low sperm counts in semen samples,men with cryptozoospermia are often reliant on intracytoplasmic sperm injection(ICSI)for paternity.
文摘The effect of fermented milk on micronuclei andapoptosis induced by DimethyIhydraziine(DMH)in thecolon crypt cells of mouse was studied.Fermented milk,milk and tap water were fed to three groups of C57BL mice.The animals were given DMH i.p.at a dosage of 20mg/kg onthe 7th day.The animals were sacrificed 24 hours
文摘The intestinal epithelial lining plays a central role in the digestion and absorption of nutrients,but exists in a harsh luminal environment that necessitates continual renewal.This renewal process involves epithelial cell proliferation in the crypt base and later cell migration from the crypt base to the luminal surface.This process is dependent on multi-potent progenitor cells,or stem cells,located in each crypt.There are about 4 to 6 stem cells per crypt,and these stem cells are believed to generate distinct end-differentiated epithelial cell types,including absorptive cells,goblet cells,enteroendocrine cells and Paneth cells,while also maintaining their own progenitor cell state.Earlier studies suggested that intestinal stem cells were located either in the crypt base interspersed between the Paneth cells [i.e.crypt base columnar(CBC) cell model] or at an average position of 4 cells from the crypt base [i.e.label-retaining cells(LRC +4) model].Recent studies have employed biomarkers in the in vivo mammalian state to more precisely evaluate the location of these progenitor cells in the intestinal crypt.Most notable of these novel markers are Lgr5,a gene that encodes a G-protein-coupled receptor with expression restricted to CBC cells,and Bmi 1,which encodes a chromatin remodeling protein expressed by LRC.These studies raise the possibility that there may be separate stem cell lines or different states of stem cell activation involved in the renewal of normal mammalian intestinal tract.
文摘Background:Ventricular crypts are quite a common finding during cardiac imaging,but their etiology is unclear.A possible final result of a spontaneous ventricular septal defect closure has been supposed but never investigated in earlier studies.Method:From January 1997 to December 2020,all newborns diagnosed to have a ventricular septal defect were prospectively entered in our database and those with an isolated defect were included in the study.Ventricular septal defects were classified into four types:perimembranous,trabecular muscular,inlet and outlet.A long-term follow up was performed in order to visualize the possible residual formation of a septal myocardial crypt.Results:A total of 376 isolated ventricular septal defects(314 muscular and 54 perimembranous,4 inlet,4 outlet)were detected.Follow up ranged from 1 to 23 years and showed that,among muscular type,a spontaneous closure occurred in 284(91%),26 did not close(8,28%),2 required surgical intervention(0,63%),3 were lost at follow up(0,95%).During this period,after spontaneous defect closure closure,20 crypts were found(6,4%).Conclusion:This study shows that a muscular ventricular septal defect may evolve in the 6.4%of cases in a residual septal crypt.Although septal crypts occur more frequently in patients affected by hypertrophic and hypertensive cardiomyopathy,they may also represent the evolution of a spontaneous closure of a muscular interventricular defect.
文摘In this paper epithelial cell necroses(apoptosis)of mouse intestinal crypts induced by βRays fromtritiated water(HTO)was reported.The resultsshowed that the number of apoptotic cells perintestinal crypt 20 hrs after injection of
基金This subject is supported by the Fund for Returned Scientists and Scholars,[1999]363.Chinese Ministry of Education.
文摘AIM:To study the genetic alteration in ACF and to define the possibility that ACF may be a very early morphological lesion with molecular changes,and to explore the relationship between ACF and colorectal adenoma even carcinoma. METHODS: DNA from 35 CRC, 15 adenomas, 34 ACF and 10 normal mucus was isolated by means of microdissection. Direct gene sequencing of K-ras gene including codon 12, 13 and 61 as well as the mutation cluster region (MCR) of APC gene was performed. RESULTS: K-ras gene mutation frequency in ACF, adenoma and carcinoma was 17.6% (6/34), 13.3% (2/15), and 14.3% (5/35) respectively, showing no difference (P 】 0.05) in K-ras gene mutation among three pathologic procedures. The K-ras gene mutation in adenoma, carcinoma and 4 ACF restricted in codon 12 (GGT GAT), but the other 2 mutations from ACF located in codon 13 (GGC GAC). K-ras gene mutation was found more frequently in older patients and patients with polypoid cancer. No mutation in codon 61 was found in the three tissue types. Mutation rate of APC gene in adenoma and carcinoma was 22.9% (8/35) and 26.7% (4/15), which was higher than ACF (2.9%) (P 【0.05). APC gene mutation in carcinoma was not correlated with age of patients, location, size and differentiation of tumor. CONCLUSION: ACF might be a very early morphological lesion in the tumorogenesis of colorectal tumor. The morphological feature and gene mutation status was different in ACF and adenoma. ACF is possibly putative microadenoma that might be the precursor of adenoma. In addition, the development of a subgroup of colorectal carcinomas might undergo a way of normal epithelium ACF carcinomas .
基金the National Natural Science Foundation of China(32130099)the Science and Technology Program of Changsha(kq2004078)。
文摘Reportedly,proteins involved in lipid metabolism change significantly in the jejunal crypt cells of earlyweaned piglets,but the exact lipid profile change remains uncertain.In the present study,32 piglets weaned at 21 d of age were randomly divided into 4 groups with 8 replicates.The jejunal crypt cells of a group of piglets on the post-weaning day(PWD)1,3,7,and 14 were isolated per time point.Crypt cell lipid profiles were analyzed using ultra-high-performance liquid chromatography coupled with hybrid quadrupole time-of-flight mass spectrometry.This study showed that piglets suffered the greatest weaning stress on PWD 3 in terms of the lowest relative weight of the small intestine,the highest relative weight of the spleen,and the highest levels of malondialdehyde,cholesterol,and low-density lipoprotein cholesterol.The lipid profile of jejunal crypt cells including carnitine,sulfatide,sphingomyelin,hexosylceramide,and ceramide greatly changed after weaning,especially between PWD3 and 14(P<0.05).The differential lipid species between these 2 d were mainly involved in the glycerophospholipid metabolism pathway.In addition,potential lipid biomarkers for weaning stress in crypt cells such as phosphatidylcholine(PC)(9:0/26:1),PC(17:0/18:2),carnitine(24:0),carnitine(22:0),sphingomyelin(d14:1/22:0),PC(P-18:0/18:4),phosphatidylethanolamine(P-16:0/20:4),phosphatidylinositol(15:1/24:4),and dihexosylceramide(d14:1/26:1)were identified.The changes in lipid profile might be related to the inflammation caused by early weaning.These findings might provide new therapeutical targets for intestinal dysfunctions caused by weaning stress.
文摘Intestinal cancers are developed from intestinal epithelial stem cells(ISCs)in intestinal crypts through a multi-step process involved in genetic mutations of oncogenes and tumor suppressor genes.ISCs play a key role in maintaining the homeostasis of gut epithelium.In 2009,Sato et al established a three-dimensional culture system,which mimicked the niche microenvironment by employing the niche factors,and successfully grew crypt ISCs into organoids or Mini-guts in vitro.Since then,the intestinal organoid technology has been used to delineate cellular signaling in ISC biology.However,the cultured organoids consist of heterogeneous cell populations,and it was technically challenging to introduce genomic changes into three-dimensional organoids.Thus,there was a technical necessity to develop a twodimensional ISC culture system for effective genomic manipulations.In this study,we established a conditionally immortalized mouse intestinal crypt(ciMIC)cell line by using a piggyBac transposon-based SV40 T antigen expression system.We showed that the ciMICs maintained long-term proliferative activity under two-dimensional niche factor-containing culture condition,retained the biological characteristics of intestinal epithelial stem cells,and could form intestinal organoids in three-dimensional culture.While in vivo cell implantation tests indicated that the ciMICs were non-tumorigenic,the ciMICs overexpressing oncogenic b-catenin and/or KRAS exhibited high proliferative activity and developed intestinal adenoma-like pathological features in vivo.Collectively,these findings strongly suggested that the engineered ciMICs should be used as a valuable tool cell line to dissect the genetic and/or epigenetic underpinnings of intestinal tumorigenesis.
