Pub Date : 2019-08-01Epub Date: 2019-07-15DOI: 10.15761/IMM.1000375
Marcin Duleba, Rajasekaran Mahalingam, Audrey-Ann Liew, Yutao Qi, Rahul Neupane, Matthew Vincent, Suneal Agarwal, Francisco A Sylvester, Jeffrey S Hyams, Khek Yu Ho, Jason K Hou, Frank McKeon, Wa Xian
The recent technical advance in cloning and culturing ground-state intestinal stem cells (ISC) provides us an opportunity of accurate assessment of age-related impact on the function of highly proliferative intestinal stem cells. Our ability of indefinitely and robustly expanding single-stem-cell derived pedigrees in vitro allows us to study intestinal stem cells at the clonal level. Interestingly, comparable number of ISC clones was yielded from 1mm endoscopic biopsy of all donors despite the age. They were passaged in vitro as pedigrees and expanded to 1 billion cells in approximately sixty days without changes in stemness demonstrated by clonogenicity and multipotency. Therefore, our study shows that ISCs from a wide range of ages can be cloned and expanded to unlimited number in vitro with similar efficiency and stability. These patient-derived ISCs harbor intrinsic immortality and are ideal for autologous transplantation, supporting the promise of adult-stem-cell based personalized medicine.
{"title":"Unlimited expansion of intestinal stem cells from a wide range of ages.","authors":"Marcin Duleba, Rajasekaran Mahalingam, Audrey-Ann Liew, Yutao Qi, Rahul Neupane, Matthew Vincent, Suneal Agarwal, Francisco A Sylvester, Jeffrey S Hyams, Khek Yu Ho, Jason K Hou, Frank McKeon, Wa Xian","doi":"10.15761/IMM.1000375","DOIUrl":"10.15761/IMM.1000375","url":null,"abstract":"<p><p>The recent technical advance in cloning and culturing ground-state intestinal stem cells (ISC) provides us an opportunity of accurate assessment of age-related impact on the function of highly proliferative intestinal stem cells. Our ability of indefinitely and robustly expanding single-stem-cell derived pedigrees <i>in vitro</i> allows us to study intestinal stem cells at the clonal level. Interestingly, comparable number of ISC clones was yielded from 1mm endoscopic biopsy of all donors despite the age. They were passaged <i>in vitro</i> as pedigrees and expanded to 1 billion cells in approximately sixty days without changes in stemness demonstrated by clonogenicity and multipotency. Therefore, our study shows that ISCs from a wide range of ages can be cloned and expanded to unlimited number <i>in vitro</i> with similar efficiency and stability. These patient-derived ISCs harbor intrinsic immortality and are ideal for autologous transplantation, supporting the promise of adult-stem-cell based personalized medicine.</p>","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/aa/21/nihms-1040965.PMC6713279.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41224762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rina Nakamura, M. Konishi, Y. Higashi, M. Saito, T. Akizawa
We previously reported the catalytic activity of 9-mer peptide, JAL-TA9 (YKGSGFRMI), derived from the Box A region of Tob/BTG family of proteins. This was the first report of the catalytic activity of shorter synthetic peptides. Therefore, we used ‘Catalytide’ (catalytic peptide) as the general term for peptides possessing the hydrolase activity. NMR study of JAL-TA9 suggested that the minimum sequence required for the catalytic activity is a 5-mer peptide (GSGFR). In this study, we examined the catalytic activity of this 5-mer peptide against Aβ fragment peptides, Aβ1-20 and Aβ11-29, to find the next Catalytide. Activity of all peptides identified as Catalytides, especially, GQAYR (BTG3) and GQAFR (BTG4), was higher activity than that of GSGFR (Tob1 and 2) and GSGYR (BTG1 and 2). The cleavage mechanism of these Catalytides is still not well understood and needs further investigation. Nonetheless, 5-mer Catalytides are attractive candidates for the development of peptide drugs as a new strategy for treating Alzheimer’s disease (AD). Abbreviations: APP: Amyloid Precursor Protein; Aβ: Amyloid Beta; AD: Alzheimer’s Disease; HSA: Human Serum Albumin; TFA: Trifluoroacetic Acid; HPLC: High-Performance Liquid Chromatography; NMR: Nuclear Magnetic Resonance.
{"title":"Comparison of the catalytic activities of 5-mer synthetic peptides derived from Box A region of Tob/BTG family proteins against the amyloid-beta fragment peptides","authors":"Rina Nakamura, M. Konishi, Y. Higashi, M. Saito, T. Akizawa","doi":"10.15761/imm.1000374","DOIUrl":"https://doi.org/10.15761/imm.1000374","url":null,"abstract":"We previously reported the catalytic activity of 9-mer peptide, JAL-TA9 (YKGSGFRMI), derived from the Box A region of Tob/BTG family of proteins. This was the first report of the catalytic activity of shorter synthetic peptides. Therefore, we used ‘Catalytide’ (catalytic peptide) as the general term for peptides possessing the hydrolase activity. NMR study of JAL-TA9 suggested that the minimum sequence required for the catalytic activity is a 5-mer peptide (GSGFR). In this study, we examined the catalytic activity of this 5-mer peptide against Aβ fragment peptides, Aβ1-20 and Aβ11-29, to find the next Catalytide. Activity of all peptides identified as Catalytides, especially, GQAYR (BTG3) and GQAFR (BTG4), was higher activity than that of GSGFR (Tob1 and 2) and GSGYR (BTG1 and 2). The cleavage mechanism of these Catalytides is still not well understood and needs further investigation. Nonetheless, 5-mer Catalytides are attractive candidates for the development of peptide drugs as a new strategy for treating Alzheimer’s disease (AD). Abbreviations: APP: Amyloid Precursor Protein; Aβ: Amyloid Beta; AD: Alzheimer’s Disease; HSA: Human Serum Albumin; TFA: Trifluoroacetic Acid; HPLC: High-Performance Liquid Chromatography; NMR: Nuclear Magnetic Resonance.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74758023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Kim, Y. Y. Kyaw, Mi So Seong, K. Kim, J. Cheong
Curcumin is a natural polyphenolic compound extracted from the spice, turmeric and has been reported to evidence anti-inflammatory, antioxidant, and antiproliferative properties via the modulation of multiple cellular mechanisms. Endometriosis, the presence of ectopic endometrial tissue outside the uterine cavity, is a common disease affecting women during their reproductive years. In this study, we showed the effects of curcumin on endometrial cell inflammation. Curcumin inhibited expression of cyclooxygenase-2, which is a pivotal player in inflammatory processes, in the endometrium cells by using luciferase assays, real-time PCR and Western blotting analyses. Furthermore, curcumin exerted inhibitory effects via NF-κB-dependence in part. Decrease of inflammatory gene expression by curcumin in ovary cells was mediated by inhibition of transcription factor SREBP-1 and Akt signaling. In conclusion, the results indicate that curcumin may be potentially useful as novel anti-inflammatory reagents when administered in endometriosis. Introduction There is general agreement that endometriosis is a chronic pelvic inflammatory process, characterized by enhanced numbers of activated peritoneal immune cells and pro-inflammatory factors [1,2]. In particular, increased concentrations of prostaglandins (PGs) and leukotrienes have been found in the peritoneal fluid of endometriosis patients [3]. These are the major constituents of a group of biologically active oxygenated fatty acids known as eicosanoids and have been implicated in various inflammatory diseases. In endometriosis, they appear to play an important role in disease-associated pain, essentially treated with non-steroidal anti-inflammatory drugs [4]. These inflammatory mediators, particularly PGs, may also be directly involved in the pathogenesis of endometriosis, as recent in vitro studies have demonstrated that improved synthesis is involved in enhancing proliferation while inhibiting apoptosis, increasing both angiogenesis and immunosuppression [5]. The cyclooxygenase (COX) pathway leads to the formation of PGs. Curcumin is a natural polyphenolic compound extracted from the spice, turmeric and has been reported to evidence anti-inflammatory, antioxidant, and anti-proliferative properties via the modulation of multiple cellular [6]. However, it remains to be determined whether curcumin affects in the process of endometriosis. The evolution of hepatic inflammation is controlled by specific transcriptional regulators, some of which are well known in the context of cholesterol-inducible inflammation (SREBPs, NF-κB, AP-1, C/EBPs) [7]. Interestingly, some of these factors may also represent molecular links between lipid/cholesterol metabolism and inflammation. Considering that SREBP-1 can promote inflammation and be regulated by hypoxia, we showed that low cellular oxygen tension in endometriotic stromal cells up-regulated SREBP1 expression *Correspondence to: JaeHun Cheong, Department of Molecular Biolo
{"title":"Curcumin suppresses an endometrial cell inflammation through inhibition of SREBP-1","authors":"S. Kim, Y. Y. Kyaw, Mi So Seong, K. Kim, J. Cheong","doi":"10.15761/imm.1000384","DOIUrl":"https://doi.org/10.15761/imm.1000384","url":null,"abstract":"Curcumin is a natural polyphenolic compound extracted from the spice, turmeric and has been reported to evidence anti-inflammatory, antioxidant, and antiproliferative properties via the modulation of multiple cellular mechanisms. Endometriosis, the presence of ectopic endometrial tissue outside the uterine cavity, is a common disease affecting women during their reproductive years. In this study, we showed the effects of curcumin on endometrial cell inflammation. Curcumin inhibited expression of cyclooxygenase-2, which is a pivotal player in inflammatory processes, in the endometrium cells by using luciferase assays, real-time PCR and Western blotting analyses. Furthermore, curcumin exerted inhibitory effects via NF-κB-dependence in part. Decrease of inflammatory gene expression by curcumin in ovary cells was mediated by inhibition of transcription factor SREBP-1 and Akt signaling. In conclusion, the results indicate that curcumin may be potentially useful as novel anti-inflammatory reagents when administered in endometriosis. Introduction There is general agreement that endometriosis is a chronic pelvic inflammatory process, characterized by enhanced numbers of activated peritoneal immune cells and pro-inflammatory factors [1,2]. In particular, increased concentrations of prostaglandins (PGs) and leukotrienes have been found in the peritoneal fluid of endometriosis patients [3]. These are the major constituents of a group of biologically active oxygenated fatty acids known as eicosanoids and have been implicated in various inflammatory diseases. In endometriosis, they appear to play an important role in disease-associated pain, essentially treated with non-steroidal anti-inflammatory drugs [4]. These inflammatory mediators, particularly PGs, may also be directly involved in the pathogenesis of endometriosis, as recent in vitro studies have demonstrated that improved synthesis is involved in enhancing proliferation while inhibiting apoptosis, increasing both angiogenesis and immunosuppression [5]. The cyclooxygenase (COX) pathway leads to the formation of PGs. Curcumin is a natural polyphenolic compound extracted from the spice, turmeric and has been reported to evidence anti-inflammatory, antioxidant, and anti-proliferative properties via the modulation of multiple cellular [6]. However, it remains to be determined whether curcumin affects in the process of endometriosis. The evolution of hepatic inflammation is controlled by specific transcriptional regulators, some of which are well known in the context of cholesterol-inducible inflammation (SREBPs, NF-κB, AP-1, C/EBPs) [7]. Interestingly, some of these factors may also represent molecular links between lipid/cholesterol metabolism and inflammation. Considering that SREBP-1 can promote inflammation and be regulated by hypoxia, we showed that low cellular oxygen tension in endometriotic stromal cells up-regulated SREBP1 expression *Correspondence to: JaeHun Cheong, Department of Molecular Biolo","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77198532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Berlanga-Acosta, Y. Mendoza-Marí, Ariana García-Ojalvo, Jose Angel Acosta-Buxado, M. Fernández-Mayola, G. Nieto
Diabetes mellitus remains with an ever-increasing prevalence, indefectibly associated to progressive and irreversible complications. Diabetic lower extremities ulcerations contribute to amputations, disability, and mortality. Ulcers result from a wound healing failure characterized by proliferative arrest, apoptosis, and senescence of granulation tissue-producing cells. Diabetic wounds are also distinguished by an inflamed, toxic, and degradative environment, acting as deterrents for local growth factors availability and receptors’ physiology. The emergence of growth factors caused expectation as biological modifiers for wounds repair arrest. The clinical introduction of growth factors was precocious when critical pieces of chronicity pathophysiology and growth factors pharmacology remained elusive. Mounting observations indicated that topical administration of these agents failed by the effect of local proteolysis, narrow bioavailability window, inadequate local kinetics/ diffusion, and a regenerating polymicrobial biofilm. As an alternative to circumvent these pharmacodynamics obstacles as to preserve EGF biological capabilities, we developed a series of experiments which provided the rationale and fundamentals for an intra-ulcer infiltrative delivery route. The clinical development program has included from a proof-of-concept to post-marketing studies in poor-prognosis ischemic, neuropathic and neuroischemic wounds. Along 18 years of clinical progress more than 259 000 patients were treated. As demonstrated by pharmacovigilance studies, aside from the success in the primary healing, the infiltrated EGF accounted for a reduction of amputation risks, negligible rates of annual recurrence, and prolonging survival of the healed patients. This pharmacological intervention is added to conventional treatments and surgical procedures. Infiltrated EGF has proved to reverse wound cells arrest being efficacious and safe for long terms of follow up. Brief reflections on diabetes and the wound healing failure Since the seminal contribution of Banting and Best diabetes treatment was revolutionized. Hereafter, insulin therapy eliminated ketoacidosis as a principal cause of death among diabetics who enjoyed a longer lifespan. However, traditional insulin therapy combined with emerging novel approaches did not translate into a significant reduction of major complications that nowadays lead to morbidity and mortality [1]. Type 2 Diabetes Mellitus (T2-DM) is a heterogeneous and complex process comprising multiple pathogenic factors [2] and multi-organs complications’ that remain as a challenge for scientists and clinicians. T2-DM has progressively expanded as a pandemic condition accounting for 90% to 95% of all the diabetic population [3,4]. Diabetic foot ulceration (DFU) is one of the most frightened diabetic complications, leading to amputation-disability, social exclusion and early mortality [5]. The lifetime incidence of foot ulcers has been estimated to re
{"title":"Epidermal Growth Factor (EGF) intralesional infiltrations: From the bench to the diabetic ulcers cells","authors":"J. Berlanga-Acosta, Y. Mendoza-Marí, Ariana García-Ojalvo, Jose Angel Acosta-Buxado, M. Fernández-Mayola, G. Nieto","doi":"10.15761/IMM.1000354","DOIUrl":"https://doi.org/10.15761/IMM.1000354","url":null,"abstract":"Diabetes mellitus remains with an ever-increasing prevalence, indefectibly associated to progressive and irreversible complications. Diabetic lower extremities ulcerations contribute to amputations, disability, and mortality. Ulcers result from a wound healing failure characterized by proliferative arrest, apoptosis, and senescence of granulation tissue-producing cells. Diabetic wounds are also distinguished by an inflamed, toxic, and degradative environment, acting as deterrents for local growth factors availability and receptors’ physiology. The emergence of growth factors caused expectation as biological modifiers for wounds repair arrest. The clinical introduction of growth factors was precocious when critical pieces of chronicity pathophysiology and growth factors pharmacology remained elusive. Mounting observations indicated that topical administration of these agents failed by the effect of local proteolysis, narrow bioavailability window, inadequate local kinetics/ diffusion, and a regenerating polymicrobial biofilm. As an alternative to circumvent these pharmacodynamics obstacles as to preserve EGF biological capabilities, we developed a series of experiments which provided the rationale and fundamentals for an intra-ulcer infiltrative delivery route. The clinical development program has included from a proof-of-concept to post-marketing studies in poor-prognosis ischemic, neuropathic and neuroischemic wounds. Along 18 years of clinical progress more than 259 000 patients were treated. As demonstrated by pharmacovigilance studies, aside from the success in the primary healing, the infiltrated EGF accounted for a reduction of amputation risks, negligible rates of annual recurrence, and prolonging survival of the healed patients. This pharmacological intervention is added to conventional treatments and surgical procedures. Infiltrated EGF has proved to reverse wound cells arrest being efficacious and safe for long terms of follow up. Brief reflections on diabetes and the wound healing failure Since the seminal contribution of Banting and Best diabetes treatment was revolutionized. Hereafter, insulin therapy eliminated ketoacidosis as a principal cause of death among diabetics who enjoyed a longer lifespan. However, traditional insulin therapy combined with emerging novel approaches did not translate into a significant reduction of major complications that nowadays lead to morbidity and mortality [1]. Type 2 Diabetes Mellitus (T2-DM) is a heterogeneous and complex process comprising multiple pathogenic factors [2] and multi-organs complications’ that remain as a challenge for scientists and clinicians. T2-DM has progressively expanded as a pandemic condition accounting for 90% to 95% of all the diabetic population [3,4]. Diabetic foot ulceration (DFU) is one of the most frightened diabetic complications, leading to amputation-disability, social exclusion and early mortality [5]. The lifetime incidence of foot ulcers has been estimated to re","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91531390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Kalamitsou, S. Masino, E. Pavlou, M. Gogou, Irene Katsanika, K. Papadopoulou-Legbelou, A. Serdari, M. Spilioti, A. Evangeliou
{"title":"The effect of creatine supplementation on seizure control in children under ketogenic diet. a pilot study","authors":"S. Kalamitsou, S. Masino, E. Pavlou, M. Gogou, Irene Katsanika, K. Papadopoulou-Legbelou, A. Serdari, M. Spilioti, A. Evangeliou","doi":"10.15761/imm.1000357","DOIUrl":"https://doi.org/10.15761/imm.1000357","url":null,"abstract":"","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88771679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The cultivation of human pluripotent stem cells (hPSCs) has become an important factor in regenerative medicine and the development of drugs. Similar to other mammalian cells, human pluripotent stem cells are important in culture for the formation of microenvironment, including intercellular interactions, growth factors, and contact between cells and matrix [1]. The culture of stem cells is similar to that of standard mammalian cell culture, but differentiation or maintenance of undifferentiated state may be necessary for the purpose. Phenotypic characteristics in pluripotent stem cells (morphology, colony assessment, pluripotent potential) and in differentiated cells (morphology, differentiation markers, functionality) should be evaluated [1].
{"title":"Culture medium, extracellular components and differentiation in culturing of human pluripotent stem cells","authors":"Hea-Jo Yoon, Woo Jung Ho","doi":"10.15761/IMM.1000360","DOIUrl":"https://doi.org/10.15761/IMM.1000360","url":null,"abstract":"The cultivation of human pluripotent stem cells (hPSCs) has become an important factor in regenerative medicine and the development of drugs. Similar to other mammalian cells, human pluripotent stem cells are important in culture for the formation of microenvironment, including intercellular interactions, growth factors, and contact between cells and matrix [1]. The culture of stem cells is similar to that of standard mammalian cell culture, but differentiation or maintenance of undifferentiated state may be necessary for the purpose. Phenotypic characteristics in pluripotent stem cells (morphology, colony assessment, pluripotent potential) and in differentiated cells (morphology, differentiation markers, functionality) should be evaluated [1].","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86965925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Artem Kim, B. Izac, N. Lebrun, N. Ramoz, C. Blanchet, F. Letourneur, M. Moro, P. Gorwood, M. Tayrac, T. Bienvenu
Purpose: Anorexia nervosa (AN) is a serious psychiatric disorder characterized by abnormal eating behaviors, resulting in weight loss and increased mortality. Although more common in females, an estimated 5 to 10% of affected patients are males. Up to now, the exact cause of male AN is unknown. As with many psychiatric diseases, it's probably a combination of genetic, biological, psychological and environmental factors. Here, we used whole-genome bisulfite sequencing to determine the methylome of male individuals with AN. Methods: We analyzed by bisulfite sequencing 3,340,894 biologically relevant CpG sites (Illumina TruSeqMethyl Capture EPIC kit) of 6 male patients affected with AN restrictive type. To reduce the environment effect, 4 related unaffected individuals were selected as controls. Results: Comparisons between male patients affected with AN restrictive type and unaffected controls showed 153 differentially methylated regions and 1812 differentially methylated CpGs that corresponded to genes relevant to metabolic and nutritional status, psychiatric status and immune function. Moreover, the String network analysis software identified a subnetwork, related to MAPK signaling pathway, PI3K-Akt signaling pathway and neurotrophin signaling pathway. Conclusions: Our findings replicate several results concerning several target genes such as PRKAG2, RPTOR, and ICAM5 previously identified in female AN, and identified novel signaling pathways involving PI3K-Akt and neurotrophin signaling pathway disturbed in AN.
{"title":"Altered DNA methylation associated with nervosa anorexia in males","authors":"Artem Kim, B. Izac, N. Lebrun, N. Ramoz, C. Blanchet, F. Letourneur, M. Moro, P. Gorwood, M. Tayrac, T. Bienvenu","doi":"10.15761/imm.1000376","DOIUrl":"https://doi.org/10.15761/imm.1000376","url":null,"abstract":"Purpose: Anorexia nervosa (AN) is a serious psychiatric disorder characterized by abnormal eating behaviors, resulting in weight loss and increased mortality. Although more common in females, an estimated 5 to 10% of affected patients are males. Up to now, the exact cause of male AN is unknown. As with many psychiatric diseases, it's probably a combination of genetic, biological, psychological and environmental factors. Here, we used whole-genome bisulfite sequencing to determine the methylome of male individuals with AN. Methods: We analyzed by bisulfite sequencing 3,340,894 biologically relevant CpG sites (Illumina TruSeqMethyl Capture EPIC kit) of 6 male patients affected with AN restrictive type. To reduce the environment effect, 4 related unaffected individuals were selected as controls. Results: Comparisons between male patients affected with AN restrictive type and unaffected controls showed 153 differentially methylated regions and 1812 differentially methylated CpGs that corresponded to genes relevant to metabolic and nutritional status, psychiatric status and immune function. Moreover, the String network analysis software identified a subnetwork, related to MAPK signaling pathway, PI3K-Akt signaling pathway and neurotrophin signaling pathway. Conclusions: Our findings replicate several results concerning several target genes such as PRKAG2, RPTOR, and ICAM5 previously identified in female AN, and identified novel signaling pathways involving PI3K-Akt and neurotrophin signaling pathway disturbed in AN.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91366913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yue Jia, P. Ji, Luan Nguyen, Felicita E. Baratelli, S. French
Making a distinction between adenoma, intramucosal carcinoma, and invasive carcinoma on small biopsies of colon polypoid lesions can occasionally pose a challenge to pathologists. In our study, we aimed to assess the staining patterns and utilities of the two immunohistochemical stains CAM5.2 and caldesmon in helping with this endeavor. Routinely processed colon polyps biopsies’ specimens from 57 patients with CAM5.2 and caldesmon ordered were reviewed by three pathologists. We found CAM5.2 and caldesmon to be very useful in classifying these colon polypoid lesions. CAM5.2 highlighted single cells and cribriform architecture. Caldesmon stained the lamina propria, the smooth muscle, and the desmoplastic stroma surrounding invasive tumor in colonic submucosa with different morphologic characteristics. First, in the lamina propria, caldesmon was mostly negative with faint brown lines surrounding glands and small vessels. Second, in the smooth muscle of muscularis mucosa, caldesmon stained the cytoplasm lightly with solid and diffuse pattern. Third, in the desmoplastic area of the submucosa, caldesmon stained the cytoplasm strongly with a clear space or groove seen at the middle of the cytoplasm (tram-tracking appearance). We described our findings in this study with hope that more pathologists will utilize these two stains in their common practice to reliably diagnose invasion by colon carcinoma.
{"title":"The roles of CAM5.2 and caldesmon IHC stains in challenge of diagnosing adenoma, intramucosal carcinoma, and invasive adenocarcinoma on colon biopsies","authors":"Yue Jia, P. Ji, Luan Nguyen, Felicita E. Baratelli, S. French","doi":"10.15761/imm.1000386","DOIUrl":"https://doi.org/10.15761/imm.1000386","url":null,"abstract":"Making a distinction between adenoma, intramucosal carcinoma, and invasive carcinoma on small biopsies of colon polypoid lesions can occasionally pose a challenge to pathologists. In our study, we aimed to assess the staining patterns and utilities of the two immunohistochemical stains CAM5.2 and caldesmon in helping with this endeavor. Routinely processed colon polyps biopsies’ specimens from 57 patients with CAM5.2 and caldesmon ordered were reviewed by three pathologists. We found CAM5.2 and caldesmon to be very useful in classifying these colon polypoid lesions. CAM5.2 highlighted single cells and cribriform architecture. Caldesmon stained the lamina propria, the smooth muscle, and the desmoplastic stroma surrounding invasive tumor in colonic submucosa with different morphologic characteristics. First, in the lamina propria, caldesmon was mostly negative with faint brown lines surrounding glands and small vessels. Second, in the smooth muscle of muscularis mucosa, caldesmon stained the cytoplasm lightly with solid and diffuse pattern. Third, in the desmoplastic area of the submucosa, caldesmon stained the cytoplasm strongly with a clear space or groove seen at the middle of the cytoplasm (tram-tracking appearance). We described our findings in this study with hope that more pathologists will utilize these two stains in their common practice to reliably diagnose invasion by colon carcinoma.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72918628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yoshitaka Ishihara, Yugo Miura, N. Miura, Keigo Miura
{"title":"A novel anti-cancer effect of atelocollagen-conjugated miR-520d-5p on pancreatic cancer cells in vitro and in a mouse xenograft model","authors":"Yoshitaka Ishihara, Yugo Miura, N. Miura, Keigo Miura","doi":"10.15761/IMM.1000364","DOIUrl":"https://doi.org/10.15761/IMM.1000364","url":null,"abstract":"","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84527677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evolution of stress hormones and proteins in relation to developmental origins of health and disease","authors":"Viktor I Goudochnikov","doi":"10.15761/imm.1000362","DOIUrl":"https://doi.org/10.15761/imm.1000362","url":null,"abstract":"","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83289831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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